Antibiotics

Can J Gastroenterol, 2000 Jul-Aug, 14 Suppl B, 81B - 82B
Fasciitis complicating subcutaneous injection of interferon beta; Cooper CL et al.; Data pertaining to 65 patients treated at the Health Sciences Center Hepatology Research Unit in Winnipeg, Manitoba describing local complications related to subcutaneous interferon (IFN) injection administered to treat hepatitis C virus infection are presented . Nine patients experienced local erythematous reactions at the injection region . No life-threatening complications were identified . One case of fasciitis complicating IFN beta injection - a complication not previously reported - was successfully managed with surgical debridement and antibiotic therapy . This case is a dramatic example of why sterile technique during infections must be adhered to.

Am J Otolaryngol, 2000 Jul-Aug, 21(4), 281 - 3
Submasseteric abscess: report of two cases; Leu YS et al.; Submasseteric abscess is a rare infection with the symptoms of cheek tenderness and marked trismus . Submasseteric abscess is located between the masseter muscle and mandibular ramus with different appearances as sepsis, infection, or tumor . Two cases of submasseteric abscess are reported along with symptoms, causes, and management techniques . Adequate drainage and antibiotic infusion are the treatment of choice . The differential diagnosis of cheek swelling and tenderness that should be considered are parotitis, parotid gland tumor, temporomasseter joint arthritis, and submasseteric abscess.

Bioorg Med Chem Lett, 2000 Aug 7, 10(15), 1701 - 5
One-pot synthesis and biological evaluation of aspergillamides and analogues; Beck B et al.; A one-pot total synthesis of aspergillamide and analogues by a solution phase Ugi multi component reaction (MCR) is described . The reaction is easily performed in 96-well plates and offers a facile access to diverse aspergillamide analogue compound libraries . The antibiotic and cytotoxic activity of these compounds is measured . Several of them are more potent than the natural product.

J Mol Microbiol Biotechnol, 2000 Jul, 2(3), 271 - 6
Generation of hybrid elloramycin analogs by combinatorial biosynthesis using genes from anthracycline-type and macrolide biosynthetic pathways; Rodriguez L et al.; Elloramycin and oleandomycin are two polyketide compounds produced by Streptomyces olivaceus Tu2353 and Streptomyces antibioticus ATCC11891, respectively . Elloramycin is an anthracycline-like antitumor drug and oleandomycin a macrolide antibiotic . Expression in S . albus of a cosmid (cos16F4) containing part of the elloramycin biosynthetic gene cluster produced the elloramycin non-glycosylated intermediate 8-demethyl-tetracenomycin C . Several plasmid constructs harboring different gene combinations of L-oleandrose (neutral 2,6-dideoxyhexose attached to the macrolide antibiotic oleandomycin) biosynthetic genes of S . antibioticus that direct the biosynthesis of L-olivose, L-oleandrose and L-rhamnose were coexpressed with cos16F4 in S . albus . Three new hybrid elloramycin analogs were produced by these recombinant strains through combinatorial biosynthesis, containing elloramycinone or 12a-demethyl-elloramycinone (= 8-demethyl-tetracenomycin C) as aglycone moiety encoded by S . olivaceus genes and different sugar moieties, coded by the S . antibioticus genes . Among them is L-olivose, which is here described for the first time as a sugar moiety of a natural product.

Nature, 2000 Jul 27, 406(6794), 435 - 9
Humanized xenobiotic response in mice expressing nuclear receptor SXR; Xie W et al.; The cytochrome CYP3A gene products, expressed in mammalian liver, are essential for the metabolism of lipophilic substrates, including endogenous steroid hormones and prescription drugs . CYP3A enzymes are extremely versatile and are inducible by many of their natural and xenobiotic substrates . Consequently, they form the molecular basis for many clinical drug-drug interactions . The induction of CYP3A enzymes is species-specific, and we have postulated that it involves one or more cellular factors, or receptor-like xeno-sensors . Here we identify one such factor unequivocally as the nuclear receptor pregnenolone X receptor (PXR) and its human homologue, steroid and xenobiotic receptor (SXR) . We show that targeted disruption of the mouse PXR gene abolishes induction of CYP3A by prototypic inducers such as dexamethasone or pregnenolone-16alpha-carbonitrile . In transgenic mice, an activated form of SXR causes constitutive upregulation of CYP3A gene expression and enhanced protection against toxic xenobiotic compounds . Furthermore, we show that the species origin of the receptor, rather than the promoter structure of CYP3A genes, dictates the species-specific pattern of CYP3A inducibility . Thus, we can generate 'humanized' transgenic mice that are responsive to human-specific inducers such as the antibiotic rifampicin . We conclude that SXR/PXR genes encode the primary species-specific xeno-sensors that mediate the adaptive hepatic response, and may represent the critical biochemical mechanism of human xenoprotection.

Neoplasia, 1999 Oct, 1(4), 356 - 67
The "comparative growth assay": examining the interplay of anti-cancer agents with cells carrying single gene alterations; Hausner P et al.; We have developed a "comparative growth assay" that complements current assays of drug effects based on cytotoxicity . A co-culture of two cell lines, one of which is fluorescently labeled, is exposed to a cytotoxic agent and the proportion of fluorescent cells is compared with that of a baseline unexposed co-culture . For demonstration purposes, two HCT116 cell lines (an hMLH1 homozygous and an hMLH1 heterozygous mutant), altered by insertion of vector alone or the same vector carrying an insert for the expression of enhanced green fluorescent protein (EGFP), were exposed to numerous "anti-cancer" agents . The assay was further validated in a system of two cell lines differing only in the expression of the breast cancer resistance protein (BRCP) . The assay allowed the estimation of the duration of action of a particular agent . Assessment of the agent's differential activity over a given time in culture could be expressed as a selection rate, which we chose to describe on an "average selection per day" basis . We conclude that this assay: 1) provides insight into the differential dynamic effects of chemotherapeutic agents or radiation; and 2) allows, through the use of matched cell lines, the investigation of critical physiologic features that govern cell sensitivity.

Acta Pol Pharm, 2000 Mar-Apr, 57(2), 105 - 11
The in vitro study of influence of antioxidant enzymes level and repair capacity on cytotoxic bleomycin activity in human and mouse cells; Gruber BM et al.; Bleomycin, an antitumour antibiotic was used to study the possible relationship between DNA single strand breaks repair capacity, antioxidant enzymes level and cytotoxic activity of the drug in mouse cells: AKR and BALB/c and in human cells: CRL 2088 and CRL 1307 (xeroderma pigmentosum) . The BALB/c and CRL 1307 cells were used because of having defects in DNA repair capacity . A positive correlation was shown to exist between IC50 values and repair ability which suggested that DNA single strand breaks could be responsible for cytotoxic effects of bleomycin in human and mouse cells . Also antioxidant enzymes level have occurred as, at least partly, participating in bleomycin cytotoxic efficiency . About 10-fold higher resistance of AKR cells to bleomycin in comparison with the other cells, as appeared here, did not exhibit the straight correlation with antioxidant status of the cells . It prompts participation of the other mechanism in bleomycin cytotoxic action than that based on free radical generation . Also drug distribution and metabolism should be considered as a possible factor needed in bleomycin efficacy evaluation.

Ophthalmic Epidemiol, 2000 Jun, 7(2), 149 - 57
A survey of vernal keratoconjunctivitis and other eosinophil-mediated external eye diseases amongst Palestinians; O'Shea JG; PURPOSE: To determine the morbidity of vernal, atopic and other disease mediated by eosinophils amongst the Palestinian Community of East Jerusalem, West Bank and Gaza Strip . METHOD: In a prospective outpatient study, 840 people were screened for evidence of eosinophilic external eye disease by history taking and medical examination of the external eye, conjunctiva, nose and paranasal sinuses in the outpatient clinic . The surgical and iatrogenic morbidity of the condition was concurrently estimated, and the prescribing habits of local West Bank ophthalmologists were carefully evaluated . The favoured regime was locally manufactured antihistamine drops, usually in combination with an aminoglycoside antibiotic that characteristically exacerbates the condition . Topical steroids, such as guttae prednisolone forte, were also overused as a modality to treat the condition . CONCLUSIONS: Since the recent decline of endemic trachoma, vernal eye disease is now the leading cause of outpatient ophthalmic morbidity amongst Palestinians of East Jerusalem . The disease accounts for at least 9 . 8% of approximately 74,400 annual outpatient attendances to ophthalmic clinics in East Jerusalem, the West Bank and Gaza . The manifestations of the disease, however, are more protean than this . In the context of poor hygiene and sometimes dubious medical practice, vernal eye disease is often responsible for serious anterior segment and external ophthalmic disease.

J Mass Spectrom, 2000 Jul, 35(7), 919 - 24
Optimization of capillary electrophoresis conditions for coupling to a mass spectrometer via a sheathless interface; Samskog J et al.; When optimizing a capillary electrophoresis/electrospray ionization mass spectrometry (CE/ESI-MS) system, consideration has to be given not only to the separation but also to the electrospray stability . Methods developed for CE/UV analysis of drugs and peptides were considered and modified to be suitable for a CE/MS system with a robust sheathless interface . Different concentrations of the organic modifiers acetonitrile, methanol and 2-propanol were used in the separation buffer . The type and concentrations of these modifiers were also compared with reference to electrospray stability, sensitivity and time of analysis . In addition, different ionic strengths in the buffers were evaluated with reference to electrospray stability . The repeatability was used for the estimation of electrospray stability . The degree to which these parameters influenced the separation and the ESI stability was studied using a nine-peptide standard mixture and the antibiotic drugs bacampicillin and ampicillin as test substances . The analysis time and resolution were used as measures of the efficiency of the separation . A time-of-flight MS analyzer was used since it has the potential advantages of becoming a better fit for integration of CE with MS owing to the speed and sensitivity of this mass analyzer . The detection limit, i.e . 1 microM, for bacampicillin was comparable to what could be achieved with CE/MS on a quadrupole instrument using selected ion monitoring and sheath flow ESI .

J Cell Sci, 2000 Sep, 113 ( Pt 17), 2977 - 89
Intracellular distribution and mobilization of unesterified cholesterol in adipocytes: triglyceride droplets are surrounded by cholesterol-rich ER-like surface layer structures; Prattes S et al.; In addition to their central role in triglyceride storage, fat cells are a primary depot of unesterified cholesterol (FC) in the body . In comparison, peripheral cells contain very little FC . This difference in adipocytes versus peripheral tissues is inconsistent with the current theory of cholesterol homeostasis . Attempting to resolve this discrepancy, we examined intracellular storage sites of FC in murine 3T3-F442A adipocytes . Using the cholesterol-binding antibiotic, filipin, in combination with high resolution fluorescence microscopy, intense fluorescent staining characteristically decorated the periphery of triglyceride droplets (TGD) as well as the plasma membrane (PM) of fat cells . Filipin-staining was not visible inside the lipid droplets . Purification of TGD by subcellular fractionation demonstrated that the rise in total FC content of adipocytes upon differentiation was attributable to an increase in TGD-FC, which contributed up to one third of the total cellular FC . The protein component of purified TGD from cultured adipocytes as well as from murine adipocytes obtained from fresh tissues contained the lumenal endoplasmic reticulum (ER) immunoglobulin binding protein (BiP) and the integral ER membrane protein calnexin . Efflux experiments using the extracellular FC acceptors (&bgr;)-cyclodextrin or apolipoprotein A-I demonstrated that TGD-associated FC was releasable from TGD . Whereas FC efflux from adipocytes was unaffected in the presence of brefeldin A or monensin, the secretion of a control protein, lipoprotein lipase, was effectively reduced . In summary, our findings identify the TGD surface layer as primary intracellular storage site for FC within adipocytes . We suggest that the structural role of ER-resident proteins in this adipocyte TGD envelope has been previously neglected . Our findings support the suggestion that an ER-like structure, albeit of modified lipid composition, constitutes the lipid droplets' surface layer . Finally, the efflux process of FC from adipocytes upon extracellular stimulation with (beta)-cyclodextrin provides evidence for an energy-dependent intracellular trafficking route between the TGD-FC pool and the PM-FC sites which is distinct from the secretory pathway of proteins.

Biochemistry, 2000 Aug 15, 39(32), 9975 - 83
Catalase-peroxidase (Mycobacterium tuberculosis KatG) catalysis and isoniazid activation; Chouchane S et al.; Resonance Raman spectra of native, overexpressed M . tuberculosis catalase-peroxidase (KatG), the enzyme responsible for activation of the antituberculosis antibiotic isoniazid (isonicotinic acid hydrazide), have confirmed that the heme iron in the resting (ferric) enzyme is high-spin five-coordinate . Difference Raman spectra did not reveal a change in coordination number upon binding of isoniazid to KatG . Stopped-flow spectrophotometric studies of the reaction of KatG with stoichiometric equivalents or small excesses of hydrogen peroxide revealed only the optical spectrum of the ferric enzyme with no hypervalent iron intermediates detected . Large excesses of hydrogen peroxide generated oxyferrous KatG, which was unstable and rapidly decayed to the ferric enzyme . Formation of a pseudo-stable intermediate sharing optical characteristics with the porphyrin pi-cation radical-ferryl iron species (Compound I) of horseradish peroxidase was observed upon reaction of KatG with excess 3-chloroperoxybenzoic acid, peroxyacetic acid, or tert-butylhydroperoxide (apparent second-order rate constants of 3.1 x 10(4), 1.2 x 10(4), and 25 M(-1) s(-1), respectively) . Identification of the intermediate as KatG Compound I was confirmed using low-temperature electron paramagnetic resonance spectroscopy . Isoniazid, as well as ascorbate and potassium ferrocyanide, reduced KatG Compound I to the ferric enzyme without detectable formation of Compound II in stopped-flow measurements . This result differed from the reaction of horseradish peroxidase Compound I with isoniazid, during which Compound II was stably generated . These results demonstrate important mechanistic differences between a bacterial catalase-peroxidase and the homologous plant peroxidases and yeast cytochrome c peroxidase, in its reactions with peroxides as well as substrates.

Clin Experiment Ophthalmol, 2000 Apr, 28(2), 89 - 95
The New Zealand cataract and refractive surgery survey 1997/1998; Elder M et al.; BACKGROUND: This study documents the current practice for cataract and refractive surgery in New Zealand . METHOD: A postal questionnaire was distributed in late 1997 to all consultant members of the Ophthalmological Society of New Zealand that were resident in the country at that time . Most questions were identical to the 1997 survey of the American Society of Cataract and Refraction Surgeons (ASCRS) to enable a comparison . RESULTS: There were 98 returns from 101 surveys distributed . Of the returns, 72 performed cataract surgery, 23 performed PRK and 11 performed LASIK.ASCRS members did more refractive surgery than did New Zealanders: 28 versus 1% of 1-5 RK per month, 7 versus 1% of 1-2 clear lens extractions per month and 85 versus 51% had access to an excimer laser . For cataract surgery, ASCRS members used more topical anaesthesia (30 vs 5.5%), used no sutures more often (73 vs 51%), used more preoperative antibiotics (76 vs 26%) and used fewer injections of antibiotic/steroids (38 vs 61%) . Otherwise the two groups were broadly similar.

J Pharm Biomed Anal, 2000 Aug 15, 23(2-3), 275 - 80
A rapid high performance liquid chromatographic (HPLC) assay for the determination of oxytetracycline in commercial pharmaceuticals; Papadoyannis IN et al.; In the present study, a simple, sensitive and rapid reversed-phase high performance liquid chromatographic (HPLC) method with ultraviolet detection for the analysis of oxytetracycline (OTC) is developed and applied to the determination of the antibiotic in commercial pharmaceutical preparations (powder, capsules, vaginal tablets and ointment) . The isocratic elution is performed with methanol-0.01 M oxalic acid, pH 3.0 (30:70, v/v) at a flow rate of 0.95 ml min, using a Silasorb C8 analytical column, 250 x 4 mm, 10 microm . Codeine is used as internal standard . Absorbance is monitored at 250 nm where both analyte of interest and internal standard have significant absorption . Total analysis time was approximately 7 min . Data with respect to precision and accuracy and limits of detection are reported and discussed . The described method can be readily utilised for analysis of pharmaceutical products and pharmacokinetic studies as well.

Eur Respir J, 2000 Jul, 16(1), 91 - 4
Sputum induction in young cystic fibrosis patients; De Boeck K et al.; A culture from the lower airway secretions is the optimal sample to guide antibiotic therapy in cystic fibrosis (CF) lung disease . The authors therefore examined whether sputum induction is an efficient, safe and acceptable procedure in CF children without spontaneous expectorations . Nineteen patients were studied . Their mean age (range) was 8.6 yrs (4.3-15.2 yrs) . Their mean forced expiratory volume in one second (FEV1) was 88% predicted (46-122%) . NaCl solutions from 0.9-6% were inhaled, after baseline lung function tests before and after salbutamol . All patients did produce secretions . Alveolar macrophages were present in 16/19 induced samples . The procedure induced minor but significant bronchoconstriction: the mean change (range) in postsalbutamol FEV1 (% pred) was -7 (-24-16) . Percutaneous oxygen saturation remained above 90% in all children . The test had to be discontinued in one child because of cough and wheeze . Acceptability of the procedure evaluated using a visual analogue scale from -7-7 showed a mean value (range) at the final concentration of -1.23 (-6.16-5.88) . It is concluded that sputum induction is possible, safe and acceptable in cystic fibrosis children who do not expectorate spontaneously.

Analyst, 2000 Jun, 125(6), 1037 - 9
Enantioselective supercritical fluid chromatography using ristocetin A chiral stationary phases; Svensson LA et al.; Racemic mixtures of five acidic drugs have been successfully separated by supercritical fluid chromatography (SFC) using macrocyclic antibiotic chiral stationary phases (CSPs) . A ristocetin A CSP has been prepared 'in-house' and effectively applied in packed capillary SFC to separate the enantiomers of dichlorprop (R(s) = 1.4), ketoprofen (R(s) = 0.9) and warfarin (R(s) = 0.9) . The commercial ristocetin A CSP (Chirobiotic R) was subsequently studied in packed column SFC with similar results where the enantiomers of warfarin (R(s) = 2.2), coumachlor (R(s) = 2.5) and thalidomide (R(s) = 0.6) were separated . Interestingly, differences were observed between the two differently immobilised CSPs where the enantiomers of dichlorprop and ketoprofen, which were separated on the 'in-house' CSP, could not be separated on the commercial phase.

Microbiology, 2000 Aug, 146 ( Pt 8), 1987 - 97
The ABC transporter AtrB from Aspergillus nidulans mediates resistance to all major classes of fungicides and some natural toxic compounds; Andrade AC et al.; This paper reports the functional characterization of AtrBp, an ABC transporter from Aspergillus nidulans . AtrBp is a multidrug transporter and has affinity to substrates belonging to all major classes of agricultural fungicides and some natural toxic compounds . The substrate profile of AtrBp was determined by assessing the sensitivity of deletion and overexpression mutants of atrB to several toxicants . All mutants showed normal growth as compared to control isolates . DeltaatrB mutants displayed increased sensitivity to anilinopyrimidine, benzimidazole, phenylpyrrole, phenylpyridylamine, strobirulin and some azole fungicides . Increased sensitivity to the natural toxic compounds camptothecin (alkaloid), the phytoalexin resveratrol (stilbene) and the mutagen 4-nitroquinoline oxide was also found . Overexpression mutants were less sensitive to a wide range of chemicals . In addition to the compounds mentioned above, decreased sensitivity to a broader range of azoles, dicarboximides, quintozene, acriflavine and rhodamine 6G was observed . Decreased sensitivity in overexpression mutants negatively correlated with levels of atrB expression . Interestingly, the overexpression mutants displayed increased sensitivity to dithiocarbamate fungicides, chlorothalonil and the iron-activated antibiotic phleomycin . Accumulation of the azole fungicide {(14)C}fenarimol by the overexpression mutants was lower as compared to the parental isolate, demonstrating that AtrBp acts by preventing intracellular accumulation of the toxicant . Various metabolic inhibitors increased accumulation levels of {(14)C}fenarimol in the overexpression mutants to wild-type levels, indicating that reduced accumulation of the fungicide in these mutants is due to increased energy-dependent efflux as a result of higher pump capacity of AtrBp.

Environ Health Perspect, 2000 Aug, 108 Suppl 4, 725 - 31
Specific and nonspecific obstructive lung disease in childhood: causes of changes in the prevalence of asthma; Platts-Mills TA et al.; Reversible airway obstruction in childhood includes two major groups of patients: those with recurrent wheezing following bronchiolitis in early childhood, and those with allergic asthma, which represents an increasingly large proportion of cases through the school years . Over the last 40 years of the 20th century, allergic asthma has increased in many countries and in relation to several different allergens . Although this increase has differed in magnitude in different countries and also in the social groups most affected, it has had several features in common . The increase generally started between 1960 and 1970, has been progressive since then, and has continued into the 1990s without a defined peak . Among children 5-18 years of age, the increase has predominantly been among allergic individuals . Theories about the causes of the increase in asthma have focused on two scenarios: a) that changes in houses combined with increased time spent indoors have increased exposure to relevant allergens, or b) that changes in diet, antibiotic use, immunizations, and the pattern of infections in childhood have led to a change in immune responsiveness such that a larger section of the population makes T(H)2, rather than T(H)1 responses including IgE antibodies to inhalant allergens . There are, however, problems with each of these theories and, in particular, none of the proposed changes can explain the progressive nature of the increase over 40 years . The fact that the change in asthma has much in common with epidemic increase in diseases such as Type II diabetes or obesity suggests that similar factors could be involved . Several lines of evidence are reviewed that suggest that the decline in physical activity of children, particularly those living in poverty in the United States, could have contributed to the rise in asthma . The hypothesis would be that the progressive loss of a lung-specific protective effect against wheezing has allowed allergic children to develop symptomatic asthma . What is clear is that current theories do not provide either an adequate explanation of the increase or a practical approach to reversing the current trend.

Clin Ther, 2000 Jun, 22(6), 748 - 59
Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial; Jara-Perez JV et al.; BACKGROUND: Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children . The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults . OBJECTIVES: This trial reports results of a double-masked, placebo-controlled, parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage . METHODS: Two hundred girls (age range, 6 to 13 years) living in an orphanage entered the trial . Participants were randomly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months . Patients were followed up for 6 months, including the administration period . The trial began in September 1996 and finished in March 1997 . Primary end points were the type and number of infections . Secondary end points included when an infection occurred, time to clinical cure, severity of infection, absenteeism from school due to an ARTI, number of antibiotics or other drugs prescribed, and duration of concomitant drug treatment . RESULTS: During the trial, patients in the OM-85 BV group experienced 143 ARTIs (135 upper ARTIs and 8 otitis episodes) and patients in the placebo group experienced 299 ARTIs (273 upper ARTIs, 1 lower ARTI, and 25 otitis episodes) . The median number of ARTIs was 1.0 (0.0, 3.0; 5th percentile, 95th percentile) in the OM-85 BV group compared with 3.0 (2.0, 4.0; 5th percentile, 95th percentile) in the placebo group . This difference was statistically significant (P < 0.001) . Participants who received OM-85 BV also showed significantly better results (P < 0.001) than participants who received placebo in terms of median duration of illness, median number of missed school days due to an ARTI, median number of antibiotic and drug courses, and median duration of concomitant treatment . There were significant differences (P < 0.05) in severity of ARTIs during month 4 of the trial, with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month . No adverse events related to the trial medications were reported . Conclusions: OM-85 BV had a preventive effect on ARTIs in the school girls, with a reduction in the antibiotic requirements and the duration of ARTIs . Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs.

Int J Antimicrob Agents, 2000 Aug, 15(4), 277 - 82
Helicobacter pylori: ureA, cagA and vacA expression during conversion to the coccoid form; Sisto F et al.; As viability of coccoid forms of Helicobacter pylori can only be verified by demonstrating the integrity of the DNA and active protein synthesis, we analysed the expression of ureA, cagA, vacA genes after prolonged incubation in a liquid medium . Exponentially growing and ageing phase cultures were used . Our results showed that, although the coccoid forms had decreased DNA and RNA levels after 31 days, they were not degraded and still expressed the urease, cytotoxic island and vacuolating toxin genes . Coccoid forms are therefore viable and may act as a transmissible agent that plays a crucial role in disease relapses after antibiotic therapy.

Curr Opin Clin Nutr Metab Care, 2000 Jul, 3(4), 293 - 7
Cystic fibrosis: nutritional status and micronutrients; Winklhofer-Roob BM; Recent studies have focused on the current dietary intake of cystic fibrosis patients, the impact of nutritional support on both the nutritional status and clinical outcome variables, and the effects on the nutritional status of antibiotic therapy and surgical treatment of meconium ileus . In addition to weight and height, skinfold measurements, bioelectrical impedance analysis and dual energy X-ray absorptiometry have been employed for the determination of nutritional status . A proton pump inhibitor has been used successfully along with pancreatic enzymes for the improvement of fat absorption . Attention has been paid to resting energy expenditure during pulmonary exacerbations, to vitamin K function in bone mineralization and to risk factors for low bone mineral density in cystic fibrosis . The relationships between glutathione and nutritional status have been studied, along with possible interactions with albumin, a potent antioxidant . Finally, a beneficial effect of docosahexaenoic acid on cystic fibrosis pathology has been suggested, but this requires further critical evaluation.

Clin Chem Lab Med, 2000 Apr, 38(4), 313 - 20
Suitability of collection tubes with separator gels for collecting and storing blood samples for therapeutic drug monitoring (TDM); Karppi J et al.; In this study, we present significant changes occurring in serum drug concentrations while using blood collection tubes that contain a barrier gel . This report also contains results with antidepressant drugs, which have not been studied before with human samples . The drug concentrations were measured either with high performance liquid chromatography (HPLC) or fluorescence polarization immunoassay (FPIA) . The results show that gel tubes are suitable for blood collection for antiepileptic, antibiotic, asthma and cardioactive drug measurements, since only slight adsorption was seen (0-5%) . However, the studied tubes are not suitable for blood collection of antidepressants nor benzodiazepines, because the adsorption can be 5-30% . The adsorption was even higher (up to 40%) when samples were stored for 24 h after centrifugation in gel tubes . When the centrifugation step was performed after storage the effect of the barrier gel was lower (only 0-13%) . Antidepressant drug measurements performed from patient specimens collected in the studied gel tubes and stored for 3 h showed <10% adsorption of the studied drugs . After 24 h storage time, concentrations of all analysed drugs decreased even more: adsorbed amount of drugs were about 5-20% . The studied gel tubes are proposed to be satisfactory for blood collection for antidepressant drug measurements if separation step is performed within 3 h after blood clotting . With the spiked samples the adsorption to barrier gel was higher, so it seems that adsorption is faster when drugs are not highly bound to serum proteins.

Eur J Anaesthesiol, 2000 Jun, 17(6), 390 - 4
Anaesthetic implications of osteo-odonto-keratoprosthesis surgery; Skelton VA et al.; Patients with bilateral corneal blindness in whom corneal transplantation has either been unsuccessful or inappropriate may be considered for osteo-odonto-keratoprosthesis surgery . During a two-stage procedure the surface of the cornea is removed and covered with a graft of buccal mucosa . An optical cylinder, supported by an osteo-odonto lamina planed from a tooth is then inserted into the mucosa to act as a lens . The anaesthetic implications of this operation include care of patients from a wide age range, often with underlying medical problems undergoing two operations of prolonged duration . The eye can be 'open' during both stages of the operation and anaesthetic techniques directed towards prevention of rises in vitreal pressure are essential . This article outlines the surgical process of osteo-odonto-keratoprosthesis surgery with reference to our anaesthetic experiences from nine cases.

Arch Neurol, 2000 Aug, 57(8), 1210 - 2
A case of Balamuthia mandrillaris meningoencephalitis; Katz JD et al.; Balamuthia mandrillaris is a newly described pathogen that causes granulomatous amebic encephalitis, an extremely rare clinical entity that usually occurs in immunosuppressed individuals . We report a case of pathologically proven Balamuthia encephalitis with unusual laboratory and radiologic findings . A 52-year-old woman with idiopathic seizures and a 2-year history of chronic neutropenia of unknown cause had a subacute illness with progressive lethargy, headaches, and coma and died 3 months after the onset of symptoms . Cerebrospinal fluid (CSF) glucose concentrations were extremely low or unmeasurable, a feature not previously described (to our knowledge) . Cranial magnetic resonance imaging scans showed a single large temporal lobe nodule, followed 6 weeks later by the appearance of 18 ring-enhancing lesions in the cerebral hemispheres that disappeared after treatment with antibiotics and high-dose corticosteroids . The initial brain biopsy specimen and analysis of CSF samples did not demonstate amebae, but a second biopsy specimen and the postmortem pathologic examination showed Balamuthia trophozoites surrounded by widespread granulomatous inflammation and vasculitis . The patient's neutropenia and antibiotic use may have caused susceptibility to this organism . Amebic meningoencephalitis should be considered in cases of subacute meningoencephalitis with greatly depressed CSF glucose concentrations and multiple nodular lesions on cerebral imaging . Arch Neurol . 2000;57:1210-1212

Twin Res, 2000 Jun, 3(2), 71 - 5
Conservative management of triplet pregnancy after delivery of one foetus; Biard JM et al.; This paper intends to demonstrate that the conservative management of triplet pregnancy after delivery of one foetus is a feasible and reasonable approach . Three cases of triplet pregnancy with successful conservative management after miscarriage of one foetus, are presented and compared with cases in the literature . The route of delivery, as well as the role of tocolysis, cerclage, prophylactic antibiotic therapy and corticosteroids are discussed . Guidelines for conservative treatment are proposed . The deliveries of our three pregnancies were delayed by 63, 44 and 22 days respectively . Foetal and neonatal evolution are normal in five of the remaining foetuses . Only one intrauterine death is observed . No maternal complications with sequelae are reported . After abortion of the first triplet, contractions often persist and the birth of the two remaining foetuses may be unavoidable . Nevertheless, in our experience, confirmed by some reports in the literature, prolongation of the pregnancy after expulsion of the first foetus is possible . It can be achieved by cervical cerclage associated with tocolytic and antibiotic therapy . This management is not associated with significantly increased foetal-maternal morbidity.

Aust N Z J Obstet Gynaecol, 2000 May, 40(2), 200 - 2
Successful pregnancy outcome following first trimester pelvic inflammatory disease; Stitely ML et al.; Pelvic inflammatory disease rarely complicates pregnancy . Although few in number, most of the previously reported cases have resulted in spontaneous abortion or intrauterine fetal demise . At 5 weeks gestation, a 20 year old gravida 2 para 1 underwent uterine curettage and diagnostic laparoscopy for a suspected ectopic gestation . Seventeen days later, she presented with severe bilateral lower abdominal pain, cervical motion tenderness, uterine tenderness, and bilateral adnexal tenderness . After 84 hours of intravenous cefazolin, gentamycin, and clindamycin, the patient had resolution of all symptoms . She then completed 14 days of outpatient antibiotic therapy with oral cephalexin . At 39 weeks gestation, she delivered a 3611 g male fetus via spontaneous vaginal delivery . Successful pregnancy outcome can occur after first trimester pelvic inflammatory disease.

J Formos Med Assoc, 2000 Jul, 99(7), 544 - 8
Clinical features of and risk factors for fungal peritonitis in peritoneal dialysis patients; Huang JW et al.; BACKGROUND AND PURPOSE: Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients and can result in technical failure and mortality . Catheter removal remains the mainstay of treatment . This study sought to identify the risk factors for FP in order to facilitate the prevention of this catastrophic complication . METHODS: A total of 246 patients who received long-term PD from 1985 to 1998 were included in this retrospective study . Twenty episodes of FP occurred in 19 patients . The clinical characteristics, pathogens, treatment modalities, and outcomes of the FP episodes were retrospectively reviewed . The FP incidence in various demographic and clinical groups, classified according to sex, age, education, and underlying cause of uremia, were compared with the Poisson test . RESULTS: Thirteen episodes of FP were caused by yeast, and the remaining episodes were caused by Aspergillus spp . Age, sex, and education did not affect the FP incidence . Lupus patients (969 patient-months) had a higher incidence of FP than patients with other underlying diseases (p < 0.05) . The 19 FP patients also had a higher incidence of bacterial peritonitis than other PD patients (p < 0.01) . Among the 20 FP episodes, 14 (70%) were preceded by antibiotic use, and eight (40%) developed during hospitalization . Steroids were used at the time of FP in five of six lupus patients . Seven patients (37%) died within 1 month after diagnosis of FP . Five patients were able to remain on PD after FP, but only three patients were able to maintain catheter placement . CONCLUSION: The risk factors for FP identified in this study include the use of antibiotics and steroids, underlying lupus, frequent occurrence of bacterial peritonitis, and hospitalization . Antifungal therapy may allow the catheter to be kept in place in a few patients, but catheter removal should be considered in patients whose FP is refractory to medical treatment.

Biochemistry, 2000 Aug 8, 39(31), 9077 - 83
Rho transcription factor: symmetry and binding of bicyclomycin; Vincent F et al.; The antibiotic bicyclomycin inhibits rho-dependent termination processes by interfering with RNA translocation by preventing RNA binding at the translocation site or by uncoupling the translocation process from ATP hydrolysis . Previous studies have shown that bicyclomycin binds near the ATP hydrolysis pocket on rho . The hexameric structure of rho indicates that it is in a class of enzymes with strong sequence similarity to F(1)-ATP synthase . The bicyclomycin derivative 5a-formylbicyclomycin, an inhibitor comparable to bicyclomycin, was previously shown to form a stable imine with rho and when reduced to the amine with NaBH(4) to singly label five of the six rho subunits . Lysine-336 was identified by mass spectrometric analysis of trypsin-digested fragments as the site of 5a-formylbicyclomycin adduction . A model of rho was made by threading the rho sequence on the known crystal structure of the alpha and beta subunits of F(1)-ATP synthase . The model, along with information concerning the extent and site of 5a-formylbicyclomycin adduction, indicates an overall C6 symmetry for rho subunit organization . We propose that the sequence similarity between rho and F(1)-ATP synthase extends to a similar quaternary structure and an equivalent enzyme mechanism . The proposed mechanism of RNA translocation coupled with ATP hydrolysis changes the overall symmetry of rho from C6 to C6/C3.

Biochemistry, 2000 Aug 8, 39(31), 9067 - 76
5a-formylbicyclomycin: studies on the bicyclomycin-Rho interaction; Vincent F et al.; Bicyclomycin (1) is a commercial antibiotic whose primary site of action is the rho transcription termination factor . A new bicyclomycin irreversible inactivator, 5a-formylbicyclomycin (3), was prepared to provide information concerning the bicyclomycin-rho inactivation process and the drug's binding pocket within rho . The apparent I(50) value for 3 was 35 microM, showing that 3 was a more effective inhibitor of rho poly C-dependent ATPase activity than 1 (I(50) = 60 microM) . Mechanistic studies demonstrated that 3 inhibited poly C-dependent ATP hydrolysis, in part, by a reversible, noncompetitive pathway with respect to ATP (K(i) = 62 microM) . Incubation of 3 with rho led to efficient imine formation . Adding excess 1 to solutions containing 3 and rho prevented imine formation, demonstrating that 1 and 3 bind to the same active site in the protein . The 3-rho imine was stabilized by either ATP or ADP or by both, and was converted to the nonreversible 3-rho amine adduct upon treatment with NaBH(4) . Mass spectrometric analysis of the amine provided a stoichiometry of approximately five bound 3 per rho hexamer indicating the number of bicyclomycin binding sites for the rho hexamer is between five and six . Monomer exchange experiments using modified 3-rho amine and wild type rho demonstrated that no more than two modified subunits per rho hexamer are sufficient to halt poly C-dependent rho ATPase activity.

Cancer Res, 2000 Jul 15, 60(14), 3921 - 6
Histone H3 and heat shock protein GRP78 are selectively cross-linked to DNA by photoactivated gilvocarcin V in human fibroblasts; Matsumoto A et al.; Gilvocarcin V (GV) is an antitumor antibiotic with a coumarin-based aromatic structure that promotes protein-DNA cross-linking when photoactivated by near-UV light . We have now identified several proteins that are selectively cross-linked to DNA in human fibroblasts by photoactivated GV, using NH2-terminal amino acid sequencing and Western blot analysis of the purified cross-linked proteins . The selectively cross-linked proteins are histone H3 and GRP78, a heat shock protein belonging to the heat shock protein-70 family . The hydrophobic leader sequence is missing from the cross-linked GRP78, suggesting that only the processed form of the protein is cross-linked to DNA . It is primarily the phosphorylated form of histone H3 that is cross-linked to DNA . Gel retardation analysis from four different GV-treated human fibroblast cell lines revealed two distinct shifted bands, and subsequent immunoblotting confirmed in situ that the slower and the faster bands, respectively, contained GRP78 and histone H3 cross-linked to DNA . The selective cross-linking of these particular proteins is dependent on UV irradiation in the presence of GV, which may help to clarify the unique molecular mechanism of this potent antitumor agent.

Prim Care, 2000 Sep, 27(3), 725 - 40;vii
Valvular heart disease; Hara JH; Given the high prevalence of valvular heart disease, primary care physicians need to be familiar with the most common valvular heart diseases and their clinical manifestations . Knowledge of the natural history of the most common valvular heart diseases is important because the onset of symptoms often is the point at which intervention becomes necessary . Most valvular heart diseases are amenable to surgical intervention, which can afford a symptom-free and relatively normal life span . Therefore, primary care physicians must be familiar with the indications for therapeutic interventions and the most appropriate interventions currently recommended.

Bone Marrow Transplant, 2000 Jul, 26(2), 225 - 6
Brucellosis transmitted by bone marrow transplantation; Ertem M et al.; We report a unique case of brucellosis transmitted by BMT . An 8-year-old boy with the diagnosis of Fanconi's anemia received an allogeneic BMT from his HLA-identical sibling . Routine culture from the infused marrow suspension grew Brucella abortus on day +4 post BMT . Spiking fevers occurred on days +2 and +16 . The first febrile episode responded to broad-spectrum antibiotic therapy . However, the second episode did not . B . abortus was isolated from blood cultures taken during the second febrile episode . The Brucella agglutination titer was negative . Antibiotic therapy with oral doxycycline and i.v . gentamycin was successful with no recurrence of infection during 13 months of follow-up . The donor's blood culture was also positive for B . abortus and Brucella antibodies were detectable at 1:320 titer when he presented with fever and hepatosplenomegaly on day +32 . We emphasize the need to consider brucellosis in patients undergoing BMT . We suggest that donor and recipient be evaluated for brucellosis especially in countries where the incidence of this infection is relatively high.

Vet Surg, 2000 Jul-Aug, 29(4), 317 - 25
Cecal amputation within the right ventral colon for surgical treatment of nonreducible cecocolic intussusception in 8 horses; Hubert JD et al.; OBJECTIVES: To report a surgical technique for treatment of nonreducible cecocolic intussusception and outcome in 8 horses . STUDY DESIGN: Retrospective study . ANIMALS: Eight horses with nonreducible cecocolic intussusception treated by cecal amputation through a right ventral colotomy . METHODS: Data were obtained from medical records and telephone conversations by using a standardized questionnaire . The large colon was exteriorized and, if necessary, evacuated of its contents through a pelvic flexure enterotomy . A second colotomy was made on the ventral surface of the right ventral colon (RVC) centered over or immediately distal to the intussusceptum . In most horses, attempts to manually reduce the intussusception by pushing the cecum from within the RVC through the cecocolic orifice were unsuccessful . Invaginated cecum was then pulled into the RVC and amputated; the cecum was either ligated with umbilical tape or sutured proximal to the site of amputation . After amputation, the remainder of the invaginated cecum was reduced . After further resection to healthy tissue, the typhlectomy was closed with a double-inverting suture pattern . RESULTS: The median horse age was 2 years (range, 1 to 8 years) . Duration of colic ranged from 6 hours to 6 months . Median surgical time was 180 minutes (range, 135 to 300 minutes) . Median duration of antibiotic therapy was 7 days (range, 5 to 14 days) . Median duration of hospitalization was 12 days (range, 6 to 21 days) . All horses survived to hospital discharge . One horse died 3 months postoperatively; however, the remainder survived (median survival, 30 months; range, 6 to 96 months) and returned to or exceeded previous function . CLINICAL RELEVANCE: Despite some contamination during surgery, horses with nonreducible cecocolic intussusception that underwent this method of surgical treatment had a good prognosis.

G Chir, 2000 Jun-Jul, 21(6-7), 306 - 9
{Current role of open window thoracostomy}; Torresini G et al.; The Open Window Thoracostomy (OWT) surgical method find its origin in the treatment of chronic tuberculous empyemas, in the cases where the drainage alone not permitted a sufficient cleaning of pleural cavity . In the recent years the indications for the execution of this method are extended also to metapneumoniae and post-pneumonectomy empyemas (for benign and malignant pathology), with or without bronco-pleural fistula, when these pathologies produces a general severe decline in the patient (septic shock) . This method permit to effect a daily cleaning of a pleural cavity, through the introduction of a sterile gauzes imbued of specific antibiotic, reducing at least the purulent infection effects's previously present and favouring the reduction of the same cavity, in prevision of other reconstructive operations (thoracoplasty) . Generally not many beloved by surgeons and patients (for the difficult management, aesthetic outcomes, the long stay in hospital), the OWT can often reestablish a dangerous situation, especially in the patients with a risk of septic shock . This study aims to analyse present indications, problems and therapeutics outcomes of this method, through the evaluation of 27 cases of OWT treated in the Department of Thoracic Surgery University of L'Aquila between the 1984 and the 1998.

Arch Pediatr Adolesc Med, 2000 Aug, 154(8), 817 - 21
Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis; Nigrovic LE et al.; BACKGROUND: Infants with fever and cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital for parenteral antibiotic therapy for potential bacterial meningitis pending results of CSF culture . Published estimates suggest that 90% of all episodes of meningitis are caused by enterovirus . Enteroviral polymerase chain reaction (ePCR) has a sensitivity of 92% to 100% and a specificity of 97% to 100% in CSF . OBJECTIVE: To compare a management strategy using ePCR with current practice to determine potential savings by allowing earlier discharge . METHODS: Decision analysis comparing 2 strategies for the care of a retrospective cohort of infants with fever and CSF pleocytosis: standard practice vs ePCR testing of all CSF samples . Model assumptions include the following: (1) standard practice patients continue parenteral antibiotic therapy until CSF cultures are negative at 48 hours, (2) patients with positive ePCR results would be discharged after 24 hours, (3) patients with positive ePCR results have a negative CSF culture, and (4) costs are calculated from actual patient charges with a cost-to-charge ratio of 0.65 . SUBJECTS: All infants aged 28 days to 12 months admitted to an urban teaching hospital with fever, CSF pleocytosis, and a negative CSF Gram stain from January 1996 through December 1997 . OUTCOME MEASURE: Total cost of hospitalization . RESULTS: A total of 126 infants were identified . One hundred twelve (89%) were discharged with a diagnosis of aseptic meningitis; 72% of these cases occurred during the peak enterovirus season (June to October) . Three of 3 patients with positive CSF cultures had bacterial growth within 24 hours of admission . Mean length of stay for patients with aseptic meningitis was 2.3 days (SD, +/-1.4 days) . Total cost of hospital care for all 126 infants was $381,145 . In our patient population, total patient costs would be reduced by the ePCR strategy if enterovirus accounts for more than 5 . 9% of all meningitis cases . Varying the sensitivity of the ePCR assay from 100% to 90% changes the "break-even" prevalence from 5.8% to 6.5% . Total cost savings of 10%, 20%, and 30% would occur at an enteroviral meningitis prevalence of 36.3%, 66.7%, and 97.1%, respectively . CONCLUSIONS: Enteroviral PCR analysis of CSF for infants admitted to the hospital with meningitis can result in cost savings when the prevalence of enteroviral meningitis exceeds 5.9% . Limiting use of ePCR to the enterovirus season would increase cost savings . A prospective study is needed to validate these results . Arch Pediatr Adolesc Med . 2000;154:817-821

Arch Ophthalmol, 2000 Aug, 118(8), 1125 - 8
Mycobacterium chelonae conjunctivitis and scleritis following vitrectomy; Margo CE et al.; The atypical, or nontuberculous, mycobacteria are opportunistic pathogens that usually cause infection following accidental trauma or surgery . These organisms are ubiquitous in nature but have been found with increasing frequency in other environments that include medical offices and surgical suites . Management of atypical mycobacterial ocular infections can be difficult because in vitro antibiotic activity does not always correlate with in vivo efficacy and because normal immune defenses against mycobacteria may work too slowly to prevent irreversible damage to infected ocular tissues . This report describes a patient who developed a severe ocular infection due to Mycobacterium chelonae after vitrectomy . Despite eradication of the infection, the eye became blind and painful . Arch Ophthalmol . 2000;118:1125-1128

J Clin Microbiol, 2000 Aug, 38(8), 2824 - 8
Clinical and financial benefits of rapid detection of respiratory viruses: an outcomes study; Barenfanger J et al.; To assess the expected benefits of rapid reporting of respiratory viruses, we compared patients whose samples were processed using standard techniques such as enzyme immunoassays, shell vial assays, and culture tube assays (year 1) to patients whose samples were processed with the same standard techniques in addition to immunofluorescent testing (FA) directly on cytocentrifuged samples (year 2) . The cytospin FA screened for influenza A and B viruses, respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3, and adenovirus (DAKO Diagnostics Ltd.) . The specificity of the cytospin FA for all viruses was 100% . The sensitivities for influenza A virus and RSV were 90 and 98%, respectively, but the sensitivities for influenza B virus and adenovirus were unacceptable (14.3 and 0%, respectively) . However, since the former viruses account for >85% of our isolates from clinical specimens, the cytospin FA is an excellent screening test since the positive result was available within hours . The mean turnaround time for all positive viruses was 4.5 days in year 1 and 0.9 day in year 2 (P = 0.001) . This rapid reporting resulted in physicians having access to information sooner, enabling more appropriate treatment . The mean length of stay in the hospital for inpatients with respiratory viral isolates was 10.6 days for year 1 versus 5.3 days for year 2 . Mean variable costs for these patients was $7,893 in year 1 and $2,177 in year 2 . After subtracting reagent costs and technological time, the savings in variable costs was $144,332/year . Summarizing, the cytospin FA markedly decreased turnaround time and was associated with decreased mortality, length of stay, and costs and with better antibiotic stewardship.

No Shinkei Geka, 2000 Jul, 28(7), 631 - 7
{Two cases of pyogenic cervical discitis presenting tetraparesis}; Nishimura H et al.; The authors reported two cases of pyogenic cervical discitis presenting tetraparesis . Case 1: A 66-year-old male patient entered the hospital because of tetraparesis . Two weeks before the hospitalization, he had become feverish and awakened with motor weakness in all extremities . Magnetic Resonance Imaging (MRI) study revealed a lesion filling the anterior epidural space from C4 to C6 levels and posterior displacement of the spinal cord . Findings suggesting discitis of C5/6 and osteomyelitis of C5 and C6 were also obtained on MRI . These findings suggested that the tetraparesis was caused by cord compression by the epidural abscess as the acute stage of pyogenic spinal infection . On the day following admission, surgical removal of the epidural abscess and of the infected bodies was performed . Spinal fusion through C4 to C7 was also carried out with iliac bone graft . Antibiotic administration and Halo-vest application were performed after the operation . The postoperative course was good and the tetraparesis had completely disappeared within 12 months after the operation . Case 2: A 60-year-old male patient entered the hospital because of tetraparesis . Since 6 weeks before the hospitalization, he had become feverish and suffered from pain in the neck . He had also awakened with motor weakness of all extremities . The tetraparesis was progressive . Plain X-ray films of the cervical spine showed destructive change of C5 and C6 and kyphotic displacement . An epidural abscess of the cervical spine at the level of C4 to C6, discitis of C5/6 and osteomyelitis of C5 and C6 were diagnosed on MRI findings . The disarranged kyphotic vertebral bodies and the epidural abscess caused posterior displacement of the spinal cord . Based on these findings, it was concluded that the abscess and the kyphotic change of the bodies had been induced by spinal infection in the subacute stage . On the 8th hospital day, surgical removal of the anterior portion of the infected bodies as well as fusion of the vertebral column from C4 to C7 was performed . Iliac bone was used for the fusion graft . Postoperative administration of antibiotics and Halo-vest application for external fixation were carried out . On the 7th postoperative day, symptoms caused by radiculopathy of the left C5 appeared, but gradually ameliorated . The patient was free from motor weakness in the 8th month after the surgical treatment . Surgical intervention is a useful treatment for pyogenic cervical discitis with symptoms due to compression of the spinal cord both in the acute and subacute stages.

Ann Ital Med Int, 2000 Apr-Jun, 15(2), 144 - 55
Infections, atherosclerosis, and coronary heart disease; Famularo G et al.; There is growing evidence that the immune response is involved in atherosclerosis . Studies done over the past several years have shown an association between markers of inflammation and coronary atherosclerosis with an exacerbation of the inflammatory process during acute myocardial ischemia . Overall, these data have greatly renewed interest in the infectious theory of atherosclerosis and coronary heart disease . Search of bibliographic databases (from January 1991 through December 1999) and manual scanning of both peer-reviewed publications and other documents were used to identify pertinent literature . Infections and coronary heart disease were indexed as key words . A large number of studies have reported an association of human coronary heart disease and certain persistent bacterial and viral infections . The association between Chlamydia pneumoniae and coronary heart disease appears quite significant although the sequence of infection and disease is uncertain . The association between Helicobacter pylori and coronary heart disease may be accounted for by residual confounding from classic risk factors . Preliminary findings indicate that this association could be due to a higher prevalence of more virulent Helicobacter strains . Infection with Cytomegalovirus appears to be associated with a greater risk of restenosis after angioplasty rather than primary atherosclerosis . Early trials of appropriate antibiotic therapy in subjects with recent acute myocardial infarction have been encouraging . A causal relationship between infections and coronary heart disease is still elusive . Improved studies involving prospective collection of data are required to demonstrate such an association with potential implications for public health worldwide.

Am J Respir Cell Mol Biol, 2000 Aug, 23(2), 204 - 12
A CD36 synthetic peptide inhibits bleomycin-induced pulmonary inflammation and connective tissue synthesis in the rat; Yehualaeshet T et al.; Transforming growth factor (TGF)-beta1 is an important regulator of inflammation and fibrosis . TGF-beta1 is usually secreted as a biologically latent protein called latent TGF-beta1 (L-TGF-beta1) . L-TGF-beta1 has no biologic effect unless L-TGF-beta1 is converted to its active form . Using a well-recognized model of lung injury induced by the antineoplastic antibiotic bleomycin (Blm), we demonstrated that 7 d after intratracheal Blm administration, total lung TGF-beta was maximally increased . This induction was due to TGF-beta1 production by alveolar macrophages that, when explanted, generated increased quantities of L-TGF-beta1 complexed with the glycoprotein thrombospondin (TSP)-1 . The TSP-1/L-TGF-beta1 complex was associated with CD36, a receptor for TSP-1 . The association of TSP-1/L-TGF-beta1 to CD36 was critical for plasmin-mediated release of mature TGF-beta1 . In this paper we show that, compared with administration of Blm by itself, when a synthetic peptide of CD36 between amino acids 93 and 110 is given concomitantly with Blm to rats, alveolar macrophages generate markedly less active TGF-beta1, the rats gain weight more rapidly, and there is less inflammation, collagen I and III, and fibronectin synthesis . These findings demonstrate a novel in vivo mechanism of activation of L-TGF-beta1 in lung injury and the importance of alveolar macrophage- derived active TGF-beta1 in the pathogenesis of pulmonary inflammation and fibrosis.

Hum Mol Genet, 2000 Jul 22, 9(12), 1787 - 93
A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity; Guan MX et al.; The A1555 G mutation in mitochondrial 12S rRNA has been found to be associated with non-syndromic deafness and aminoglycoside-induced deafness . The sensitivity to the aminoglycoside paromomycin has been analyzed in lymphoblastoid cell lines derived from five deaf individuals and five hearing individuals from an Arab-Israeli family carrying the A1555G mutation, and three married-in controls from the same family . Exposure to a high concentration of paromomycin (2 mg/ml), which caused an 8% average increase in doubling time (DT) in the control cell lines, produced higher average DT increases (49 and 47%) in the A1555G mutation-carrying cell lines derived from symptomatic and asymptomatic individuals, respectively . The ratios of translation rates in the presence and absence of paromomycin, which reflected the effect of the drug on mitochondrial protein synthesis, were significantly decreased in the cell lines derived from symptomatic and asymptomatic individuals (by 30 and 28% on average, respectively), compared with the ratios in the control cell lines . These ratios showed, in both groups of mutant cell lines, a significant negative correlation with the ratios of DTs in the presence and absence of the antibiotic . These results have provided the first direct evidence that the mitochondrial 12S rRNA carrying the A1555G mutation is the main target of aminoglycosides . They suggest that these antibiotics exert their detrimental effect through an alteration of mitochondrial protein synthesis, which exacerbates the inherent defect caused by the mutation, reducing the overall translation rate down to and below the minimal level required for normal cellular function (40-50%).

Aust Fam Physician, 2000 Jul, 29(7), 639 - 45
Community acquired pneumonia . A perspective for general practice; Tsirgiotis E et al.; BACKGROUND: Community acquired pneumonia (CAP) occurs in approximately two per 1000 of the adult population per year . About 2% of adult overnight hospital admissions are due to CAP and there is a continuing mortality rate of 7-10% . OBJECTIVE: To present an approach for the community and hospital assessment and management of CAP based on current concepts and evidence . DISCUSSION: Clinical and radiological assessments are unable to identify the nature of the causative organism . However, knowledge of the patient risk profile and a clinical severity assessment enable appropriate management decisions to be made . Early antibiotic therapy according to the guidelines and appropriate supportive management should reduce CAP mortality . It is essential that the CAP patient is followed to ensure radiological resolution . The incidence of community acquired pneumonia (CAP) can be reduced by rigid application of National Health and Medical Research Council (NH&MRC) vaccination recommendations for pneumococcal and influenza immunisation.

J Laryngol Otol, 2000 May, 114(5), 376 - 7
When a mastoid swelling is not mastoiditis; Hung T et al.; A case is reported of swelling over the mastoid process due to subgaleal abscess possibly secondary to trivial cutaneous trauma . The diagnosis was difficult as subgaleal abscess is an extremely rare condition especially after the advent of the antibiotic era . The route of entry of the infection to the subgaleal space was unclear as there was no skin puncture . The absence of substantial trauma excluded subgaleal haematoma as a precondition . We would like to discuss the possible aetiologies and the management of this rare case in the light of the limited information available in the world literature.

Mol Biotechnol, 2000 May, 15(1), 77 - 81
Comparison of two kinds of methods to determine the titer of recombinant retrovirus containing beta-globin gene based on G418 selection; Dong W et al.; Four recombinant retrovirus (RV) vectors containing human beta-globin gene and regulatory elements were constructed . To determine the titers of recombinant RV from corresponding producer cell lines, we compared two kinds of method (the simple and the conventional) based on G418 resistance, which is conferred by neo gene of RV vector . The results demonstrated that the simple method shortened the selection period to 3 d instead of 10-12 d with the conventional method and reduced the amount of work; importantly, the titers determined by the simple method were not different significantly from those measured by the conventional method . It can be concluded that the simple method can be used to determine the titers of recombinant RV containing not only cDNA but also genomic DNA with introns and complex regulatory elements instead of the conventional method.

Harefuah, 1998 Nov 1, 135(9), 364 - 6, 407
{Aphthous stomatitis as a first manifestation of Crohn's disease in a 5 year-old boy}; Gold Y et al.; The incidence of Crohn's disease has risen dramatically over the past few years . The peak age of onset is in late adolescence, but it rarely occurs in the first few years of life . We describe a 5-year-old boy with recurrent bouts of fever, aphthous stomatitis, and anemia which did not respond to routine antibiotic therapy . It was only after a few months, when the characteristic symptoms of inflammatory bowel disease (IBD): abdominal pain and diarrhea appeared, that the diagnosis of Crohn's disease was made . This case illustrates the difficulty in diagnosing IBD in young children . The presenting symptoms of IBD in children are often nonspecific and extra-intestinal . There is usually a low index of suspicion by the physician as to the possibility of IBD in a young child.

Acta Paediatr Taiwan, 1999 Jul-Aug, 40(4), 268 - 70
Sonographic and color Doppler sonographic diagnosis of acute osteomyelitis: report of one case; Chao HC et al.; Acute osteomyelitis in childhood is uncommon . Early diagnosis is often difficult . We present a 7-year-old boy with clinical manifestation of fever and progressive left thigh swelling for one week . Sonography of the left thigh showed periosteal thickening with subperiosteal abscess around the metaphysis of the left distal femur . Tc-99m bone scintigraphy showed increased uptakes at the left distal femur . Osteomyelitis was suspected from the examination of ultrasound and bone scan examinations . His symptoms were not relieved following systemic antibiotic therapy and a follow-up color Doppler sonography showed vascular flows within and around the periosteum indicating active inflammation . He finally received surgical drainage and the operative findings confirmed the diagnosis of osteomyelitis . In conclusion, ultrasound may be a helpful and convenient tool for establishing the early diagnosis of pediatric osteomyelitis . Ultrasound and color Doppler sonography can be used as clinical parameters to evaluate the disease severity and the progression of osteomyelitis in children.

Acta Paediatr Taiwan, 1999 Sep-Oct, 40(5), 344 - 7
Kikuchi's disease (histiocytic necrotizing lymphadenitis): report of one case; Lien CH et al.; Kikuchi's disease (histiocytic necrotizing lymphadenitis) is a self-limited disease of unknown cause . The disease often presents with persistently intermittent fever and enlarged cervical lymph nodes . It usually occurs in adult group and is unresponsive to antibiotic therapy . The diagnosis can be confirmed by histopathological findings of lymph node in open biopsy . We report a pediatric case of Kikuchi's disease in an 8-year-8-month-old school-age boy with generalized lymphadenopathy . He was hospitalized under the impression of fever of unknown origin . A diagnosis of Kikuchi's disease was made by cervical lymph node histology . Reviewing the literature of Kikuchi's disease, we found very few reports in young pediatric group . We conclude that Kikuchi's disease should be considered in the differential diagnosis of fever of unknown origin in children, even in the absence of cervical lymphadenopathy.

FEBS Lett, 2000 Jul 21, 477(3), 263 - 7
A direct photo-activated affinity modification of tetracycline transcription repressor protein TetR(D) with tetracycline(1); Beliakova MM et al.; Results of a first successful application of a direct photo-induced affinity modification of Tet repressor (TetR(D)) protein with tetracycline within a complex of known three-dimensional structure are described . The conditions of the modification have provided suitable yields of the modified complex and allowed characterization of the modified segments of the protein . The potential of tetracycline as a fine modifying reagent was established . In the complex of TetR(D) protein with tetracycline, the antibiotic modifies at least two segments, Ile59-Glu73 and Ala173-Glu183, which form a binding tunnel for the drug according to the X-ray analysis . These data open possibilities for the use of different tetracycline targets for structural studies in solution.

J Antibiot (Tokyo), 2000 May, 53(5), 525 - 31
Glomosporin, a novel antifungal cyclic depsipeptide from Glomospora sp . II . Structure elucidation; Ishiyama D et al.; The structure of glomosporin, an antifungal antibiotic, was elucidated by NMR and MS spectroscopic studies . Glomosporin is a novel cyclic depsipeptide with an amino acid sequence Ser-Ala-Asp-Asn-Asn-Ser-Thr, and a 3,4-dihydroxy-4-methylhexadecanoic acid side chain.

J Anim Sci, 2000 Jul, 78(7), 1716 - 25
Effect of a trainer cow on health, behavior, and performance of newly weaned beef calves; Gibb DJ et al.; Experiments were conducted to investigate the effects of the presence of a trainer cow on behavior, performance, health, and feeding patterns of newly weaned beef calves . In Exp . 1,252 weaned calves (270+/-18 kg) were allocated to 22 pens (11 to 15 calves per pen) . A trainer cow was randomly assigned to each of 11 pens . Calves were weighed prior to feeding on d 0, 3, 7, 14, 21, and 28 . Rectal temperatures were taken on each of these days (except d 28) and blood samples were collected on d 0, 3, and 7 and subsequently analyzed for serum haptoglobin and leukotoxin antibody titers . Instantaneous scan observations of calf behavior were made at 10-min intervals between 0730 and 1730 on d 1, 2, 4, 5, and 6 . A similar protocol was used in Exp . 2, in which 297 calves (258+/-17 kg) were allocated to 24 pens . Blood analyses included haptoglobin, white blood cell counts (WBC), and neutrophil:lymphocyte (NL) ratios . In Exp . 3, the above protocol was followed and patterns of feed bunk attendance of individual calves were also monitored using radio frequency identification by passive transponder ear tags . Trainer cows did not influence (P > .10) calf rectal temperatures, requirements for antibiotic therapy, WBC, NL ratios, or leukotoxin antibody titers . Pooled across treatments, NL ratios were lower (P < .01) on d 0 (.31) than on d 3 (.36) or d 7 (.39) . Although differences in weight gain were detected in some periods within the three experiments, there were no differences (P > .10) overall (d 0 to 28) . Trainer cows did not affect (P > .05) frequency or duration of bunk visits by the calves . Averaged across treatments, frequency and duration of bunk visits increased (P < .001) from 9.6 visits/d and 56.7 min/d between d 0 and 3 to 12.3 visits/d and 108.9 min/d between d 15 and 21 . The number of calves observed eating during scan sampling observations also increased from 16.4% on d 1 to 25% on d 4 (P < .10) and 29% on d 5 and 6 (P < .05) . More (P < .05) calves were observed lying on d 1 (41.7%) and d 2 (45.3%) than on d 4 (37.5%), d 5 (34.8%), or d 6 (36.2%) . With a trainer cow present, fewer (36.7% vs 41.5%; P < .001) calves were observed lying and more (11.7% vs 10.2%; P = .08) were observed walking than when no cow was present . Trainer cows did not improve calf health, time spent at the feed bunk, or performance of newly weaned calves.

EXS, 1999, 87, 265 - 77
Veterinary practice with chitin and chitosan; Minami S et al.; Dramatic effects of chitin and chitosan on wound healing were demonstrated in field cases of many small animals (dogs and cats), food animals (338 cows) and 142 zoo animals . In comparison with conventional therapy with irrigation and antibiotic administration to wound, new treatment with chitin and chitosan permitted a substantial decrease in treatment frequency with minimum scar formation.

Presse Med, 2000 Jun 17, 29(21), 1159 - 65
{Prescription of beta-lactams for community-acquired broncho-pulmonary infections in adults . Observations in the hospital environment}; Germaud P et al.; OBJECTIVE: Analyze beta-lactam prescription patterns used in hospitals for the treatment of community-acquired lower respiratory tract infections in adults . PATIENTS AND METHODS: A prospective study was carried out over 4 months (October 1997 to January 1998) in 54 medical units caring for lung disease, internal medicine/infectious disease, geriatric and general medicine patients in 27 hospitals representative of the public facilities in France . Data were collected on the medical unit, the patients, and the antibiotic prescriptions, including discharge prescriptions . The cost analysis of antibiotic therapy took into account all antibiotics given to the patients during their hospital stay . RESULTS: One thousand eighteen patients were included in the study: 266 were treated for acute bronchitis, 405 for bronchitis infection with underlying chronic respiratory disease, and 347 for pneumonia . Noteworthy findings included: low percentage of protocols within the medical units (25.3%), an unexpected frequency of hospitalization for acute bronchitis generally among elderly women, and prolonged intravenous antibiotic therapy and hospitalization (5 to 6 days and 9 to 12.5 days respectively) . CONCLUSION: This study confirms the need to reinforce measures aimed at optimizing antibiotic prescriptions in hospitals.

Int J Pediatr Otorhinolaryngol, 2000 Jun 30, 53(2), 111 - 20
Office-based laser assisted tympanic membrane fenestration in adults and children: pilot data to support an alternative to traditional approaches to otitis media; Siegel G et al.; OBJECTIVES: To determine the role of intermediate duration ( approximately 3 weeks) middle ear ventilation using office-based laser assisted tympanic membrane fenestration in resolving an episode of otitis media with effusion in adults and children who otherwise would have been treated with insertion of pressure equalization tubes . METHODS: A retrospective chart review of 92 patients (162 ears) was conducted to identify the utility and technical challenges associated with laser assisted tympanic membrane fenestration in an office setting . Clinical characteristics reviewed included: age, gender, duration of effusion, season performed, and hearing and health status of middle ear upon healing of the fenestration . RESULTS: 69% of all patients were effusion free upon closure of the fenestration; 68% of those <3 years; 70% of those 3-7 years; and 70% of those 25-80 years . Some episodes recurred and at final follow-up 64% had normal middle ear structure and function (range of follow-up =1-18 months, mean 2.5 months, median 2.0) . Shorter duration of effusion pre-fenestration was more often associated with return to normal middle ear structure and function (P<0.01) . Season performed, number of previous episodes of otitis media and pre-treatment tympanometry were not predictive of result . No significant complications were observed . CONCLUSIONS: The use of office-based laser assisted tympanic membrane fenestration is a reasonably safe and effective procedure for the treatment of otitis media in most adults and children . As a minimally invasive otologic procedure, laser assisted tympanic membrane fenestration has great potential to decrease the rates of both antibiotic usage and insertion of ear tubes.

Biol Blood Marrow Transplant, 2000, 6(3A), 335 - 43
Novobiocin in combination with high-dose chemotherapy for the treatment of advanced breast cancer: a phase 2 study; Hahm HA et al.; We conducted the first phase 2 and pharmacologic study to evaluate the combination of novobiocin (a coumeromycin antibiotic that has been shown to augment alkylating agent cytotoxicity in experimental models) and high-dose cyclophosphamide and thiotepa followed by autologous marrow support in women with chemosensitive advanced breast cancer . Its aims were (1) to determine progression-free survival (PFS) and overall survival (OS), (2) to evaluate the pharmacokinetics of cyclophosphamide and thiotepa, and (3) to measure the ability of novobiocin to reverse alkylator drug resistance in vitro . Forty-one women with chemotherapy-responsive advanced breast cancer received cyclophosphamide (4 g/m2) for peripheral blood stem cell mobilization (treatment 1) followed by high-dose cyclophosphamide (1.5 g/m2 per day for 4 days), thiotepa (200 mg/m2 per day for 4 days), and novobiocin (4 g/day orally for 7 days) (treatment 2) and autologous marrow support . The median PFS was 10 months (range, 0.2-70.6 months) and OS, 21.5 months (range, 0.2-70.6 months) . There was no statistically significant relationship between PFS or OS and area-under-the-curve values of cyclophosphamide, thiotepa, or 4-hydroxycyclophosphamide . Patient plasma samples (n = 12) obtained during novobiocin therapy were able to reverse alkylator drug resistance in an in vitro colony-forming assay . Correlative laboratory studies in an in vitro model system demonstrated that patient plasma after novobiocin treatment resulted in the magnitude of resistance reversal that had been predicted by prior preclinical experiments . Clinically, however, this activity of novobiocin did not translate into a substantial increase in PFS or OS compared with historical controls treated with high-dose alkylator therapy alone.

Antisense Nucleic Acid Drug Dev, 2000 Jun, 10(3), 177 - 84
A cationic derivative of amphotericin B as a novel delivery system for antisense oligonucleotides; Garcia-Chaumont C et al.; A novel approach based on a plasma membrane permeability-disturbing agent was proposed as an antisense oligonucleotide delivery system . AMA, a derivative of the polyene antibiotic amphotericin B, formed a stable complex when mixed with phosphodiester oligodeoxynucleotides and enhanced the intracellular uptake of a 5' fluoresceinated anti-mdr1 20-mer into NIH-MDR-G185 cells . The nonlabeled phosphorothioate form of the oligodeoxynucleotide, complexed to AMA, inhibited P-glycoprotein expression with better efficiency and less nonspecific effects than when vectorized by Lipofectin . AMA may thus be a good agent for antisense strategy.

J Ethnopharmacol, 2000 Jul, 71(1-2), 1 - 21
The traditional uses, chemical constituents and biological activities of Plantago major L . A review; Samuelsen AB; Plantago major L . leaves have been used as a wound healing remedy for centuries in almost all parts of the world and in the treatment of a number of diseases apart from wound healing . These include diseases related to the skin, respiratory organs, digestive organs, reproduction, the circulation, against cancer, for pain relief and against infections . P . major contains biologically active compounds such as polysaccharides, lipids, caffeic acid derivatives, flavonoids, iridoid glycosides and terpenoids . Alkaloids and some organic acids have also been detected . A range of biological activities has been found from plant extracts including wound healing activity, anti-inflammatory, analgesic, antioxidant, weak antibiotic, immuno modulating and antiulcerogenic activity . Some of these effects may attribute to the use of this plant in folk medicine.

J Mol Biol, 2000 Jul 28, 300(5), 1309 - 22
Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro; Tagliavini F et al.; Prion diseases are characterized by the accumulation of altered forms of the prion protein (termed PrP(Sc)) in the brain . Unlike the normal protein, PrP(Sc) isoforms have a high content of beta-sheet secondary structure, are protease-resistant, and form insoluble aggregates and amyloid fibrils . Evidence indicates that they are responsible for neuropathological changes (i.e . nerve cell degeneration and glial cell activation) and transmissibility of the disease process . Here, we show that the antibiotic tetracycline: (i) binds to amyloid fibrils generated by synthetic peptides corresponding to residues 106-126 and 82-146 of human PrP; (ii) hinders assembly of these peptides into amyloid fibrils; (iii) reverts the protease resistance of PrP peptide aggregates and PrP(Sc) extracted from brain tissue of patients with Creutzfeldt-Jakob disease; (iv) prevents neuronal death and astrocyte proliferation induced by PrP peptides in vitro . NMR spectroscopy revealed several through-space interactions between aromatic protons of tetracycline and side-chain protons of Ala(117-119), Val(121-122) and Leu(125) of PrP 106-126 . These properties make tetracycline a prototype of compounds with the potential of inactivating the pathogenic forms of PrP .

Br J Dermatol, 2000 Jul, 143(1), 117 - 26
An open clinical trial of sulphamethoxypyridazine in the treatment of mucous membrane pemphigoid; Thornhill M et al.; Twenty-five patients with mucous membrane pemphigoid (MMP), whose oral lesions were unresponsive to topical steroid treatment, were treated with 1 g daily of sulphamethoxypyridazine (SMXP), a long-acting sulphonamide antibiotic, in an open prospective clinical trial . Lesion severity was assessed objectively in a semiquantitative fashion before treatment and after 14 weeks of treatment . The patient's subjective assessment of the associated pain or discomfort, using a visual analogue scale, was also recorded at these times . Three patients (12%) were withdrawn from the study owing to side-effects or complications, one due to an allergic reaction, the other two because of significant haemolysis . For the remainder there was a significant improvement in the mean objective clinical scores for desquamative gingivitis, other oral lesions, conjunctival inflammation, nasal, vulvovaginal and skin involvement, after 14 weeks treatment with SMXP (all P < 0.001, except skin P < 0 . 01) . Only conjunctival scarring showed no improvement . In addition, there was a significant improvement (P < 0.001) in the pain scores for the mouth, eyes, nose, vulvovaginal region and skin . The results indicate that with appropriate monitoring SMXP is an effective treatment for MMP and compares favourably with other systemic agents used in the management of this condition.

Nucleic Acids Res, 2000 Aug 1, 28(15), 2935 - 42
Recognition of a cognate RNA aptamer by neomycin B: quantitative evaluation of hydrogen bonding and electrostatic interactions; Cowan JA et al.; Aminoglycosides are an important class of antibiotic that selectively target RNA structural motifs . Recently we have demonstrated copper derivatives of amino-glycosides to be efficient cleavage agents for cognate RNA motifs . To fully develop their potential as pharmaceutical agents it is necessary to understand both the structural mechanisms used by aminoglycosides to target RNA, and the relative contributions of hydrogen bonding and electrostatic interactions to recognition selectivity . Herein we report results from a calorimetric analysis of a stem-loop 23mer RNA aptamer complexed to the aminoglycoside neomycin B . Key thermodynamic parameters for complex formation have been determined by isothermal titration calorimetry, and from the metal-ion dependence of these binding parameters the relative contributions of electrostatics and hydrogen bonding toward binding affinity have been assessed . The principal mechanism for recognition and binding of neomycin B to the RNA major groove is mediated by hydrogen bonding.

Hosp Pract (Off Ed), 1999 Sep 1, 34(9), 79 - 82, 85-6, 89-90
Atherosclerosis: an infectious disease?
Benitez RM.
Traditional risk factors do not fully account for atherogenesis . There is increasing evidence that infectious pathogens, such as Helicobacter pylori, cytomegalovirus, and Chlamydia pneumoniae, may promote the atherosclerotic cascade . Proposed mechanisms include macrophage transformation, endothelial injury, chronic inflammation, and thrombosis . Specific antibiotic therapy may affect outcome.

Hosp Pract (Off Ed), 1999 Sep 15, 34(10), 77 - 8, 81-2, 86-92
Nosocomial pneumococcal infection: an outbreak; Leggiadro RJ et al.; When an outbreak of pneumococcal disease occurs an institution--be it a hospital, nursing home, day care center, or other facility--management includes treatment of affected cases and prevention of new cases . Patients and staff should be tested for nasopharyngeal carriage and their vaccination status ascertained . Antibiotic use should be reviewed, especially if the causative strain is resistant.

BJOG, 2000 Jul, 107(7), 877 - 84
The relationships between antenatal management, the cause of delivery and neonatal outcome in a large cohort of very preterm singleton infants; Baud O et al.; OBJECTIVE: To determine whether the cause of very preterm delivery influences neonatal outcome . DESIGN: A cohort study of 685 consecutive singletons born before 33 weeks of gestation . METHODS: Causes of birth and perinatal outcome variables were correlated for statistical significance by uni- and multi-variate analyses . RESULTS: Intrauterine growth retardation or pre-eclampsia were associated with a higher rate of respiratory distress syndrome compared with prolonged rupture of membranes, after controlling for gestational age, antenatal corticosteroid therapy, antenatal antibiotic administration, mode of delivery and origin (inborn or outborn) (adjusted OR 3.12; 95% CI 1.55-6.28) . The prevalence of grade 3-4 intraventricular haemorrhage or cystic periventricular leukomalacia was 25% in newborn babies born after intrauterine infection or prolonged rupture of membranes . Among infants born after intrauterine growth retardation/pre-eclampsia, the rate of severe intraventricular haemorrhage was 3.2% and the rate of periventricular leukomalacia was 0.9% . Compared with intrauterine infection and after controlling for potential confounding covariates, intrauterine growth retardation/pre-eclampsia was associated with a lower rate of periventricular leukomalacia (adjusted OR 0.08; 95% CI 0.02-0.41) . In the same multiple logistic regression model, antenatal corticosteroid administration was associated with a lower incidence of periventricular leukomalacia (adjusted OR 0.36; 95% CI 0.16-0.79) . CONCLUSIONS: The cause of very preterm delivery has an important influence on neonatal outcome.

J Cardiovasc Surg (Torino), 2000 Apr, 41(2), 259 - 62
Aortobronchial fistula after aortic dissection type B; Aidala E et al.; Although rare, aortobronchial fistula complicates thoracic aortic surgery . Correct diagnosis and the infectious nature of the lesion are the most important conditions to define, for the following best therapy . We presented a case of non-infectious postsurgical aortobronchial fistula, revealed by computed-tomographic scan and angiography procedure, treated with prosthetic graft replacement and broad spectrum antibiotic therapy . In the case of infection our policy is homograft replacement . Computed tomography, being able to make diagnosis, should be performed as the initial technique.

Arch Esp Urol, 2000 May, 53(4), 291 - 303
{Nanobacteria . An experimental neo-lithogenesis model}; Garcia Cuerpo E et al.; OBJECTIVE: To study the phenomenon of biomineralization in an experimental model of lithogenesis by percutaneous renal punction without laparotomy and no antibiotics . METHODS/RESULTS: The study comprised 4 Brown-Norway rats . Nanobacteria inoculum (X, 2X and 4X) was administered to three rats and the remaining one was used as control . The analytical and radiological findings showing the development of obstructive pyelocaliceal lithiasis in the kidneys of rats no . 2 and 3 are presented . CONCLUSIONS: Translumbar percutaneous renal puncture has permitted performing laparotoy without antibiotic coverage, which was the main difficulty of the experimental model of lithogenesis . Nanobacteria were cultured successfully, but not without difficulty, and formation of calculi in the rat pyelocaliceal system was achieved . This experimental model will provide further insight into lithogenesis and will allow us to find the answers to some of the many questions concerning this condition that remain.

J Pharmacol Exp Ther, 2000 Aug, 294(2), 548 - 54
Radicicol suppresses expression of inducible nitric-oxide synthase by blocking p38 kinase and nuclear factor-kappaB/Rel in lipopolysaccharide-stimulated macrophages; Jeon YJ et al.; We show that radicicol, a fungal antibiotic, produces a marked inhibition of p38 kinase, nuclear factor-kappaB/Rel (NF-kappaB/Rel), and inducible nitric-oxide synthase (iNOS) transcription by the macrophage line RAW 264.7 in response to lipopolysaccharide (LPS) . Treatment of RAW 264.7 with radicicol inhibited LPS-stimulated p38 kinase phosphorylation in a dose-related manner . iNOS transcription, which is regulated in part by the NF-kappaB/Rel family of transcription factors, has been shown to be under the control of the p38 kinase signaling cascade . Our data also show that the p38 kinase pathway is specifically involved in LPS-induced NF-kappaB/Rel activation and iNOS expression because NF-kappaB/Rel DNA binding and iNOS mRNA production in the presence of a specific inhibitor of p38 kinase, SB203580, were dramatically diminished . In contrast, PD98059, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase 1 had no effect on NF-kappaB/Rel activation and iNOS expression . LPS-induced loss of inhibitory proteins IkappaB-alpha and IkappaB-beta and translocation of p65, c-Rel, and p50 was inhibited by radicicol . Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking p38 kinase signaling . Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of radicicol on iNOS suggest that this potent antifungal agent may represent a useful anti-inflammatory agent.

Digestion, 2000, 62(1), 31 - 7
Dose-related stimulatory effect of clarithromycin on interdigestive gastroduodenal motility; Bortolotti M et al.; BACKGROUND/AIMS: The effect on interdigestive gastroduodenal motility of different doses of clarithromycin, an antibiotic commonly used for Helicobacter pylori eradication, has been investigated . METHODS: Gastroduodenal motility was recorded by means of a low-compliance manometric system in 15 healthy subjects . Thirty minutes after the first phase III of the migrating motor complex, clarithromycin (CLA) was infused intravenously at a dose of 100 mg in 5, 250 mg in 5 and 400 mg in 5 subjects, randomly and in a double-blind manner, continuing the recording for at least 1 h . A further study was carried out on 10 subjects, 5 of whom received 50 mg CLA and 5 normal saline with the same modalities . RESULTS: After 100 mg CLA a premature gastroduodenal phase III ensued in all cases, which showed a duration, propagation velocity and wave frequency not significantly different from the spontaneous one and was followed by a clear phase I . A premature gastroduodenal phase-III-like activity occurred in 3 cases of 250 mg CLA and 2 cases after 400 mg CLA, followed by a very short or absent phase I and characterized by a long duration of the antral phase III, while in the remaining cases a long-lasting sequence of about 1/min of antral waves propagated to the duodenum appeared, sometimes preceded by an antral phase-III-like activity not propagated to the duodenum . After 50 mg CLA a premature phase III appeared in 2 cases, while a not premature phase III appeared in 2 cases after saline . CONCLUSION: CLA shows a dose-related stimulatory effect on interdigestive gastroduodenal motility varying from the initiation of a typical phase III to a prolonged sequence of gastroduodenal coordinated waves . These motor effects of CLA suggest potential therapeutic applications .

Biochim Biophys Acta, 2000 Jul 26, 1502(1), 76 - 84
Approaches to discovery and characterization of inhibitors of amyloid beta-peptide polymerization; Findeis MA; Polymerization of the amyloid beta-peptide (Abeta) has been identified as a major feature of the pathogenesis of Alzheimer's disease (AD) . Inhibition of the formation of these toxic polymers of Abeta has thus emerged as an approach to developing therapeutics for AD . Techniques for studying Abeta polymerization include the use of fibril nucleation and extension assays in a variety of formats . Detection of polymeric forms of Abeta has been achieved using turbidity, dye binding, light scattering and toxicity among other methods . Direct and indirect methods have been described for the measurement of binding affinities for Abeta fibrils . Imaging techniques include electron microscopy, X-ray diffraction and atomic force microscopy . These techniques have been used to characterize different classes of compounds that inhibit the formation of Abeta polymers . These compounds include dyes such as Congo Red, the antibiotic rifampicin, the anthracycline 4'-iodo-4'-deoxydoxorubicin, and a large variety of Abeta-derived peptides and modified peptides, among other reported inhibitors.

J Biol Chem, 2000 Oct 27, 275(43), 33585 - 92
Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen . Role of reactive oxygen and nitrogen species; Kotamraju S et al.; Doxorubicin (DOX) is a broad spectrum anthracycline antibiotic used to treat a variety of cancers . Redox activation of DOX to form reactive oxygen species has been implicated in DOX-induced cardiotoxicity . In this work we investigated DOX-induced apoptosis in cultured bovine aortic endothelial cells and cardiomyocytes isolated from adult rat heart . Exposure of bovine aortic endothelial cells or myocytes to submicromolar levels of DOX induced significant apoptosis as measured by DNA fragmentation and terminal deoxynucleotidyltransferase-mediated nick-end labeling assays . Pretreatment of cells with 100 microm nitrone spin traps, N-tert-butyl-alpha-phenylnitrone (PBN) or alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) dramatically inhibited DOX-induced apoptosis . Ebselen (20-50 microm), a glutathione peroxidase mimetic, also significantly inhibited apoptosis . DOX (0.5-1 microm) inactivated mitochondrial complex I by a superoxide-dependent mechanism . PBN (100 microm), POBN (100 microm), and ebselen (50 microm) restored complex I activity . These compounds also inhibited DOX-induced caspase-3 activation and cytochrome c release . PBN and ebselen also restored glutathione levels in DOX-treated cells . We conclude that nitrone spin traps and ebselen inhibit the DOX-induced apoptotic signaling mechanism and that this antiapoptotic mechanism may be linked in part to the inhibition in formation or scavenging of hydrogen peroxide . Therapeutic strategies to mitigate DOX cardiotoxicity should be reexamined in light of these emerging antiapoptotic mechanisms of antioxidants.

Curr Biol, 2000 Jul 13, 10(14), 861 - 4
TOR signaling regulates microtubule structure and function; Choi JH et al.; The functional diversity and structural heterogeneity of microtubules are largely determined by microtubule-associated proteins (MAPs) {1} {2} . Bik1p (bilateral karyogamy defect protein) is one of the MAPs required for microtubule assembly, stability and function in cell processes such as karyogamy and nuclear migration and positioning in the yeast Saccharomyces cerevisiae {3} . The macrocyclic immunosuppressive antibiotic rapamycin, complexed with its binding protein FKBP12, binds to and inhibits the target of rapamycin protein (TOR) in yeast {4} {5} . We report here that TOR physically interacts with Bik1p, the yeast homolog of human CLIP-170/Restin {6} {7} . Inhibition of TOR by rapamycin significantly affects microtubule assembly, elongation and stability . This function of TOR is independent of new protein synthesis . Rapamycin also causes defects in spindle orientation, nuclear movement and positioning, karyogamy and chromosomal stability, defects also found in the bikDelta mutant . Our data suggest a role for TOR signaling in regulating microtubule stability and function, possibly through Bik1p.

J Orthop Trauma, 2000 May, 14(4), 278 - 86; discussion 277
Field hospital treatment of blast wounds of the musculoskeletal system during the Yugoslav civil war; Covey DC et al.; The spectrum of wounding and treatment of forty-one patients with musculoskeletal blast injuries at a U.S . military field hospital in the former Yugoslavia was reviewed . Patients underwent wound exploration, irrigation, debridement, broad-spectrum antibiotic therapy, early fracture stabilization, and appropriate reconstructive surgery . Four patients developed wound infections . Two patients died as a result of their injuries (overall mortality 5 percent) . There were three below-knee amputations and five other amputations (above-knee, ankle, midtarsal, partial forefoot, and finger) . Three patients sustained lumbar burst fractures from mines that exploded under their vehicles, resulting in paraplegia in one case . Our patients underwent 112 surgical procedures, an average of 2.1 per patient . Twenty-two patients (54 percent) had other injuries or conditions in addition to their orthopaedic wounds . There were wide variations in the bone and soft tissue injuries caused by detonating ordnance, and the tissue damage was qualitatively different from that caused by gunshot wounds . Early debridement, leaving wounds open, and treatment with broad-spectrum antibiotics were important factors in wound healing to allow subsequent successful reconstructive surgery in an austere field setting.

J Pharm Biomed Anal, 2000 Aug 1, 23(1), 3 - 13
New synthetic strategies for the preparation of novel chiral stationary phases for high-performance liquid chromatography containing natural pool selectors; D'Acquarica I; Twelve new chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) were generally prepared starting from the macrocyclic glycopeptide antibiotic teicoplanin, according to novel and efficient 'one-pot' synthetic strategies . Their chiral recognition abilities were evaluated under polar-organic mode HPLC, towards a variety of biopharmacological interesting racemates, such as beta-amino acids and quaternary ammonium salts (e.g . carnitine and its derivatives) . All materials were prepared by two different synthetic strategies, both leading to the formation of one or two stable ureidic functions on the CSP structure . The influence of the different spacers and of the silica matrix nature on the chiral performances was investigated . The obtained results suggested that the optimal synthetic strategy was that leading to the formation of two ureidic functions on the CSP structure, spaced-out by a six-carbon atoms aliphatic chain; the best chromatographic results were reached with the use of the spherical LiChrospher silica gel . Enantioselectivity factors (alpha) particularly high and short-time analyses characterised the analytical procedures; in addition, analytes lacking in chromophore groups were easily detected by evaporative light scattering (ELS) with no need of preliminary derivatization.

Haematologica, 2000 Jul, 85(7), 745 - 52
Computed tomographic scan of the chest, latex agglutination test and plasma (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients; Kami M et al.; BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is more useful for its early diagnosis . Aim of the study was to compare usefulness of computed tomographic (CT) scan of chest, latex agglutination (LA) test and determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of invasive pulmonary aspergillosis (IPA) . DESIGN AND METHODS: We treated 215 consecutive patients who underwent cytotoxic chemotherapy . From initiation of chemotherapy until death or discharge, blood samples were taken weekly and subjected to LA and BDG tests . We performed chest CT scans when patients had any signs of pulmonary infection or an antibiotic-resistant fever . RESULTS: Of the 215 patients, 30 (14 . 0%) were diagnosed as having IPA . In sixteen cases the diagnosis was definite and in 14 it was suspected . In patient-based analysis, sensitivities of LA and BDG were 44% and 63%, respectively . Sensitivity tended to be lower in patients with IPA localized to the lung than those with disseminated invasive aspergillosis . Specificities were 93% and 74%, respectively . Either a halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of the IPA patients showed some abnormal signs on chest CT scans . On average, CT scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by 11.5 days . In 6 of the 11 patients who became positive for either LA or BDG assay, CT scan signs preceded the positive results by more than seven days . INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood tests and X-ray for early diagnosis of IPA.

Bioorg Med Chem, 2000 Jun, 8(6), 1225 - 43
Lincomycin and clindamycin conformations . A fragment shared by macrolides, ketolides and lincosamides determined from TRNOE ribosome-bound conformations; Verdier L et al.; Two important lincosamide antibiotics, lincomycin and clindamycin were studied in the complex state with the bacterial ribosome after a conformational analysis by 1H and 13C NMR spectroscopy and molecular modelling of the unbound molecules . Lincosamide-ribosome interactions were investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY), resulting in a bound structure compatible with the experimental NMR data . The results compared with the conformational analysis of the substrates in solution indicate that specific conformations are preferred in the bound state . Clindamycin, the more bioactive antibiotic studied, displayed a stronger NMR response than lincomycin showing that in lincosamide-ribosome interactions, a low affinity binding level is associated to the tight binding one and is related to biological activity . This study shows that conformation plays an essential role for the low affinity binding site . Superimposition of lincosamide, macrolide and ketolide bound structures exhibited conformational similarities in a particular fragment which is in agreement with a hypothesis of partial overlapping lincosamide and macrolide binding sites.

Prehosp Emerg Care, 2000 Jul-Sep, 4(3), 245 - 9
Ability of EMT-Bs to determine which wounds can be repaired in the field; Hale D et al.; INTRODUCTION: In certain emergency medical services (EMS) systems, emergency medical technicians-paramedics (EMT-Ps) repair lacerations in the field . This practice is supported by studies showing equivalence between nonphysicians and physicians regarding infection rates and cosmetic outcomes . OBJECTIVE: To evaluate the ability of emergency medical technicians-basic (EMT-Bs) to identify wounds repairable in the field or requiring tetanus prophylaxis . METHODS: This was a prospective, double-blind convenience sample study at an urban teaching hospital . Eleven EMT-B volunteers, trained by a one-hour lecture and bedside teaching, evaluated lacerations for prehospital repair by answering three questions: Could this wound be repaired in the field, and if no, why not? If on an adult forearm, could this wound be repaired in the field, and if no, why not? Does this patient need tetanus prophylaxis, and if no, why not? A blinded principal investigator also answered these questions, and a person uninvolved in the study correlated results . Statistical evaluation was performed using kappa statistics . RESULTS: The EMT-Bs identified 17 of 17 potentially repairable wounds and 163 of 163 wounds excluded from prehospital repair . Placing the wound on the forearm, the EMT-Bs identified 82 of 87 potentially repairable wounds and 93 of 93 wounds excluded from prehospital repair (sensitivity 94%, specificity 100%, positive predictive value 100%, negative predictive value 95%, kappa 0.97) . For five of five wounds, physicians disagreed with the EMT-Bs and thought the wound repairable prehospital . The EMT-Bs and physicians agreed on individual wound exclusion criteria in 207 of 239 (86.6%) instances . Finally, the EMT-Bs identified 108 of 108 patients requiring tetanus prophylaxis . CONCLUSIONS: Basic EMTs can accurately identify wounds eligible for prehospital repair and/or requiring tetanus prophylaxis.

J Bacteriol, 2000 Aug, 182(15), 4337 - 42
Motility and chemotaxis of filamentous cells of Escherichia coli; Maki N et al.; Filamentous cells of Escherichia coli can be produced by treatment with the antibiotic cephalexin, which blocks cell division but allows cell growth . To explore the effect of cell size on chemotactic activity, we studied the motility and chemotaxis of filamentous cells . The filaments, up to 50 times the length of normal E . coli organisms, were motile and had flagella along their entire lengths . Despite their increased size, the motility and chemotaxis of filaments were very similar to those properties of normal-sized cells . Unstimulated filaments of chemotactically normal bacteria ran and stopped repeatedly (while normal-sized bacteria run and tumble repeatedly) . Filaments responded to attractants by prolonged running (like normal-sized bacteria) and to repellents by prolonged stopping (unlike normal-sized bacteria, which tumble), until adaptation restored unstimulated behavior (as occurs with normal-sized cells) . Chemotaxis mutants that always ran when they were normal sized always ran when they were filament sized, and those mutants that always tumbled when they were normal sized always stopped when they were filament sized . Chemoreceptors in filaments were localized to regions both at the poles and at intervals along the filament . We suggest that the location of the chemoreceptors enables the chemotactic responses observed in filaments . The implications of this work with regard to the cytoplasmic diffusion of chemotaxis components in normal-sized and filamentous E . coli are discussed.

Acad Emerg Med, 2000 Jan, 7(1), 21 - 7
Setting-based practice variation in the management of simple febrile seizure; Hampers LC et al.; OBJECTIVE: To identify provider-based differences in the ED assessment and management of children presenting with uncomplicated, first-time febrile seizures . METHODS: Multicenter, retrospective cohort study of seven EDs in-the Chicago area: two tertiary academic pediatric EDs (PEDs) and five community-based general EDs (GEDs) . The visits of all patients with a discharge diagnosis including the term "seizure" were identified from a 30-month period . Records of patients who met criteria for simple, first-time febrile seizure were reviewed (age 6-60 months; temperature > or =38.0 degrees C; single, generalized, tonic-clonic seizure <20 minutes; "alert" or "arousable" on presentation; absence of known neurologic disease) . RESULTS: Four hundred fifty-five records were included: 330 and 125 patients presenting to GEDs and PEDs, respectively . The two groups did not differ in mean age, vital signs, reported duration of seizure, or prior antibiotic use . Lumbar puncture (LP) was performed more often in the GED group (33% vs 22%) . No patients were found to have bacterial meningitis . The patients in the GED group were more likely to receive parenteral antibiotics in the ED (56% vs 22%) and to be admitted or transferred (18% vs 4%) . In a logistic regression model incorporating age, temperature, seizure duration, seizure in the ED, prior antibiotic use, primary care, and insurance status, the GED patients remained more likely to have an LP (OR 1.5), receive parenteral antibiotics (OR 2.5), and be admitted or transferred (OR 2.5) . CONCLUSIONS: There were significant setting-based differences in the evaluation and management of children with simple febrile seizures presenting to GEDs and PEDs.

Schweiz Rundsch Med Prax, 2000 May 31, 89(22), 958 - 62
{Therapy of Helicobacter pylori infection}; Treiber G; H . pylori eradication remains standard treatment for peptic ulcer disease . Until now, other indications like non-ulcer dyspepsia, reflux esophagitis, or concomitant medication with non-steroidal antirheumatics are not approved according to actual guidelines and these patients should be managed on an individual basis only . One week triple therapy consisting of a proton-pump inhibitor (PPI), a macrolide antibiotic (clarithromycin), and a imidazole antibiotic (metronidazole) or amoxicillin, given bid . Quadruple therapy including PPI, bismuth, tetracycline and metronidazole should be reserved to eradication failures.

J Urol, 2000 Aug, 164(2), 364 - 6
Penile fracture in Kermanshah, Iran: report of 172 cases; Zargooshi J; PURPOSE: Experience with 172 cases of penile fracture, in Kermanshah, Iran is reviewed . MATERIALS AND METHODS: Records of penile fracture cases were reviewed from April 1990 to October 1999 . RESULTS: Diagnosis was made clinically and there was no need to perform cavernosography in any case . The most common mechanism of fracture was referred to by patients as "taghaandan" (to click or snap when forcibly pushing the erect penis down to achieve detumescence) . All but 2 cases were treated surgically and 2 cases had concomitant urethral injury diagnosed by selective urethrography . Repair consisted of a circumferential degloving incision to evaluate the corpora . Because of unavailability of synthetic absorbables, inverted knot nylon sutures were used successfully for repair . Delay in operation did not increase difficulty in dissection or early postoperative morbidity . Preoperative and postoperative use of antibiotics was effective in eliminating risk of infection . There were no significant intraoperative or immediate postoperative complications and most patients were discharged home on postoperative day 1 . CONCLUSIONS: Patient misinformation about penile tissue properties is the main explanation for the high incidence of penile fracture . Cavernosography, and urethrography and intraoperative urethral catheterization are not routinely needed, as diagnosis can be made clinically . Preoperative and postoperative use of antibiotics, and a uniform surgical plan regardless of delay in presentation are recommended.

Laryngoscope, 2000 Jul, 110(7), 1222 - 4
In vivo interaction of cis-platinum and fosfomycin on squamous cell carcinoma; Tandy JR et al.; OBJECTIVES/HYPOTHESIS: Cis-platinum is the most frequently used chemotherapeutic agent for the treatment of head and neck squamous cell carcinoma (SCCA) . Ototoxicity and nephrotoxicity continue to be the primary dose-limiting toxicities encountered . Fosfomycin, a broad-spectrum antibiotic, has been previously shown to be both otoprotective and nephroprotective against cis-platinum toxicity . Previous in vitro work demonstrated that fosfomycin does not inhibit the tumoricidal actions of cis-platinum . This study tests whether fosfomycin inhibits cisplatinum in vivo . METHODS: An SCCA cell line was grown in vivo in four groups of nude mice, which then received no treatment, standard-dose cis-platinum, high-dose cis-platinum, or high-dose cis-platinum with fosfomycin . RESULTS: Fosfomycin did not inhibit the tumoricidal activity of cis-platinum . Mice treated with fosfomycin also had longer survival, which is probably due to lessening of immediate cis-platinum systemic toxicity . CONCLUSION: This study shows that fosfomycin in combination with cis-platinum may be useful in treating advanced, and possibly relatively chemoresistant, SCCA of the head and neck.

Biochem Biophys Res Commun, 2000 Jul 14, 273(3), 829 - 32
Enzyme destruction by a protease contaminant in bacitracin; Rogelj S et al.; Bacitracin, as purchased from biochemical supply companies, is a mixture of more than 30 different substances . The major antibiotic isoforms A and B account for about 60% of the mixture . A newly identified impurity in some, but not all, of the bacitracin lots is a powerful subtilisin-type protease capable of cleaving many proteins including protein disulfide isomerase (PDI), myosin, and a variety of artificial substrates Thus, it is important for investigators who use bacitracin as a protease or other enzyme inhibitor to determine if the bacitracin they are using is contaminated with a protease enzyme . If it is present, they may have to reinterpret their results and retest with an enzyme-free bacitracin reagent .

Biochemistry, 2000 Jul 11, 39(27), 7886 - 94
Investigations of the active site of Saccharomyces cerevisiae dolichyl-phosphate-mannose synthase using fluorescent labeled dolichyl-phosphate derivatives; Xing J et al.; Dolichol-phosphate mannose (Dol-P-Man) is a key mannosyl donor for the biosynthesis of N-linked oligosaccharides as well as for O-linked oligosaccharides on yeast glycoproteins, and for the synthesis of the glycosyl-phosphatidylinositol anchor found on many cell surface glycoproteins . It is synthesized by Dol-P-Man synthase which is the only glycosyltransferase in the dolichol pathway that has been expressed as an active protein, solubilized and purified in large enough quantities for structural investigations . Earlier studies showed that the enzyme is closely associated with membranes of endoplasmic reticulum with unique lipid requirements for its maximal activity . This potential target of antibiotic therapy is now being investigated at the molecular level to establish information about the structure of the enzyme as well as determine the nature and properties of the enzyme-phospholipid interactions . In this paper, we have determined the activities of the fluorescent labeled dolichyl-phosphate derivatives as well as the intramolecular distances between amino acid residues near the active site and/or the fluorophores of the substrate derivatives using fluorescence energy resonance transfer . These results also show that the conserved consensus sequence is not required by Dol-P-Man synthase neither for the recognition of Dol-P nor for the catalytic activity.

Curr Opin Oncol, 2000 Jul, 12(4), 303 - 7
Indications and complications of intravenous devices for chemotherapy; Freytes CO; Vascular access devices (VADs) are frequently used in patients with cancer . Vascular access devices can be divided into external catheters and subcutaneous venous access ports . Each type of device has its advantages and disadvantages, but the indications and optimal use of specific VADs remain to be defined . There are multiple complications of VADs but, with the exception of catheter-related bloodstream infections and thrombosis, most complications are rare . The use of VADs impregnated with antibiotic reduces the rates of catheter colonization and catheter-related bloodstream infections as compared with the use of unimpregnated catheters for short-term use . Thrombosis remains a major complication of VADs, and prospective, controlled studies are needed to clearly define the risk factors, natural history, and optimal treatment of this complication.

J Heart Valve Dis, 2000 May, 9(3), 439 - 44
A strategy for inducing immune tolerance to valve endothelial cells through gene transfer; Li Y et al.; BACKGROUND AND AIM OF THE STUDY: We and others have demonstrated an immune response to homograft valve endothelial cells both in vivo and in vitro . Clinically, this is particularly manifest in children . In an attempt to address this problem we have explored a strategy of inducing specific immune tolerance by genetic manipulation of valve endothelial cells . FasL is an inducer of apoptosis; it binds Fas and results in programmed cell death (apoptosis) of Fas-bearing cells such as T lymphocytes . FasL has been shown to be important in the protection of tissue grafts (testis, cornea, kidney and pancreatic islet) from rejection . The ultimate aim of this work is to determine whether the transfection of FasL into human heart valve endothelial cells can hinder immune rejection by induction of apoptosis in T cells . METHODS: The full-length human FasL cDNA was cloned into a mammalian expression vector containing the neomycin resistance marker . The endothelial cell line HMEC-1 was transfected with the plasmid and selected with antibiotic G418 . Cultures from positive clones were analyzed by semi-quantitative polymerase chain reaction (PCR) to determine approximate copy numbers of FasL . Reverse transcription (RT)-PCR was carried out to examine the production of mRNA from the construct . Western blot analysis was performed to detect the protein expression . Cytotoxic assays were subsequently performed to detect the FasL function in those transfected cells . RESULTS: High copy number transfected cell lines were produced, and mRNA and protein expression were confirmed . Preliminary results from cytotoxic assays show that transfected cells have enhanced cytotoxicity in comparison with their parent cell line . CONCLUSION: FasL can be overexpressed in endothelial cells and appears to modify the cells' immunological behavior . These findings could have important implications for enhancing homograft valve durability.

Pharmacol Res, 2000 Aug, 42(2), 115 - 21
The protective effect of glutathione administration on adriamycin-induced acute cardiac toxicity in rats; Mohamed HE et al.; Adriamycin (ADR) is a potent antitumor antibiotic drug known to cause severe cardiac toxicity . Although ADR generates free radicals, the role of these radicals in the development of cardiac toxicity is still not well understood . In the present study, we evaluated the effect of glutathione (GSH) supplementation or depletion on ADR-induced cardiotoxicity in male Wistar rats . Cardiac toxicity was induced by a single intraperitoneal injection of ADR (20 mg kg(-1)) and manifested by an increase in heart rate, blood pressure elevation, and increased serum creatine kinase (CK) and lactate dehydrogenase (LDH) . The extent of lipoprotein oxidation, lipid peroxide measured as malondialdhye (MDA), total homocysteine (tHcy), lipid profile, and atherogenic index were markedly elevated, whereas cardiac GSH content was dramatically decreased in ADR rats . Pre- and co-treatment of ADR rats with GSH (5 mm kg(-1)) (ADR +GSH) markedly reduced the levels of CK, LDH, lipoprotein oxidation susceptibility, cardiac MDA, tHcy and atherogenic index, and elevated GSH levels in cardiac tissues . In contrast, GSH depletion through administration of l-buthionine-(S,R)-sulfoximine (BSO) (15 mm kg(-1)) before and after ADR injection (ADR +BSO) greatly exacerbated ADR cardiotoxicity compared to the control and ADR groups . Finally, there were also severe cardiac histopathological changes in ADR and ADR +BSO groups, which were nearly restored by GSH treatment . These results suggest that GSH inhibits ADR cardiotoxicity and might serve as a novel combination with ADR to limit free radical-mediated organ injury .

Kidney Int, 2000 Jul, 58(1), 384 - 9
Fungal peritonitis in children receiving peritoneal dialysis: a report of the NAPRTCS; Warady BA et al.; BACKGROUND: The rarity of fungal peritonitis (FP) in children receiving chronic peritoneal dialysis (PD) has limited the amount of information available regarding the risk factors and management associated with this infection . METHODS: We reviewed all cases of FP occurring in patients entered into the dialysis registry of the NAPRTCS between January 1992 and May 1996 in an attempt to identify risk factors for infection, treatment strategies, and patient outcome data . A total of 1592 patients who were less than 21 years of age were enrolled in the dialysis registry and received maintenance PD during the period of observation . RESULTS: Of the total 1729 episodes of peritonitis in these patients occurring over 1732 patient-years of follow-up, FP accounted for 51 (2.9%) of the episodes . The patients on PD who developed FP were similar to those who did not develop FP with regard to race, gender, dialysis modality, and dialysis access characteristics . The overall peritonitis rate in patients who developed FP was 2.2 episodes per patient-year compared with 0.96 episodes per patient-year in the patients who did not develop this infection (P < 0.0001) . In 25 (49%) cases, the FP was the patient's initial episode of peritonitis . Whereas recent antibiotic usage was present in 23 (56%) of 41 patients with FP, there was no statistically significant relationship (P = 0.26) noted between the presence of a gastrostomy and the development of FP . Candida species caused 33 of 42 (78.6%) FP episodes . Therapy consisted of PD catheter removal and Amphotericin B in the majority of patients . Six months after diagnosis, 27 patients remained on PD, twelve patients were receiving hemodialysis, and only three patients had died, in each case for reasons unrelated to their FP episode . CONCLUSION: FP is an infrequent cause of peritonitis in children receiving chronic PD . The presence of a gastrostomy does not appear to predispose patients to the development of this infection, and successful therapy most often consists of a combination of antifungal medication and dialysis catheter removal . The outcome of FP in children appears to be more favorable than in the adult dialysis population.

Proc R Soc Lond B Biol Sci, 2000 Jun 7, 267(1448), 1063 - 9
Macrofilaricidal activity of tetracycline against the filarial nematode Onchocerca ochengi: elimination of Wolbachia precedes worm death and suggests a dependent relationship; Langworthy NG et al.; Filarial nematodes are important and widespread parasites of animals and humans . We have been using the African bovine parasite Onchocerca ochengi as a chemotherapeutic model for O . volvulus, the causal organism of 'river blindness' in humans, for which there is no safe and effective drug lethal to adult worms . Here we report that the antibiotic, oxytetracycline is macrofilaricidal against O . ochengi . In a controlled trial in Cameroon, all adult worms (as well as microfilariae) were killed, and O . ochengi intradermal nodules resolved, by nine months' post-treatment in cattle treated intermittently for six months . Adult worms removed from concurrent controls remained fully viable and reproductively active . By serial electron-microscopic examination, the macrofilaricidal effects were related to the elimination of intracellular micro-organisms, initially abundant . Analysis of a fragment of the 16S rRNA gene from the O . ochengi micro-organisms confirmed them to be Wolbachia organisms of the order Rickettsiales, and showed that the sequence differed in only one nucleotide in 858 from the homologous sequence of the Wolbachia organisms of O . volvulus . These data are, to our knowledge, the first to show that antibiotic therapy can be lethal to adult filariae . They suggest that tetracycline therapy is likely to be macrofilaricidal against O . volvulus infections in humans and, since similar Wolbachia organisms occur in a number of other filarial nematodes, against those infections too . In that the elimination of Wolbachia preceded the resolution of the filarial infections, they suggest that in O . ochengi at least, the Wolbachia organisms play an essential role in the biology and metabolism of the filarial worm.

J Thorac Cardiovasc Surg, 2000 Jul, 120(1), 148 - 55
Pulmonary homograft: should it be used in the aortic position?
Choudhary SK, Saxena A, Dubey B, Kumar AS.
OBJECTIVE: Retrospective analysis was performed to determine the suitability of pulmonary homograft as an aortic valve substitute . METHODS: From January 1994 through June 1999, 147 patients (mean age, 32.2 +/- 17.3 years) underwent aortic valve replacement with either an aortic homograft (group 1: n = 103, 25 fresh antibiotic preserved and 78 cryopreserved) or a pulmonary homograft (group 2: n = 44, 11 antibiotic preserved and 33 cryopreserved) . In group 1 a scalloped subcoronary technique was used in 64 patients, and a root replacement technique was used in 39 patients . In group 2 the scalloped subcoronary technique was used in 34 patients, and the root replacement technique was used in 10 patients . RESULTS: There were 131 operative survivors (group 1 = 91; group 2 = 40) . Follow-up ranged from 2 to 62 months . In group 1 none of the patients had significant aortic regurgitation during the hospital stay . Three patients (all having undergone the scalloped subcoronary technique) had moderate aortic regurgitation after 6 to 32 months . In group 2, 10 patients (9 having undergone the scalloped subcoronary technique and 1 having undergone the root replacement technique) developed significant regurgitation: 2 intraoperatively, 5 in the early postoperative period before discharge from the hospital, and 3 during late follow-up 6 to 12 months postoperatively . Among the various risk factors analyzed for overall homograft failure, use of a pulmonary homograft was the single independent predictor of valve failure (odds ratio, 8.6; 95% confidence interval, 1.9-39; P =.006) . CONCLUSION: Pulmonary homograft, when inserted by means of a scalloped subcoronary technique, is not a suitable aortic valve substitute.

J Control Release, 2000 Jul 31, 68(1), 121 - 34
Formulation of calcium phosphates/poly (d,l-lactide) blends containing gentamicin for bone implantation; Soriano I et al.; Implants to prevent or treat osteomyelitis are described, composed of phosphate/poly(d,l-lactide) blends containing the antibiotic gentamicin . Seven formulations of implants containing 3% gentamicin sulfate (GS) were prepared at 433 MPa and 693 MPa of compression pressure . The blends contained phosphates (25% hydroxyapatite (HAP), 75% tricalcium phosphate (TCP)) and 20% dl-PLA (weight average molecular weight, M(w): 30 kD) . To prolong GS release, implants were coated with PLGA (M(w):100 kD) or dl-PLA (M(w): 200 kD) . Various durations of GS release from these devices were demonstrated as feasible . Release times of more than 10 weeks were attained with implants coated with dl-PLA (M(w): 200 kD), greatly exceeding the performance of the commercial formulation.

Proc Natl Acad Sci U S A, 2000 Jul 5, 97(14), 7814 - 8
On the kinetics of distamycin binding to its target sites on duplex DNA; Baliga R et al.; Distamycin A is a well known polyamide antibiotic that can bind in the minor groove of duplex DNA primarily at AT-rich sequences both as a monomer or as a side-by-side antiparallel dimer . The association phase of the distamycin binding reaction has not been studied in either of its binding modes, because of the lack of an adequate UV or CD signal at the low concentrations needed to monitor the fast bimolecular reaction . We report a significant increase in fluorescence amplitude, accompanied by a small red shift, on binding distamycin to its specific target sites . This signal can be used to monitor drug binding in steady-state and time-resolved processes . Distamycin shows extremely fast association with the 1:1 binding site, with a bimolecular rate of 7 x 10(7) M(-1) small middle dots(-1) and also fairly rapid dissociation ( approximately 3 s(-1)) . When DNA is in excess, there is a slow component in the association reaction whose rate decreases strongly with increasing DNA concentration . Binding of the drug to the 2:1 site occurs in two distinct steps: fast, sequential binding of each drug molecule to the DNA with a bimolecular rate comparable to that at the 1:1 site, followed by a slow ( approximately 4 s(-1)) equilibration to the final population . Dissociation from the 2:1 site is approximately 40-fold slower than from the 1:1 site . This study provides the groundwork for analysis of the binding kinetics of longer polyamides and covalently linked polyamides that have recently been shown to inhibit transcription in vivo.

Cad Saude Publica, 1997, 13 Suppl 1, 15 - 25
Implications of Helicobacter pylori infection for stomach cancer prevention; Goodman KJ; Accumulating evidence has implicated Helicobacter pylori, an established cause of chronic gastritis and peptic ulcer, in the etiology of gastric cancer . Control of this infection would reduce the occurrence of chronic gastritis and peptic ulcer and might substantially lower the risk of stomach cancer as well . The public health impact of this infectious agent warrants efforts to identify preventive measures . This paper reviews the evidence linking H . pylori infection to gastric cancer and evaluates the potential for control in high-risk populations . Current obstacles to H . pylori control are discussed, including the link to poor socioeconomic conditions, difficulty in identifying incident cases, lack of natural immunity to reinfection, limited effectiveness of antibiotic therapy in high-prevalence populations, and incomplete knowledge regarding the reservoir of infection, mode of transmission, host susceptibility factors, and the potential for developing an effective vaccine . Worthwhile avenues of research include studies designed to identify modifiable risk factors for acquisition of the infection, modifiable host factors that may increase resistance to chronic infection, more effective antibiotic therapies, and effective vaccines.

J Oral Maxillofac Surg, 2000 Jul, 58(7), 754 - 60
Perioperative complications in corrective facial orthopedic surgery: a 5-year retrospective study; Acebal-Bianco F et al.; PURPOSE: Frequency and severity of complications have a profound impact on referral patterns for facial orthopedic surgery . Therefore, a retrospective study was undertaken to determine the incidence of such problems in a large series of patients, with the intent to use these data to make possible changes in the perioperative protocol used in our clinic . PATIENTS AND METHODS: The files of all patients operated on between 1992 and 1996 were studied . These comprised 1,108 patients with 1,872 osteotomy procedures . The following parameters were descriptively analyzed: airway obstruction, hemorrhage, hematoma, infection, neurosensory disturbances, unfavorable fractures, malposition of condyles and nasal septum, and vascularization problems . RESULTS: The most frequent complication was impairment of trigeminal nerve function . In 31.5% of the mandibular base osteotomies, 43.6% of the combined mandibular base and chin osteotomies, and 13% of the chin osteotomies, lip sensibility was decreased immediately postoperatively . After 1 year, this number was reduced to approximately 5% . The function of 17 lingual nerves and 45 infraorbital nerves was temporarily impaired . A wound infection was next in frequency . Fifty-three infections (mandible-to-maxilla ratio, 2.5:1) were treated with drainage under local anesthesia and antibiotic therapy . Loss of part or all of an osteotomized segment did not occur . Other complications were rare and/or temporary . CONCLUSIONS: The most frequent complication was impairment of inferior alveolar nerve function . Life-threatening complications were not encountered . The frequency of infections (<5%) requires further consideration regarding ways to reduce the incidence.

Harefuah, 2000 Feb 1, 138(3), 195 - 9, 271
{Endoscopic sinus surgery for extracranial complications of sinusitis}; Deutsch E et al.; Orbital subperiosteal abscess (SPA) and Pott's puffy tumor (PPT) are the major extracranial complications of acute sinusitis . These complications are aggravated by the close anatomic relationships between the nasal sinuses and the orbits and frontal bone . Furthermore, the rich diploic venous drainage of the region enhances the spread of the infection . Between 1992 and 1997, 16 patients (mean age 12 years, range 2-15, 10 of them males), 11 of them with SPA and 4 with PPT were operated on by the senior author by means of endoscopic sinus surgery (ESS) . Indications for operation included: CT findings of abscess formation and lack of clinical improvement after 48 hours of i.v . antibiotic therapy . Clinical resolution of symptoms was achieved in all and there were no operative or postoperative complications . We emphasize and explain the advantages of ESS over external approaches in surgery for extracranial complications of acute sinusitis by several facts: the technique treats the source of the disease, clinical success rate is high, morbidity is low, and facial distortion and poor cosmetic results completely avoided.

J R Coll Surg Edinb, 2000 Jun, 45(3), 189 - 91
A case of multiple splenic abscesses managed non-operatively; Murray AW et al.; We report the case of a previously fit 22-year-old man who developed multiple splenic abscesses of unclear aetiology and was successfully treated with percutaneous drainage of the largest abscess and antibiotic therapy.

Rev Chir Orthop Reparatrice Appar Mot, 2000 Jun, 86(4), 381 - 9
{Comminuted fractures in multiple trauma patients: an analysis of 31 cases}; Castel E et al.; PURPOSE OF THE STUDY: We analyzed calcaneum burst fractures in multiple trauma patients and propose a management scheme . MATERIAL AND METHODS: In a retrospective study, we isolated 23 patients with 31 calcaneum burst fractures . All were stage V in the Duparc classification . We call them "pied de mine" fractures as they resembled those described in military reports . Half of them (16 cases; 54%) were open fractures . All patients suffered multiple injuries and 12 had a psychiatric history . These fractures were associated with spinal fracture in 17 cases (73%) and half had neurologic deficit, limb fracture in 16 (73%), and pelvic fracture in 12 (52%) . The most frequent associated foot injuries were a talus fracture in 9 cases (29%) and Chopart displacement in 10 cases (32%) . Clinical evaluation used the Maryland foot score, foot print and radiologic evaluation with lateral retrotibial view . RESULTS: Mean follow-up was 35 months . Mean Maryland foot score was 62.7 and 13 cases were pain free . Pain was due to conflict with the lateral malleolus, bony plantar thorns, medial malleolus and subtalar osteoarthritis . Orthopedic shoes were used 11 times . The other patients used sports shoes . Subtalar mobility was most frequently absent (23/29 cases, 2 amputations) . Foot print showed 13/16 flat feet; 6 thorns were indirectly visible . Two patients had retraction toes and were initially treated by external fixation . Radiologic evaluation showed 23/29 complete subtalar arthrodeses, 23/29 migration of the great tuberosity, often(17/23 cases) associated with varus angulation . Eleven patients needed subsequent surgery: 5 for arthrodeses and 6 for resection of bony thorns . Rate of complication was high, especially for open fractures: 2 infections for 15 closed fractures, and 8 infections (50%) for 16 open fractures with 2 cases of chronic osteitis . Secondary amputation was required in 2/31 cases due to sepsis . TREATMENT PROPOSITIONS: For closed calcaneum burst fractures, it is better to wait one week before osteosynthesis . This delay is used to decrease edema with limb elevation and compressive bandaging . Skin tension due to trauma is increased by edema and osteosynthesis gives a high risk of wound disunion . We recommend reduction and Y-plate fixation even for burst fracture . Reduction must lower the tuberosity and correct the varus . After surgery, subtalar spontaneous arthrodesis is usually observed in a good position . Any bony plantar thorn must be resected . For open calcaneum burst fracture, the risk of sepsis is high . First treatment is debridement, stabilization and external fixation with antibiotic therapy . Stabilization should improve vascularization and facilitate internal fixation . The external fixation can be placed on the medial side to free the lateral approach to the calcaneum . Flap repair can be performed after one week when skin tension has subsided and areas of necrosis controlled.

Clin Infect Dis, 2000 Jun, 30(6), 976 - 80
Value of quantitative serology for confirmation of Helicobacter pylori eradication: an 18-month follow-up study; Gisbert JP et al.; In this study several therapies were administered to 124 H . pylori-positive patients and IgG antibody titers were measured by ELISA at months 0, 2, 3, 6, 12, and 18 months . Serum titers of IgG antibody progressively decreased after H . pylori eradication; at 3 months, the area under the receiver operating characteristic curve for the decrease of IgG antibody titers for confirming H . pylori eradication was 0.99, with 100% sensitivity and 99% specificity (when the cutoff point was set at 3 U/mL) . We conclude that a decrease in serum titers of IgG antibody to H . pylori relatively early after completion of therapy (1 month after ranitidine or bismuth therapy is completed and 2.5 months after antibiotic therapy is completed) can be used as a noninvasive, simple, and inexpensive method to confirm H . pylori eradication.

Cancer Gene Ther, 2000 Jun, 7(6), 920 - 6
T-lymphocyte function after retroviral-mediated thymidine kinase gene transfer and G418 selection; Di Ianni M et al.; Generation of an efficient graft-versus-leukemia (GVL) effect in patients with hematological malignancies who relapse after allogeneic bone marrow transplantation depends in part upon the number of infused T lymphocytes . Currently, a GVL reaction cannot be achieved without inducing concomitant graft-versus-host disease (GVHD); thus, one strategy is to try to modulate this GVL/GVHD ratio . We engineered human T lymphocytes with herpes simplex virus-thymidine kinase and neomycin resistance genes, with an LXSN-derived vector that confers a ganciclovir-specific sensitivity to the transduced T cells . We analyzed proliferation, interleukin-2 production, alloreactivity in a mixed lymphocyte culture, and clonogenicity during the different stages of retroviral infection and G418 selection . Our results confirm that a sufficient number of transduced T lymphocytes can be obtained after selection for clinical studies . Their proliferative activity, alloresponsiveness, and ability to produce and respond to interleukin-2 were retained . Compared with control populations, their clonogenicity, as assessed by limiting dilution assays, was reduced after retroviral infection and G418 selection by 1.6 and 2.9 logs, respectively, with both viral supernatant incubation and coculture procedures . This study shows that infection and selection with the thymidine kinase-neomycin resistance gene retroviral vector significantly reduces the number of functional T lymphocytes . This finding should be taken into account when establishing the dose of T lymphocytes necessary to trigger a modulated GVL/GVHD effect.

Optom Vis Sci, 2000 Jun, 77(6), 286 - 92
Relapsing polychondritis; Chow MT et al.; BACKGROUND: Relapsing polychondritis (RPC) is a rare, chronic, and potentially fatal multisystemic inflammatory disorder targeting cartilaginous structures . This disorder is frequently associated with rheumatoid arthritis, systemic vasculitis, connective tissue diseases, and/or hematologic disorders . RPC afflicts patients with recurrent and often progressive episodes of inflammation with the potential for destruction of the affected structures . Tissues involved include the ears, joints, nose, larynx, trachea, eyes, heart valves, kidneys,and skin . Ocular manifestations commonly include episcleritis, scleritis, conjunctivitis, iridocyclitis, chorioretinitis, and proptosis . Lid edema, orbital inflammation, muscle palsies, and corneal melting may also occur . CASE REPORT: An 83-year-old man previously diagnosed with RPC presented to our clinic with acute unilateral chemosis, conjunctivitis, lid edema, proptosis, and extraocular muscle restriction . After orbital cellulitis was ruled out, further evaluation revealed posterior scleritis with choroidal detachment OS . A course of oral indomethacin and topical antibiotic-steroid combination drops was implemented in the treatment of the ocular manifestations . The quick positive response to the anti-inflammatory agents confirmed the diagnosis of ocular complications secondary to RPC . DISCUSSION: The presenting ocular signs and symptoms of RPC often resemble other commonly encountered ocular conditions . It is important for the eye care practitioner to be familiar with the ocular manifestations of RPC because the eyes are sometimes the initial site of involvement and may be a marker of severity . Early diagnosis and intervention may significantly improve the patient's outcome . This case report with literature review will hopefully bring to light features of this disease which will help the eye care practitioner in the diagnosis and management of this condition.

Infect Control Hosp Epidemiol, 2000 Jun, 21(6), 411 - 6
Reasons for noncompliance with infection control guidelines; Farr BM; Concern frequently is voiced about individuals not complying with guidelines intended to prevent spread of antibiotic-resistant pathogens from patient to patient, but institutional decisions to ignore Centers for Disease Control and Prevention guidelines recommending detection and isolation of colonized patients also have contributed greatly to the increasing rate of infections due to these pathogens . This is so because colonized patients are the main reservoir for spread, and barrier precautions prevent spread much more effectively than Standard Precautions . Providing effective leadership and changing this culture of noncompliance must begin with the infection control team believing that spread is both important and preventable.

Lik Sprava, 2000 Jan-Feb, (1), 56 - 60
{Aspergillosis of the heart and liver in leptospirosis}; Anisimova IuN et al.; A study made in three autopsies suggested development during the second to third week of leptospirosis icterohaemorrhagica against the background of secondary immunodeficiency (due to severity of the underlying condition or induced by glucocortocoid and antibiotic therapy) Aspergillus affection of the heart that had significantly aggravated the clinical course of leptospirosis and appeared to be the immediate provoking cause of acute cardiovascular insufficiency with a fatal result to follow . Two cases demonstrated an isolated fungal infection of the myocardium . In one of these running a longer (20 days in duration) course there took place a hematogenic dissemination of the aspergilli present in the liver during the development of the metastatic focus in the myocardium . The observations done suggest that each case requires individual consideration as to part the fungus infection plays in the outcome of the pathological process depending upon its type and extension in the organ.

J Antimicrob Chemother, 1999 Nov, 44 Suppl B, 23 - 9
Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis; Monto AS et al.; Zanamivir, a potent, highly selective inhibitor of influenza virus A and B neuraminidase, has been evaluated in seven, similarly designed, placebo-controlled studies of the treatment of influenza . Patients with typical influenza symptoms were recruited when influenza was known to be circulating in the community . Six of these studies included a zanamivir 10 mg inhaled bd (for 5 days) treatment arm, the dose regimen submitted to regulatory agencies . Pooled analyses were conducted to evaluate efficacy more precisely in terms of the alleviation of symptoms in population subgroups and for secondary endpoints . Median time to alleviation of symptoms, the primary endpoint, was reduced from 6.0 days in the placebo group (n = 1,102) to 5.0 days in the zanamivir group (n = 1,133), P< 0.001 . In febrile, laboratory-confirmed, influenza-positive (IP) patients, time to alleviation was reduced from 6.5 days to 5.0 days, a treatment benefit of 1.5 days (P < 0.001) . A larger treatment benefit (3 days) was seen in IP patients who had severe symptoms at entry (n = 474, P < 0.001), compared with 1 day in patients whose symptoms were not severe (n = 1,098, P< 0.001) . Similarly, a 3 day treatment benefit (P = 0.003) was observed in IP patients aged >50 years (n = 263), compared with 1 day (P < 0.001) in patients aged <50 years . In 'high-risk' IP patients (recruited into all treatment studies), there was a treatment benefit of 2.5 days (n = 305, P = 0.006) . Pooled analyses of secondary endpoints showed statistically significant reductions in antibiotic use, time to return to normal activities and use of relief medication . In addition, reductions in symptom scores were apparent shortly after commencing zanamivir treatment . By the evening of the second day of treatment, the median total symptom score had fallen by 44% in zanamivir recipients compared with 33% in placebo recipients (P < 0.001) . These results highlight the groups likely to show greatest benefit from zanamivir treatment, and confirm the clinical relevance of the treatment benefit.

Semin Oncol, 2000 Apr, 27(2 Suppl 5), 9 - 14
Pentostatin (Nipent): a review of potential toxicity and its management; Margolis J et al.; Pentostatin (Nipent; SuperGen, San Ramon, CA) is a safe and well-tolerated medication but, like all chemotherapeutic agents, it may be associated with some toxicity . The toxicity seen with pentostatin is dose and schedule dependent and can be minimized by appropriate dosing . The dose of pentostatin should never exceed 4 mg/m2 . A dose reduction is required for patients with renal insufficiency . Renal and neurological toxicities may occur, yet are uncommon with appropriate dosing . Nausea and vomiting also occur; however, they are usually controlled with antiemetic therapy . Like the other purine nucleoside analogs, pentostatin is an immunosuppressive drug that may increase the risk of infection, especially with opportunistic organisms . Prophylactic antibiotics should be considered when treating patients with pentostatin.

J Voice, 2000 Jun, 14(2), 282 - 6
Preliminary results of intraoperative mitomycin-C in the treatment and prevention of glottic and subglottic stenosis; Rahbar R et al.; Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis . It can inhibit cell division, protein synthesis, and fibroblast proliferation . The purpose of this pilot study is to investigate intraoperative applications of topical mitomycin-C in treatment and prevention of glottic and subglottic stenosis . Eight patients with posterior glottic and/or subglottic stenosis were treated with endoscopic CO2 laser excision followed by topical application of 0.5 cc of 0.4 mg mitomycin-C per milliliter of saline for 4 minutes at the surgical site . After mean follow-up of 15 months (10-20) all patients had clinical improvement of their airway and resolution of their preoperative symptoms . No complications were noted in this study . Although a longer follow-up and further controlled studies are needed, the use of topical mitomycin-C may prove useful in the treatment and prevention of subsequent restenosis and scar formation in the larynx and trachea.

Hum Reprod Update, 2000 May-Jun, 6(3), 259 - 67
Cochrane review: post-operative procedures for improving fertility following pelvic reproductive surgery; Johnson NP et al.; The objectives of the study was to determine the effectiveness of post-operative procedures following female pelvic reproductive surgery . A systematic review employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was used . Five randomized controlled trials were included . Participants were women undergoing pelvic reproductive surgery; interventions were any post-operative procedure designed to improve fertility; outcomes were pregnancy, live birth, ectopic pregnancy and miscarriage rates and the rates of tubal patency and procedure-related complications . Summary statistics were expressed as odds ratios . The results showed that the odds of pregnancy, live birth, ectopic pregnancy and miscarriage were not significantly altered by post-operative hydrotubation nor second-look laparoscopy with adhesiolysis . Whether hydrotubation was early or late and whether hydrotubation fluid contained steroid or not had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage . The odds of pregnancy and live birth were significantly increased and infective complications significantly decreased by hydrotubation with fluid containing antibiotic compared with hydrotubation with fluid containing no antibiotic, in late hydrotubation following tubal stent removal 6 weeks after tubal surgery . The odds of at least one patent Fallopian tube were significantly increased with late hydrotubation following tubal stent removal compared with early hydrotubation in women who had no tubal stenting, but this intervention had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage . In conclusion, there is insufficient evidence to support the routine practice of hydrotubation or second-look laparoscopy following female pelvic reproductive surgery . The studies on which this conclusion is based were either poor quality or underpowered . Post-operative hydrotubation with fluid containing antibiotic following tubal surgery may offer benefit over hydrotubation fluid without antibiotic . A randomized controlled trial of post-operative hydrotubation with antibiotic-containing fluid versus no hydrotubation for improving fertility following tubal surgery is justified.

Ann Fr Anesth Reanim, 2000 May, 19(5), 388 - 94
{The economic impact of inadequate prescriptions}; Montravers P; The impact of antibiotic therapy has gone to considerable expense . The review of literature demonstrates that an optimal use of economical resources can be achieved by an improvement of medical prescriptions . This improvement of prescriptions can be obtained for prophylaxy and for curative therapy . Cost savings can be as high as one-year budget for the recruitment of an infectious diseases consultant.

Presse Med, 2000 May 27-Jun 3, 29(19), 1091 - 7
{Acne today . What's new?}; Auffret N; WELL-CONDUCTED TREATMENT: Acne is a common condition in adolescents and requires careful management both in terms of therapeutic care and psychological support . Treatment is long and requires strict compliance . A well-conducted treatment can be expected to provide major improvement in most patients . LOCAL CARE: Local care is often sufficient for retentional or discretely inflammatory acne . A retinoid and/or a benzoyl peroxide can be associated with a local antibiotic . SEVERE FORMS: An oral antibiotic regimen for at least 3 months is proposed in association with the local treatment (retinoid, benzoyl peroxide, local antibiotic) in case of severe acne . ISOTRETINOIN: In case of unsuccessful treatment for nodular or conglobata acne, isotretinoin can be proposed in an oral preparation . This highly teratogenic drug must not be prescribed for women of reproductive age unless a well proven contraception has been instituted for more than 1 month and maintained for the entire duration of the treatment and 1 month after discontinuation . The patient must be informed of the risk in case of pregnancy and consent to regular monitoring of beta hCG less than 3 days before treatment onset, every 2 months during treatment and 5 weeks after treatment withdrawal).

J Pediatr Surg, 2000 Jun, 35(6), 923 - 6
Perforated appendicitis: prospective outcome analysis for 150 children; Fishman SJ et al.; BACKGROUND/PURPOSE: Controversy persists in the management of perforated appendicitis with regard to antibiotic choice and duration, operative timing, drain utilization, and wound closure . For 2 decades at the authors' institution, patients were treated with ampicillin, gentamicin, and clindamycin for 10 inpatient days, with drains in the abdomen, resulting in lower complication rates than most other published series . Managed care pressures have led to less aggressive medical management regimens with length of stay and financial factors viewed as principal outcome measures with little emphasis on clinical outcomes . In addition, there are little prospective data on clinical outcomes . The authors sought to determine whether our previously documented excellent quality outcomes could be maintained when modifications aimed at decreasing cost and length of stay in our protocol were instituted . METHODS: The authors monitored prospectively clinical outcomes in patients with perforated appendicitis treated according to their clinical practice guidelines over a 43-month period . Patients received a single antibiotic, piperacillin-tazobactam, intravenously for 10 days . They were permitted to go home with a percutaneous intravenous catheter for the final 5 days if medical and social criteria were met . Other practices from our earlier protocol were continued, including immediate operation, placement of Penrose drains, and primary wound closure . RESULTS: Of 150 patients treated on our protocol, major complications included intraabdominal abscess in 5 (3.3%), cecal fistula in 2 (1.3%), phlegmon in 3 (2.0%), wound infection in 4 (2.7%), and no small bowel obstructions requiring operation . None of these complications, nor their aggregate, were significantly more common than those reported in 373 patients treated over 11 years on the authors' prior protocol (chi2, P > .05) . CONCLUSIONS: Prospective outcome analysis of our protocol shows that a single broad-spectrum antibiotic (allowing portions of therapy to be delivered less expensively on an outpatient basis) effectively can treat postoperative appendicitis with very few infectious complications . These outcome data provide baseline against which future protocols can be compared . All treatment modifications aimed at decreasing costs must be analyzed to ensure quality of care is not unduly compromised.

J Periodontol, 2000 May, 71(5), 803 - 9
Pluronic polyol effects on human gingival fibroblast attachment and growth; Hokett SD et al.; BACKGROUND: Enhanced speed of human gingival fibroblast (HGF) spreading and attachment, as affected by ionic bonding interactions, may facilitate cell orientation and subsequent collagen synthesis to promote early wound healing . The purpose of this study was to determine the in vitro effects of pluronic polyols, a family of widely used surfactants currently used as drug carriers for antibiotic, anti-inflammatory, and anti-neoplastic agents, on the attachment and growth of human gingival fibroblasts (HGF) to dentin and plastic surfaces using established tissue culture techniques . METHODS: Plastic culture wells containing Eagle's minimal essential media (EMEM) with 10% fetal calf serum and Pluronic F-68 or F-127 in concentrations from 1.2 x 10(-2) to 1.2 x 10(-10) M were incubated with HGF and run in replicates of ten . Attached cells were quantified by measuring the optical density of methylene blue-stained cells . Additional experiments were conducted using human dentin sections as a substrate and Pluronic F-68 or F-127 at a concentration of 1.2 x 10(-8) M . In these experiments, HGF were stained with acridine orange and quantified per unit area of dentin by fluorescence microscopy . RESULTS: Attachment and growth of HGF to both plastic and dentin were significantly increased over serum controls by very low concentrations of Pluronic F-68 and F-127 by 30 minutes, with attachment reaching a plateau at 2 hours . CONCLUSIONS: Pluronic polyols, a family of widely used surfactants, in very low dosages may be beneficial in early postsurgical wound healing by facilitating early attachment and enhancing the growth rate of human gingival fibroblasts.

Am J Obstet Gynecol, 2000 Jun, 182(6), 1382 - 8
Transrectal ultrasonographically guided drainage of gynecologic pelvic abscesses; Nelson AL et al.; OBJECTIVE: This study assessed the feasibility of ultrasonographically guided transrectal aspiration of gynecologic pelvic abscesses to treat patients for whom intravenous antibiotic therapies failed and whose abscesses were not optimally amenable to colpotomy drainage or transabdominal or transvaginal ultrasonographically guided aspiration.Study Design: This was a retrospective review of the first 15 women with pelvic abscesses that resulted from salpingitis or complications of gynecologic surgery who underwent transrectal pelvic abscess drainage after failure of antibiotic therapy . RESULTS: Purulent material was aspirated from the abscesses in 14 of the 15 women . All 14 women with aspirated material were successfully treated with real-time ultrasonographically guided transrectal drainage; only 4 of the 14 had indwelling catheter placement . CONCLUSION: Ultrasonographically guided transrectal drainage of gynecologic pelvic abscesses is a safe and effective treatment of pelvic abscesses for women who do not have an adequate response to antibiotic therapy.

J Auton Nerv Syst, 2000 Jul 3, 81(1-3), 75 - 81
Regulated expression of the rat recombinant P2X(3) receptor in stably transfected CHO-K1 tTA cells; Lachnit WG et al.; In this report, the regulatable expression by tetracycline of the rat recombinant P2X(3) receptor in stably transfected Chinese hamster ovary (CHO-K1) expressing the tetracycline-controlled transactivator (tTA) is described . cDNA encoding the rat P2X(3)-receptor was subcloned into pTRE (a tetracycline-repressible expression vector) which was used to transfect stably CHO-K1 tTA cells . Using whole cell patch clamp techniques, 100 microM ATP evoked inward currents of 2.9+/-1.6 nA in transfected cells grown in the absence of tetracycline (tet-) . The P2X(3) receptor protein was detectable by immunoblot as early as 24 h and protein expression levels continued to increase as much as 192 h following activation of tTA by the removal of the antibiotic . Saturation binding isotherms using {35S}ATP gamma S yielded a pK(d) of 8.2+/-0.1 and a B(max) of 31.9+/-3.5 pmol/mg protein in tet- cell membranes and a pK(d) of 8.1+/-0.1 and a B(max) of 5.8+/-0.8 pmol/mg protein in tet+ cell membranes . The agonist ligands 2MeSATP and alpha beta MeATP displaced the binding of {35S}ATP gamma S in tet- cell membranes with very high affinity, yielding pIC(50) values of 9.4+/-0.2 and 7.5+/-0 . 2, respectively . In tet+ cell membrane, displacement of {35S}ATP gamma S by 2MeSATP and alpha beta MeATP was of much lower affinity (pIC(50) values of 7.8 and 6.2, respectively) . ATP, ADP and UTP showed similar displacement of {35S}ATP gamma S binding in tet- and tet+ cell membranes . In other experiments, cytosolic Ca(2+) was monitored using the fluorescent indicator, fluo-3 . Increases in cytosolic Ca(2+) were elicited by 100 nM alpha beta MeATP in tet- cells while no increases in cytosolic Ca(2+) were detected below 100 microM alpha beta MeATP in either tet+ cells or untransfected cells . These calcium responses to alpha beta MeATP had a pEC(50) of 6.7 and were transient, returning to baseline within 120 s . Suramin produced concentration-dependent, parallel, dextral shifts of E/{A} curves to alpha beta MeATP yielding a pK(B) of 5.6 . PPADS produced non-parallel, dextral shifts of E/{A} curves to alpha beta MeATP which were insurmountable . These results show for the first time, expression of a functional, homomeric recombinant rat P2X(3) receptor which is under regulated expression in a stably transfected mammalian cell line.

Toxicol Sci, 2000 Jul, 56(1), 229 - 39
Gentamicin-induced apoptosis in renal cell lines and embryonic rat fibroblasts; El Mouedden M et al.; Gentamicin, an aminoglycoside antibiotic, induces apoptosis in the proximal tubule epithelium of rats treated at low, therapeutically relevant doses (El Mouedden et al., Antimicrob . Agents Chemother . 44, 665-675, 2000) . Renal cell lines (LLC-PK(1) and MDCK-cells) have been used to further characterize and quantitate this process (electron microscopy; terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling of fragmented DNA {TUNEL}; and DNA size analysis {oligonucleosomal laddering}) . Cells were exposed for up to 4 days to gentamicin concentrations of up to 3 mM . Apoptosis developed, almost linearly, with time and drug concentration, and was (i) preventable within the time-frame of the experiments by overexpression of the anti-apoptotic protein Bcl-2, and by co-incubation with cycloheximide (MDKC but not LLC-PK(1) cells); (ii) associated with an increased activity of caspases (MDCK cells; bcl-2 transfectants showed no increase of caspase activities and Z-VAD.fmk afforded full protection) . Gentamicin-induced apoptosis also developed to a similar extent in embryonic fibroblasts cultured under the same conditions . In the 3 cell types, apoptosis (measured after 4 days) was directly correlated with cell gentamicin content (apoptotic index {approximately 10 to 18% of TUNEL (+) cells for a content of 20 microg of gentamicin/mg protein; kidney cortex of rats showing apoptosis in proximal tubule epithelium typically contains approximately 10 microg of gentamicin/mg protein) . Thus, gentamicin has an intrinsic capability of inducing apoptosis in eucaryotic cells . Development of apoptosis in proximal tubules of kidney cortex in vivo after gentamicin systemic administration is therefore probably related to its capacity to concentrate in this epithelium after systemic administration.

Diabetes, 2000 Mar, 49(3), 424 - 30
Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion; Hohmeier HE et al.; The biochemical mechanisms involved in regulation of insulin secretion are not completely understood . The rat INS-1 cell line has been used to gain insight in this area because it secretes insulin in response to glucose concentrations in the physiological range . However, the magnitude of the response is far less than that seen in freshly isolated rat islets . In the current study, we have stably transfected INS-1 cells with a plasmid containing the human proinsulin gene . After antibiotic selection and clonal expansion, 67% of the resultant clones were found to be poorly responsive to glucose in terms of insulin secretion (< or =2-fold stimulation by 15 mmol/l compared with 3 mmol/l glucose), 17% of the clones were moderately responsive (2- to 5-fold stimulation), and 16% were strongly responsive (5- to 13-fold stimulation) . The differences in responsiveness could not be ascribed to differences in insulin content . Detailed analysis of one of the strongly responsive lines (832/13) revealed that its potent response to glucose (average of 10-fold) was stable over 66 population doublings (approximately 7.5 months of tissue culture) with half-maximal stimulation at 6 mmol/l glucose . Furthermore, in the presence of 15 mmol/l glucose, insulin secretion was potentiated significantly by 100 pmol/l isobutylmethylxanthine (320%), 1 mmol/l oleate/palmitate (77%), and 50 nmol/l glucagon-like peptide 1 (60%), whereas carbachol had no effect . Glucose-stimulated insulin secretion was also potentiated by the sulfonylurea tolbutamide (threefold at 3 mmol/l glucose and 50% at 15 mmol/l glucose) and was abolished by diazoxide, which demonstrates the operation of the ATP-sensitive K+ channel (K(ATP)) in 832/13 cells . Moreover, when the K(ATP) channel was bypassed by incubation of cells in depolarizing K+ (35 mmol/l), insulin secretion was more effectively stimulated by glucose in 832/13 cells than in parental INS-1 cells, which demonstrates the presence of a K(ATP) channel-independent pathway of glucose sensing . We conclude that clonal selection of INS-1 cells allows isolation of cell lines that exhibit markedly enhanced and stable responsiveness to glucose and several of its known potentiators . These lines may be attractive new vehicles for studies of beta-cell function.

Ann Chir, 1997, 51(9), 1028 - 31
{Ileocaecal tuberculosis . Apropos of a case}; Jouan MH et al.; The authors report a case of ileocaecal tuberculosis in a 27-year-old man with no particular risk factor for this disease . The initial diagnosis was terminal ileitis discovered at appendicectomy . The diagnosis of ileal tuberculosis was suspected in the presence of giant cell follicles on ileal biopsies, and was confirmed by the presence of AFB in the gastric intubation fluid . This patient presented known atypical pulmonary images for several years, which had never been investigated in more detail . A favourable course was observed in response to triple-agent, then double-agent antibiotic therapy . This case illustrates the fact that ileal tuberculosis still exists today, and that it does not exclusively affect "high-risk" patients.

Prikl Biokhim Mikrobiol, 2000 May-Jun, 36(3), 312 - 6
{Development of a new method for preparing biologically active compounds based on the typed strain Streptomyces werraensis}; Rusanova EP et al.; The regulatory function of a DNA fragment responsible for actinomycin resistance in the typed strain Streptomyces werraensis ATCC 1365, which produces a macrotetrolide antibiotic, was studied . Metabolic changes made this strain capable of producing an antibiotic complex, which comprises four biologically active compounds absent from the parent culture.

J Toxicol Clin Toxicol, 2000, 38(3), 305 - 8
Ecbalium elaterium (squirting cucumber)--remedy or poison?
Raikhlin-Eisenkraft B, Bentur Y.
BACKGROUND: Ecbalium elaterium is a plant endemic to the Mediterranean basin . Its roots and cucumber-shaped fruit have been used in folk medicine since antiquity . The alleged uses of the fruit juice are as a potent cathartic, analgesic, and antiinflammatory agent . Cucurbitacin B, a triterpene derivative is the active antiinflammatory principal . PATIENTS: We present a series of 13 patients who were exposed to the juice of Ecbalium elaterium in its natural form . In 3 patients, exposure was intranasal for the treatment of sinusitis or liver cirrhosis . In 3 other cases, children ingested the fruit unwittingly . In 6 patients, exposure was ocular and, in one, dermal . Within minutes of exposure, the patients exhibited irritation of mucous membranes at various degrees of severity manifested as edema of pharynx, dyspnea, drooling, dysphagia, vomiting, conjunctivitis, corneal edema, and erosion, depending on the route of the exposure . Recovery began within several to 24 hours after administration of oxygen, steroids, antihistamines, and beta-2-agonists . Ocular exposures responded to topical steroid and antibiotic eyedrops within a few days . The toddler with the dermal exposure remained asymptomatic . CONCLUSION: Exposure to the juice of Ecbalium elaterium, mainly in its undiluted form, may cause irritation of mucous membranes, supposedly of inflammatory nature . Patients exposed orally or intranasally should be closely followed for upper airway obstruction . Patients exposed ocularly should have their eyes promptly irrigated to prevent corneal and conjunctival injury.

AACN Clin Issues, 1999 Nov, 10(4), 464 - 77
Necrotizing pancreatitis: pathophysiology, diagnosis, and acute care management; Wrobleski DM et al.; Severe acute necrotizing pancreatitis is a disease that is caused by premature activation of pancreatic enzymes . Cytokine release contributes to systemic manifestations such as systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), adult respiratory distress syndrome (ARDS), and sepsis . Diagnosis is based on a history of abdominal pain, laboratory values such as serum amylase and lipase levels, and CT scan . Medical management focuses on fluid and electrolyte balance, antibiotic therapy, pain control, and decreasing systemic complications . Surgery is indicated when infectious pancreatic necrosis has been identified . This article addresses incidence and etiology; pathophysiology; clinical manifestations; diagnostics; and medical and surgical patient care management.

Arch Otolaryngol Head Neck Surg, 2000 Jun, 126(6), 777 - 81
Isolated sphenoid sinus diseases: report of 39 cases; Ruoppi P et al.; OBJECTIVE: To detail the underlying pathological conditions, symptoms, signs, and outcomes of patients with isolated sphenoid sinus involvement . DESIGN: A retrospective survey . SETTING: An academic referral center of a university hospital . PATIENTS: All 39 patients, aged 7 to 85 years, treated in the Department of Otorhinolaryngology, Kuopio University Hospital, Kuopio, Finland, from 1988 through 1997 for isolated sphenoid sinus disease . RESULTS: Sinusitis was characterized as acute in 26 patients, subacute in 5 (including 1 pyocele), and chronic in 8 (including 2 fungal infections) . No tumors were found . Isolated sinus cysts were excluded from the study . Headache, the main symptom in 32 patients (82%), was localized most commonly on the vertex . Other common complaints were rhinitis, dizziness, eye symptoms, and fever . In 2 patients, the finding was occult . Eight patients (21%) presented with cranial nerve deficits, and 1 patient had an intracranial complication . Sinus irrigation was performed in 16 patients (41%) and sphenoidotomy was performed in 10 (26%) . Fifteen patients (38%) were treated with antibiotic drugs alone . Within 3 months, 31 (84%) of 37 patients had recovered from the illness; 5 still experienced headaches despite having normalized radiographic findings; and 1 had permanent unilateral visual loss . Two patients were lost to follow-up . CONCLUSIONS: Sphenoid sinus opacity is mostly inflammatory in origin . Despite the benign nature of the disease, there is a risk of complications with high morbidity and mortality . Early and, if necessary, aggressive therapy to guarantee drainage of the sinus is recommended.

Ann Dermatol Venereol, 2000 May, 127(5), 513 - 6
{Erythema migrans with multiple lesions}; Constantin C et al.; INTRODUCTION: Erythema migrans with multiple lesions is observed in Europe in only 5-20 p . 100 of Borrelia infections . The number of lesions observed simultaneously in one patient is less than 7, considering all the cases published in the literature to date . CASE REPORTS: We report three patients who presented multiple macular, erythematous and centrifugal lesions localized on the trunk and the limbs . The first patient presented about thirty lesions, the second more than seventy, and the third about twenty . Serology investigation and immunoblots allowed to establish the diagnosis of a recent Borrelia Burgdorferi infection, with multiples lesions of erythema migrans . PCR performed on a skin biopsy of one of the patients confirmed the presence of Borrelia burgdorferi . Response to antibiotic therapy was immediate in all 3 patients . DISCUSSION: These 3 cases are of particular interest because the number of simultaneous lesions is much higher than what is reported in the European literature . These observations remind the clinician that the diagnosis of erythema migrans with multiple lesions should be included, in Europe as well, in the differential diagnosis of multiple annular dermatoses.

J Biol Chem, 2000 Aug 25, 275(34), 26625 - 31
Geldanamycin induces ErbB-2 degradation by proteolytic fragmentation; Tikhomirov O et al.; Exposure of carcinoma cell lines to the antibiotic geldanamycin induces the degradation of ErbB-2, a co-receptor tyrosine kinase that is frequently overexpressed in certain tumors . Using ErbB-2 mutants expressed as chimeric receptors or green fluorescent protein fusion proteins, we report that the kinase domain of ErbB-2 is essential for geldanamycin-induced degradation . The kinase domain of the related epidermal growth factor receptor was not sensitive to this drug . The data further indicate mechanistic aspects of ErbB-2 degradation by geldanamycin . The data show that exposure to the drug induces at least one cleavage within the cytoplasmic domain of ErbB-2 producing a 135-kDa fragment and a 23-kDa fragment . The latter represents the carboxyl-terminal domain of ErbB-2, whereas the former represents the ectodomain and part of the cytoplasmic domain . Degradation of the carboxyl-terminal fragment is prevented by proteasome inhibitors, whereas degradation of the membrane-anchored 135-kDa ErbB-2 fragment is blocked by inhibitors of the endocytosis-dependent degradation pathway . Confocal microscopy studies confirm a geldanamycin-induced localization of ErbB-2 on intracellular vesicles.

Anal Biochem, 2000 Jun 15, 282(1), 107 - 14
Development of a scintillation proximity assay for beta-ketoacyl-acyl carrier protein synthase III; He X et al.; Assays of beta-ketoacyl-acyl carrier protein synthases III (KASIII; FabH), a key enzyme initiating bacterial type II fatty acid biosynthesis, usually involve incubation of radiolabeled acetyl-coenzyme A and malonyl-acyl carrier protein (MACP) . The radiolabeled acetoacetyl-ACP product is precipitated and separated from the substrate before quantitation . We have developed a scintillation proximity assay (SPA) where use of biotinylated MACP (BMACP) allows the generation of a biotinylated acetoacetyl-ACP . This product, when captured by the streptavidin-coated scintillant-impregnated microspheres, generates an SPA signal . A BMACP K(m) of 7.1 microM was determined using this SPA with the Streptomyces glaucescens FabH . A similar MACP K(m) (6 microM) was determined in a precipitation assay, demonstrating that BMACP is an effective substrate for FabH . IC(50) values of 15.2 microM (SPA) and 24.8 microM were obtained with iodoacetamide and the S . glaucescens FabH . Comparable IC(50) values of 160 microM (SPA) and 125 microM were also obtained with the antibiotic thiolactomycin and the Escherichia coli FabH . These observations demonstrate that FabH inhibitors can be readily detected using a SPA with BMACP and that the effectiveness of inhibitors in the SPA is comparable to that obtained using MACP and a standard TCA precipitation assay . A FabH SPA adaptable to high-throughput screening should facilitate the discovery of potential novel antibiotics .

Chemotherapy, 2000 Jul-Aug, 46(4), 293 - 302
Intensive intravenous amphotericin B for prophylaxis of systemic fungal infections . Results of a prospective controlled pilot study in acute leukemia patients; Karthaus M et al.; BACKGROUND: Invasive fungal infections are an increasing cause of morbidity in acute leukemia (AL) patients . METHODS: In a prospective pilot trial, the safety and efficacy of antifungal prophylaxis with intravenous (i.v.) amphotericin B (AMB; 1 mg/kg every 48 h) was studied in 46 consecutive cycles . Prophylaxis with i.v . AMB was carried out in patients treated with intensive chemotherapy for AL and compared with a control of 49 cycles without prophylaxis . RESULTS: Pulmonary infiltrates (5 vs . 23; p < 0.001) and fungal microabscesses in the liver or spleen (0 vs . 6; p = 0.014) occurred significantly less frequently in the prophylaxis group . While there were 3 deaths related to systemic fungal infections in the control group, there were none in the prophylaxis group . Escalation to conventional AMB (1.0 mg/kg/day) was significantly less frequent in the prophylaxis group (9 out of 46 cycles) compared with the control arm (29 out of 49 cycles; p = 0.001) . A total of 695 mg of AMB per cycle was administered in the prophylaxis arm, compared with 634 mg/cycle for empirical treatment in the control group (p = 0.6) . Infusion-related toxicity was documented in 29% of the cycles of prophylaxis compared with 55% of the cycles of empirical treatment with i.v . AMB in the control group . The nephrotoxicity of AMB prophylaxis was moderate, with >/= WHO degree II reported in 1 out of 46 cycles only . CONCLUSION: Intensive i.v . AMB prophylaxis reduced invasive fungal infections and led to a reduction in fungal microabscesses in the liver or spleen, as well as pulmonary infiltrates, in patients treated for AL . The need for escalation to empirical i.v . AMB treatment was significantly reduced . Intensive AMB prophylaxis was feasible, with moderate adverse effects .

Plant Physiol, 2000 Jun, 123(2), 427 - 38
Genetic repair of mutations in plant cell-free extracts directed by specific chimeric oligonucleotides; Rice MC et al.; Chimeric oligonucleotides are synthetic molecules comprised of RNA and DNA bases assembled in a double hairpin conformation . These molecules have been shown to direct gene conversion events in mammalian cells and animals through a process involving at least one protein from the DNA mismatch repair pathway . The mechanism of action for gene repair in mammalian cells has been partially elucidated through the use of a cell-free extract system . Recent experiments have expanded the utility of chimeric oligonucleotides to plants and have demonstrated genotypic and phenotypic conversion, as well as Mendelian transmission . Although these experiments showed correction of point and frameshift mutations, the biochemical and mechanistic aspects of the process were not addressed . In this paper, we describe the establishment of cell-free extract systems from maize (Zea mays), banana (Musa acuminata cv Rasthali), and tobacco (Nicotiana tabacum) . Using a genetic readout system in bacteria and chimeric oligonucleotides designed to direct the conversion of mutations in antibiotic-resistant genes, we demonstrate gene repair of point and frameshift mutations . Whereas extracts from banana and maize catalyzed repair of mutations in a precise fashion, cell-free extracts prepared from tobacco exhibited either partial repair or non-targeted nucleotide conversion . In addition, an all-DNA hairpin molecule also mediated repair albeit in an imprecise fashion in all cell-free extracts tested . This system enables the mechanistic study of gene repair in plants and may facilitate the identification of DNA repair proteins operating in plant cells.

Chest, 2000 Jun, 117(6), 1666 - 71
Reliability, repeatability, and sensitivity of the modified shuttle test in adult cystic fibrosis; Bradley J et al.; STUDY OBJECTIVES: The purpose of this study was to investigate the test-retest reliability, repeatability, and sensitivity of the modified shuttle test (MST) in adult patients with cystic fibrosis (CF) . DESIGN:: Prospective study . SETTING: Adult CF Unit, Belfast City Hospital . PATIENTS:: Adult patients with CF . INTERVENTIONS: Test-retest reliability-none; sensitivity-inpatient IV antibiotic therapy for an acute exacerbation of respiratory disease . MEASUREMENTS: The test-retest reliability and repeatability of the MST was assessed by comparing performance on two consecutive MSTs performed in 12 patients with CF and stable disease . The sensitivity of the MST was assessed by measuring the change in MST performance after 2 weeks of IV antibiotic therapy in 24 patients admitted to hospital with acute exacerbations of their respiratory disease . RESULTS: In the assessment of test-retest reliability and repeatability (n = 12), there was a significant and strong correlation between trials for distance completed (Pearson's r = 0 . 99; p < 0.01), peak heart rate (Pearson's r = 0.99; p < 0.01), peak arterial oxygen saturation (SaO(2); Pearson's r = 0.99; p < 0.01), and peak Borg rating of perceived breathlessness (Pearson's r = 0 . 99; p < 0.01) . The coefficients of repeatability for these variables were small (coefficient of repeatability: distance completed, 4 shuttles; peak heart rate, 6 beats/min; peak SaO(2), 4%; and peak Borg rating of perceived breathlessness, 0.9) . In the assessment of sensitivity (n = 24), the standardized response mean (SRM) for distance completed on MST (SRM = 1.18) was the SRMs for spirometric measures of lung function (FEV(1), SRM = 0.96; FEV(1) percent predicted, SRM = 0.88) . CONCLUSIONS: This study demonstrates that the MST is a reliable, repeatable, and sensitive measure of exercise capacity in adult CF . The MST may be of value in determining prognosis, evaluation for lung transplantation, exercise prescription, and establishing the impact of new treatments on the disability associated with CF.

Chest, 2000 Jun, 117(6), 1638 - 45
Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD; Stockley RA et al.; STUDY OBJECTIVES: To stratify COPD patients presenting with an acute exacerbation on the basis of sputum color and to relate this to the isolation and viable numbers of bacteria recovered on culture . DESIGN: Open, longitudinal study of sputum characteristics and acute-phase proteins . SETTING: Patients presenting to primary-care physicians in the United Kingdom . Patients were followed up as outpatients in specialist clinic . PATIENTS: One hundred twenty-one patients with acute exacerbations of COPD were assessed together with a single sputum sample on the day of presentation (89 of whom produced a satisfactory sputum sample for analysis) . One hundred nine patients were assessed 2 months later when they had returned to their stable clinical state . INTERVENTIONS: The expectoration of green, purulent sputum was taken as the primary indication for antibiotic therapy, whereas white or clear sputum was not considered representative of a bacterial episode and the need for antibiotic therapy . RESULTS: A positive bacterial culture was obtained from 84% of patients sputum if it was purulent on presentation compared with only 38% if it was mucoid (p < 0.0001) . When restudied in the stable clinical state, the incidence of a positive bacterial culture was similar for both groups (38% and 41%, respectively) . C-reactive protein concentrations were significantly raised (p < 0.0001) if the sputum was purulent (median, 4.5 mg/L; interquartile range {IQR}, 6 . 2 to 35.8) . In the stable clinical state, sputum color improved significantly in the group who presented with purulent sputum from a median color number of 4.0 (IQR, 4.0 to 5.0) to 3.0 (IQR, 2.0 to 4 . 0; p < 0.0001), and this was associated with a fall in median C-reactive protein level to 2.7 mg/L (IQR, 1.0 to 6.6; p < 0.0001) . CONCLUSIONS: The presence of green (purulent) sputum was 94.4% sensitive and 77.0% specific for the yield of a high bacterial load and indicates a clear subset of patient episodes identified at presentation that is likely to benefit most from antibiotic therapy . All patients who produced white (mucoid) sputum during the acute exacerbation improved without antibiotic therapy, and sputum characteristics remained the same even when the patients had returned to their stable clinical state.

Biochemistry, 2000 Jun 27, 39(25), 7605 - 12
DNA bending is a determinant of calicheamicin target recognition; Salzberg AA et al.; Calicheamicin is a hydrophobic enediyne antibiotic that binds noncovalently to DNA and causes sequence-selective oxidation of deoxyribose . While the drug makes several base contacts along the minor groove, the diversity of binding-site sequences and the effects of DNA conformation on calicheamicin-induced DNA cleavage suggest that sequence recognition per se is not the primary determinant of target selection . We now present evidence that calicheamicin bends its DNA targets . Using a gel mobility assay, we observed that polymers of oligonucleotide constructs containing AGGA and ACAA binding sites for calicheamicin did not possess intrinsic curvature . Binding of calicheamicin epsilon, the aromatized form of the parent calicheamicin gamma(1)(I), to oligonucleotide constructs containing binding sites in phase with the helical repeat caused a shift to smaller circle sizes in T4 ligase-mediated circle formation assays, with a much smaller shift observed with constructs containing out-of-phase binding sites . It was also observed that binding of calicheamicin epsilon to a 273 bp construct with phased binding sites caused an increase in the molar cyclization factor, J, from 8 x 10(-8) to 9 x 10(-6) M . These results are consistent with DNA bending as part of an induced-fit mechanism of DNA target recognition and with the hypothesis that the preferred targets of calicheamicin, the 3' ends of oligopurine tracts, are characterized by unique conformational properties.

Infect Immun, 2000 Jul, 68(7), 4238 - 44
In vitro cell invasion of Mycoplasma gallisepticum; Winner F et al.; The ability of the widespread avian pathogen Mycoplasma gallisepticum to invade cultured human epithelial cells (HeLa-229) and chicken embryo fibroblasts (CEF) was investigated by using the gentamicin invasion assay and a double immunofluorescence microscopic technique for accurate localization of cell-associated mycoplasmas . The presence of intracellular mycoplasmas in both cell lines was clearly demonstrated, with organisms entering the eukaryotic cells within 20 min . Internalized mycoplasmas have the ability to leave the cell, but also to survive within the intracellular space over a 48-h period . Frequencies of invasion were shown to differ between the two cell lines, but were also considerably dependent on the mycoplasma input population . Of the prototype strain R, a low-passage population in artificial medium, R(low), was capable of active cell invasion, while a high-passage population, R(high), showed adherence to but nearly no uptake into HeLa-229 and CEF . By passaging R(low) and R(high) multiple times through HeLa-229 cells, the invasion frequency was significantly increased . Taken together, these findings demonstrate that M . gallisepticum has the capability of entering nonphagocytic host cells that may provide this pathogen with the opportunity for resisting host defenses and selective antibiotic therapy, establishing chronic infections, and passing through the respiratory mucosal barrier to cause systemic infections.

J Pharm Biomed Anal, 2000 Jul, 22(6), 1037 - 45
A surface plasmon resonance method for detecting multiple modes of DNA-ligand interactions; Ciolkowski ML et al.; A simple and general surface plasmon resonance (SPR) based method has been developed to detect and quantitate binding of low molecular weight compounds (200-1,200 Da) to double stranded DNA . Several compounds were chosen to probe three different modes of binding interactions, intercalation, minor groove binding and electrostatic interactions . Ethidium bromide (MW 390 Da), a probe of intercalative binding, was tested by plotting the steady state SPR responses measured on a DNA modified surface versus ethidium bromide concentration . The best fit of the binding isotherm gave a Keq of 1.8 x 105 M-1 . Co-solvents such as DMSO are often used in activity assays to increase the solubility of poorly water-soluble drugs . The effect of DMSO on the ethidium bromide/DNA interaction was also tested by measuring binding in the presence of 0, 1 and 5%, DMSO . No effect on the measured Keq was observed at these DMSO concentrations . The binding of actinomycin (MW 1,255 Da), an antibiotic known to bind DNA through intercalation and minor groove binding, was also tested . The Keq estimated from the steady state responses on a DNA surface was 1.9 x 106 M-1 . DAPI (MW 350 Da) (4',6-diamidino-2-phenylindole) a fluorescent probe which binds the minor groove of DNA was also tested and gave a Keq of 1.8 x 106 M-1 measured by SPR . Finally, spermine (MW 202) a compound known to bind DNA through ionic interactions gave the weakest Keq of 1.7 x 104 M-1 . All the Keq values measured by SPR and reported for these compounds were in good agreement with literature values measured by other techniques.

Eur J Cardiothorac Surg, 2000 Jun, 17(6), 624 - 30
Reconstruction of the RVOT with valved biological conduits: 25 years experience with allografts and xenografts; Homann M et al.; OBJECTIVE: The reconstruction of the RVOT in congenital heart disease often requires the implantation of a valved conduit . Although allografts are considered the conduit of choice their availability is limited and therefore xenografts are implanted as well . We compared the long-term durability of both grafts in the RVOT over a 25-year period . METHODS: Between January 1974 and August 1999, 505 patients (median age 4.0 years, range 2 days-31 years; median weight 14.5 kg, range 2.2-76.6 kg; median body length 103 cm, range 48-183 cm) with congenital malformations (PA 25.3%, TOF 14.5%, TOF+PA 2.4%, DORV 4.2%, TGA+PS 8.7%, TAC 24.8%, and other 20.2%) received their first valved conduit (174 xenografts: median diameter 14 mm, range 8-27 mm; 331 allografts: median diameter 19 mm, range 8-30 mm) . RESULTS: Follow-up is 3017 patient-years . The 10-year survival-probability for all patients . was 66% with a mean reoperation-free interval for conduit-exchange of 13.3 years (mean reoperation-free interval for allografts, 16.0 years; mean reoperation-free interval for xenograft, 10.3 years) . One hundred and thirteen patients underwent a conduit-exchange, mostly due to conduit stenosis . Fourteen patients had a second exchange and three patients a third exchange . For patients with conduit diameters <18 mm (n=235: allograft n=116, xenograft n=119; median age 9 months, range 0-27.3 years), the mean reoperation-free interval was 11.2 years (mean interval allograft, 13.1 years; mean interval xenograft, 8.6 years, P=0.03) . For conduit diameters >/=18 mm (n=270: allograft n=215, xenograft n=55, median age 7.4 years, range 0-34.3 years) the mean interval from freedom of conduit exchange was 15.1 years (for allografts 14.1 years, for xenografts 12.5 years, P<0.01) . Comparing xenografts to allografts, we found no difference in patient survival probability (P=0.62) . There was no significant difference between antibiotic (n=198) preserved vs . cryopreserved (n=133) allografts (P=0.06) . Blood group compatibility of allografts to recipients had no significant influence on allograft function (P=0.42) . The donors allograft origin, whether aortic or pulmonary valve, had also no significant influence on allograft long-term function (P=0.15) . CONCLUSION: For the reconstruction of the right ventricular outflow tract (RVOT) allografts show significantly better long-term durability than xenografts regardless of the age at implantation and the diameter.

Tumori, 2000 Mar-Apr, 86(2), 157 - 62
Modulatory effects of melatonin and vitamin E on doxorubicin-induced cardiotoxicity in Ehrlich ascites carcinoma-bearing mice; Wahab MH et al.; Doxorubicin (Dox), an anthracycline antibiotic, has a wide spectrum of antitumor activity with dose-limiting cardiotoxicity . The drug's toxicity is known to be closely related to the generation of active oxygen free radicals . In our study the normal cardiac tissue contents of total protein, glutathione (GSH) and malondialdehyde (MDA) were significantly decreased, by 25%, 33% and 92%, respectively, in the group of mice bearing Ehrlich ascites carcinoma (EAC) and treated with Dox (4 mg/kg/week x 2, ip) . Administration of melatonin (5 mg/kg/day x 15, po) starting 24 hours prior to Dox treatment significantly increased the cardiac contents of total protein and GSH as well as the superoxide dismutase (SOD) activity, by 31%, 36% and 39%, respectively, compared to treatment with Dox only, while the content of MDA was decreased by 26% . Similarly, administration of vitamin E (250 mg/kg/day x 15, po) starting 24 hours prior to Dox treatment significantly increased the cardiac contents of total protein, GSH and SOD, by 23%, 26% and 42%, respectively, while the cardiac content of MDA was decreased by 35% compared with the Dox-only-treated group . As to the oncolytic activity of Dox, pretreatment of EAC-bearing mice with melatonin (5 mg/kg/day x 30, po) or vitamin E (250 mg/kg/day x 30, po) 24 hours prior to Dox administration (4 mg/kg/week x 4, ip) improved the antitumor activity of Dox as indicated by the increase in the average life span of the animals and the number of long-term survivors as well as the decrease in body weight loss induced by Dox treatment . It is clear from these results that administration of melatonin not only protects against the cardiotoxicity induced by Dox treatment but also enhances its antitumor activity to a more significant extent than does vitamin E.

Ann Med Interne (Paris), 2000 Mar, 151(2), 150 - 1
{Infective endocarditis following incomplete ablation of a pacemaker}; Meune C et al.; Pacemaker lead-related infective endocarditis is uncommon but mortality remains high . We report the case of a 63-year-old man who presented with a history of intermittent low-grade fever and no other sign for 15 months . Fever had developed after incomplete removal of a pacemaker with the ventricular lead left in situ followed by a new implantation of cardiac stimulation material . Positive blood cultures and transesophageal echocardiography showing a vegetation on a pacemaker lead gave the diagnosis . Initial antibiotic therapy was insufficient and complete surgical extraction of the pacemaker and leads was required . A huge vegetation was seen on the old ventricular lead . The other leads were not affected . Outcome was good . The paucity of symptoms in pacemaker lead-related infective endocarditis makes diagnosis difficult . It must however be suspected in pacemaker patients with low-grade intermittent fever . Transesophageal echocardiography is required . Treatment must combine antibiotic therapy with material extraction.

Bioorg Med Chem Lett, 2000 May 1, 10(9), 971 - 4
Design, synthesis, and biological activity of a cyclic peptide: an inhibitor of HIV-1 tat-TAR interactions in human cells; Tamilarasu N et al.; Replication of human immunodeficiency virus type 1 (HIV-1) requires specific interactions of Tat protein with the transactivation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end of all HIV mRNAs . A number of cyclic peptides are known to possess antibiotic activity and increased biological stability . Here we report the design, synthesis, and biological activity of a cyclic peptide (2), which inhibits transcriptional activation by Tat protein in human cells with an IC50 of approximately 40 nM . Cyclic peptides that can target specific RNA structures provide a new class of small molecules that can be used to control cellular processes involving RNA-protein interactions in vivo.

Morfologiia, 2000, 117(2), 68 - 72
{The ultrastructural changes to the ovaries and oviducts in experimental inflammation under the influence of eplir phonophoresis}; Logvinov SV et al.; Ultrastructural changes of blood vessels of ovaries and oviducts, destruction of the part of follicular epitheliocytes and disruption of other structures of blood-follicular barrier occur at the early period of experimental inflammations of appendage uterus on the background of traditional antibiotic therapy . All changes lead to atresia of growing follicules . Fibrotic-sclerotic changes develop on the 30th day and during later period . Course of eplir phonophoresis decreases ultrastructural disruptions of vessels, follicular apparatus of ovaries and oviducts epithelium . Effect of physiotherapy is manifested though activity of fibroclasts and macrophages, that regulate collagen production/resorption ratio thus preventing the development of fibrotic changes of ovary stroma and oviduct wall.

Anaesth Intensive Care, 2000 Jun, 28(3), 328 - 30
Mortality from peripartum meningitis; Choy JC; A young primigravid parturient had an uneventful labour under epidural analgesia and delivered a healthy male infant . She returned 48 hours later with fever, vomiting and severe headache, but was misdiagnosed as having endometritis . Further signs of meningitis appeared six hours later, however she succumbed to the infection and died four weeks later despite intensive care and high-dose antibiotic management . Causes of meningitis in the peripartum period are discussed . The possibility of a causal association between the patient's epidural analgesia and her infection are considered and preventive measures discussed.

Am J Respir Crit Care Med, 2000 Jun, 161(6), 1877 - 80
Serum vascular endothelial growth factor is elevated in cystic fibrosis and decreases with treatment of acute pulmonary exacerbation; McColley SA et al.; Chronic bacterial infection and neutrophilic inflammation characterize cystic fibrosis (CF) pulmonary disease . In many disorders, inflammation and angiogenesis are codependent phenomena . We previously noted excessive angiogenesis in CF tissues and elevated vascular endothelial growth factor (VEGF) in random serum samples from subjects with CF . To further explore this finding, we measured serum VEGF in 38 subjects with stable CF and in 25 subjects with other pulmonary diseases . Mean VEGF was elevated in both groups compared with reference values, but it was higher in CF: 403 +/- 280 versus 255 +/- 169 pg/ml, p = 0.02 . VEGF was negatively correlated with FEV(1) in CF, r = -0.51, p = 0.007 . To assess the effect of airway infection on VEGF, 10 subjects with CF were studied before and after intravenous antibiotic therapy for pulmonary exacerbation . VEGF levels decreased with antibiotic therapy, from 537 +/- 220 to 259 +/- 176 pg/ml, p = 0.001 . We conclude that circulating VEGF is increased in subjects with CF and other inflammatory pulmonary disorders . In CF, VEGF elevation is related to airway infection . We speculate that increased circulating VEGF is related to chronic inflammation, which is robust in CF . Elevated circulating VEGF may result in tissue angiogenesis, furthering the progression of pulmonary disease.

Arch Esp Urol, 2000 Apr, 53(3), 275 - 8
{Fournier's gangrene after vasectomy}; de Diego Rodriguez E et al.; OBJECTIVE: An uncommon case of Fournier's gangrene following vasectomy is described . METHODS/RESULTS: A 35-year-old male with no remarkable previous history, who underwent vasectomy in another hospital, developed a clinical picture compatible with Fournier's gangrene 7-8 days later . The patient required wide, aggressive surgical debridement on several occasions with broad spectrum antibiotic coverage . After a long stay at the hospital, the patient was finally discharged and referred to another hospital for plastic surgery . CONCLUSIONS: Fournier's gangrene is a polymicrobial infection of the perineoscrotal region that manifests as a rapidly progressive necrotizing fasciitis . Most of the cases have a predisposing and/or triggering factor . Fournier's gangrene following vasectomy is uncommon . The morbidity and mortality in this severe complication depend on early diagnosis and aggressive surgical management.

Blood, 2000 Jun 15, 95(12), 3885 - 90
BCL10 gene mutation in lymphoma; Du MQ et al.; BCL10 is directly involved in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma . Wild-type BCL10 promoted apoptosis and suppressed malignant transformation in vitro, whereas truncated mutants lost the pro-apoptotic activity and exhibited gain of function enhancement of transformation . We studied 220 lymphomas for genomic BCL10 mutation by polymerase chain reaction-single-strand conformational polymorphism and DNA sequencing . Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 120 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follicular lymphomas, and 1 of 23 (4.3%) diffuse large B-cell lymphomas . No mutations were found in 14 mantle cell lymphomas or 21 T-cell lymphomas . High-grade MALT lymphoma tended to show a slightly higher mutation frequency (2 of 25, 8%) than low-grade MALT tumor (6 of 95, 6.3%) . Among low-grade gastric MALT lymphoma, mutations were found in 3 of 11 tumors that did not respond to Helicobacter pylori eradication therapy, but none were found in 22 tumors that regressed completely after H pylori eradication . All 14 potentially pathogenic mutations were distributed in the carboxyl terminal domain of BCL10 . Deletion accounted for 10 of these mutations; 10 of 14 mutations caused truncated forms of BCL10 . Western blot analysis of a mutant case confirmed the presence of truncated BCL10 products of anticipated size . Our results suggest that BCL10 mutation may play a pathogenic role in B-cell lymphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the carboxyl terminal of the molecule . (Blood . 2000;95:3885-3890)

J Invertebr Pathol, 2000 May, 75(4), 267 - 72
Wolbachia density and host fitness components in Muscidifurax uniraptor (Hymenoptera: pteromalidae); Zchori-Fein E et al.; Intracellular bacteria of the genus Wolbachia are found in a variety of arthropod hosts, where they cause various reproductive disorders . Attempts to study the fitness advantages and disadvantages of carrying these symbionts have yielded contradicting results . Using various doses of the antibiotic rifampicin, we were able to manipulate the density of Wolbachia in the uniparental parasitoid Muscidifurax uniraptor (Hymenoptera: Pteromalidae) . The effect of different titers of the symbiont on the fecundity, reproductive rate, longevity, survival rate, and sex ratio of the host was measured . The data gathered show that following antibiotic treatments, the percentage of males rises at low doses of rifampicin and then drops again . The total sex ratio of offspring produced by treated mothers was positively correlated with the numbers of Wolbachia found in eggs laid by these females . No significant effects were detected with regard to the other studied fitness components . It is concluded that in M . uniraptor, Wolbachia are not posing any burden on the life history trait studied .

Biochemistry, 2000 Jun 20, 39(24), 7236 - 44
Yeast ribosomal protein L24 affects the kinetics of protein synthesis and ribosomal protein L39 improves translational accuracy, while mutants lacking both remain viable; Dresios J et al.; Four mutant strains from Saccharomyces cerevisiae were used to study ribosome structure and function . They included a strain carrying deletions of the two genes encoding ribosomal protein L24, a strain carrying a mutation spb2 in the gene for ribosomal protein L39, a strain carrying a deletion of the gene for L39, and a mutant lacking both L24 and L39 . The mutant lacking only L24 showed just 25% of the normal polyphenylalanine-synthesizing activity followed by a decrease in P-site binding, suggesting the possibility that protein L24 is involved in the kinetics of translation . Each of the two L39 mutants displayed a 4-fold increase of their error frequencies over the wild type . This was accompanied by a substantial increase in A-site binding, typical of error-prone mutants . The absence of L39 also increased sensitivity to paromomycin, decreased the ribosomal subunit ratio, and caused a cold-sensitive phenotype . Mutant cells lacking both ribosomal proteins remained viable . Their ribosomes showed reduced initial rates caused by the absence of L24 but a normal extent of polyphenylalanine synthesis and a substantial in vivo reduction in the amount of 80S ribosomes compared to wild type . Moreover, this mutant displayed decreased translational accuracy, hypersensitivity to the antibiotic paromomycin, and a cold-sensitive phenotype, all caused mainly by the deletion of L39 . Protein L39 is the first protein of the 60S ribosomal subunit implicated in translational accuracy.

Mol Urol, 1999, 3(1), 11 - 16
Mechanism of Brefeldin A-Induced Growth Inhibition and Cell Death in Human Prostatic Carcinoma Cells; Chapman JR et al.; The mechanism of growth inhibition and triggering of cell death by the antibiotic brefeldin A (BFA) was investigated in human prostatic cancer DU-145 cells . After cells were cultured with various concentrations of BFA, cell number and viability were determined at specified times . Compared with untreated cells, a drastic growth reduction (>80%) with approximately 50% cell death was observed in the cells cultured with BFA (30 ng/mL) for 72 h . Cell-cycle analysis using flow cytometry revealed that such growth inhibition was associated with approximately 85% reduction in the S-phase population, indicating the inhibition of the G(1)-S phase progression . Western blots further showed that cell-cycle-dependent kinases (cdk2 and cdk4), cyclin D(1), and p53 were all downregulated, whereas WAF1 (p21) was upregulated with BFA treatment . Possible induction of apoptosis by BFA was also assessed by TUNEL assay and by DNA analysis using agarose gel electrophoresis . The TUNEL assay demonstrated the positive staining of BFA-treated cells, and gel electrophoresis confirmed nucleosomal DNA ladder formation . Thus, these results suggest that growth inhibition of DU-145 cells by BFA is attributable mainly to a G1 cell-cycle arrest through the modulation of specific cell-cycle regulators . The accompanying cell death may follow a p53-independent apoptotic pathway.

Anal Chem, 2000 May 15, 72(10), 2200 - 5
Design and synthesis of a more highly selective ammonium ionophore than nonactin and its application as an ion-sensing component for an ion-selective electrode
Suzuki K, Siswanta D, Otsuka T, Amano T, Ikeda T, Hisamoto H, Yoshihara R, Ohba S.
A novel ammonium ionophore, which exhibits superior NH4+ selectivity compared with that of the natural antibiotic nonactin, was successfully designed and synthesized based on a 19-membered crown compound (TD19C6) having three decalino subunits in the macrocyclic system . This bulky decalino subunit is effective for (1) increasing the structural rigidity of the cyclic compound, (2) introducing the "block-wall effect", which prevents forming a complex with a large ion, and (3) increasing the lipophilicity of the ionophore molecule . In the ammonium ionophore design, the first factor contributes to increasing the NH4+ selectivity relative to smaller ions such as Li+, Na+, or even the closest size, K+, and the second factor increases the NH4+ selectivity over larger ions such as Rb+ and Cs+ . The X-ray structural analysis proved that TD19C6 forms a size-fit complexwith NH4+ in its crown ring cavity . As an application of this ionophore, an ion sensor (ion-selective electrode) was prepared, which exhibited NH4+ to K+ and Na+ selectivity of 10 and 3,000 times, respectively . This electrode showed a better performance compared to the electrode based on nonactin, which is the only ammonium ionophore presently used in practical applications.

Br J Surg, 2000 Jun, 87(6), 771 - 6
Use of superficial femoropopliteal vein for suprainguinal arterial reconstruction in the presence of infection; Gibbons CP et al.; BACKGROUND: Conventional treatment of mycotic aneurysms or graft infections of the aortoiliac segment by in situ or extra-anatomic prosthetic reconstruction has a high mortality and morbidity rate, with a substantial risk of persistent graft infection . The use of autologous vein may reduce this . METHODS: Eleven patients with suprainguinal arterial infections including two with mycotic aortic aneurysms, four with aortic graft infections, four infected femorofemoral grafts and an infected axillofemoral graft were treated by debridement and in situ reconstruction with autologous superficial femoropopliteal vein . All patients received appropriate antibiotic therapy and were followed by regular postoperative duplex imaging . Preoperative femoral vein duplex imaging was performed in eight of the 11 patients . RESULTS: Ten of the 11 patients survived with a functioning graft and without limb loss or evidence of infection at 4-33 months . One patient died from myocardial infarction after operation . Three patients had minor swelling of one leg . Four patients required subsequent angioplasty of anastomotic stenoses detected by duplex surveillance . CONCLUSION: Superficial femoropopliteal vein is an excellent conduit for suprainguinal reconstruction in the presence of infection . Duplex imaging is useful for confirming the suitability of deep veins for use as a graft and for postoperative surveillance.

Aliment Pharmacol Ther, 2000 Jun, 14(6), 801 - 6
Open label trial of oral clarithromycin in active Crohn's disease; Leiper K et al.; BACKGROUND: Crohn's disease seems likely to be due in some way to bacteria . Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn's disease . METHODS: Twenty-five patients with active Crohn's disease were treated with oral clarithromycin 250 mg b.d . in an open label study . Treatment was for an initial 4-week period, continued to 12 weeks in patients who had shown a partial or complete response . The patients had a median age of 30 years (range 17-72), and disease duration of 5 years (range 2 months-28 years); 14 had ileocolonic, four small bowel, seven colonic disease and 10 had previous resections . Twenty patients were receiving a 5-ASA preparation, 15 corticosteroids (prednisolone median dose 10 mg range 2-30 mg) and nine azathioprine . All patients receiving corticosteroids or azathioprine had been on unchanged treatment for at least 12 weeks . RESULTS: Median pre-treatment Harvey Bradshaw index (HBI) was 9 (range 5-16) and median serum C-reactive protein was 21.5 mg/L (range < 5-117) . By 4 weeks the median HBI had decreased to 5 (range 0-18) (P < 0.001) and median CRP to 17 mg/L (range < 5-157) (P=0.16) . Sixteen patients (64%) had at least a 3 point fall in HBI and remission (defined as a HBI less than or equal to 4) was achieved in 12 patients (48%) . By 12 weeks median HBI was 5 (range 0-18) (P < 0.001) and median CRP was 14.5 mg/L (range < 5-157) (P=0.05) . Eleven of the 25 patients studied continued on oral clarithromycin after 12 weeks for a median of 28 weeks (range 20-60) . Eight (73%) remained in remission on treatment . When treatment with clarithromycin was stopped three remained in remission and five relapsed after a median of 5 months (range 4-9) . Two patients withdrew due to non-serious side-effects . Treatment was well tolerated in the remaining patients . CONCLUSION: This open label study has shown an impressive response to clarithromycin in a group of patients with active Crohn's disease, many of whom had been resistant to other therapy . A formal randomized controlled trial of clarithromycin in active Crohn's disease is needed.

Aliment Pharmacol Ther, 2000 Jun, 14(6), 719 - 28
The effectiveness of omeprazole, clarithromycin and tinidazole in eradicating Helicobacter pylori in a community screen and treat programme . Leeds Help Study Group; Moayyedi P et al.; INTRODUCTION: Helicobacter pylori screening and treatment has been proposed as a cost-effective method of preventing gastric cancer . AIM: To assess, in a randomized controlled trial, the efficacy of therapy in eradicating H . pylori as part of a screening programme, and to report the adverse events associated with this strategy . METHODS: Subjects between the ages of 40-49 years were randomly selected from the lists of 36 primary care centres . Participants attended their local practice and H . pylori status was determined by 13C-urea breath test . Infected subjects were randomized to receive omeprazole 20 mg b.d., clarithromycin 250 mg b.d . and tinidazole 500 mg b.d . for 7 days (OCT) or identical placebos . Eradication was determined by a 13C-urea breath test 6 months and 2 years after the first visit . Successful eradication was defined as two negative 13C-urea breath tests or one negative and one missing test . Adverse events and compliance were assessed at the 6-month visit . RESULTS: A total of 32 929 subjects were invited to attend, 8407 were evaluable, and 2329 (28%) of these were H . pylori-positive . A total of 1161 subjects were randomized to OCT and 1163 to placebo; over 80% returned for a repeat 13C-urea breath test on at least one occasion . The eradication rates in those allocated to OCT were as follows: intention-to-treat, 710 out of 1161 (61%; 95% confidence interval: 58-64%); evaluable 710 out of 967 (73%; 95% CI: 71-76%); took all medication 645 out of 769 (84%; 95% CI: 81-87%) . Adverse events occurred in 45% of the treatment group and in 18% of the placebo group (relative risk 2.5; 95% CI: 2.1-2.9) . Compliance, male gender, no antibiotic prescription in the subsequent 2 years and experiencing a bitter taste with the medication were independently associated with treatment success . CONCLUSIONS: The OCT regimen has an eradication rate of 61% in intention-to-treat analysis and is therefore less successful in treating H . pylori as part of a screening programme compared with hospital studies in dyspeptic patients.

J Gastroenterol Hepatol, 2000 May, 15(5), 494 - 7
Metronidazole-resistant Helicobacter pylori in an urban Asian population; Teo EK et al.; BACKGROUND: Helicobacter pylori eradication is the mainstay in the treatment of H . pylori-associated peptic ulcer disease . Metronidazole is an important component in most eradication regimens . However, the presence of metronidazole-resistant H . pylori adversely affects the efficacy of such regimens . We aimed to study the prevalence of metronidazole resistance in our population, and the factors associated with its presence . METHODS AND RESULTS: From September 1993 to September 1996, 459 H . pylori isolates were collected and analysed . The overall resistance rate was 62.7% . The rate was significantly higher among women compared with men (P < 0.05) . When the results were analysed according to each year, there was a significant increase in the resistance rate from 50.5% in the first year to 72.7% in the third year (P = 0.0039) . CONCLUSIONS: There was a significant rise in the prevalence of metronidazole resistance over a 3-year period . The presence of metronidazole resistance adversely affects the eradication rates of nitroimidazole-based regimens . Hence, in a population with a high prevalence of metronidazole resistance, the use of non-nitroimidazole-based therapy may be more efficacious . This information on resistance rates is important for the empirical choice of antibiotic against H . pylori in a population.

Nihon Kokyuki Gakkai Zasshi, 2000 Mar, 38(3), 206 - 10
{Pulmonary involvement in acute febrile neutrophilic dermatosis (Sweet's syndrome)}; Imanaga T et al.; We encountered a 55-year-old man with pulmonary involvement in acute febrile neutrophilic dermatosis (Sweet's syndrome) . He had been treated with steroids for Sweet's syndrome for 2 years, and on September 17, 1998 presented with a cough and a fever of 38.9 degrees C . Physical examination revealed fine crackles at the bases of both lungs . Chest radiography and computed tomography demonstrated reticular and nodular infiltrates in both lungs . Treatment with a variety of antibiotic agents and an antifungal agent was not effective . Sputum culture was sterile and bronchial washings were negative for infectious pathogens . Transbronchial biopsy revealed a mild chronic interstitial infiltrate and an inflammatory exudate in bronchiolo-alveolar tissue . The pulmonary lesions and cutaneous lesions were resolved by intradermal injections of triamcinolone acetonide in addition to oral prednisolone . Although the apparent neutrophilic infiltrates cited by earlier reports were not observed in transbronchial biopsy specimens, the clinical course in this case suggested that our patient had Sweet's syndrome with pulmonary involvement.

Chest, 2000 May, 117(5 Suppl 2), 380S - 5S
Infectious etiology of acute exacerbations of chronic bronchitis; Sethi S; Infectious agents are a major cause of acute exacerbations of chronic bronchitis (AECB) and COPD . Several respiratory viruses are associated with 30% of exacerbations, with or without a superimposed bacterial infection . Atypical bacteria, mostly Chlamydia pneumoniae, have been implicated in < 10% of AECB . The role of bacterial pathogens when isolated from the respiratory tract during AECB has become better defined by application of several newer investigative techniques . Bacterial pathogens can be isolated in significant concentrations from distal airways in 50% of AECB . Specific immune responses to surface exposed antigens of the infecting pathogen have been shown to develop after an exacerbation . Emerging evidence from molecular epidemiology and measurement of airway inflammation further support the role of bacteria in AECB . When properly defined, 80% of AECB are likely to be infectious in origin.

Clin Exp Dermatol, 2000 May, 25(3), 222 - 3
Tuberculous cellulitis; Lee NH et al.; We report a case of cutaneous tuberculosis presenting as cellulitis . The patient was a 63-year-old Korean woman who also had diabetes mellitus and a 20-year-history of oral corticosteroid medication prescribed for arthralgia . In addition, she had had pulmonary tuberculosis 20-year previously for which she received systemic treatment for 1 year . Her clinical cellulitis failed to respond to antibiotic therapy . Subsequent investigations, using histopathology and polymerase chain reaction, established an alternative diagnosis of cutaneous tuberculosis . The skin eruption cleared after treatment with isoniazid, rifampicin, ethambutol and pyrazinamide . This case represents a most unusual presentation of tuberculosis in the skin . The atypical features may reflect the patient's general medical state.

J Immunol, 2000 Jun 15, 164(12), 6647 - 54
Recognition of sulfamethoxazole and its reactive metabolites by drug-specific CD4+ T cells from allergic individuals; Schnyder B et al.; The recognition of the antibiotic sulfamethoxazole (SMX) by T cells is usually explained with the hapten-carrier model . However, recent investigations have revealed a MHC-restricted but processing- and metabolism-independent pathway of drug presentation . This suggested a labile, low-affinity binding of SMX to MHC-peptide complexes on APC . To study the role of covalent vs noncovalent drug presentation in SMX allergy, we analyzed the proliferative response of PBMC and T cell clones from patients with SMX allergy to SMX and its reactive oxidative metabolites SMX-hydroxylamine and nitroso-SMX . Although the great majority of T cell clones were specific for noncovalently bound SMX, PBMC and a small fraction of clones responded to nitroso-SMX-modified cells or were cross-reactive . Rapid down-regulation of TCR expression in T cell clones upon stimulation indicated a processing-independent activation irrespective of specificity for covalently or noncovalently presented Ag . In conclusion, our data show that recognition of SMX presented in covalent and noncovalent bound form is possible by the same TCR but that the former is the exception rather than the rule . The scarcity of cross-reactivity between covalently and noncovalently bound SMX suggests that the primary stimulation may be directed to the noncovalently bound SMX.

Ginekol Pol, 2000 Mar, 71(3), 116 - 22
{Laparoscopic or laparotomic surgery in the treatment of ovarian benign teratomas?}; Banaszczyk R et al.; The operation treatment of ovarian dermoid cysts by laparoscopy (examined group) and by laparotomy (control group) was compared . The mean size of teratomas measured by USG was similar: in the examined group 59 +/- 20 mm, in the control group 62 +/- 27 mm . There was no significant difference in the operation time: laparoscopy 65 +/- 27 min . (range 35-105 min.) and laparotomy 66 +/- 27 min . (range 40-120 min.) . The antibiotic therapy both intra-operation and after operation was applied twice more frequent for laparotomy operated patients . The number of patients with post-operative fever was much higher in the control group (laparotomy: 7 patients--26.9%) than in examined group (laparoscopy: only 1 patient--3.9%) . The hospitalization after operation was longer in the control group (mean: 6.8 +/- 3.7 days) than in examined group (mean: 3.1 +/- 2.8 days) . Laparoscopic surgery is valuable operating method for selected teratomas in comparison with classical surgery.

Ann N Y Acad Sci, 1999 Nov 28, 884, 312 - 27
Role of neurotrophins and lectins in prevention of ototoxicity; Gao WQ; Degeneration of hair cells (HC) and/or spiral ganglion neurons (SGN) is a major cause of hearing loss . Postnatal rat cochlear explant cultures are used to study the toxic actions of different classes of ototoxins and to identify molecules that can protect SGN and HC from ototoxic damage . Various ototoxins induce differential damage to HC and/or SGN . While gentamicin preferentially causes HC death, sodium salicylate selectively induces degeneration of SGN . In contrast, cisplatin results in destruction of both SGN and HC . Specific neurotrophins, including NT-4/5, BDNF, and NT-3, greatly protect SGN from all three types of ototoxins . In contrast, NGF and other growth factors have no effect . Of the 51 compounds examined, only concanavalin A (Con A), a lectin molecule, significantly protects HC from gentamicin . A dose-dependent study of Con A shows that maximal protection occurred at 100 nM . Further experiments indicates that preincubation of Con A with gentamicin does not form a complex, and coaddition of Con A and gentamicin to bacterial cultures, such as E . Coli cultures, does not interfere with the antibiotic activity of gentamicin . When the other 21 lectins are examined, Erythrina cristagalli lectin and Detura stramonium lectin also show activity similar to Con A . These findings may help elucidate the mechanisms of ototoxins and suggest that specific neurotrophins and lectins may be of therapeutic value in the prevention of ototoxin-induced hearing loss.

Ann N Y Acad Sci, 1999 Nov 28, 884, 60 - 8
Acute and chronic effects of aminoglycosides on cochlear hair cells; Aran JM et al.; The first detectable effect on the auditory system after a single high-dose injection of an aminoglycosidic antibiotic (AA) like gentamicin (GM) is the reversible blockade of medial efferent function, probably via blockade of calcium channels at the base of the outer hair cells (OHC) . The kinetics of this effect are compatible with that of the molecule in perilymph . In the course of chronic treatment with lower doses, however, ototoxicity develops only after several days of treatment . Still GM can be observed inside the OHCs as soon as 24 hours after the first injection, and will be still present in some OHCs as long as 11 months after a chronic, nonototoxic 6-day treatment . In vitro, the short-term viability of isolated OHCs is not affected by exposure to AAs, but their transduction channels and their response to acetylcholine are reversibly blocked . However, developing organs of Corti in culture are highly and rapidly affected by exposure to AAs . Yet during direct intracochlear perilymphatic perfusion of GM, 2-mM solutions are not ototoxic, and with perfusion with a 20-mM solution ototoxicity develops only after several days of perfusion . From these various observations one can describe some aspects of the mechanisms of ototoxicity of AAs, from their access to perilymph and endolymph, to penetration in the hair cells, likely via endocytosis at their apical pole, and intracellular cytotoxic events.

J Infect, 2000 Mar, 40(2), 171 - 5
Candidaemia in special care nurseries: comparison of albicans and parapsilosis infection; Huang YC et al.; OBJECTIVES: Candidaemia caused by Candida parapsilosis (CP) is being increasingly reported among infants in neonatal intensive care units (NICU) . To assess relative severity, clinical manifestations of candidaemia caused by C . albicans (CA) and CP in a NICU were compared . METHODS: Between January 1994 and July 1997, episodes of candidaemia occurring among infants hospitalized in the NICU were identified in a children's hospital . The demographic characteristics, associated risk factors, clinical manifestations and outcome of the infants with CP fungaemia were collected and compared with those of the infants with CA fungaemia . RESULTS: Twenty-four episodes caused by CA and 22 episodes caused by CP were included in this study . No significant differences were found between the two groups for gestational age, birth weight, male gender, post-natal age at onset of candidaemia, frequency of antecedent neonatal events, prior duration of antibiotic therapy and hyperalimentation, as well as presence of central venous catheter (CVC) . Infants with CA fungaemia were significantly more likely than those with CP fungaemia to present with hypoxaemia, bradycardia and respiratory distress requiring intubation, and have a longer prior duration of indwelling CVC and a higher dissemination rate . The eradication rate of candidaemia and overall case fatality rate were comparable in both groups . but CP fungaemia did not appear to cause acute lethal events . CONCLUSION: The presenting signs of CP fungaemia are relatively not so severe, but CP fungaemia, which is relatively difficult to eradicate, increases the morbidity and mortality of the infants.

Gastrointest Endosc, 2000 Jun, 51(6), 664 - 9
Endoscopic biopsy requirements for post-treatment diagnosis of Helicobacter pylori; Laine L et al.; BACKGROUND: Data on sensitivities of biopsy tests for Helicobacter pylori diagnosis after modern eradication therapy are limited . We assessed diagnostic yield of endoscopic biopsy tests before and after therapy in 2 U.S . multicenter double-blind trials of 10-day proton pump inhibitor-based triple therapy versus dual antibiotic therapy . METHODS: Three hundred one patients with duodenal ulcer and H pylori infection had endoscopy at baseline and at 8 weeks . Four antral and 3 body biopsies were taken at both endoscopies: 1 antral biopsy for a rapid urease test (CLOtest), 2 antral and 2 body biopsies for histologic examination (Genta stain), and 1 antral and 1 body biopsy for culture . RESULTS: The 2 same-site biopsies (antral or body) for histologic examination were in agreement in 97% of cases before treatment and 100% after triple therapy . Histologic examination of antral biopsies without body biopsies missed H pylori infection in 2% of patients before treatment and 5% after triple therapy . Posttreatment sensitivities for triple therapy were significantly lower than pretreatment sensitivities for all tests (e . g., 18% decrease in sensitivity in antral histology, 22% decrease in antral culture); decreases in sensitivity were greater after triple therapy than after the less effective dual therapy . CLOtest plus histology had a post-treatment sensitivity of 96% in the triple therapy group . CONCLUSIONS: A single antral biopsy for histology provides excellent sensitivity for H pylori in untreated patients, but, after effective therapy, sensitivities of biopsy tests decrease . Use of more than one method of testing may increase diagnostic yield when assessing post-treatment H pylori status with endoscopy, whereas the addition of multiple biopsies for each type of test is of more limited value.

J Infect Dis, 2000 Jun, 181 Suppl 3, S566 - 8
Inflammation, infection, or both in atherosclerosis: the ROXIS trial in perspective; Gurfinkel E; The role of infection in the instability of atherosclerotic plaques has been questioned because of discrepancies in the results of clinical trials that tested antibiotics in acute coronary syndromes . The results of the Randomized Trial of Roxithromycin in Non-Q-Wave Coronary Syndromes (ROXIS) are summarized and contrasted with two other pilot studies of antibiotic therapy of coronary artery disease . Relevant characteristics of patients enrolled and rationales for these trials are discussed and serologic results are presented.

Plast Reconstr Surg, 2000 May, 105(6), 2229 - 41; discussion 2242-3
The Turkish delight: a pliable graft for rhinoplasty; Erol OO; In nose surgery, carved or crushed cartilage used as a graft has some disadvantages, chiefly that it may be perceptible through the nasal skin after tissue resolution is complete . To overcome these problems and to obtain a smoother surface, the authors initiated the use of Surgicel-wrapped diced cartilage . This innovative technique has been used by the authors on 2365 patients over the past 10 years: in 165 patients with traumatic nasal deformity, in 350 patients with postrhinoplasty deformity, and in 1850 patients during primary rhinoplasty . The highlights of the surgical procedure include harvested cartilage (septal, alar, conchal, and sometimes costal) cut in pieces of 0.5 to 1 mm using a no . 11 blade . The fine-textured cartilage mass is then wrapped in one layer of Surgicel and moistened with an antibiotic (rifamycin) . The graft is then molded into a cylindrical form and inserted under the dorsal nasal skin . In the lateral wall and tip of the nose, some overcorrection is performed depending on the type of deformity . When the mucosal stitching is complete, this graft can be externally molded, like plasticine, under the dorsal skin . In cases of mild-to-moderate nasal depression, septal and conchal cartilages are used in the same manner to augment the nasal dorsum with consistently effective and durable results . In cases with more severe defects of the nose, costal cartilage is necessary to correct both the length of the nose and the projection of the columella . In patients with recurrent deviation of the nasal bridge, this technique provided a simple solution to the problem . After overexcision of the dorsal part of deviated septal cartilage and insertion of Surgicel-wrapped diced cartilage, a straight nose was obtained in all patients with no recurrence (follow-up of 1 to 10 years) . The technique also proved to be highly effective in primary rhinoplasties to camouflage bone irregularities after hump removal in patients with thin nasal skin and/or in cases when excessive hump removal was performed . As a complication, in six patients early postoperative swelling was more than usual . In 16 patients, overcorrection was persistent owing to fibrosis, and in 11 patients resorption was excessive beyond the expected amount . A histologic evaluation was possible in 16 patients, 3, 6, and 12 months postoperatively, by removing thin slices of excess cartilage from the dorsum of the nose during touch-up surgery . This graft showed a mosaic-type alignment of graft cartilage with fibrous tissue connection among the fragments . In conclusion, this type of graft is very easy to apply, because a plasticine-like material is obtained that can be molded with the fingers, giving a smooth surface with desirable form and long-lasting results in all cases . The favorable results obtained by this technique have led the authors to use Surgicel-wrapped diced cartilage routinely in all types of rhinoplasty.

Probl Tuberk, 2000, (2), 26 - 8
{Immediate outcomes of medical therapy in patients with caseous pneumonia}; Cherkasov VA et al.; The immediate outcomes of treatment were studied in 119 patients with caseous pneumonia whose age was 20 to 64 years . In most cases, caseous pneumonia was found to preserve its classic traits by characterizing by acute onset (85.8%), prompt progression, high proportion of fatal outcomes in the early postoperative period (54.1% within 3 early postoperative months) . There is an increase in cases of more "benign" course of this form of tuberculosis (subacute onset and prolonged slow progression) at the same time . The use of current methods for combined intensive antibiotic and pathogenetic therapies substantially improves the outcomes in this most severe group of patients, reduces the initiation of a phase of relative stabilization of a specific process and of cessation of bacterial isolation.

Arch Tierernahr, 2000, 53(1), 59 - 73
Blood cells and plasma proteins of chickens fed a diet supplemented with (1-->3),(1-->6)-beta-D-glucan and enrofloxacin; Fleischer LG et al.; The effects of (1-->3),(1-->6)-beta-D-glucan from Saccharomyces cerevisiae and of the fluochinolone enrofloxacin were studied on red and white blood cells and plasma proteins of growing chickens up to the 35th day of life . The prominent findings within the leukocyte population on a per cent scale are: (i) increase of leukocyte count; increase of neutrophils and decrease of lymphocytes in the control and in the antibiotic group from day 17 to day 35; (ii) a minor decrease of neutrophils and no change of lymphocytes in the glucan group; (iii) the monocytes increase from 2.5 +/- 1.8% to 6.5 +/- 7.6% in the glucan group; (iv) the basophils increase in the control group and scale down in the other groups from day 17 to day 35 . The total count of leukocytes increases in the controls and in the glucan group . The total protein content of blood plasma, beta-globulin and gamma-globulin increase and the albumin-globulin-ratio and alpha-globulin decline during chickens growth . These changes are most prominent in the glucan group . The haemoglobin concentration shows in all three dietary groups a highly significant increase from day 17 to day 35 by about 17 to 27 per cent; no changes are seen in packed cell volume and number of erythrocytes per litre blood.

J Clin Microbiol, 2000 Jun, 38(6), 2438 - 9
Culture of Helicobacter pylori from a gastric string may be an alternative to endoscopic biopsy; Samuels AL et al.; Helicobacter pylori was isolated from a swallowed string from 32 of 33 adult subjects (97%) with selective culture media . With this method, antibiotic susceptibility testing and molecular epidemiology studies of H . pylori can be carried out without the need for the collection of specimens by endoscopic biopsy.

J Clin Microbiol, 2000 Jun, 38(6), 2330 - 3
Recovery of Bordetella holmesii from patients with pertussis-like symptoms: use of pulsed-field gel electrophoresis to characterize circulating strains; Mazengia E et al.; A 4-year retrospective study showing that we isolated Bordetella holmesii, but not Bordetella pertussis, from patients with pertussis-like symptoms was performed . From 1995 through 1998, we isolated B . holmesii from 32 nasopharyngeal specimens that had been submitted from patients suspected of having pertussis . Previously, B . holmesii had been associated mainly with septicemia and was not thought to be associated with respiratory illness . A study was undertaken to describe the characteristics of the B . holmesii isolates recovered and why we were successful in detecting the organism in nasopharyngeal specimens . B . holmesii isolates were characterized for drug sensitivities and for genetic relatedness by pulsed-field gel electrophoresis (PFGE) . These isolates, an additional strain of B . holmesii isolated from a blood culture and previously confirmed by the Centers for Disease Control and Prevention, Atlanta, Ga., and 14 other clinical isolates of Bordetella spp., including 4 of B . bronchiseptica, 5 of B . parapertussis, and 5 of B . pertussis, were studied . They were all separately inoculated on three Bordet Gengou (BG) selective media containing either 0.625 microgram of oxacillin per ml, 40 microgram of cephalexin per ml, or 2.5 microgram of methicillin per ml, on BG agar with no antibiotic (control), and on charcoal agar (CA) with and without 40 microgram of cephalexin per ml . We found that cephalexin, the antibiotic commonly incorporated in both CA and BG agar for the recovery of Bordetella spp., is inhibitory to the growth of B . holmesii . In addition, the genotypic analysis of the 32 B . holmesii isolates by PFGE following restriction with XbaI and SpeI identified the dominant strains circulating during the study period.

Semin Cutan Med Surg, 2000 Mar, 19(1), 19 - 61
The immune compromised host in the twenty-first century: management of mucocutaneous infections; Johnson RA; Infectious diseases encountered in dermatology have changed tremendously during the past few decades with the emergence of the immunocompromised host . This change is a result of the human immunodeficiency virus epidemic, use of immunomodulating drugs, bone marrow transplantation, increasing prevalence of diabetes mellitus, and an aging population . New pathogens have been discovered and new disorders have occurred . In the compromised host, infection can be more aggressive and widespread locally, be caused by opportunistic pathogens, and be disseminated hematogenously from or to the skin . The prevalence of nonmelanoma skin cancer has increased, and squamous cell carcinomas can be more aggressive with more rapid local growth as well as frequency of metastasis.

Arch Gynecol Obstet, 2000 Apr, 263(4), 185 - 7
Delayed interval delivery in multiple gestations; Song TB et al.; Two multiple pregnancies with delayed delivery after expulsion of dead fetus are presented . Case 1: A woman with a twin pregnancy and one intrauterine fetal death at 20 weeks' gestation delivered a dead fetus at 27 weeks' gestation . She delivered a healthy male infant weighing 2430 g at 33 weeks' gestation (42 d after the delivery of the first twin) . Case 2: A woman with quadruplets pregnancy (2 live fetuses, one empty sac, and one fetocide at 7 weeks' gestation) got a intrauterine fetal death at 21 weeks' gestation at one fetus among 2 live fetuses and delivered a dead fetus at 24 weeks' gestation . She delivered a healthy female infant weighing 2110 g at 33 weeks' gestation (58 d after the delivery of a dead fetus) . On the basis of our experience and the review of literature, delayed delivery with careful observation of fetal and maternal condition is recommended for improved survival and decreased morbidity among latter-born siblings.

CMAJ, 2000 May 16, 162(10), 1415 - 20
Treatment and outcomes of community-acquired pneumonia at Canadian hospitals; Feagan BG et al.; BACKGROUND: Community-acquired pneumonia is a common disease with a large economic burden . We assessed clinical practices and outcomes among patients with community-acquired pneumonia admitted to Canadian hospitals . METHODS: A total of 20 hospitals (11 teaching and 9 community) participated . Data from the charts of adults admitted during November 1996, January 1997 and March 1997 were reviewed to determine length of stay (LOS), admission to an intensive care unit and 30-day in-hospital mortality . Multivariate analyses examined sources of variability in LOS . The type and duration of antibiotic therapy and the proportion of patients who were treated according to clinical practice guidelines were determined . RESULTS: A total of 858 eligible patients were identified; their mean age was 69.4 (standard deviation 17.7) years . The overall median LOS was 7.0 days (interquartile range {IQR} 4.0-11.0 days); the median LOS ranged from 5.0 to 9.0 days across hospitals (IQR 6.0-7.8 days) . Only 22% of the variability in LOS could be explained by known factors (disease severity 12%; presence of chronic obstructive lung disease or bacterial cause for the pneumonia 2%; hospital site 7%) . The overall 30-day mortality was 14.1% (95% confidence interval {CI} 11.8%-16.6%); 13.6% of the patients were admitted to an intensive care unit (95% CI 11.4%-16.1%) . The median duration of intravenous antibiotic therapy was 5 days (range 3.0-6.5 days across hospitals) . Although 79.8% of patients received treatment according to clinical practice guidelines, the rate of compliance with the guidelines ranged from 47.9% to 100% across hospitals . INTERPRETATION: Considerable heterogeneity exists in the management of community-acquired pneumonia at Canadian hospitals, the causes of which are poorly understood.

Klin Med (Mosk), 2000, 78(4), 36 - 40
{Clinical characteristics and risk factors of hepatic damage in lyme borrheliosis}; Bessonova EN et al.; The study is based on the study of data on 33 patients with Lyme Borrelia infection in the presence of typical erythema migrans in whom elevated levels of serum bilirubin or transaminases were detected simultaneously with erythema or just shortly . The obligatory criterion was no history evidence of hepatitis and abnormal hepatic functional tests . Higher levels of serum aminotransferases were a major manifestation of Lyme hepatitis in the Sverdlovsk region . In 32 patients, ALT was increased, on the average, up to 176 U/l, and AST activity was up to 113 U/l within the first 2 weeks of the disease in the absence of clinical manifestations of hepatic and biliary diseases . There were changes in the levels of serum transaminases and bilirubin following 3- and 8-month antibiotic therapy . The presence of viruses A and C in moderate chronic hepatitis induced long-term increases in the activity of transaminases in 3 cases, as evidenced by histological studies of hepatic biopsy specimens.

Biochem Biophys Res Commun, 2000 Jun 7, 272(2), 622 - 8
Functional expression, purification, and characterization of 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni; Maser E et al.; 3alpha-Hydroxysteroid dehydrogenase (3alpha-HSD) catalyzes the oxidoreduction at carbon 3 of steroid hormones and is postulated to initiate the complete mineralization of the steroid nucleus to CO(2) and H(2)O in Comamonas testosteroni . By this activity, 3alpha-HSD provides the basis for C . testosteroni to grow on steroids as sole carbon and energy source . 3alpha-HSD was cloned and overexpressed in E . coli and purified to homogeneity by an affinity chromatography system as His-tagged protein . The recombinant enzyme was found to be functional as oxidoreductase toward a variety of steroid substrates, including androstanedione, 5alpha-dihydrotestosterone, androsterone, cholic acid, and the steroid antibiotic fusidic acid . The enzyme also catalyzes the carbonyl reduction of nonsteroidal aldehydes and ketones such as metyrapone, p-nitrobenzaldehyde and a novel insecticide (NKI 42255), and, based on this pluripotent substrate specificity, was named 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) . It is suggested that 3alpha-HSD/CR contributes to important defense strategies of C . testosteroni against natural and synthetic toxicants . Antibodies were generated in rabbits against the entire 3alpha-HSD/CR protein, and may now be used for evaluating the pattern of steroid induction in C . testosteroni on the protein level . Upon gel permeation chromatography the purified enzyme elutes as a 49.4 kDa protein revealing for the first time the dimeric nature of 3alpha-HSD/CR of C . testosteroni .

Protein Expr Purif, 2000 Jun, 19(1), 173 - 8
High-level expression in Escherichia coli and purification of the membrane-bound form of cytochrome b(5); Mulrooney SB et al.; Expression of the membrane-bound form of rabbit cytochrome b(5) in Escherichia coli has been significantly improved through the use of the T7 expression vector pLW01 (A . Bridges, L . Gruenke, Y.-T . Chang, I . Vakser, G . Loew, and L . Waskell, 1998, J . Biol . Chem . 273, 17036-17049) in conjunction with strain C41(DE3) (B . Miroux and J . Walker, 1996, J . Mol . Biol . 260, 289-298) . Cell cultures expressing the cytochrome b(5) contained an average of 820 mg/liter of culture and reached peak levels as high as 1100 mg/liter when higher antibiotic concentrations were used . Maximal levels were obtained from cultures when expression was induced with 10 microM IPTG . Approximately 90% of the cytochrome b(5) was expressed as apoprotein which was reconstituted by addition of exogenous heme . The cytochrome b(5) was purified from detergent-solubilized bacterial membranes using anion-exchange chromatography on DEAE-Sepharose followed by size-exclusion chromatography on Superdex-75 . Purification of cytochrome b(5) from a 500-ml culture yielded 121 mg of protein which had a specific content of 50 nmol of heme per milligram of protein with an overall recovery of 35% . The final cytochrome b(5) was free of any detectable contaminants when analyzed by SDS-PAGE .

Pediatrics . 2000 Jun;105(6):E72.
Direct expenditures related to otitis media diagnoses: extrapolations from a pediatric medicaid cohort; Bondy J et al.; BACKGROUND: Treatment of otitis media in children is associated with substantial expenditures because of its high frequency during childhood . Vaccines against respiratory pathogens causing otitis media are now being developed . Information about otitis media-related medical expenditures will be needed to determine the cost-effectiveness of these preventive interventions . METHODS: This study used utilization data from claims to impute otitis media-related expenditures for medical visits, pharmaceuticals, and surgical procedures for 87 057 children 13 years of age and younger who were continuously enrolled in Colorado's fee-for-service Medicaid program during 1992 . International Classification of Disease, Ninth Revision diagnostic codes were used to identify visits for otitis media . An antibiotic was considered to have been prescribed to treat otitis media if it was dispensed up to 24 hours before or within 48 hours after a physician encounter showing a diagnosis of otitis media . All tympanostomies, mastoidectomies, and adenoidectomies were assumed to be related to otitis media . Expenditures were imputed from utilization using a Medicaid fee schedule.National expenditures for 1992 to treat otitis media were extrapolated from Colorado's Medicaid data . We adjusted for differences between Colorado and the United States as a whole in terms of price, number, and intensity of services; for differences in reimbursement rates by service between Medicaid and private insurance; and for differences in utilization between Medicaid enrollees and the uninsured . To provide a more current expression of medical expenditures for otitis media, we inflated the 1992 expenditure estimates to 1998 dollars using the Consumer Price Index published by the US Bureau of Labor Statistics . RESULTS: Twenty-eight percent of children experienced at least 1 episode of diagnosed otitis media . The proportion of children with a diagnosis of otitis media was highest (42%-60%) in the 7-month to 36-month age range . The proportion was also higher among white (34.5%) and Hispanic (25.3%) children than among black children (18.5%), as well as among rural (34.5%) compared with urban children (27.2%).Children 19 to 24 months of age incurred the highest total annual expenditures per child with otitis media ($239.68) . Expenditures for drugs, visits, and procedures were all highest for this group . The per-patient cost to Medicaid was greater for visits than for drugs or procedures across all age groups . Total per-patient expenditures were higher for males ($174.67) than for females ($154.47) and higher for white children ($176.59) than for Hispanic ($154.12) or black children ($134.44) . The differences among the ethnic groups can be attributed almost entirely to differences in expenditures for procedures and drugs . Although mean expenditures per patient varied substantially by some patient characteristics (eg, race), these differences accounted for only a small fraction of the enormous variation in costs per patient . Including children with and without otitis media, age-specific estimated expenditures per child peaked among children 1 ($132.94) and 2 years of age ($88.72) . Children 3 to 6 years of age incurred expenditures only one third as great as those incurred by children 1 year of age.Total national expenditures were estimated to have been approximately $4.1 billion in 1992 dollars and $5.3 billion in 1998 dollars . Over 40% of national expenditures to treat otitis media in children younger than 14 years of age were incurred for children between 1 and 3 years of age ($453 per capita in 1992 dollars over these 2 years vs $1027 for all years of age from 2 to 13) . Nationally, expenditures for visits remained the largest component of expenditures . LIMITATIONS: This study assessed expenditures from the point of view of the health care system; that is, no social costs, such as lost work time, or expenditures not normally covered by insurance, such as those for transportation, we

J Vasc Interv Radiol, 2000 May, 11(5), 578 - 84
Stent-graft therapy for subclavian artery aneurysms and fistulas: single-center mid-term results; Hilfiker PR et al.; PURPOSE: To evaluate the potential of covered stents to replace surgery in the treatment of subclavian artery aneurysms and traumatic injuries . MATERIALS AND METHODS: Nine patients (five men, four women; age range, 20-83 years; mean, 54 years) with subclavian artery aneurysms (n = 5) or fistulas (n = 4) were treated with stent-grafts . All devices used were custom-made, consisting of polytetrafluoroethylene (PTFE)-covered Palmaz (n = 5), Wallstent (n = 2), Z stents (n = 8), or a polyester-covered Z stent (n = 1) . One patient was lost to follow-up after 2 months . All others were followed up with clinical evaluation, computed tomography (CT), and/or ultrasound . RESULTS: All devices were deployed successfully with exclusion of the aneurysms and fistulas . There were two procedure-related complications (22%), consisting of groin pseudoaneurysms requiring surgical repair 3 and 9 days after the procedure . One of those patients required additional oral antibiotic therapy for a postsurgical groin wound infection . One patient developed a stenosis at 12 months, which required angioplasty . The stent-graft thrombosed in one patient because of a kink 2 months after placement, which was successfully treated by thrombolysis and placement of a Wallstent . The primary and secondary patencies are 89% and 100%, respectively, after a mean follow-up of 29 months (2-66 mo) . CONCLUSION: Mid-term results of stent-graft therapy of subclavian artery aneurysms and fistulas are encouraging, with low morbidity and excellent clinical outcome.

Minerva Anestesiol, 2000 Apr, 66(4), 207 - 14; discussion 214-6
{Surgical treacheotomy in intensive care}; Leonelli V et al.; BACKGROUND: To test validity, safety, costs and healing-outcome of surgical minitracheotomy after cannula removing . METHODS: Design: Opened, perspective . Site: Polyvalent ICU . Patients: 40 patients underwent surgical minitracheotomy, in a year . Traditional surgical technique was adopted . Minitracheotomy was performed by intravenous general anesthesia with curarization and in mechanical ventilation . Intra-operative monitoring: ECG, non-invasive blood pressure and SaO2 by digital pulse oximetry . If a bleeding appeared, hemorrhage was stopped by vessel binding . RESULTS: Technical difficulty was the same in every tracheotomy carried out . Complications appeared in 7 patients . There were 2 infectious cases for stoma, resolved in 7 and 12 days respectively by local disinfection and antibiotic therapy . There were 5 cases with moderate bleeding; in one patient only a surgical procedure was necessary . CONCLUSIONS: Surgical tracheotomy represents a good and safe method in ICU; complications are few, if safety conditions are observed . Tracheotomy made in ICU reduced the use of medical and paramedical staff and operative rooms; unlike percutaneous procedure, in the surgical technique an always the same set after simple sterilization is used . Healing-outcome of surgical tracheotomy, after cannula removing, is the same with both techniques.

J Clin Psychopharmacol, 2000 Jun, 20(3), 317 - 24
Studies on the mechanism of a fatal clarithromycin-pimozide interaction in a patient with Tourette syndrome; Flockhart DA et al.; The authors report in detail the case of a 27-year-old man who experienced sudden cardiac death 2 days after coprescription of the neuroleptic pimozide and the macrolide antibiotic clarithromycin after the documentation of a prolonged QT interval . To determine the prevalence of this interaction, the authors referred to the Spontaneous Reporting System of the Food and Drug Administration and identified one similar case in which clarithromycin was coprescribed with pimozide and sudden cardiac death occurred shortly thereafter . In addition, the search identified 39 cases of cardiac arrhythmia associated with pimozide, 11 with pimozide alone, and 6 with clarithromycin alone, 1 of which had a positive rechallenge . The mechanism of the interaction between clarithromycin and pimozide seems to involve the inhibition of the hepatic metabolism of pimozide by the macrolide . The authors demonstrated that clarithromycin is able to inhibit the metabolism of pimozide in human liver microsomal preparations (K(i) = 7.65 +/- 1.18 microM) and that pimozide, but not clarithromycin or its primary metabolite, is able to prolong the electrocardiac QT interval in a dose-dependent manner in the isolated perfused rabbit heart . The increase was 9.6 +/- 1.1% in male hearts (N = 5) and 13.4 +/- 1.2% in female hearts (N = 4) (p < 0.05).

Acta Obstet Gynecol Scand, 2000 May, 79(5), 379 - 83
A follow-up study of birth outcome in users of pivampicillin during pregnancy; Larsen H et al.; BACKGROUND: Pivampicillin is a prodrug which is widely used in Scandinavian countries for oral antibiotic therapy . The pivaloyl moiety has a carnitine depleting effect, which has caused doubts about the safety of administering pivampicillin during pregnancy . The aim of the study was to evaluate the risk of congenital malformations in general, preterm delivery and low birth weight in users of pivampicillin . METHODS: Seven hundred and ninety-one women who had redeemed a prescription of pivampicillin during their first pregnancy from 1 January 1991 to 31 December 1996 were identified in the North Jutland Pharmaco-Epidemiological Prescription Database . By linkage to the Danish Medical Birth Registry and Regional Hospital Discharge Registry we compared their birth outcomes (malformations, preterm delivery and low birth weight) with the outcomes in 7472 reference pregnancies on which the mother had not redeemed any prescription at all during pregnancy . RESULTS: The prevalence of malformations was 5.5% (11 cases) in offspring of 199 women who had used pivampicillin during the first trimester, and 5.6% (420 cases) in offspring of controls (OR: 0.95, 95% CI: 0.51-1.76) . Furthermore, we did not find any significant risk of preterm delivery (OR: 0.75, 95% CI: 0.54-1.05) or low birth weight (OR: 0.93, 95% CI: 0.55-1.57) . CONCLUSION: This study showed no increased risk of congenital malformations, preterm delivery or low birth weight in offspring of women who had redeemed a prescription for pivampicillin during pregnancy.

Cancer Gene Ther, 2000 May, 7(5), 806 - 12
Enhanced green fluorescent protein fusion proteins of herpes simplex virus type 1 thymidine kinase and cytochrome P450 4B1: applications for prodrug-activating gene therapy; Steffens S et al.; To monitor therapeutic transgene expression, we developed fusion genes of enhanced green fluorescent protein (EGFP) with two different prodrug-activating enzyme genes: herpes simplex virus type 1 thymidine kinase (HSV-tk) and rabbit cytochrome P450 4B1 (cyp4b1) . Expression of the resulting fusion proteins, TK-EGFP and 4B1-EGFP, rendered transduced human and rodent glioma cells sensitive to cytotoxic treatment with the corresponding prodrugs ganciclovir and 4-ipomeanol . Ganciclovir and 4-ipomeanol sensitivity was comparable with that achieved with the native HSV-TK and CYP4B1 proteins . As shown by fluorescence microscopy, TK-EGFP was expressed predominantly intranuclearly, whereas 4B1-EGFP was detectable in the cytoplasm, thereby displaying the orthotopic subcellular distribution of the corresponding native enzymes . The fluorescence intensity correlated well with the corresponding prodrug sensitivity, as shown by fluorescence-activated cell sorter analysis . EGFP expression was also used for the selection of stably HSV-tk-transduced cells by flow cytometric cell sorting . Resulting cell populations showed a homogeneity of fluorescence intensity similar to single-cell clones after antibiotic selection . In conclusion, tk-egfp and 4b1-egfp fusion genes are valuable tools for monitoring prodrug-activating gene therapy in living cells . EGFP fusion genes/proteins provide a simple and reproducible means for the detection, selection, and characterization of cells expressing enzyme genes for prodrug activation.

Indian J Pediatr, 1995 Nov-Dec, 62(6), 725 - 9
Epidemiology of chronic suppurative otitis media and deafness in a rural area and developing an intervention strategy; Verma AK et al.; Of 613 children evaluated in a village in Haryana 94 (15.3%) were observed to have chronic suppurative otitis media (CSOM) . Fifty eight (61.7%) children had hearing impairment . CSOM contributed to 71.6% of the hearing impaired (58/81) . On analysis of association of CSOM with literacy and socio-economic status of mothers, and age, sex, and upper respiratory tract infections (URI) in children positive correlation was observed only with URIs (P < 0.001) . Literacy and socio-economic status of the mothers did not correlate significantly with knowledge about treatment seeking, and ear cleaning practices, probably due to the narrow range of incomes and literacy levels . An intervention program consisting of play, demonstrations, health charts and slogans, and aural cleaning and antibiotic drops was introduced.

An Otorrinolaringol Ibero Am, 2000, 27(1), 67 - 75
{Maxillary sinusitis caused by Aspergillus}; Guillen Guerrero VS et al.; Naso-sinusal aspergillosis is an infrequent ailment which true incidence is not correctly assumed and furthermore the cases are increasing because of the progression of immunodeficiency problems . Suspicious become accentuated when repeated antibiotic treatments fail or in patients with previous dental pathology or radiologically show inside of sinus images of forcing bodies . Despite of which the diagnosis should be histological thanks to the examination of the surgical piece gained following the classic approaches through the canine fossa or endoscopic surgery . The only real treatment is surgery . We report one clinical case of an acute naso-sinusal aspergillosis with ineffectiveness of all used treatments and whose diagnose was achieved only through the anatomopathological study of the piece supplied by the Caldwell-Luc procedure.

Spine, 2000 Jun 1, 25(11), 1450 - 2
Neonatal infectious spondylitis of the cervical spine presenting with quadriplegia: a case report; van Dalen IV et al.; STUDY DESIGN: A case report.- OBJECTIVE: To highlight the evaluation and treatment of neonatal infectious spondylitis of the cervical spine . SUMMARY OF BACKGROUND DATA: Most authors advise intravenous antibiotics as first-choice treatment . The place of aspiration or operative drainage is debated, as is the position and duration of immobilization . METHODS: A 3-week-old neonate was presented with intermittent quadriplegia . RESULTS: Additional investigation demonstrated an osteolytic process in the body of C3 with a large epidural abscess compressing the spinal cord . Because an infectious spondylitis of C3 was suspected, aspiration of the abscess was performed, and antibiotic therapy was started . The patient improved to neurologically normal within 3 weeks and remains asymptomatic throughout a follow-up period of 7 years . CONCLUSIONS: Neonatal infectious spondylitis should be diagnosed early and treated promptly; otherwise, it may have devastating consequences.

FEMS Microbiol Lett, 2000 Jun 1, 187(1), 95 - 101
Structural and functional analysis of the gene cluster encoding carotenoid biosynthesis in Mycobacterium aurum A+; Viveiros M et al.; The fragment containing the carotenoid gene cluster from Mycobacterium aurum A+, a 3,3'-dihydroxy-isoneriatene and 3-monohydroxy-isoneriatene accumulator, has been sequenced and the exposed eight genes are organised in two operons . The function of three of these genes, a phytoene desaturase (crtI), a phytoene cyclase (crtY) and a beta-carotene desaturase (crtU), was demonstrated by complementation of M . aurum carotenoid mutants . The eight genes of the carotenoid cluster are highly homologous to other carotenoid gene clusters and thus this cluster is a candidate for its introduction into mycobacteria as a non-antibiotic reporter gene(s) as well as a source of new regulated promoters.

Eur Rev Med Pharmacol Sci, 1999 May-Jun, 3(3), 105 - 10
A randomized openly comparative study between rifaximin suspension versus rifaximin pills for the eradication of Helicobacter pylori; Dell'Anna A et al.; BACKGROUND: It has been recently shown that Rifaximin, although given as a suspension, plus omeprazole, may be a promising antibiotic against Helicobacter pylori (H pylori) and worthy of further study . AIM: We have therefore evaluated Rifaximin suspension versus Rifaximin pills, in a randomly openly allocated fashion study, in H pylori positive patients . METHODS: Twenty patients with upper gastrointestinal symptoms (M/F: 13/7, age range 28-68; mean 49.6 yrs) were found to have H . pylori associated gastritis . They were allocated in an open randomized study to two different treatment groups for two weeks: (A) Rifaximin suspension 1800 mg three times a day plus Omeprazole 20 mg twice a day (n = 10), (B): Rifaximin pills 1800 mg three times a day plus Omeprazole twice a day (n = 10) . Symptoms such as pirosis, bloating, epigastric pain and nausea were recorded by diary card and were evaluated before and four weeks after stopping treatment . Patients were assessed by endoscopy, histology and urease testing at entry and four weeks after stopping treatments . All the twenty patients were available four weeks after stopping treatment . RESULTS: A statistically significant improvement of the symptoms were found overall after Rifaximin treatments for pirosis, bloating, epigastric pain (p < 0.001 respectively) . A significant difference in the symptom's score at the end of the two treatments were recorded between the two groups for bloating alone (p < 0.070) . A different and major fall in the neutrophils, between the two treatments was observed with Rifaximin pills compared to Rifaximin suspension . The same observation was obtained according to the intensity of H . pylori reaching an eradication rate of 40% and 60% for Rifaximin suspension versus Rifaximin pills plus omeprazole respectively . In conclusion, these data suggest that Rifaximin pills may be an effective antibiotic against H pylori and worthy of further study.

Clin Ther, 2000, 22 Suppl B, B101 - 121
Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus; MacDonald A et al.; BACKGROUND: Sirolimus is a novel macrocyclic antibiotic that has an immunosuppressive mechanism of action distinct from that of cyclosporine and tacrolimus . OBJECTIVE: The objective of this report is to provide an overview of the clinical development of sirolimus with emphasis on the mechanism of immunosuppressive activity, prevention of acute renal allograft rejection, clinical pharmacokinetics, concentration-effect relationships, and therapeutic drug monitoring (TDM) . RESULTS: Pharmacokinetic studies in adult renal transplant patients have shown that sirolimus may be characterized as a drug with rapid absorption (t(max) = 1 to 2 hours), low systemic availability (F = 14%), linear dose proportionality (2 to 24 mg), extensive partitioning into formed blood elements (B/P = 36), large apparent volume of distribution (1.7 L/kg), prolonged terminal half-life (62 hours), and large intersubject (CV = 52%) and intrasubject (CV = 26%) variability in oral-dose clearance . Results from phase 111 pivotal trials showed that sirolimus (2 or 5 mg/d) reduced acute renal graft rejection (generally, P < 0.01) without TDM . Although TDM may not be required for a regimen consisting of full-dose cyclosporine and corticosteroids with sirolimus 2 mg/d (4 hours after cyclosporine), it may be warranted in patients (1) with hepatic impairment, (2) who are young children, (3) who are receiving concurrent doses of strong CYP3A/p-glycoprotein inhibitors or inducers, (4) in whom cyclosporine dosing is markedly reduced or discontinued, and (5) who are at a high risk for rejection . A whole-blood sirolimus therapeutic window of 5 to 15 ng/mL (measured by microparticle enzyme immunoassay) is recommended for patients at standard risk of rejection . The large intrapatient variability observed in trough sirolimus concentrations indicates that dose adjustments should be optimally based on more than a single trough sample . Because of the time required to reach steady state, sirolimus dose adjustments would optimally be based on trough levels obtained >5 to 7 days after a dose change . CONCLUSIONS: The effective use of sirolimus in an immunosuppressive regimen for the prevention of acute renal allograft rejection requires an understanding of the drug's clinical pharmacokinetics, concentration/adverse-effect relationship, concentration-efficacy relationship, and TDM.

Clin Ther, 2000, 22 Suppl B, B25 - 37
Therapeutic monitoring of sirolimus in human whole-blood samples by high-performance liquid chromatography; Maleki S et al.; BACKGROUND: Sirolimus is a macrolide antibiotic isolated from Streptomyces hygroscopicus that has demonstrated immunosuppressive activity . Human and animal studies have shown a good correlation of trough sirolimus concentrations with immunosuppressive efficacy . OBJECTIVE: This report describes a reverse-phase high-performance liquid chromatography (HPLC) method used for therapeutic drug monitoring of sirolimus . METHODS: A reverse-phase C18 column method was developed using an automated HPLC system and ultraviolet (UV) detection . Whole-blood samples collected in ethylenediamine-tetraacetic acid (EDTA) are first hemolyzed, and an internal standard (desmethoxysirolimus) is added to 1.0 mL of sample, which is then extracted with 1-chlorobutane and, after the organic layer is removed, evaporated to dryness . The residue is reconstituted in a 70% methanol/water mixture . Reconstituted extracts are analyzed by HPLC at a column temperature of 60 degrees C and a flow rate of 1.0 mL/min . Typically, chromatography requires 35 minutes between each sample injection . The UV detector is set at 278 nm with a response sensitivity of 0.010 AUFS (absorbance units full scale) . Standards and controls prepared in hemolyzed EDTA-anticoagulated whole blood are extracted and run in parallel . Identification of peaks of interest is by retention time; quantification of sirolimus in controls and clinical samples uses a peak-height ratio (sirolimus/internal standard) . RESULTS: The assay's precision (coefficients of variation, 5.7%-14.4%) and sensitivity (2.5 ng/mL) were found to be appropriate for therapeutic monitoring purposes . Analytical recovery of 88.0% to 106.3% was observed throughout the assay's linear range (2.5-150.0 ng/mL) . Stability studies at 20 degrees C to 25 degrees C and 2 degrees C to 8 degrees C showed an estimated recovery of sirolimus ranging from 85% to 110% of target concentrations (10-90 ng/mL) . In a study comparing the results of 194 samples from kidney transplant recipients assayed by the HPLC-UV assay and by a microparticle enzyme immunoassay, the HPLC-UV method provided approximately 10% lower values . CONCLUSION: The HPLC-UV assay is analytically capable of providing useful data for the clinical assessment of patients receiving sirolimus.

Org Lett, 1999 Sep 23, 1(6), 941 - 4
Total synthesis of reveromycin B; Masuda T et al.; {formula: see text} The stereoselective total synthesis of reveromycin B (2), a novel polyketide-type antibiotic, has been accomplished.

J Trop Pediatr, 2000 Apr, 46(2), 107 - 10
Paediatric HIV infection in a rural South African district hospital; Yeung S et al.; The objective of this study was to determine the prevalence, clinical spectrum, and outcome of paediatric HIV infection in 281 consecutive children admitted to hospital in rural South Africa between October 1996 and January 1997 . HIV infection was defined as two positive ELISAs in those aged > 12 months; a positive ELISA plus a positive IgG3 in those aged 6-12 months; and a positive ELISA plus positive p24 antigen or PCR in those aged 0-5 months . In all, 72 (26 per cent) children were HIV infected . Age-specific HIV prevalence was at least 25 per cent in all 1-5 year age groups . HIV-infected children were more likely to have been previously admitted (46 per cent vs . 23 per cent; p = 0.0002), and were more likely to have severe malnutrition (52 per cent vs . 17 per cent; p < 0.0001) . Both HIV-infected and HIV-uninfected most frequently presented with diarrhoeal disease (51 per cent vs . 32 per cent), acute respiratory infection (13 per cent vs . 23 per cent), and malnutrition (18 per cent vs . 11 per cent) . Satisfactory response to antibiotic therapy was less likely among the HIV-infected (56 per cent vs . 73 per cent; p = 0.02), and mortality was higher among the HIV-infected (21 per cent vs . 7 per cent; p = 0.005) . It is concluded that HIV-infected children present with disease syndromes common to this setting, but do so more frequently and with worse outcome than their uninfected counterparts . The high burden of paediatric HIV disease in this setting poses a substantial challenge for health resources.

Cardiovasc Intervent Radiol, 2000 May-Jun, 23(3), 187 - 93
Peripheral venous access ports: outcomes analysis in 109 patients; Bodner LJ et al.; PURPOSE: To perform a retrospective outcomes analysis of central venous catheters with peripheral venous access ports, with comparison to published data . METHODS: One hundred and twelve central venous catheters with peripherally placed access ports were placed under sonographic guidance in 109 patients over a 4-year period . Ports were placed for the administration of chemotherapy, hyperalimentation, long-term antibiotic therapy, gamma-globulin therapy, and frequent blood sampling . A vein in the upper arm was accessed in each case and the catheter was passed to the superior vena cava or right atrium . Povidone iodine skin preparation was used in the first 65 port insertions . A combination of Iodophor solution and povidone iodine solution was used in the last 47 port insertions . Forty patients received low-dose (1 mg) warfarin sodium beginning the day after port insertion . Three patients received higher doses of warfarin sodium for preexistent venous thrombosis . Catheter performance and complications were assessed and compared with published data . RESULTS: Access into the basilic or brachial veins was obtained in all cases . Ports remained functional for a total of 28,936 patient days . The port functioned in 50% of patients until completion of therapy, or the patient's expiration . Ports were removed prior to completion of therapy in 18% of patients . Eleven patients (9.9% of ports placed) suffered an infectious complication (0.38 per thousand catheter-days)-in nine, at the port implantation site, in two along the catheter . In all 11 instances the port was removed . Port pocket infection in the early postoperative period occurred in three patients (4.7%) receiving a Betadine prep vs two patients (4.2%) receiving a standard O.R . prep . This difference was not statistically significant (p = 0.9) . Venous thrombosis occurred in three patients (6.8%) receiving warfarin sodium and in two patients (3%) not receiving warfarin sodium . This difference was not statistically significant (p = 0.6) . Aspiration occlusion occurred in 13 patients (11.7%) . Intracatheter urokinase was infused in eight of these patients and successfully restored catheter function in all but two instances . These complication rates are comparable to or better than those reported with chest ports . CONCLUSION: Peripheral ports for long-term central venous access placed by interventional radiologists in the interventional radiology suite are as safe and as effective as chest ports.

J Endovasc Ther, 2000 Apr, 7(2), 150 - 4
Osteomyelitis of the spine and abscess formation in the left thigh after stent-graft implantation in the superficial femoral artery; Brodmann M et al.; PURPOSE: To present a rare case of abscess formation around a covered stent in the superficial femoral artery . METHODS AND RESULTS: Two weeks after balloon dilation of a left superficial femoral artery (SFA) occlusion, during which a Hemobahn covered stent had been placed to treat dissection, a 77-year-old nondiabetic male developed intolerable pain and swelling of his left thigh . An abscess had formed around the stent, which was patent; intravenous antibiotic therapy quelled the symptoms, and the patient discontinued his oral antibiotic regimen weeks after discharge . General septicemia ensued . Acute lower limb ischemia and excruciating back pain prompted readmission . The SFA stent-graft occlusion required femoropopliteal bypass; the abscess and spondylodiskitis that had developed in the T12 and L1 vertebrae responded to intravenous antibiotics . The patient is without signs of infection at 6 months . CONCLUSIONS: Local and systemic infections associated with intraluminal prostheses are rare, and prophylactic antibiotic therapy is not commonly employed . Balloon- or device-induced arterial injury may expose the arterial wall to bacterial colonization, suggesting that patients receiving lengthy stents or experiencing arterial injury during angioplasty should receive antibiotics as a precautionary measure.

J Formos Med Assoc, 2000 Mar, 99(3), 252 - 6
Swyer-James syndrome complicated by lung abscess; Wang JY et al.; Swyer-James syndrome, a rare disease with unilateral hyperlucent lung due to bronchiolitis obliterans and pulmonary artery hypoplasia, generally develops after lower respiratory tract infection during early childhood . Invasive procedures, including bronchoscopy and angiography, are often necessary for a definitive diagnosis . We report a 17-year-old man admitted because of cystic bronchiectasis complicated by lung abscess . Chest roentgenography showed the typical findings of Swyer-James syndrome . Noninvasive magnetic resonance angiography was used to confirm hypoplasia of the right pulmonary artery . The patient received antibiotic therapy, underwent a right lower lobectomy for the lung abscess, and recovered.

J Agric Food Chem, 2000 May, 48(5), 1673 - 7
Liquid chromatographic analysis of incurred amoxicillin residues in catfish muscle following oral administration of the drug; Ang CY et al.; Improper application of antibiotic chemicals to livestock and aquaculture species may lead to the occurrence of residues in food supplies . An appropriate depletion period is needed after the administration of drugs to animals for ensuring that residues in edible tissues are below established tolerance levels . This study was conducted to determine incurred amoxicillin residues in catfish muscle following oral administration . Dosed fish were harvested after four depletion periods, and muscle fillets were analyzed for amoxicillin residues using an HPLC method with precolumn derivatization and fluorescence detection . The residue levels in fish after a 6-h depletion ranged from 40 to 64 ng/g with one exception at 297 ng/g . Average residue levels decreased to 5.4 and 2 . 8 ng/g after 24- and 48-h depletions, respectively . Residue levels after a 72-h depletion decreased to below the method's limit of quantitation (1.2 ng/g) . An LC-MS/MS confirmatory method was developed . Confirmation of the presence of amoxicillin was demonstrated in incurred fish samples containing residues at approximately 50-300 ng/g.

Biochemistry, 2000 May 2, 39(17), 5004 - 12
Determination of the structural role of the linking moieties in the DNA binding of adozelesin; Cameron L et al.; Adozelesin (formerly U73975, The Upjohn Co.) is a monofunctional DNA alkylating analogue of the antitumor antibiotic (+)-CC-1065 . Adozelesin consists of a cyclopropa{c}pyrrolo{3,2-e}indol-4(5H)-one (CPI) alkylating subunit of (+)-CC-1065 and a indole and benzofurans subunit replacing the more complex pyrroloindole B and C subunits, respectively, of (+)-CC-1065 . Previous studies have shown that adozelesin forms a reversible covalent DNA duplex adduct via a reaction between the N3 of adenine and the cyclopropyl of the cyclopropapyrroloindole (CPI) subunit . Gel electrophoresis studies have shown that adozelesin, like all the monofunctional (CPI)-based antitumor antibiotics, has a sequence preference for 5'-TTA-3' {the asterisk () indicates covalently modified base} . Molecular-modeling studies have shown that the bound adozelesin ligand spans a total of five base pairs including the modified adenine . These studies have also indicated that, owing to the orientation of the ligand within the base minor groove, there should be an overall preference for sequences rich in A.T base pairs, thus avoiding steric crowding around the exocyclic NH(2) of any guanines present . In this study, we have prepared and studied, by high-field NMR and restrained molecular mechanics (rMM) and dynamics (rMD), the duplex adduct formed between adozelesin and 5'-CGTAAGCGCTTACG-3' . Previous molecular-modeling studies suggested that this sequence should be less preferred, since the two GC base pairs should lead to extensive steric crowding within the adduct, and this hypothesis has, however, never been supported by DNA-footprinting data . (1)H NMR of the adozelesin duplex adduct has reveals that, although Watson-Crick base pairing is maintained throughout the DNA duplex, there is significant distortion around the central base pairs . This distortion is the result of strong hydrogen-bonding between the amide linker of the indole and benzofuran subunits, and the carbonyl of a central thymine base and second, weaker, hydrogen bond to the exocyclic NH(2) of the central guanine was also observed . (1)H NMR and rMD also indicate that, to accommodate this hydrogen-bond system, the bound adozelesin is not positioned centrally within the minor groove but pushed toward the modified DNA strand . Previous studies on the dimeric CPI analogue bizelesin have indicated the important role the ureylene linker plays in the DNA binding . This study indicates that a similar situation exists in the reaction of adozelesin with double-stranded DNA and provides a possible explanation into the unpredicted sequence selectivity of these ligands.

MMWR CDC Surveill Summ, 2000 Apr 28, 49(3), 1 - 11
Surveillance for Lyme disease--United States, 1992-1998; Orloski KA et al.; PROBLEM/CONDITION: Lyme disease is caused by infection with the spirochete Borrelia burgdorferi and is the most commonly reported vector-borne disease in the United States . Borrelia burgdorferi is transmitted to humans by infected Ixodes scapularis and I . pacificus ticks . Lyme disease is typically evidenced in its early stage by a characteristic rash (erythema migrans), accompanied by nonspecific symptoms (e.g., fever, malaise, fatigue, headache, myalgia, and arthralgia) . Lyme disease can usually be treated successfully with standard antibiotic regimens . REPORTING PERIOD: 1992-1998 . DESCRIPTION OF SYSTEM: Lyme disease surveillance data are reported to CDC through the National Electronic Telecommunication System for Surveillance, a computerized public health database for nationally notifiable diseases . During 1992-1998, data regarding reported cases of Lyme disease included county and state of residence, age, sex, and date of onset . Descriptive analyses were performed, and cumulative incidence by state, county, age group, and sex were calculated . RESULTS: During 1992-1998, a total of 88,967 cases of Lyme disease was reported to CDC by 49 states and the District of Columbia, with the number of cases increasing from 9,896 in 1992 to 16,802 in 1998 . A total of 92% of cases was reported from eight northeastern and mid-Atlantic states and two north-central states . Children aged 5-9 years and adults aged 45-54 years had the highest mean annual incidence . INTERPRETATION: Lyme disease is a highly focal disease, with the majority of reported cases occurring in the northeastern and north-central United States . The number of reported cases of Lyme disease increased during 1992-1998 . Geographic and seasonal patterns of disease correlate with the distribution and feeding habits of the vector ticks, I . scapularis and I . pacificus . PUBLIC HEALTH ACTION: The results presented in this report will help clinicians evaluate the prior probability of Lyme disease and provide the framework for targeting human Lyme disease vaccine use and other prevention and treatment interventions.

Endoscopy, 2000 May, 32(5), 425 - 7
Bedside endosonography and endosonography-guided fine-needle aspiration in critically ill patients: a way out of the deadlock?
Fritscher-Ravens A, Sriram PV, Pothman WP, Fullekrug B, Jackle S, Thonke F, Soehendra N.
Endosonography and endosonography-guided fine-needle aspiration (EUS-FNA) are now established diagnostic techniques, which are performed electively in endoscopy suites . We report here the bedside use of EUS-FNA in three critically ill patients in an intensive-care unit, with a significant impact on the outcome . A mediastinal abscess after percutaneous dilational tracheotomy was aspirated in one patient, leading to appropriate antibiotic therapy and complete recovery . A paratracheal hematoma compressing the right main bronchus was aspirated in a patient with polytrauma, relieving the pressure effects . The third patient, who had end-stage dilated cardiomyopathy and was being evaluated for cardiac transplantation, was found to have an apical lung lesion suspicious for bronchogenic carcinoma . EUS was performed to exclude mediastinal metastasis and allow simultaneous resection at the time of transplantation . Although a metastasis was excluded by EUS-FNA, the patient died while awaiting surgery . We conclude that bedside EUS-FNA is a feasible procedure, and in experienced hands it can offer an alternative in life-threatening situations.

J Org Chem, 2000 May 19, 65(10), 2851 - 5
Hybrid anthracyclines from a genetically engineered Streptomyces galilaeus mutant; Kunnari TJ et al.; The genetic engineering of antibiotic-producing Streptomyces strains is an approach that is emerging and ready to become established as a successful methodology in developing analogues of the original, pharmaceutically important, natural products obtained from the organisms . The current report highlights this succes by demonstrating the high-level production of novel anthracyclines . The biosynthetic pathways of the nogalamycin-producing Streptomyces nogalater and the aclacinomycin-producing S . galilaeus were combined by transferring the genes of S . nogalater polyketide synthetase into a nonproducing S . galilaeus mutant . The resulting anthracycline antibiotics that were produced possessed structural features characteristic of compounds from both of the undoctored Streptomycesstrains.

J Org Chem, 2000 Mar 10, 65(5), 1399 - 406
A practical and efficient preparation of the releasable naphthosultam side chain of a novel anti-MRSA carbapenem; Miller RA et al.; A practical large-scale synthesis of the naphthosultam-based side chain of the anti-MRSA antibiotic 1 has been achieved in 29% overall yield over seven steps from 1-methylnaphthalene . The synthesis was completed without the use of protecting groups, featuring a novel naphthosultam annelation, a chemoselective acid-catalyzed triflation, and the use of a novel naphthosultam dianion to effect functionalization through benzylic metalation.

J Org Chem, 2000 Jan 14, 65(1), 89 - 95
An efficient synthesis of peri-hydroxy aromatic compounds via a strong-base-induced
Iio K, Ramesh NG, Okajima A, Higuchi K, Fujioka H, Akai S, Kita Y.
An efficient synthesis of peri-hydroxy aromatic compounds has been accomplished via a strong-base-induced {4+2} cycloaddition of homophthalic anhydrides with alpha-sulfinyl-substituted derivatives of enolizable enones . The unsubstituted enones did not undergo an efficient {4+2} cycloaddition reaction with homophthalic anhydrides, presumably due to their enolization under the basic reaction conditions . The sulfinyl group not only promotes the cycloaddition reaction but also undergoes in situ elimination under the reaction conditions to afford the peri-hydroxy aromatic compounds in a single step . The application of this methodology for the synthesis of a key intermediate of antitumor antibiotic fredericamycin A is described . PM3 calculations of various 2-substituted cyclopentenones as well as the mechanism of the cycloaddition are also discussed.

Cancer, 2000 May 1, 88(9), 2033 - 6
Prospective randomized comparison of morning versus night daily single subcutaneous administration of granulocyte-macrophage-colony stimulating factor in patients with soft tissue or bone sarcoma; Dincol D et al.; BACKGROUND: Hematopoietic growth factors (HGFs) have been used to reduce the neutropenic complications of cytotoxic chemotherapy so that higher doses may be given . The authors have previously shown that endogenous serum granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) levels at night (p.m.) were significantly higher than those in the morning (a.m.) . METHODS: Twenty-four patients with soft tissue or bone sarcoma who were treated with high dose ifosfamide-based chemotherapy were enrolled in this study . Patients were randomized to either a.m . or p.m . treatment . GM-CSF was administered at a dose of 5 microg/kg/day at 10 a.m . or 10 p.m., beginning 36-48 hours after the last chemotherapy dose . GM-CSF therapy was continued until the neutrophil count exceeded 1,000/mm3 for 2 consecutive days . Leukocyte, neutrophil, monocyte, and platelet counts were measured immediately before GM-CSF administration and exactly 12 hours after the first dose of GM-CSF, and every 24 hours until 3 days after the cessation of GM-CSF . RESULTS: The mean duration of Grade 3-4 neutropenia was 5.3 +/- 0.4 days for the a.m . treatment arm and 6.5 +/- 0.3 days for the p.m . treatment arm (P = 0.017) . Although the duration of neutropenia in the a.m . arm was significantly shorter than in the p.m . arm, there were no differences related to the number of febrile neutropenic episodes or the duration of antibiotic administration . Also, there were no differences in the side effects observed in the a.m . and p.m . arms . CONCLUSIONS: The finding of 1.2 days' difference in the duration of Grade 3-4 neutropenia warrants further study of chronotherapy with HGFs.

CMAJ, 2000 May 2, 162(9), 1285 - 8
Otolaryngologists' perceptions of the indications for tympanostomy tube insertion in children; McIsaac WJ et al.; BACKGROUND: Bilateral myringotomy with insertion of tympanostomy tubes is the most common operation that children in Canada undergo . Area variations in surgical rates for this procedure have raised questions about indications used to decide about surgery . The objective of this study was to describe the factors that influence otolaryngologists to recommend tympanostomy tube insertion in children with otitis media and their level of agreement about indications for surgery . METHODS: A survey was sent to all 227 otolaryngologists in Ontario in the fall of 1996 . The influence of 17 clinical and social factors on recommendations to insert tympanostomy tubes were assessed . Case vignettes were used to determine the effect of multiple factors in decisions about the need for surgical management . RESULTS: Surveys were returned by 138 (68.3%) of the 202 eligible otolaryngologists . There was agreement (more than 90% of respondents) about 6 indications for surgery: persistent effusion, a lack of improvement after 3 months of antibiotic therapy, a history of persistent effusion for 3 or more months per episode of otitis media, more than 7 episodes of otitis media in 6 months, a bilateral conductive hearing loss of 20 dB or more and a persistently abnormal tympanic membrane . Some respondents were more likely to recommend tube insertion if there were parental concerns about hearing problems or the frequency or severity of episodes of otitis media . Otolaryngologists agreed about the role of tympanostomy tubes in 1 of 4 case vignettes but disagreed about whether adenoidectomy should also be performed in that instance . Most viewed tympanostomy tube insertion as beneficial, with few adverse effects . INTERPRETATION: There is a lack of consensus among practising otolaryngologists in Ontario as to which children with recurrent otitis media or persistent effusion should undergo bilateral myringotomy with tympanostomy tube insertion . These findings suggest the need to revisit clinical guidelines for this procedure.

Am J Bot, 2000 May, 87(5), 711 - 715
Pollen viability reduction as a potential cost of ant association for Acacia constricta (Fabaceae); Wagner D; Field studies investigating the impact of ants on the reproduction of plants bearing extrafloral nectaries have traditionally focused on seed production, a component of female fitness . The purpose of this study was to test whether ants can affect the pollen viability, a component of male fitness, when they visit flowers of the shrub Acacia constricta . Acacia constricta inflorescences hand-pollinated with flowers over which Formica perpilosa ants had crawled set significantly fewer seed pods than inflorescences hand-pollinated by control flowers that had no contact with ants . Many ant species secrete antibiotic substances onto the integument that render pollen inviable, and these secretions are probably the mechanism for reduced pollen viability in this study . The ratio of seed pods produced by self-pollinated inflorescences to those produced by cross-pollinated inflorescences was 0.16, indicating that A . constricta is largely self-incompatible . Because F . perpilosa workers forage primarily on the acacia tree under which they nest, they are unlikely to serve as efficient vectors of outcrossing . Previous work showed that A . constricta shrubs with F . perpilosa ants produce approximately twice as many seeds as similarly sized plants not so associated . The results indicate that association with F . perpilosa could cause a reproductive trade-off for A . constricta: benefits to female function may be accompanied by costs to male function . Selection to discourage ant visitation to flowers may have affected the pollination biology of this and other ant-associated plant species.

Ann Oncol, 2000 Mar, 11(3), 333 - 8
A phase I study of rhizoxin (NSC 332598) by 72-hour continuous intravenous infusion in patients with advanced solid tumors; Tolcher AW et al.; BACKGROUND: Rhizoxin (NSC 332598) is a novel macrolide antitumor antibiotic that inhibits microtubule assembly and also depolymerizes preformed microtubules . In preclinical evaluations, rhizoxin demonstrated broad antitumor activity in vitro and in vivo including both vincristine- and vindesine-resistant human lung cancers . Prolonged exposure schedules in xenograft models demonstrated optimal efficacy indicating schedule-dependent antitumor activity . The early phase I and II evaluations a five-minute bolus infusion schedule was studied, however, only modest anti-tumor activity was noted, possibly due to rapid systemic clearance . To overcome these limitations and to exploit the potential for schedule-dependent behavior of rhizoxin, the feasibility of administering rhizoxin as a 72-hour continuous intravenous (i.v.) infusion was evaluated . PATIENTS AND METHODS: Patients with advanced solid malignancies were entered into this phase I study, in which both the infusion duration and dose of rhizoxin were increased . The starting dose was 0.2 mg/m2 over 12 hours administered every 3 weeks . In each successive dose level, the dose and infusion duration were incrementally increased in a stepwise fashion . Once a 72-hour i.v . infusion duration was reached, rhizoxin dose-escalations alone continued until a maximum tolerated dose (MTD) was determined . RESULTS: Nineteen patients were entered into the study . Rhizoxin was administered at doses ranging from 0.2 mg/m2 i.v . over 12 hours to 2.4 mg/m2 i.v . over 72 hours every 3 weeks . The principal dose-limiting toxicities (DLT) were severe neutropenia and mucositis, and the incidence of DLT was unacceptably high at rhizoxin doses above 1.2 mg/m2, which was determined to be the MTD and dose recommended for phase II studies . At these dose levels, rhizoxin could not be detected in the plasma by a previously validated and sensitive high-performance liquid chromatography assay with a lower limit of detection of 1 ng/ml . No antitumor responses were observed . CONCLUSIONS: Rhizoxin can be safely administered using a 72-hour i.v . infusion schedule . The toxicity profile is similar to that observed previously using brief infusion schedules . Using this protracted i.v . infusion schedule the maximum tolerated dose is 1.2 mg/m2/72 hours.

Cancer Res, 2000 May 1, 60(9), 2512 - 9
A spontaneous murine melanoma lung metastasis comprised of host x tumor hybrids; Chakraborty AK et al.; Cells from a lung metastasis, arising from Cloudman S91 melanoma cells implanted s.c . in the tail of a BALB/c nu/nu mouse, were comprised chiefly of host x tumor hybrids . These lung metastasis cells showed: (a) 30-40% increased DNA content; (b) resistance to 10(-4) M hypoxanthine, 4 x 10(-7) M aminopterin, and 1.6 x 10(-5) M thymidine (HAT) + G418; and (c) the presence in genomic DNA of genes for both wt and albino tyrosinase, reflecting the DBA/2J (Cloudman S91) and BALB/c mouse genotypes, respectively . Individual clones of lung metastasis cells expressed enhanced pigmentation, motility, and responsiveness to MSH/IBMX, a behavior similar to that recently reported for artificially generated melanoma x macrophage fusion hybrids . These similarities suggested that the host fusion partner generating the lung metastasis hybrids might have been a macrophage, although formal proof for this was not possible . The results provide the first direct evidence that host x tumor hybridization could serve as an initiating mechanism for melanoma metastasis.

Indian J Cancer, 1999 Mar, 36(1), 32 - 7
Granulocyte macrophage--colony stimulating factor (GM-CSF) as adjunct in induction therapy of acute myeloid leukemia; Gangadharan VP et al.; Use of growth factors (G-CSF/GM-CSF) as adjunct in induction therapy of AML is controversial . Possible stimulation of leukemia cell clones has been the major cause of concern . We treated 50 cases of AML with GM-CSF as an adjunct during induction therapy . 35 patients (70%) achieved complete remission out of which 13 patients relapsed at a median relapse period of 15 months . Average duration of neutropenia was 10.5 days . (15 days in the control) Febrile episodes were fewer and antibiotic support was required for an average period of only 7.6 days (16.9 days in the control) . The benefits including the economic analysis of the role of GM-CSF in this setting is discussed.

Bone Marrow Transplant, 2000 Apr, 25(8), 853 - 9
Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group; Wolff SN et al.; Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids . Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections . To determine which prophylactic agent is better, we performed a prospective randomized study . Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p . o . or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl . Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics) . Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day) . Patients were randomized at each institution and stratified for the type of transplant . The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge . From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole . Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia . Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05) . Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection . Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively . Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05) . In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.

Gut, 2000 Jun, 46(6), 813 - 8
A randomised controlled trial evaluating the use of enteral nutritional supplements postoperatively in malnourished surgical patients; Beattie AH et al.; BACKGROUND: Patients who undergo surgery are at risk of malnutrition due to periods of starvation, the stress of surgery, and subsequent increase in metabolic rate . There are limited data on nutritional outcome of surgical patients . AIMS: To investigate changes in nutritional status and the influence of oral supplements on nutritional status, morbidity, and quality of life in postoperative surgical patients . METHODS: Entry was determined by the presence of malnutrition, as defined by a body mass index (BMI) < or =20 kg/m(2), anthropometric measurements < or =15th percentile on admission, or initiation of oral diet postoperatively and/or a weight loss of 5% or more during the operative period . We studied 101 patients: 52 were randomised to the treatment group (TG) and prescribed a 1.5 kcal/ml nutritional supplement; 49 patients were randomised to the control group (CG) and continued with routine nutritional management . Nutritional status was assessed by weight, anthropometry, and grip strength, with measurements taken at two weekly intervals for 10 weeks . Complications, namely wound infection, chest infection, and antibiotic use were documented . Quality of life (QOL) was assessed using the UK SF-36 questionnaire . RESULTS: Patients in the control group lost a maximum mean (SD) of 5.96 (4.21) kg in weight over a period of eight weeks while patients in group TG lost less weight overall (maximum mean (SD) 3.40 (0.89) kg (p<0.001) occurring at four weeks and progressively regained weight from week 4) . Anthropometry, grip strength, and QOL were similarly significantly different between groups (p<0.001) . Fewer patients in the treatment group (7/52) required antibiotic prescriptions compared with the control group (15/49) . CONCLUSIONS: Nutritional status declined for two months after discharge . Postoperative nutritional supplementation improved nutritional status, QOL, and morbidity in these patients.

Chest, 2000 May, 117(5), 1386 - 92
Acute chest syndrome in adults with sickle cell disease; Maitre B et al.; STUDY OBJECTIVES: Acute chest syndrome (ACS) is a frequent and potentially severe pulmonary illness in sickle cell disease (SCD) . The aim of the study was to report the clinical features and outcome of consecutive ACS episodes in adult patients in a French SCD center . All patients were treated according to an uniform therapeutic protocol applying transfusion only in the more severe clinical form of ACS . RESULTS: There were 107 consecutive episodes in 77 adult patients (mean age, 29 +/- 7 years; 78% hemoglobin {Hb} SS; 14% Hb SC; and 8% Hb Sbeta + thalassemia) over a 6-year period . Seventy-eight percent of our patients had an associated vaso-occlusive crisis that preceded the chest signs in half of the cases . Comparison between acute and baseline levels showed a statistically significant difference in Hb levels (drop of 1.6 to 2 . 25 g/dL depending on Hb genotype), WBC count (increase of 9.2 +/- 8 . 3 x 10(9)/L); platelet count (increase of 67 +/- 209 x 10(9)/L); and lactate dehydrogenase values (increase of 358 +/- 775 IU/L) in ACS patients . Hypercapnia was detected in 42% of patients without sign of narcotic abuse . We identified a high percentage of alveolar macrophages containing fat droplets in 31 of 43 (77%) patients who underwent BAL . Bacterial culture findings were almost always negative, but were performed after starting antibiotic therapy that was administered in 96 episodes . Transfusion was required in 50 of 107 ACS events (47%) . Five patients died, and all were transfused . CONCLUSIONS: These results confirm that fat embolism is probably a frequent mechanism of ACS in adult patients . However, fat embolism was not associated with a more severe clinical course, suggesting that bronchoscopy and BAL have little impact on the management of these patients . Restricting transfusion to the most severe ACS cases does not seem to increase the mortality rate.

Chest, 2000 May, 117(5), 1378 - 85
Process of care performance, patient characteristics, and outcomes in elderly patients hospitalized with community-acquired or nursing home-acquired pneumonia; Meehan TP et al.; STUDY OBJECTIVES: To compare process of care performance, patient characteristics, and outcomes in a contemporary cohort of elderly (> or = 65 years) patients hospitalized with community-acquired pneumonia (CAP) or with nursing home-acquired pneumonia (NHAP) . DESIGN: State-wide retrospective cohort study . SETTING: Thirty-four acute-care hospitals in Connecticut . PATIENTS: Elderly Medicare patients hospitalized in 1995-1996 with CAP (1,131) or with NHAP (528) . MEASUREMENTS: Antibiotic administration within 8 h of hospital arrival, blood culture collection within 24 h of hospital arrival, oxygenation assessment within 24 h of hospital arrival, demographic and clinical characteristics, in-hospital complications, mortality, and length of stay . RESULTS: Process of care performance rates for patients with CAP and NHAP were equivalent for antibiotic administration within 8 h of hospital arrival (76.8% vs 76.3%, respectively; p = 0.82), blood culture collection within 24 h of hospital arrival (78.1% vs 81.1%, respectively; p = 0.31), and oxygenation assessment within 24 h of hospital arrival (94.7% vs 95 . 3%, respectively; p = 0.70) . Patients with CAP were younger than those with NHAP (median age, 80 vs 84 years, respectively; p < 0 . 001), had less cerebrovascular disease (16.8% vs 34.7%, respectively; p < or = 0.001), and lower mortality risk scores at hospital presentation (median, 100 vs 137, respectively; p < or = 0 . 001) than patients with NHAP . The median length of stay was equivalent (7 days), but the in-hospital mortality rate was lower in patients with CAP than in patients with NHAP (8.0% vs 18.6%, respectively; p < or = 0.001) . CONCLUSION: Initial hospital processes of care are performed at the same rate in patients hospitalized with CAP or NHAP . However, patients with CAP are younger, are less acutely and chronically ill, and have lower in-hospital mortality rates than patients with NHAP.

Chest, 2000 May, 117(5), 1368 - 77
Implementation of admission decision support for community-acquired pneumonia; Dean NC et al.; STUDY OBJECTIVES: Considerable variation exists in hospital admission rates for patients with community-acquired pneumonia . Logic to determine need for admission has been proposed by several authors . We compared Intermountain Health Care pneumonia guideline recommendations for inpatient vs outpatient care with actual physician decision making and clinical outcomes before vs after implementation . A secondary objective was to determine whether the pneumonia severity index predicts need for admission in this population . DESIGN: Prospective study after implementation vs historic controls . SETTING: Four ambulatory, urgent-care facilities . PATIENTS: Four hundred sixty-three immunocompetent adults with radiographically confirmed community-acquired pneumonia . INTERVENTION: A pneumonia practice guideline including decision support logic was implemented for a 12-month period . MEASUREMENTS AND RESULTS: After implementation, physicians used the pneumonia guideline form in 90% of cases . The percentage of patients admitted within 30 days decreased from 13.6% to 6.4% (p = 0.01) . Only five patients before (2.5%) and three patients after (1.1%, p = 0.3) guideline implementation required subsequent hospital admission within 30 days after initial outpatient treatment . Only two deaths occurred in the study cohort, both outpatients before implementation . The positive predictive value was 14.4%, and the negative predictive value for admission was 98.8% after guideline implementation . Guideline recommendation for admission was more likely to be followed in patients with more risk factors and hypoxemia . CONCLUSIONS: Decreased admission rate was observed after implementation of admission decision support in combination with specific recommendations for outpatient antibiotic therapy . Favorable outpatient outcomes suggest that implementation of decision support was safe.

Arch Otolaryngol Head Neck Surg, 2000 May, 126(5), 581 - 3
Nasally inhaled dornase alfa in the postoperative management of chronic sinusitis due to cystic fibrosis; Raynor EM et al.; OBJECTIVE: To determine the benefit of nasally inhaled dornase alfa in cystic fibrosis (CF) sinusitis . DESIGN: Retrospective chart review comparing postsurgical course, radiographic studies, and pulmonary function test results in patients who were treated with nasally inhaled dornase alfa with those in patients who were not treated with dornase alfa . PATIENTS: Twenty consecutive patients with CF who underwent functional endoscopic sinus surgery from 1993 to 1997 were included in the study . Treatment with nasally inhaled dornase alfa was initiated in 5 of the 20 patients after they underwent functional endoscopic sinus surgery . SETTING: Tertiary care academic center . RESULTS: The dornase alfa-treated patients had less mucosal edema and no polyps at serial endoscopy over 3 years compared with the non-dornase alfa-treated patients . The patients who received nasally inhaled dornase alfa also underwent fewer revision functional endoscopic sinus surgical procedures (1.6 vs 3.2), even though there was essentially no change in pulmonary function test results in these patients . CONCLUSIONS: Sinusitis continues to be a major cause of morbidity in patients with CF . Symptomatic patients frequently require multiple drug regimens, including long-term systemic antibiotic therapy, topical and systemic steroid therapy, and antibiotic nasal irrigations . This preliminary study indicates the potential impact of nasally inhaled dornase alfa in controlling postoperative symptoms in CF sinusitis.

Wiad Lek, 2000, 53(1-2), 43 - 8
{Erythema multiforme in children versus Stevens-Johnson syndrome}; Czubkowska I et al.; 30 children treated between 1984-98 for erythema multiforme (versus SJS) in Department of Allergology at the Children's Memorial Health Institute in Warsaw . 25 children suffered from erythema multiforme minor and 5 suffered from Stevens-Johnson Syndrome . Before symptoms of the illness 13 children had been treated with antibiotics and 27 children demonstrated different symptoms of infections, mostly viral . Drug therapies and viral or bacterial infections probably induce symptoms in patients susceptible to erythema multiforme or severe versus Stevens-Johnson Syndrome . CONCLUSION: 1 . Erythema multiforme (EM) rather seldom occurs in children . The Most commonly its course is benign (EM minor) . In another type of erythema multiforme--Stevens-Johnson Syndrome (EM major), in which mucous membranes are involved, the course of disease and the prognosis are always severe . 2 . Both viral and bacterial infections as well as administered drugs play the important role in the etiopathogenesis of erythema multiforme . 3 . The treatment of erythema multiforme in children is symptomatic (general and local) . In Stevens-Johnson Syndrome early administration of glicocorticoids is recommended . Children with bacterial infection (contagion, contamination) should be treated with antibiotic.

Ann Plast Surg, 2000 May, 44(5), 502 - 7
Oral sedation allows for comfort and amnesia during office surgery; Gatti JE; Surgical procedures commonly associated with parenteral sedation or general anesthesia were completed in an office operating room with local anesthesia and oral medication . Diazepam and alprazolam were used in combination to produce a relaxed state, allowing local anesthesia to be instilled . Surgery was completed successfully in all patients, and no untoward effects were seen in the patients . Amnesia was associated with the drug combination, and a protective action of the long-lived drugs against lidocaine toxicity is theorized.

Acta Otorrinolaringol Esp, 2000 Mar, 51(2), 183 - 7
{Diffuse deep cervical infection . Report of three cases}; Naya Galvez MJ et al.; Deep cervical infections still appear despite antibiotic use . Necrotizing fasciitis of the head and neck is a rare but serious infection caused by mixed, predominantly anaerobic bacterial flora . The natural course of the disease is spreading necrosis of the soft tissues of the neck and septicemia . Three recent cases of cervical necrotizing soft-tissue infection are presented . The importance of early and aggressive surgical treatment complemented by parenteral antibiotics with an aerobic-anaerobic spectrum is emphasized.

Immunol Res, 2000, 21(1), 1 - 6
Peroral immunotherapy with yolk antibodies for the prevention and treatment of enteric infections; Carlander D et al.; Oral administration of specific antibodies is an attractive approach to establish protective immunity against gastrointestinal pathogens in humans and animals . The increasing number of antibiotic-resistant bacteria emphasize the need to find alternatives to antibiotics . Immunotherapy can also be used against pathogens that are difficult to treat with traditional antibiotics . Laying hens are very good producers of specific antibodies . After immunization, the specific antibodies are transported to the egg yolk from which the antibodies then can be purified . A laying hen produces more than 20 g of yolk antibodies (IgY) per year . These antibodies also have biochemical properties that make them attractive for peroral immunotherapy: They neither activate mammalian complement nor interact with mammalian Fc receptors that could mediate inflammatory response in the gastrointestinal tract . Eggs are also normal dietary components and thus there is practically no risk of toxic side effects of IgY . Yolk antibodies have been shown in several studies to prevent bacterial and viral infections.

Clin Cardiol, 2000 May, 23(5), 327 - 30
Seropositivity against Chlamydia pneumoniae in patients with coronary atherosclerosis; Romeo F et al.; BACKGROUND: Results of therapy in patients with unstable coronary syndromes with antibiotics directed against Chlamydia pneumoniae have been variable, perhaps due to the heterogeneity of patients in these trials . HYPOTHESIS: The aim of the present study was to correlate the severity of coronary artery disease (CAD) with seropositivity against C . pneumoniae prospectively . METHODS: We measured the frequency of seropositivity (IgG levels > or = 1/64 and IgA levels > or = 1/16 against Chlamydia pneumoniae) in 110 patients with CAD and in 49 controls . RESULTS: As expected, traditional CAD risk factors were seen more often in patients with CAD than in controls . Mean values of total cholesterol (184 +/- 52 and 166 +/- 44 mg/dl, respectively) and triglyceride (143 +/- 60 and 112 +/- 63 mg/dl, respectively) in serum were significantly higher in patients with CAD than in controls (both p < 0.04) . There were no significant differences between the two groups in serum high-density lipoprotein cholesterol (34 +/- 13 and 32 +/- 14 mg/dl, respectively) and lipoprotein (a) (Lp(a):241 +/- 247 and 223 +/- 263 mg/l, respectively) levels . The rate of IgG seropositivity was 52% (28/54) in patients with stable CAD, 41% (23/56) in patients with unstable CAD, and 35% in controls (p = NS) . The rate of IgA seropositivity was 25% (14/54) in patients with stable CAD, 12% (6/49) in patients with unstable angina, and 12% (6/49) in controls (all p = NS) . CONCLUSIONS: Only a small percentage of patients with CAD demonstrate seropositivity against Chlamydia pneumoniae . Antibiotic therapy in these selected patients, but not in the remaining patients, may be considered rational . These considerations may underlie the failure to see consistent benefits of antibiotic therapy in patients with CAD.

Med Dosw Mikrobiol, 1999, 51(3-4), 213 - 9
{Typing of methicillin resistant strains of S . haemolyticus isolated from patients and from the hospital ward environment}; Chylak J et al.; Biotyping, antibiograms and fingerprinting were used to determine the relation of 16 methicillin-resistant S . haemolyticus isolated from drains in patients who underwent intraabdominal surgery to 9 methicillin-resistant strains of S . haemolyticus isolated at the same time from hospital environment . The comparison of biochemical properties of the examined strains showed a large variety of biochemical profiles as well as antibiotic patterns of susceptibility . The differences in sensitivity to the antibiotics used were not distinct . Biotyping and antibiograms did not permit determination of the relation of the investigated strains . Only the results of fingerprinting allowed for the division of the 25 examined strains into three genotypes demonstrating three main patterns of PCR products . 16 strains of 25 showed the same pattern of PCR products . This results suggests the presence of a source of infection on the clinical ward . A nurse may have been the source of infection because the same genotype of S . haemolyticus was isolated from her nasal anterior as from the majority of patients.

Eur J Endocrinol, 2000 May, 142(5), 500 - 5
Calcium stimulates parathyroid hormone-related protein production in Leydig tumor cells through a putative cation-sensing mechanism; Buchs N et al.; The production of parathyroid hormone-related protein (PTHrP) is regulated by a variety of hormones and growth factors . Previous research has shown that several PTHrP-producing cells are influenced by extracellular calcium (Ca(2+)(o)) concentration, with elevated levels increasing PTH-like activity released by cultured H500 rat Leydig tumor cells through a post-transcriptional mechanism . We have investigated the hypothesis that calcium stimulates PTHrP production in H500 cells by interacting with a cell membrane-associated cation-sensing receptor . Besides increased Ca(2+)(o) concentration, magnesium and the polycationic antibiotic neomycin also increased PTHrP production in a concentration-dependent manner . In the presence of the calcium ionophore, ionomycin, which markedly elevated cytosolic free calcium, the stimulation by Ca(2+)(o) of PTHrP could still be detected . These results indicate that increasing Ca(2+)(o) stimulates PTHrP production, possibly through a putative cell membrane-associated calcium-sensing mechanism . RT-PCR revealed the presence of a very small amount of calcium-sensing receptor coding mRNA.

Eur J Radiol, 2000 Apr, 34(1), 57 - 9
Coil embolization of a false aneurysm with aorto-cutaneous fistula after prosthetic graft replacement of the ascending aorta; Miguel B et al.; AIM: To report palliative embolization of a false aneurysm over the distal suture line of an ascending aorta graft replacement . MATERIAL AND METHOD: A 78-year-old male patient was admitted for increasing bleeding of a chronic Manubrium ulceration, 20 months after coronary artery bypass complicated by perioperative ascending aorta dissection requiring prosthetic graft replacement . One month later, he underwent epiploplasty for a mediastinitis followed by long-term antibiotic therapy . Five months later, he presented with a Manubrium ulceration of the sternotomy . Spiral computerized tomography (CT) and aortography revealed a 20 mm anterior peri-prosthetic false aneurysm with a wide neck . Advanced age, active mediastinitis and patient's objection led us to perform percutaneous occlusion according to the Moret remodeling technique while protecting the coils release with balloon catheter inflation . RESULTS: No post-operative complication was observed and at 1-year follow-up the patient was doing well with no recurrent bleeding . Magnetic resonance imaging (MRI) and spiral CT controls confirmed coils stability without any internal flow . CONCLUSION: Percutaneous coils embolization of a large false aneurysm in the ascending aorta can be a palliative treatment in a surgically unsuited patient.

FEMS Microbiol Lett, 2000 May 15, 186(2), 287 - 91
Stable transformation of trypanosomatids through targeted chromosomal integration of the selectable marker gene encoding blasticidin S deaminase; Brooks DR et al.; The susceptibilities of the protozoan parasites Leishmania mexicana and Trypanosoma brucei to the nucleoside antibiotic blasticidin S were assessed . A concentration of 10 microg ml(-1) was sufficient to cause cell death within 72 h of L . mexicana promastigotes and bloodstream forms of T . brucei in vitro . The gene encoding blasticidin S deaminase (BSD) was therefore incorporated into cassettes for targeting to the cysteine proteinase C locus of L . mexicana (CPC::BSD) and the tubulin locus of T . brucei (tub::RAD51-BSR) . Following transfection of mutant parasites that contained other well-established selectable marker genes (HYG, NEO, BLE, PAC and SAT), clones resistant to 10 microg ml(-1) blasticidin S were shown by PCR and Southern blotting to have integrated the cassettes by homologous recombination . The results confirm that BSD can be used as a selectable marker gene for targeted chromosomal integration during genetic manipulations of trypanosomatids.

FEMS Microbiol Lett, 2000 May 15, 186(2), 203 - 8
Development and application of molecular tools in the study of IncN-related plasmids from lakewater sediments; Osborn AM et al.; Homology to IncN, P, Q and W inc regions was investigated amongst 114 Hg(2+)-resistant or antibiotic-resistant bacteria isolated from lakewater sediments . No hybridisation signals were found with Inc P, Q and W probes, and only one plasmid, pLV1402, hybridised to the IncN probe . PCR primers designed to conserved regions in the replicon of the IncN plasmid pCU1 and the related beta replicon from pGSH500 were used to amplify a 978-bp fragment from pLV1402, with sequence analysis showing a close relationship (99.2% identity) between their replication genes . A 387-bp region from the pLV1402 rep gene was used to re-screen the isolates and identified another related plasmid, pLV1403 . A 3.7-kb probe containing the alpha replicon from pGSH500 hybridised to both pLV1402 and pLV1403, suggesting that both are multi-replicon plasmids . The PCR primers and probes described will be useful in future studies of plasmid diversity.

J Biol Chem, 2000 Jul 14, 275(28), 21754 - 60
Cloning, overexpression, and purification of novobiocic acid synthetase from Streptomyces spheroides NCIMB 11891; Steffensky M et al.; Novobiocic acid synthetase, a key enzyme in the biosynthesis of the antibiotic novobiocin, was cloned from the novobiocin producer Streptomyces spheroides NCIMB 11891 . The enzyme is encoded by the gene novL, which codes for a protein of 527 amino acids with a calculated mass of 56,885 Da . The protein was overexpressed as a His(6) fusion protein in Escherichia coli and purified to apparent homogeneity by affinity chromatography and gel chromatography . The purified enzyme catalyzed the formation of an amide bond between 3-dimethylallyl-4-hydroxybenzoic acid (ring A of novobiocin) and 3-amino-4,7-dihydroxy-8-methyl coumarin (ring B of novobiocin) in an ATP-dependent reaction . NovL shows homology to the superfamily of adenylate-forming enzymes, and indeed the formation of an acyl adenylate from ring A and ATP was demonstrated by an ATP-PP(i) exchange assay . The purified enzyme exhibited both activation and transferase activity, i.e . it catalyzed both the activation of ring A as acyl adenylate and the subsequent transfer of the acyl group to the amino group of ring B . It is active as a monomer as determined by gel filtration chromatography . The reaction was specific for ATP as nucleotide triphosphate and dependent on the presence of Mg(2+) or Mn(2+) . Apparent K(m) values for ring A and ring B were determined as 19 and 131 micrometer respectively . Of several analogues of ring A, only 3-geranyl-4-hydroxybenzoate and to a lesser extent 3-methyl-4-aminobenzoate were accepted as substrates.

J Oral Maxillofac Surg, 2000 May, 58(5), 531 - 7
Dental extraction wound management: medicating postextraction sockets; Vezeau PJ; The rather impressive percentage of extraction sites undergoing clot loss and deranged healing results in significant morbidity for the patient and frequent visits to the surgeon to effect relief of discomfort, most often by the use of anodyne dressings . The amount of work lost by patients needing such palliative treatment, and loss of productive time for the surgeon, translate into an unknown, but potentially large, economic loss to society . This would mandate that economical methods of ensuring normal extraction socket healing with minimal morbidity be developed . The most useful socket medicaments to prevent socket healing derangements would include broad-spectrum antibiotics, specifically clindamycin and tetracycline . Not discussed in this article, but possibly germane to the subject of clot stabilization and healing, is consideration of resorbable substances such as gelatin sponge, polylactic acid, and methylcellulose as clot-stabilizing socket implants . The record of such substances in preventing AO is mixed, but the combinations of these inexpensive materials with topical socket medicaments may yield a decreased tendency for clot lysis and greater mechanical strength to the bulk blood clot, as has been demonstrated with difficult mandibular third molar impactions in one study involving polylactic acid, tetracycline, and hydrocortisone.

Cancer Treat Res, 1999, 101, 311 - 30
Engineering hematopoietic grafts using elutriation and positive cell selection to reduce GVHD; Noga SJ; A systematic approach to hematopoietic graft manipulation has minimized several of the variables inherent to allogeneic BMT . Through this approach, we have been able to significantly impact on morbidity and quality of life following allogeneic transplantation . Acute and chronic GVHD, blood product and antibiotic usage, in patient hospitalization, acuity, costs and survival (especially in patients older than 40) have been improved . The HLA barrier still presents a formidable obstacle to achieving a more widespread use of this therapy . The complications encountered in HLA matched/TCD grafts occur with even greater magnitude in the HLA-mismatched or unrelated donor setting . Several centers are now engaged in studies using TCD grafts that are augmented with high doses of CD34+ cells to ensure engraftment while reducing the incidence of GVHD (50-53) . Mobilized allogeneic PBSC appear to be an excellent source of stem cells for BMT (5,6) . The earlier reports showed decreased rates of GVHD, despite having T cell burdens 10 times higher than those found in unmanipulated bone marrow . However, several of these centers now report an unacceptably high incidence of chronic GVHD (along with its attendant morbidity) following allogeneic PBSC transplantation (54-55) . Initial results of TCD in these PBSC grafts using CD34+ selection are disappointing in that recipients developed unexpectedly high incidences of both acute and chronic GVHD (56) . No doubt, significant differences exist between marrow and PBSC ancillary cell populations . For example, two laboratories now report the presence of natural suppressor cells in these allogeneic PBSC products in both mice (57) and humans (58) . Thus, the same, step-wise approach would be expected to improve graft performance when using PBSC, cord blood, fetal tissue, xenografts or genetically engineered products as a stem cell source . Indeed, there are new reports of improved clinical outcome (especially in the incidence of GVHD) in the PMRD setting using both CD34+ selected (59) and sequential CD34+/CD2+ selected (60) PBSC grafts . It is hoped that future graft engineering approaches will be as successful as previous studies and will extend this form of therapy to an even larger patient population.

Forsch Komplementarmed Klass Naturheilkd, 2000 Feb, 7(1), 17 - 20
Tea tree oil: a systematic review of randomized clinical trials; Ernst E et al.; AIM: Tea tree oil (TTO) is immensely popular for various topical applications . In vitro studies have repeatedly demonstrated that it has antibiotic activity . This article is an attempt to systematically review the evidence from randomised clinical trials for or against effectiveness of external TTO in dermatological conditions . METHODS: Six electronic databases were searched . Methodological quality was assessed by Jadad score . Data were extracted and validated in a standardised fashion by two independent reviewers . RESULTS: Only 4 trials were located . They suggest that TTO may be effective as a treatment of acne and fungal infections . The evidence is promising but by no means compelling . The adverse effects of TTO are usually mild and transient . They mainly consist of allergic reactions . CONCLUSIONS: It is concluded that, so far, there is no compelling evidence to show that TTO is efficacious in any dermatological condition . However, in view of promising findings, TTO deserves to be investigated more closely.

Jpn J Clin Oncol, 2000 Mar, 30(3), 153 - 8
A successful and simplified filgrastim primed single apheresis method without large volume apheresis for peripheral blood stem cell collection; Arpaci F et al.; BACKGROUND: There is a tendency to use only one apheresis collection to reduce the morbidity and the cost of peripheral blood stem cell collection . We studied whether rapid and complete engraftment could be achieved by single apheresis by using only Filgrastim without large volume apheresis in previously treated patients . METHODS: Engraftment of single apheresis in 25 patients was compared with those of multiple apheresis in 26 patients; 52% of patients in the single apheresis group and 62% of patients in the multiple apheresis group were heavily pretreated . All patients received 10-15 microg/kg/day of Filgrastim starting on day 14 after 3-4 cycles of induction chemotherapy . Apheresis was performed using Cobe Spectra on day 4, 5 or 6 in the single apheresis group and every other day in the multiple apheresis group after day 3 . RESULTS: The median collection volume was 250 ml (250-300 ml) in the single apheresis group and 750 ml (200-1500 ml) in the multiple apheresis group . The median CD34(+) cell number was not significantly different in the two groups (11.79 vs . 9.38x10(6)/kg) . The median times to achieve leukocytes > or =1x10(9)/l and platelets > or =50x10(9)/l counts were 10 days (8-21 days) and 15 days (9-38 days) in the single apheresis group vs 11 days (8-23 days) and 20 days (10-32 days) in the multiple apheresis group, respectively (p<0.05) . Antibiotic use was less in the single apheresis group than the multiple apheresis group (9 vs . 12 days, p<0.05) . CONCLUSION: Adequate numbers of peripheral stem cells were harvested by G-CSF in a single apheresis without large volume apheresis even in heavily pretreated patients . Rapid and complete engraftment occurred in all patients and it was faster in single than multiple apheresis.

J Biomol Struct Dyn, 2000 Apr, 17(5), 887 - 901
NMR investigation of the complexation of daunomycin with deoxytetranucleotides of different base sequence in aqueous solution; Davies DB et al.; 500 MHz NMR spectroscopy has been used to investigate the complexation of the anthracycline antibiotic daunomycin (DAU) with self-complementary deoxytetranucleotides, 5'-d(CGCG), 5'-d(GCGC), 5'-d(TGCA), 5'-d(ACGT) and 5'-d(AGCT), of different base sequence in aqueous salt solution . 2D homonuclear 1H NMR spectroscopy (TOCSY and NOESY) and heteronuclear 1H - 31P NMR spectroscopy (HMBC) have been used for complete assignment of the non-exchangeable protons and the phosphorus resonance signals, respectively, and for a qualitative determination of the preferred binding sites of the drug . Analysis shows that DAU intercalates preferentially into the terminal sites of each of the tetranucleotides and that the aminosugar of the antibiotic is situated in the minor groove of the tetramer duplex, partly eclipsing the third base pair . A quantitative determination of the complexation of DAU with the deoxytetranucleotides has been made using the experimental concentration and temperature dependences of the drug proton chemical shifts; these have been analysed in terms of the equilibrium reaction constants, limiting proton chemical shifts and thermodynamical parameters (enthalpies deltaH, entropies deltaS) of different drug-DNA complexes (1:1, 1:2, 2:1, 2:2) in aqueous solution . It is found that DAU interacts with sites containing three adjacent base pairs but does not show any significant sequence specificity of binding with either single or double-stranded tetranucleotides, in contrast with other intercalating drugs such as proflavine, ethidium bromide and actinomycin D . The most favourable structures of the 1:2 complexes have been derived from the induced limiting proton chemical shifts of the drug in the intercalated complexes with the tetranucleotide duplex, in conjunction with 2D NOE data . It has been found that the conformational parameters of the double helix and the orientation of the DAU chromophore in the intercalated complexes depend on base sequence at the binding site of the tetramer duplexes in aqueous solution.

Dakar Med, 1999, 44(1), 88 - 93
{Ocular burns at the ophthalmologic clinic of the Central University Hospital of Le Dantec apropos of 28 patients}; Seye-Ndiaye C et al.; Chemical and thermal ocular burns are emergencies in ophthalmology because of the blindness sequels they occur . All patients were included in a prospective study form during 18 months . 28 patients were admitted for ocular burns, representing an incidence of 5.21% . 13 of them had occupational ocular burns, 11 homely ocular burns and 4 public way injuries . 18 had chemical burns and 10 thermal burns, with a total of 44 eyes . The clinical observations was dominated by conjunctival lesions: 90.9%, corneal lesions: 79.5%, and plapebral lesions: 43.2% . 11 of them who had chemical burns, the ocular irrigation was made immediately after the accident, and all of them had antibiotic and cicatrizing treatment . The seriousness of ocular burns, the youngness of patients must instigate the authorities to improve the working conditions in the factories, and a better information in manipulation of dangerous chemical product.

J Neurosci Res, 2000 May 15, 60(4), 437 - 49
Redistribution of cholesterol in oligodendrocyte membrane sheets after activation of distinct signal transduction pathways; Lintner RN et al.; Cultured oligodendrocytes produce extensive membrane sheets that contain an internal lacy network of vein-like structures composed of microtubules, actin filaments, and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) . These cytoplasmic vein-like structures surround domains of myelin basic protein (MBP) . Using the antibiotic filipin, that binds to cholesterol, the relationship between plasma membrane cholesterol and cytoskeleton in membrane sheets was examined . Our results show that cholesterol was relatively uniformly distributed within the plasma membranes of prefixed control oligodendrocyte membrane sheets . When live cultures were extracted with Triton X-100, however, a subpopulation of cholesterol molecules remained colocalized with cytoskeleton in the membrane sheets . Activation of two well-characterized signaling pathways that differentially affect microtubule and actin filament stability in membrane sheets resulted in an apparent massive lateral movement of cholesterol molecules away from membrane regions overlying internal MBP domains to membrane tracts directly overlying cytoplasmic cytoskeletal veins . Depolymerization of microtubules by colchicine resulted in redistribution of cholesterol directly over actin filaments, whereas depolymerization of actin filaments by cytochalasin B resulted in redistribution of cholesterol directly over CNPase/microtubular veins . These data suggest that cholesterol forms an association with cytoskeletal components or proteins associated with cytoskeleton . These data also suggest that cholesterol, via interactions with cytoskeleton, plays a role in signaling pathways in oligodendrocyte membrane sheets .

J Am Acad Orthop Surg, 1996 Nov, 4(6), 297 - 304
Human Immunodeficiency Virus Infection: Complications and Outcome of Orthopaedic Surgery; Luck JV Jr et al.; Orthopaedic surgeons practicing in areas with a high prevalence of human immunodeficiency virus (HIV) infection may expect that up to 7% of their patients who undergo emergent procedures and 1% to 3% of those who undergo elective surgery will be HIV-positive . Although basic science studies have demonstrated impairment of defenses to routine orthopaedic pathogens as well as to opportunistic organisms, clinical studies have shown that this impairment has not resulted in an increased incidence of postoperative infections or failure of wound healing in the asymptomatic HIV-positive patient . Even for the symptomatic patient, current medical management appears adequate to reduce the risk of early postoperative infection . The HIV-positive patient with a pros-thetic implant may be at increased risk for late hematogenous implant infection as host defenses diminish . Regular medical attention, prophylactic antibiotic therapy before dental work and invasive procedures, and early evaluation and treatment of possible infections are especially important in this setting . Decisions regarding elective surgery should be made on a risk-benefit basis . Because the risk of surgical complications increases with progression of the dis-ease, guidelines for elective surgery should include an assessment of the HIV-positive patient's immune status, including the CD4 lymphocyte count, history of opportunistic infection, serum albumin level, the presence of skin anergy, and the state of nutrition and general health.

Cochrane Database Syst Rev . 2000;(2):CD002033.
Nystatin prophylaxis and treatment in severely immunodepressed patients; Gotzsche PC et al.; BACKGROUND: Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal . OBJECTIVES: To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency . SEARCH STRATEGY: MEDLINE and The Cochrane Library using a comprehensive search strategy . Contacted industry and scanned reference lists . SELECTION CRITERIA: Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B . DATA COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently . The outcomes were weighted by the inverse variance . A random effects model was used unless p>0.10 for the test of heterogeneity . MAIN RESULTS: We included 10 trials (1, 122 patients) . The drugs were given prophylactically in eight trials and as treatment in two . Six trials were in acute leukaemia, one mainly in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients . Nystatin had been compared with placebo in three trials and with fluconazole in seven; the dose varied from 1.5 MIE to 72 MIE daily . The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0 . 65 to 1.13) . There was no difference between fluconazole and nystatin on mortality (relative risk 0.87, 0.52 to 1.44) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.42, 0.16 to 1.12) and colonisation (relative risk 0.50, 0.36 to 0.71) . The results were very similar if the three studies which were not performed in cancer patients were excluded . REVIEWER'S CONCLUSIONS: Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.

Cochrane Database Syst Rev . 2000;(2):CD001897.
Postoperative procedures for improving fertility following pelvic reproductive surgery; Johnson NP et al.; BACKGROUND: Hydrotubation with oil-soluble contrast media for unexplained infertility and adhesiolysis for infertility due to peritubal adhesions are primary procedures of recognised benefit . It is less clear whether postoperative procedures such as hydrotubation or second-look laparoscopy with adhesiolysis are beneficial following pelvic reproductive surgery . OBJECTIVES: To assess the value of postoperative hydrotubation and second-look laparoscopy with adhesiolysis following female pelvic reproductive surgery . SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of all relevant randomised controlled trials . SELECTION CRITERIA: All trials where a postoperative procedure following pelvic reproductive surgery was compared with a control group generated by randomisation were considered for inclusion in the review . DATA COLLECTION AND ANALYSIS: Five randomised controlled trials were identified and included in this review, after an attempt to obtain further information from authors of all five trials . All trials were assessed for quality criteria . The studied outcomes were pregnancy, live birth, ectopic pregnancy and miscarriage rates and the rates of tubal patency and procedure-related complications . Reviewers extracted the data independently and odds ratios for these dichotomous outcomes were estimated from the data . MAIN RESULTS: The odds of pregnancy, live birth, ectopic pregnancy and miscarriage were not significantly different with postoperative hydrotubation versus no hydrotubation nor with second-look laparoscopy and adhesiolysis versus no second-look laparoscopy . Whether hydrotubation was early or late and whether hydrotubation fluid contained steroid or not had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage . The odds of pregnancy and live birth were significantly increased and infective complications significantly decreased by hydrotubation with fluid containing antibiotic versus hydrotubation with fluid containing no antibiotic, in late hydrotubation following tubal stent removal six weeks after tubal surgery . The odds of at least one patent fallopian tube were significantly increased with late hydrotubation following tubal stent removal versus early hydrotubation in women who had no tubal stenting, but this intervention had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage . REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the routine practice of hydrotubation or second-look laparoscopy following female pelvic reproductive surgery . The studies on which this conclusion is based were either poor quality or underpowered . These interventions should be performed in the context of a good quality, adequately powered randomised controlled trial . Postoperative hydrotubation with fluid containing antibiotic following tubal surgery may offer benefit over hydrotubation fluid without antibiotic . A randomised controlled trial of postoperative hydrotubation with antibiotic-containing fluid versus no hydrotubation for improving fertility following tubal surgery is justified.

Cochrane Database Syst Rev . 2000;(2):CD001505.
Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis; Dezateux C et al.; BACKGROUND: Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people . It has been hypothesised that lung damage results from inflammation and that prolonged use of non-steroidal anti-inflammatory drugs may prevent progressive pulmonary deterioration and respiratory morbidity in cystic fibrosis . It is thus important to establish the current level of evidence about the potential benefits and harms of treatment with non-steroidal anti-inflammatory drugs . OBJECTIVES: The aim of this systematic review is to assess the effectiveness of treatment with non-steroidal anti-inflammatory agents in cystic fibrosis . SEARCH STRATEGY: Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings . Pharmaceutical companies manufacturing non-steroidal anti-inflammatory drugs were also contacted to identify any trials of non-steroidal anti-inflammatory drugs in cystic fibrosis . Date of the most recent search of the Group's specialised register: November 1999 . SELECTION CRITERIA: All randomised or pseudorandomised controlled trials, published and unpublished, comparing non-steroidal anti-inflammatory drugs, administered orally at any dose for a period of at least two months, to placebo in patients with cystic fibrosis . DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: objective measures of lung function, nutritional status, radiological assessment of pulmonary involvement, use of intravenous antibiotics, hospital admissions, survival, frequency of major and minor adverse effects and compliance with therapy . MAIN RESULTS: Three trials involving 145 patients aged from five to 39 years with a maximum follow up of four years met the inclusion criteria . Methodological quality was deemed good or adequate in two . Two trials, both reporting effectiveness of ibuprofen in subjects with mild lung disease, were from the same centre and included some patients in common, while the third assessed piroxicam in subjects with more severe impairment of respiratory function . Variation in outcomes reported and their summary measures precluded calculation of pooled treatment estimates . Only one trial reported within-subject changes in pulmonary function and the findings of this trial suggested that there was a greater absolute annual decline in percentage predicted forced expiratory volume in one second among controls than among those treated with ibuprofen . In a post-hoc sub-group analysis this effect was confined to children aged five to 13 years . In addition, in this one trial long term use of high dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status . No major adverse effects were reported but the power of the trials to identify clinically important differences in the incidence of adverse effects was low . REVIEWER'S CONCLUSIONS: While there is preliminary evidence to suggest that non-steroidal anti-inflammatory drugs may prevent pulmonary deterioration in subjects with mild lung disease due to cystic fibrosis, currently their routine use cannot be recommended . Further trials are required to confirm that their use prevents pulmonary deterioration and is associated with improved nutritional status . Such trials should also address the age group of subjects most likely to benefit, the prevalence of important adverse effects and the optimal dosage schedule as well as any reduction in concomitant therapy . Multi-centre trials will add to the validity of findings by enhancing their generalisability . The question of whether anti-inflammatory treatment prevents lung damage in pre-symptomatic

Cochrane Database Syst Rev . 2000;(2):CD000473.
Interventions for chronic suppurative otitis media; Acuin J et al.; BACKGROUND: Chronic suppurative otitis media (CSOM) is a serious bacterial infection of the middle ear that can follow untreated acute otitis media . OBJECTIVES: To assess the effects of different treatments for CSOM . SEARCH STRATEGY: We searched Medline from 1966 to 1996 and a bibliographic collection of the Hearing Impairment Research Group in Liverpool, UK . We handsearched two otolaryngology journals and contacted members of an international hearing network . SELECTION CRITERIA: Randomized trials of any method of management for patients with eardrum perforation and persistent otorrhea . DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed eligibility and trial quality . One reviewer extracted data . We contacted investigators for clarifications . MAIN RESULTS: Twenty-four trials involving 1660 people were included . Clinical definitions and severity of CSOM varied, methodological quality was generally low and follow-up was short . Treatment with antibiotics or antiseptics accompanied by aural toilet was more effective in resolving otorrhea than no treatment (two trials, odds ratio 0.37, 95% confidence interval 0.24 to 0 . 57) or aural toilet alone (six trials, odds ratio 0.31, 95% confidence interval 0.23 to 0.43) . Topical treatment with antibiotics or antiseptics was more effective than systemic antibiotics (six trials, odds ratio 0.46, 95% confidence interval 0.30 to 0.69) . Combining topical and systemic antibiotics was not more effective than topical antibiotics . Topical quinolones were more effective than non-quinolones (five trials, odds ratio 0.26, 95% confidence interval 0.16 to 0.41) . No difference in the effectiveness of topical antibiotics and topical antiseptics was found (three studies, odds ratio 1.34, 95% confidence interval 0.64 to 2.81) . Some topical antibiotic combinations may be more effective than others in resolving otorrhea . Rates of adverse drug events were low and equal between groups . REVIEWER'S CONCLUSIONS: Treatment of CSOM with aural toilet and topical antibiotics, particularly quinolones, is effective in resolving otorrhea and eradicating bacteria from the middle ear . Longterm outcomes such as preventing recurrences, closure of tympanic perforation and hearing improvement need to be further evaluated.

Cochrane Database Syst Rev . 2000;(2):CD000336.
Expanding the roles of outpatient pharmacists: effects on health services utilisation, costs, and patient outcomes; Bero LA et al.; BACKGROUND: In recent years pharmacists' roles have expanded from simply packaging and dispensing medications to working with other health care professionals and the public . OBJECTIVES: To assess the effects of expanding outpatient pharmacists' roles on health services utilisation, the costs of health services, and patient outcomes . SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, MEDLINE, EMBASE, Pharmline, International Pharmaceutical Abstracts and reference lists of articles up to December 1995 . We also searched the published abstracts of three meetings and hand searched five journals and two bibliographies . SELECTION CRITERIA: Randomised trials, controlled clinical trials, controlled before-and-after studies and interrupted time series analyses of interventions comparing 1 . Pharmacist services targeted at patients versus services delivered by other health professionals; 2 . Pharmacist services targeted at patients versus no intervention; 3 . Pharmacist services targeted at health professionals versus services delivered by other health professionals; and 4 . Pharmacist services targeted at health professionals versus no intervention . DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality . MAIN RESULTS: Fourteen studies were included involving more than 1991 patients . In the one study identified for comparison 1 the relative changes in professional outcome measures ranged from a 24% increase in clinic visits to a 16% decrease in hospital admissions . Relative differences in patient outcome measures were not statistically significant . Seven studies were identified for comparison 2 . Four measured process of care and demonstrated decreases in health services utilisation from -67% for hospital admissions to -564% for total ambulatory care visits, as well as decreases in the numbers and costs of drugs compared to control patients . Five measured patient outcomes and consistently reported improvements in the targeted patient condition . In the one study identified for comparison 3 the intervention delivered by the pharmacist was less successful than that delivered by physician counsellors in decreasing inappropriate antibiotic prescribing . All six studies identified for comparison 4 demonstrated that the pharmacist intervention produced the intended effect on physician prescribing practices . These studies did not measure patient outcomes . REVIEWER'S CONCLUSIONS: The limited number of studies analysed support the expanded roles of pharmacists in patient counselling and physician education . However, doubts about the generalisability of the studies, the poorly defined nature of the interventions tested, and the lack of studies including cost assessments and patient outcome data indicate that more rigorous research is needed to document the effects of outpatient pharmacist interventions.

J Am Acad Orthop Surg, 1997 Oct, 5(5), 249 - 260
Septic Arthritis of the Hip in Children; Sucato DJ et al.; Recent advances in the management of septic arthritis of the hip in children include a better understanding of the effects of infection on articular cartilage; improvements in diagnostic tests, including erythrocyte sedimentation rate, C-reactive protein analysis, and ultrasonography; and more efficacious home intravenous and oral antibiotic therapy . Early diagnosis is essential to successful treatment . Needle aspiration is the most specific diagnostic test; however, false-negative results are possible . Prompt surgical drainage and postoperative antibiotic therapy until signs of infection resolve are necessary to prevent late sequelae . Surgical treatment of limb-length inequality is more useful than attempts to salvage the destroyed or incongruent joint.

J Am Acad Orthop Surg, 1996 Jul, 4(4), 219 - 230
Hand Infections: Treatment Recommendations for Specific Types; Abrams RA et al.; Hand infections can be associated with considerable morbidity . Expeditious treatment is needed to minimize permanent dysfunction, loss of work, and medical cost . Hand infections can affect the skin, subcutaneous tissues, fascia, subfascial and synovial spaces, joints, and bone . Pathogens include a variety of bacteria, viruses, yeasts, fungi, and mycoplasmata . Management frequently involves rest, elevation, incision and drainage, and appropriate antibiotic therapy . The orthopaedic surgeon must be knowledgeable about the pertinent anatomy and how this influences the behavior of specific types of infections, the role of immunocompromise, and the importance of early mobilization.

J Am Acad Orthop Surg, 1996 Jan, 4(1), 44 - 53
Halo Skeletal Fixation: Techniques of Application and Prevention of Complications; Botte MJ et al.; The halo skeletal fixator provides the most rigid cervical immobilization of all orthoses . However, complications such as pin loosening and infection are common . Appreciation of local anatomy and adherence to established application guidelines should minimize pin-related problems . A relatively safe zone for anterior pin placement is located 1 cm above the orbital rim and superior to the lateral two thirds of the orbit . Posterior pin-site locations are less critical; positioning on the posterolateral aspect of the skull, diagonal to the contralateral anterior pins, is generally desirable . Pins should enter the skull perpendicular to the cortex, with the ring or crown sitting below the widest portion of the skull and passing about 1 cm above the helix of the ear . Pins are inserted at a torque of 8 in-lb and retightened once to 8 in-lb at 48 hours . A loose pin can be retightened to 8 in-lb if resistance is met; otherwise, a loose pin should be replaced at a nearby site . Superficially infected pins are managed with local pin care and oral antibiotics . Persistent or severe infections require pin replacement to a nearby site, parenteral antibiotic therapy, and incision and drainage as needed . In-ability to maintain acceptable cervical reduction with a halo fixator is an indication for alternative treatment, such as internal fixation or traction.

J Am Acad Orthop Surg, 1995 Jul, 3(4), 183 - 193
Ankle Pain in Children: Diagnostic Evaluation and Clinical Decision Making; Churchill JA et al.; Ankle pain in children can be caused by traumatic injuries to bone, ligament, or tendon or by nontraumatic conditions, such as congenital and developmental anomalies, infections and other inflammatory disorders, neural compression, metabolic derangements, and neoplasia . Evaluation of children with this complaint should include a focused history and an anatomically oriented physical examination . Depending on the findings, further diagnostic workup and laboratory evaluation should be done . Appropriate treatment-whether casting, surgery, antibiotic therapy, or a combination thereof-can then be selected on a rational basis.

Mol Biol Cell, 2000 May, 11(5), 1673 - 85
Identification and characterization of Saccharomyces cerevisiae Cdc6 DNA-binding properties; Feng L et al.; Recent studies have shown that Cdc6 is an essential regulator in the formation of DNA replication complexes . However, the biochemical nature of the Cdc6 molecule is still largely unknown . In this report, we present evidence that the Saccharomyces cerevisiae Cdc6 protein is a double-stranded DNA-binding protein . First, we have demonstrated that the purified yeast Cdc6 can bind to double-stranded DNA (dissociation constant approximately 1 x 10(-7) M), not to single-stranded DNA, and that the Cdc6 molecule is a homodimer in its native form . Second, we show that GST-Cdc6 fusion proteins expressed in Escherichia coli bind DNA in an electrophoretic mobility shift assay . Cdc6 antibodies and GST antibodies, but not preimmune serum, induce supershifts of GST-Cdc6 and DNA complexes in these assays, which also showed that GST-Cdc6 binds to various DNA probes without apparent sequence specificity . Third, the minimal requirement for the binding of Cdc6 to DNA has been mapped within its N-terminal 47-amino acid sequence (the NP6 region) . This minimal binding domain shows identical DNA-binding properties to those possessed by full-length Cdc6 . Fourth, the GST-NP6 protein competes for DNA binding with distamycin A, an antibiotic that chelates DNA within the minor groove of the A+T-rich region . Finally, site-direct mutagenesis studies revealed that the (29)KRKK region of Cdc6 is essential for Cdc6 DNA-binding activity . To further elucidate the function of Cdc6 DNA binding in vivo, we demonstrated that a binding mutant of Cdc6 fails to complement either cdc6-1 temperature-sensitive mutant cells or Deltacdc6 null mutant cells at the nonpermissive temperature . The mutant gene also conferred growth impairments and increased the plasmid loss in its host, indicative of defects in DNA synthesis . Because the mutant defective in DNA binding also fails to stimulate Abf1 ARS1 DNA-binding activity, our results suggest that Cdc6 DNA-binding activity may play a pivotal role in the initiation of DNA replication.

Plant J, 2000 Apr, 22(2), 97 - 104
The two largest chloroplast genome-encoded open reading frames of higher plants are essential genes; Drescher A et al.; The chloroplast genomes of most higher plants contain two giant open reading frames designated ycf1 and ycf2 . In tobacco, ycf1 potentially specifies a protein of 1901 amino acids . The putative gene product of the ycf2 reading frame is a protein of 2280 amino acids . In an attempt to determine the functions of ycf1 and ycf2, we have constructed several mutant alleles for targeted disruption and/or deletion of these two reading frames . The mutant alleles were introduced into the tobacco plastid genome by biolistic chloroplast transformation to replace the corresponding wild-type alleles by homologous recombination . Chloroplast transformants were obtained for all constructs and tested for their homoplastomic state . We report here that all transformed lines remained heteroplastomic even after repeated cycles of regeneration under high selective pressure . A balanced selection was observed in the presence of the antibiotic spectinomycin, resulting in maintenance of a fairly constant ratio of wild-type versus transformed genome copies . Upon removal of the antibiotic and therewith release of the selective pressure, sorting out towards the wild-type plastid genome occurred in all transplastomic lines . These findings suggest that ycf1 and ycf2 are functional genes and encode products that are essential for cell survival . The two reading frames are thus the first higher plant chloroplast genes identified as being indispensable.

Pediatr Dermatol, 2000 Mar-Apr, 17(2), 123 - 5
Disfiguring draining sinus tracts in a female acne patient; Jansen T et al.; A 17-year-old girl with a 9-month history of papulopustular acne developed disfiguring, highly inflammatory, fluctuant nodules in both nasolabial folds within 2 months . Periodically she experienced discharge of pus and blood from these lesions . A diagnosis of disfiguring draining sinus tracts associated with acne vulgaris was made . The therapeutic regimen included intralesional corticosteroid injection, systemic corticosteroids along with a macrolide antibiotic, and systemic isotretinoin to reduce the inflammatory process . Outcome was favorable, with no recurrences during the following 10 months . Draining sinus is a malevolent lesion usually seen in severe forms of acne such as acne conglobata, acne fulminans, and acne inversa . Treatment is difficult and often unsatisfactory . In many cases, excision of the lesion is necessary to provide a permanent cure.

J Cell Biol, 2000 May 1, 149(3), 537 - 46
Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF); Hyman J et al.; Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15 . The NH(2)-terminal portion of epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (epsin NH(2)-terminal homology domain) . We have now solved the crystal structure of rat epsin 1 ENTH domain to 1.8 A resolution . This domain is structurally similar to armadillo and Heat repeats of beta-catenin and karyopherin-beta, respectively . We have also identified and characterized the interaction of epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF) . Leptomycin B, an antifungal antibiotic, which inhibits the Crm1- dependent nuclear export pathway, induces an accumulation of epsin 1 in the nucleus . These findings suggest that epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function.

Clin Pediatr (Phila), 2000 Apr, 39(4), 203 - 8
Detection of enteroviruses in the cerebrospinal fluid by polymerase chain reaction: prospective study of impact on the management of hospitalized children; Spicher VM et al.; A polymerase chain reaction kit (AMPLICOR EV) for the detection of enteroviruses (EV-PCR) in the cerebrospinal fluid (CSF) was evaluated in clinical conditions in a prospective blinded-intention study . Forty-three children (mean age 2.7 years) hospitalized for suspected meningitis or fever of unclear etiology were enrolled . EV-PCR was performed on a daily basis . Results were available in less than 2 days in 72% of cases . EV-PCR was positive in nine (21%) children, including three infants without CSF pleocytosis . Knowing their EV-PCR result would have allowed a saving of 18 hospital days and 12 days of antibiotic therapy . The EV-PCR in the CSF can thus be practically useful for children hospitalized for meningitis or fever if available on-site on a daily basis.

Med Hypotheses, 2000 Feb, 54(2), 310 - 1
Diseases of plants transmissible between plants and man (Phytonoses) exist--follow-up paper; Van der Riet FS; The purpose of this paper is to revise the original paper by qualifying a statement made therein and making two sections more inclusive . The qualification is the insertion of the word 'adult' before the word 'volunteers' in one sentence . The scope of the first section is increased by: (i) drawing attention to the possibility that besides other organisms (i.e . non-mycoplasma-like organisms (non-MLOs)) and viruses that could be inadvertently transmitted between members of the plant and animal kingdoms, other infectious entities including viroids and prions and/or prion-like elements should also be considered in this regard; and (ii) the need to consider the possible transmission of either antibiotic-resistant MLOs and/or MLOs harbouring entities that are either naturally infectious and pathogenic for man or may opportunistically infect man . The scope of the second section is increased by proposing additional possible mechanisms of transmission of MLOs between plants and man .

J Chir (Paris), 2000 Feb, 137(1), 45 - 50
{Prevention of anastomotic dehiscence in colorectal surgery}; Gainant A; Anastomotic leakage is a major cause of mortality in colorectal surgery . Some variables associated with a high-risk level for anastomotic leakage have been identified, including denutrition, obesity, smoking, level of the anastomoses, qualification of the surgeon . Several methods have been evaluated in order to prevent anastomotic leakage . Prophylactic antibiotic therapy has been recommended, but has no effect on the rate of anastomotic leakage . Optimal preoperative colonic preparation appears to be obtained with povidone iodine enemas associated with a low residue diet . Stapling gives better results than sutures only for difficult anastomoses . Colostomy does not prevent leakage but minimizes its consequences . Omentoplasty, peritoneal drainage, gastric tube, biofragmentable anastomotic ring, and Coloshield have demonstrated their efficacy.

Support Care Cancer, 2000 May, 8(3), 198 - 202
Low-dose continuous-infusion ceftazidime monotherapy in low-risk febrile neutropenic patients; Marshall E et al.; One hundred and thirty-five cancer patients admitted with low-risk neutropenic fever received a low-dose schedule of ceftazidime as infusional monotherapy over a total of 180 episodes . Ceftazidime was administered as a 1-g bolus followed by a continuous infusion of 2 g per day . In this patient population the ceftazidime was both practical and well tolerated . Sixty-eight percent of patients responded with clinical improvement and complete resolution of fever within 48 h . Overall, 95% of patients responded, although 18% subsequently required antibiotic modification for persistent fever . Only 5% of episodes were considered failures due to clinical deterioration, and over the study period there was only 1 fatality due to respiratory failure . The median duration of hospitalisation was only 4 days (2-20) . In conclusion, monotherapy with low-dose infusional ceftazidime appears safe and highly effective in this low-risk population of neutropenic patients and may reduce antibiotic costs appreciably.

Spine, 2000 May 1, 25(9), 1185 - 7
Eikenella corrodens vertebral osteomyelitis secondary to direct inoculation: a case report; Lehman CR et al.; STUDY DESIGN: A case report . OBJECTIVE: To present a unique method of inoculation with an unusual bacterial organism, Eikenella corrodens, which led to vertebral osteomyelitis and to heighten awareness of different bacterial organisms that may cause orthopedic infections . SUMMARY OF BACKGROUND DATA: E . corrodens has been known to cause orthopedic infections for more than 20 years . The usual mechanism is from "Fight bite" injuries to the hand or metacarpal phalangeal joint . Eikenella osteomyelitis of the vertebral body is extremely rare . METHODS: A 65-year-old man from Indonesia developed slowly progressive vertebral collapse and worsening neck pain . History suggested a previous pharyngeal injury while eating fish . Work up for malignancy was negative, and imaging studies were suggestive of osteomyelitis . An open biopsy and culture as well as fusion were performed for treatment of the osteomyelitis . RESULTS: After a complete work up was undertaken, cultures grew out E . corrodens as the causative organism of this patient's osteomyelitis . Computed tomography scan and history were consistent with inoculation of the paravertebral space with E . corrodens secondary to a fish bone transgressing the patient's pharynx . The patient was treated with surgery and the appropriate antibiotics and healed without any significant sequela . CONCLUSION: Vertebral osteomyelitis due to E . corrodens is extremely rare . Direct inoculation as a cause of vertebral osteomyelitis with Eikenella has never been reported . If diagnosed properly with appropriate cultures and antibiotic sensitivities, Eikenella osteomyelitis can be treated successfully according to standard orthopedic practices including debridement, fusion, and appropriate antibiotics . Awareness of unusual bacteria as potential causative organisms of osteomyelitis is imperative for appropriate treatment.

Pediatr Surg Int, 2000, 16(3), 182 - 8
Peritonitis in childhood: aspects of pathogenesis and therapy; Haecker FM et al.; The pathogenesis of peritonitis due to hollow-viscus perforation is currently accepted as being mainly based on the local and systemic release of pro- and anti-inflammatory mediators triggered by the presence of bacteria and bacterial products in the abdominal cavity . Therefore, treatment consists in focal restoration, intraoperative debridement and lavage, and postoperative measures such as drainage, continuous peritoneal lavage, or scheduled reoperation aiming at the removal of infectious agents from the peritoneal cavity to prevent persisting peritonitis and sepsis . In order to evaluate the pathophysiologic relevance of the bacterial and endotoxin load of the peritoneal exudate, we examined the peritoneal fluid of 20 children with perforated appendicitis for qualitative and quantitative analysis of bacteria, antibiotic concentrations, and endotoxin content . The time period ranged in 12-h intervals from intraoperatively to day 5 . Eighteen of 20 fluid specimens (90%) showed endotoxin levels above 1.5 endotoxin units EU/ml (standard <0.1 EU/ml) . The most common bacterial species isolated was Escherichia coli, mostly in high concentrations . Despite persisting high endotoxin concentrations and bacterial loads in the peritoneal cavity during the 5 postoperative days, the children recovered uneventfully and the systemic signs of infection disappeared rapidly . In conclusion, neither the bacterial nor the endotoxin load of the peritoneal cavity proved to be associated with the clinical course . Therefore, we hypothesize that during peritonitis compartmentalization of the focus of infection prevents further systemic reactions and ultimately leads to removal of the infectious agents by endogenous mechanisms . At least in peritonitis due to perforated appendicitis in children, adjuvant surgical measures in addition to appendectomy and intraoperative debridement are not necessary.

Intensive Care Med, 2000, 26 Suppl 1, S22 - 5
Prevention and control of infections in intensive care; Scott G; Small intensive care units (ICUs) functioning within their capacity and caring mainly for post-operative patients have fewer problems with infection control than larger ICUs with a varied case mix, sub-optimal staffing levels, and high levels of antibiotic consumption . Under these circumstances chronic cross colonisation and infection are inevitable and outbreaks may occur . Little can be done to reduce the risks of infection which arise as a direct result of the patient's clinical condition and prior colonisation status . However, selection pressure from antibiotic usage can be modified, as can environmental hygiene, ventilation and architectural design . One of the simplest measures for reducing cross infection remains one of the most intractable: compliance by staff with protocols and standards for maintaining hand hygiene . Simplification of procedures by the ready availability of alcohol hand rub preparations with or without chlorhexidine may improve matters.

Cancer Res, 2000 Apr 15, 60(8), 2090 - 4
Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases; Zheng FF et al.; Geldanamycin (GM) is a natural antibiotic that binds Hsp90 and induces the degradation of receptor tyrosine kinases, steroid receptors, and Raf . It is a potent inhibitor of cancer cells that overexpress HER-kinases, but its effects on other important proteins may cause significant toxicity and limit its clinical use . We report the synthesis and identification of a GM dimer, GMD-4c, which had selective activity against HER-kinases . Selectivity was a function of linker length and required two intact GM moieties . GMD-4c is a potent inducer of G1 block and apoptosis of breast cancer cell lines that overexpress HER2, but does not appreciably inhibit the growth of 32D cells that lack HER-kinases . GMD-4c could be useful in the treatment of carcinomas dependent on HER-kinases.

Eur J Cancer, 2000 May, 36(7), 889 - 94
C-reactive protein, procalcitonin and interleukin-8 in the primary diagnosis of infections in cancer patients; Kallio R et al.; The diagnostic utility of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-8 (IL-8) were studied in 66 cancer patients with suspected infection (39 with definite foci of infection, 17 with antibiotic responses without foci and 10 with neoplastic fever without infection) and 26 patients scheduled for chemotherapy . The infection group (n=56) had higher median CRP (91 versus 19 mg/l, P<0 . 001), PCT (0.28 versus 0.12 ng/ml, P<0.001) and IL-8 values (27.7 versus 16.9 pg/ml, P=0.032) than the non-infection group (n=36) . In patients with suspected infection, only PCT was a good marker to discriminate bacteraemia with an area under the receiver operating characteristics curve of 0.92 (95% confidence interval (CI), 0.77-1 . 0), but even PCT was less well able to differentiate between non-bacteraemic infections and neoplastic fever (0.56; 95% CI, 0 . 35-0.77) . In conclusion, PCT was a good indicator for bacteraemia, but none of the three markers were reliable indicators for minor infections in non-neutropenic cancer patients.

Anal Chem, 2000 Apr 15, 72(8), 1767 - 80
Role of the carbohydrate moieties in chiral recognition on teicoplanin-based LC stationary phases; Berthod A et al.; For this study, we used the macrocyclic antibiotic teicoplanin, a molecule consisting of an aglycone peptide "basket" with three attached carbohydrate (sugar) moieties . The sugar units were removed and the aglycone was purified . Two chiral stationary phases (CSPs) were prepared in a similar way, one with the native teicoplanin molecule and the other with the aglycone . Twenty-six compounds were evaluated on the two CSPs with seven RPLC mobile phases and two polar organic mobile phases . The compounds were 13 amino acids or structurally related compounds (including DOPA, folinic acid, etc.) and 13 other compounds (such as carnitine, bromacil, etc.) . The chromatographic results are given as the retention, selectivity, and resolution factors along with the peak efficiency and the enantioselective free energy difference corresponding to the separation of the two enantiomers . The polarities of the two CSPs are similar . It is clearly established that the aglycone is responsible for the enantioseparation of amino acids . The difference in enantioselective free energy between the aglycone CSP and the teicoplanin CSP was between 0.3 and 1 kcal/mol for amino acid enantioseparations . This produced resolution factors 2-5 times higher with the aglycone CSP . Four non amino acid compounds were separated only on the teicoplanin CSP . Six and five compounds were better separated on the teicoplanin and aglycone CSPs, respectively . Although the sugar units decrease the resolution of alpha-amino acid enantiomers, they can contribute significantly to the resolution of a number of non amino acid enantiomeric pairs.

J Magn Reson, 2000 May, 144(1), 156 - 61
Three-dimensional solid-state NMR spectroscopy is essential for resolution of resonances from in-plane residues in uniformly (15)N-labeled helical membrane proteins in oriented lipid bilayers; Marassi FM et al.; Uniformly (15)N-labeled samples of membrane proteins with helices aligned parallel to the membrane surface give two-dimensional PISEMA spectra that are highly overlapped due to limited dispersions of (1)H-(15)N dipolar coupling and (15)N chemical shift frequencies . However, resolution is greatly improved in three-dimensional (1)H chemical shift/(1)H-(15)N dipolar coupling/(15)N chemical shift correlation spectra . The 23-residue antibiotic peptide magainin and a 54-residue polypeptide corresponding to the cytoplasmic domain of the HIV-1 accessory protein Vpu are used as examples . Both polypeptides consist almost entirely of alpha-helices, with their axes aligned parallel to the membrane surface . The measurement of three orientationally dependent frequencies for Val17 of magainin enabled the three-dimensional orientation of this helical peptide to be determined in the lipid bilayer .

J Magn Reson, 2000 May, 144(1), 150 - 5
A solid-state NMR index of helical membrane protein structure and topology; Marassi FM et al.; The secondary structure and topology of membrane proteins can be described by inspection of two-dimensional (1)H-(15)N dipolar coupling/(15)N chemical shift polarization inversion spin exchange at the magic angle spectra obtained from uniformly (15)N-labeled samples in oriented bilayers . The characteristic wheel-like patterns of resonances observed in these spectra reflect helical wheel projections of residues in both transmembrane and in-plane helices and hence provide direct indices of the secondary structure and topology of membrane proteins in phospholipid bilayers . We refer to these patterns as PISA (polarity index slant angle) wheels . The transmembrane helix of the M2 peptide corresponding to the pore-lining segment of the acetylcholine receptor and the membrane surface helix of the antibiotic peptide magainin are used as examples .

Pediatr Infect Dis J, 2000 Apr, 19(4), 303 - 7
Effect of rapid diagnosis on management of influenza A infections; Noyola DE et al.; BACKGROUND: Few studies have examined the impact of rapid viral diagnostic tests on patient management . OBJECTIVE: To assess the effect of rapid diagnosis of influenza A infections on patient management . METHODS: The medical records of children with respiratory infections who were evaluated at a children's hospital between July 1, 1995, and June 30, 1997, were reviewed . Children (n = 56) evaluated in the Emergency Department (ED) who had a positive influenza A enzyme immunoassay (EIA) were compared with two control groups for the likelihood of admission, antibiotic use and duration of hospitalization and antibiotic administration . RESULTS: Patients discharged from the ED with a positive EIA test were less likely to receive antibiotics than those with a negative EIA test (20% vs . 53%; P = 0.04) . Patients admitted to the hospital with a positive EIA test were as likely to receive antibiotics as those without a rapid diagnosis, but the duration of antibiotic administration was significantly shorter in the group with a positive EIA test (3.5 vs . 5.4 days; P = 0.03) . Patients with a positive EIA test also were more likely to receive antiviral therapy than either control group (25% vs . 0 and 1.8%; P < 0.001) . CONCLUSIONS: The detection of influenza A by EIA has a positive impact on medical management by decreasing antibiotic use in pediatric patients evaluated in an ED, by decreasing the duration of antibiotic use in hospitalized patients and by encouraging antiviral therapy.

J Hepatol, 2000 Apr, 32(4), 596 - 602
Amoxicillin-clavulanic acid versus cefotaxime in the therapy of bacterial infections in cirrhotic patients; Ricart E et al.; BACKGROUND/AIM: Cefotaxime is considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing bacterial infections . It has been suggested that amoxicillin-clavulanic acid could be an alternative to cefotaxime, particularly in patients developing bacterial infections while on prophylactic norfloxacin . The aim of the present study was to compare amoxicillin-clavulanic acid with cefotaxime in the treatment of bacterial infections in cirrhosis . METHODS: Ninety-six hospitalized cirrhotic patients with suspicion of bacterial infection were prospectively included and randomized into two groups: one group (n=48) received amoxicillin-clavulanic acid, first intravenously 1 g-0.2 g every 8 h, and then orally 500 mg-125 mg every 8 h, and the other group (n=48) received intravenous cefotaxime 1 g every 6 h . Patients were stratified for previous prophylaxis with norfloxacin and ascitic fluid infection . RESULTS: Sixteen patients were excluded from the analysis because bacterial infection was not demonstrated or because of secondary peritonitis . Therefore, 38 patients from the amoxicillin-clavulanic acid group and 42 from the cefotaxime group were finally analyzed . There were 24 ascitic fluid infections in each group . Infection resolution (86.8% vs 88%, 95% CI: -0.15 to 0.13, p NS), spontaneous bacterial peritonitis resolution (87.5% vs 83.3%, 95% CI: -0.15 to 0.24, p NS), duration of treatment, incidence of complications, time of hospitalization and hospital mortality were similar in both groups . Considering patients on prophylactic norfloxacin, infection resolution was also similar (100% vs 83.3%, 95% CI: -0.04 to 0.37, p NS) . No adverse events were observed in either of the two groups . The cost of antibiotics was statistically lower in the amoxicillin-clavulanic acid group (p<0.001) . CONCLUSIONS: Amoxicillin-clavulanic acid is as effective as cefotaxime in the treatment of bacterial infections in cirrhotic patients, but is less expensive and can be administered orally . These results suggest that amoxicillin-clavulanic acid is an effective alternative to cefotaxime for the empirical treatment of bacterial infections in cirrhosis.

Curr Opin Pulm Med, 2000 May, 6(3), 234 - 9
Pyogenic lung infections: factors for predicting clinical outcome of lung abscess and thoracic empyema; Mwandumba HC et al.; Lung abscess and thoracic empyema continue to cause significant morbidity and mortality despite appropriate antibiotic therapy and various options for drainage of empyema . Multiple factors, including the patient's general state of health, the presence of underlying disease, the virulence of the pathogen responsible, and the promptness of drainage of empyema, appear to dictate the clinical outcome . However, the available data are derived from uncontrolled, retrospective studies and the high morbidity and mortality rates underscore the need for large prospective studies to better evaluate factors that may predict the clinical outcome of these conditions.

Am J Med, 2000 Apr 15, 108(6), 453 - 9
Effect of clarithromycin on experimental rhinovirus-16 colds: a randomized, double-blind, controlled trial; Abisheganaden JA et al.; PURPOSE: Macrolide antibiotics are frequently prescribed to patients with symptoms of a common cold . Despite their lack of proven antiviral activity, macrolide antibiotics may have anti-inflammatory actions, such as inhibition of mucus secretion and production of interleukins 6 and 8 by epithelial cells . Because the symptoms of rhinovirus colds are attributed to the inflammatory response to infection, we studied the effects of treatment with clarithromycin on the symptomatic and inflammatory response to nasal inoculation with rhinovirus . SUBJECTS AND METHODS: We performed a prospective, double-blind, controlled trial in 24 healthy subjects who were seronegative for antibodies to rhinovirus-16 . Subjects were randomly assigned to receive either clarithromycin (500 mg) or trimethoprim-sulfamethoxazole (800/160 mg, as a control antibiotic) twice a day for 8 days, beginning 24 hours before inoculation with rhinovirus-16 . RESULTS: All 12 subjects in each group were infected and developed symptomatic colds . The groups did not differ in the intensity of cold symptoms (median {25th to 75th percentile} score in the clarithromycin group of 25 {5 to 33} versus 21 {11 to 26} in the trimethoprim-sulfamethoxazole group, P = 0.86), weight of nasal secretions (25 g {8 to 56 g} versus 12 g {5 to 28 g}, P = 0.27), or decline in nasal peak flow during the 8 days following viral inoculation . In both groups, similar and significant increases from baseline were observed in the numbers of total cells and neutrophils, and in the concentrations of interleukins 6 and 8, in nasal lavage fluid during the cold . The changes that we observed did not differ from those in an untreated historical control group . CONCLUSIONS: We conclude that clarithromycin treatment has little or no effect on the severity of cold symptoms or the intensity of neutrophilic nasal inflammation in experimental rhinovirus-16 colds.

Neth J Med, 2000 May, 56(5), 190 - 2
Acute epiglottitis as a cause of airway obstruction in an adult patient; Kuppens SP et al.; Epiglottitis in adults is a dangerous infectious disease with a rising incidence and potential fatal complications as illustrated in this case report . Like in children, skilled and aggressive airway protection with appropriate antibiotic therapy have been effective in reducing mortality.

Neth J Med, 2000 May, 56(5), 186 - 9
Need to increase awareness among family doctors and medical specialists of rickettsioses as an import disease in non-endemic areas; Nur YA et al.; Europeans travelling to (sub)-tropical countries have an increased risk for infections with Rickettsia . As serious consequences are associated with delay in specific antibiotic therapy, unequivocal diagnosis of this condition is needed . We focus here on the benefits of early, and consequences of late laboratory diagnosis, and emphasise the need of an increased awareness of rickettsioses among family doctors, as well as medical specialists, in non-endemic areas when evaluating patients with travel associated fever.

Br J Pharmacol, 2000 Apr, 129(8), 1655 - 67
Identification of the cytochrome P450 enzymes involved in the metabolism of cisapride: in vitro studies of potential co-medication interactions; Bohets H et al.; Cisapride is a prokinetic drug that is widely used to facilitate gastrointestinal tract motility . Structurally, cisapride is a substituted piperidinyl benzamide that interacts with 5-hydroxytryptamine-4 receptors and which is largely without central depressant or antidopaminergic side-effects . The aims of this study were to investigate the metabolism of cisapride in human liver microsomes and to determine which cytochrome P-450 (CYP) isoenzyme(s) are involved in cisapride biotransformation . Additionally, the effects of various drugs on the metabolism of cisapride were investigated . The major in vitro metabolite of cisapride was formed by oxidative N-dealkylation at the piperidine nitrogen, leading to the production of norcisapride . By using competitive inhibition data, correlation studies and heterologous expression systems, it was demonstrated that CYP3A4 was the major CYP involved . CYP2A6 also contributed to the metabolism of cisapride, albeit to a much lesser extent . The mean apparent K(m) against cisapride was 8.6+/-3.5 microM (n = 3) . The peak plasma levels of cisapride under normal clinical practice are approximately 0.17 microM; therefore it is unlikely that cisapride would inhibit the metabolism of co-administered drugs . In this in vitro study the inhibitory effects of 44 drugs were tested for any effect on cisapride biotransformation . In conclusion, 34 of the drugs are unlikely to have a clinically relevant interaction; however, the antidepressant nefazodone, the macrolide antibiotic troleandomycin, the HIV-1 protease inhibitors ritonavir and indinavir and the calcium channel blocker mibefradil inhibited the metabolism of cisapride and these interactions are likely to be of clinical relevance . Furthermore, the antimycotics ketoconazole, miconazole, hydroxy-itraconazole, itraconazole and fluconazole, when administered orally or intravenously, would inhibit cisapride metabolism.

Schweiz Med Wochenschr Suppl, 2000, 116, 58S - 61S
{Cervicofacial necrotizing fasciitis}; Peter B; INTRODUCTION: Necrotising fasciitis is still a severe disease whose outcome is occasionally fatal . METHODS: Between August 1994 and August 1998, 6 patients with necrotising fasciitis, 5 in the neck area and one in the facial area, were treated . The source of the infection was odontogenic in 3 cases, pharyngeal in 2 and an insect sting in the left upper eyelid in one case . RESULTS: Following evaluation by CT scan, immediate surgical exploration with debridement and drainage was performed . Revision proved necessary in most cases . One patient suffered severe complications . Median stay in the intensive care unit was 7 days and in hospital 20 days . DISCUSSION: Deep and extensive neck infections require investigation by CT scan . All affected areas must be explored and drained immediately, including thoracotomy if mediastinitis is present . Apart from appropriate antibiotic therapy, the further course of the disease should be carefully monitored to detect further spread of the infection as well as complications.

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