Antibiotics

Aliment Pharmacol Ther, 2000 Dec, 14(12), 1605 - 11
One-week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease; Veldhuyzen Van Zanten S et al.; BACKGROUND: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases . METHODS: Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d . (n=224), in combination with amoxicillin 1 g b.d . and clarithromycin 500 mg b.d . for 1 week (EAC and OAC, respectively) . A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H . pylori eradication . RESULTS: Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185) . Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%) . Between-group differences in eradication rates were not statistically significant . Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy . CONCLUSIONS: Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H . pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.

Clin Exp Pharmacol Physiol, 2000 Dec, 27(12), 980 - 6
Changes in absorptive function of rat intestine injured by methotrexate; Naruhashi K et al.; 1 . Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine . The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino-beta-lactam antibiotic cephalexin (CEX) . Time-dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg) . 2 . Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration-time curve of CEX (AUC(CEX)) following oral administration of 20 mg/kg tended to decrease . Thereafter, the AUC(CEX) increased significantly and the histopathological changes diminished within 5 days . 3 . Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day . Methotrexate-induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUC(CEX), but did not correlate with mucosal DAO and ALP activity . 4 . These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX . In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function.

Rev Prat, 2000 Oct 1, 50(15), 1665 - 71
{Infectious endocarditis}; Delahaye F et al.; The incidence of infective endocarditis has not decreased over the last years . Infective endocarditis remains severe: the mortality rate during the initial hospital stay is 15%, and a surgical intervention is needed in 25% of the cases . Stricter application of prophylaxis guidelines and better diagnostic and therapeutic management should decrease the frequency and severity of infective endocarditis.

Indian J Exp Biol, 2000 Jun, 38(6), 617 - 20
Nitrosomethylurea induced streptomycin resistance in Lycopersicon esculentum Mill; Rao AV et al.; High frequency of streptomycin resistant variants of Lycopersicon esculentum were isolated on selective shoot regeneration medium supplemented with IAA (0.5 mg/L), zeatin (1.5 mg/L) and streptomycin sulphate (500 mg/L) . Nonmutagenized (controls) and NMU treated cotyledons were placed on shoot regeneration medium supplemented with antibiotic streptomycin . Resistant shoots appeared at a high frequency in mutagenized cotyledons, whereas in controls morphogenesis was suppressed, accompanied by bleaching . Shoot regeneration occurred from the nodular tissues developed at the cut ends of cotyledons . Resistant shoots developed into complete plantlets on rooting medium containing selective concentration of antibiotic . Stability of streptomycin resistance was confirmed by leaf assay and reciprocal crosses between streptomycin-resistant and sensitive plants.

Arch Fam Med, 2000 Nov-Dec, 9(10), 997 - 1001
Does drug treatment of patients with acute bronchitis reduce additional care seeking? Evidence from the Practice Partner Research Network; Hueston WJ et al.; BACKGROUND: Considerable discussion has focused on treatment methods for patients with acute bronchitis . OBJECTIVE: To examine whether antibiotic or bronchodilator treatment is associated with differences in follow-up visit rates for patients with acute bronchitis . METHODS: A retrospective medical chart review was conducted for patients with a new episode of acute bronchitis over a 3-year period in the Practice Partner Research Network (29,248 episodes in 24,753 patients) . Primary outcomes of interest were another visit in the next 14 days (early follow-up) or 15 to 28 days after initial treatment (late follow-up) . RESULTS: Antibiotics were used more commonly in younger patients (<18 years), whereas older patients (>65 years) were more likely to receive no treatment . Younger patients treated with antibiotics were less likely to return for an early follow-up visit, but no differences were seen in adults and older patients . Late follow-up rates were not affected by the initial treatment strategy . When patients did return for a follow-up visit, no new medication was prescribed to most (66% of younger patients and 78% of older adults) . However, compared with patients who did not receive an antibiotic at their first visit, patients initially treated with an antibiotic were about 50% more likely to receive a new antibiotic at their second visit . CONCLUSIONS: Initial prescribing of an antibiotic reduces early follow-up for acute bronchitis in younger patients but seems to have no effect in adults . However, reductions in future follow-up visits might be outweighed by increases in antibiotic consumption because patients who return for a follow-up visit seem to receive additional antibiotic prescriptions . Arch Fam Med . 2000;9:997-1001

Int J Androl, 2000 Dec, 23(6), 357 - 9
Penile prosthesis surgery under local penile block anaesthesia via the infrapubic space; Ghanem H et al.; The aim of this study was to evaluate the effectiveness and patient tolerance to local penile block anaesthesia via the infrapubic space with penile prosthesis implantation . Local anaesthesia was administered using a 23-guage 1.5-inch needle . A 50-50 mixture of 0.5% bupivicaine (Marcaine) and 0.5% lidocaine (Xylocaine) without adrenaline was injected into the infrapubic space with additional subcutaneous penile ring infiltration at the level of the penile root . A total number of 159 patients underwent this technique, mean age 57 years (range 34-86) . In 148 (93%) patients, no booster sedation was needed; eight (5%) patients needed a boost of the pre-operative sedative during crural dilatation; three (1.8%) patients required general anaesthesia owing to insufficiently effective local anaesthesia and unexpectedly difficult dilatation . It is concluded that local anaesthesia was effective and safe to produce a pain-free procedure in 93% of cases . However, as the need for booster sedation or general anaesthesia exists, the procedure should be performed under monitored anaesthetic care and pre-operative evaluation should be performed as for general anaesthesia.

J Mass Spectrom, 2000 Nov, 35(11), 1342 - 50
Determination of gentamicin in swine and calf tissues by high-performance liquid chromatography combined with electrospray ionization mass spectrometry; Cherlet M et al.; Gentamicin is a broad-spectrum aminoglycoside antibiotic widely used in veterinary medicine for the treatment of serious infections . The purpose of this study was to develop and validate a method to determine gentamicin residues in edible tissues of swine and calf . Extraction of gentamicin was performed using a liquid extraction with phosphate buffer containing trichloroacetic acid, followed by a solid-phase clean-up procedure on a CBA weak cation-exchange column . Tobramycin was used as the internal standard . After drying of the eluate, the residue was redissolved and further analyzed by reversed-phase liquid chromatography/electrospray ionization tandem mass spectrometry (MS/MS) . Chromatographic separation of the internal standard tobramycin and the gentamicin components was achieved on a Nucleosil (5 microm) column using a mixture of 10 mM pentafluoropropionic acid in water and acetonitrile as the mobile phase . The gentamicin components C1a, C2 + C2a and C1 could be identified with the MS/MS detection, and subsequently quantified . The method was validated according to the requirements of the EC at the maximum residue limit (MRL) (100 ng g(-1) for muscle and fat, 200 ng g(-1) for liver and 1000 ng g(-1) for kidney), half the MRL and double the MRL levels . Calibration graphs were prepared for all tissues and good linearity was achieved over the concentration ranges tested (r > 0.99 and goodness of fit <10%) . Limits of quantification of 25.0 ng g(-1) were obtained for the determination of gentamicin in muscle, fat, liver and kidney tissues of swine and calf, which correspond in all cases to at least half the MRLs . Limits of detection ranged between 0.5 and 2.5 ng g(-1) for the tissues . The within-day and between-day precisions (RSD) and the results for accuracy fell within the ranges specified . The method was successfully used for the determination of gentamicin in tissue samples of swines and calves medicated with gentamicin by intramuscular injection .

J Pediatr, 2000 Dec, 137(6), 856 - 64
The burden of influenza illness in children with asthma and other chronic medical conditions; Neuzil KM et al.; OBJECTIVE: Although influenza immunization is recommended for children with high-risk medical conditions, the majority of such children do not receive influenza vaccine . This study was designed to measure the burden of influenza among children with asthma and other chronic medical conditions . STUDY DESIGN: We performed a retrospective cohort study of children younger than 15 years with medically treated asthma or other chronic medical conditions enrolled in the Tennessee Medicaid program from 1973 to 1993 . We determined rates of hospitalization for acute cardiopulmonary disease, outpatient visits, and antibiotic courses throughout the year . Annual differences between event rates when influenza virus was circulating and event rates during winter months when there was no influenza in the community were used to calculate influenza-attributable morbidity . RESULTS: Influenza accounted for an average of 19, 8, and 2 excess hospitalizations for cardiopulmonary disease yearly per 1000 high-risk children aged <1 year, 1 to <3 years, and 3 to <15 years, respectively . For every 1000 children, an estimated 120 to 200 outpatient visits and 65 to 140 antibiotic courses were attributable to influenza annually . CONCLUSIONS: Children younger than 15 years with asthma and other chronic medical conditions experience substantial morbidity requiring inpatient and outpatient care during influenza season . More effective targeting of this population for annual influenza immunization is warranted.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000 Dec, 90(6), 746 - 9
Paresthesia of the mental nerve induced by periapical infection: a case report; Di Lenarda R et al.; Paresthesia can be a rare complication of infections of dental origin . This article presents a case of anesthesia/paresthesia caused by a periapical infection of the right mandibular second premolar . The sensory disturbance disappeared 2 weeks after conventional endodontic treatment associated with antibiotic therapy . Twelve months later, the tooth was still asymptomatic . The possible mechanisms responsible for paresthesia associated with periapical infection are discussed.

J Org Chem, 2000 Dec 15, 65(25), 8595 - 607
Total synthesis of (-)-mniopetal E, a novel biologically intriguing drimane sesquiterpenoid; Suzuki Y et al.; We have achieved the total synthesis of (-)-mniopetal E, a drimane sesquiterpenoid which inhibits the reverse transcriptase of human immunodeficiency virus (HIV)-1 . Our enantiospecific total synthesis of this target molecule in naturally occurring form commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using the Sharpless asymmetric epoxidation strategy . The key steps of our total synthesis were as follows: (1) a combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations for construction of a butenolide tethering a 1,2,4, 9-functionalized nona-5,7-diene moiety at the beta-carbon, (2) stereoselective thermal intramolecular Diels-Alder reaction of the thus-formed trienic compound, providing preferentially an endo-cycloadduct with the desired pi-facial selection, and (3) efficient transformation of the gamma-lactone moiety in the major cycloadduct to the gamma-hydroxy-gamma-lactone part in mniopetal E . Our total synthesis of (-)-mniopetal E established the unsettled absolute stereochemistry of the antibiotic.

J Arthroplasty, 2000 Dec, 15(8), 990 - 3
Patient satisfaction and outcome after septic versus aseptic revision total knee arthroplasty; Barrack RL et al.; A consecutive series of revision total knee arthroplasties performed at 3 university-affiliated centers by 3 surgeons was prospectively studied . The same implant was used in all cases . The evaluation included a Knee Society clinical score (KSCS); SF-36; satisfaction survey; and radiographs preoperatively, at 6 and 12 months postoperatively, and annually thereafter . Follow-up averaging 36 months (range, 24-60 months) was obtained in 125 of 138 knees (91%) . Twenty-eight knees were infected, and 26 of 28 knees were treated successfully with 2-stage exchange with an interval of 4 to 6 weeks using an antibiotic-impregnated spacer block and intravenous antibiotics . The remaining 99 knees were revised for reasons other than infection, including aseptic component loosening, progressive osteolysis, and component instability . Preoperatively, patients with infection had a significantly decreased arc of motion compared with patients without infection (79 degrees vs 92 degrees; P<.05) . There was a strong trend for the infected knees to have a lower preoperative KSCS than the noninfected knees, although this trend did not achieve statistical significance (76 vs . 92; P =.11) . Postoperatively, patients with infection continued to have a significantly decreased range of motion (89 degrees vs . 99 degrees; P =.05) . The postoperative KSCS was markedly lower in the septic versus aseptic revisions (115 vs . 135; P =.02) . Patients with infection had a significantly lower function score (44 vs . 57; P =.03) . A significantly higher percentage of patients stated that they were unable to return to normal activities of daily living after septic versus aseptic revision total knee arthroplasty (24% vs . 7%; P<.05) . Despite the inferior functional result, patients expressed an equal degree of satisfaction with the results of their treatment in septic versus aseptic revision cases.

ASAIO J, 2000 Nov-Dec, 46(6), S41 - 6
Infection in patients after implantation of an orthopedic device; Stocks G et al.; During the last several decades, the use of appropriate antibiotics has significantly improved our ability to prevent and treat infection that occurs after implantation of an orthopedic device . Despite improved prevention and treatment of this condition, patients who develop an infection secondary to implantation of an orthopedic device face increased mortality, morbidity, and/or delayed recovery . The presence of an orthopedic device significantly reduces the number of bacteria required to produce colonization and decreases the ability of the body's own defense mechanism and antibiotics to resolve this condition . Efforts devoted to prevention of infection are much more effective than those spent treating the condition once it has developed . Pretreatment of patients with antibiotics and the use of ultra clean surgical rooms have been shown effective . Prevention will become increasingly important as antibiotic resistant strains of bacteria become more prevalent and the number of arthroplasty procedures performed also increases.

ASAIO J, 2000 Nov-Dec, 46(6), S28 - 36
Infectious complications associated with ventricular assist systems; Myers TJ et al.; Infectious complications during support with a ventricular assist system (VAS) can cause severe morbidity and mortality, affecting nearly one-half of all VAS recipients . Because of the lack of a uniform definition of infection, the incidence of this complication is hard to determine accurately . It is approximately 50% for patients being supported by an implantable VAS as a bridge to heart transplantation and 28% for patients supported by an external, short-term VAS . Infections can be classified according to the involvement or noninvolvement of the implanted device and according to the severity of the infection . Severe infections involving the implanted device may preclude heart transplantation for some patients, but numerous patients with milder infections have undergone successful transplantation . Numerous factors predispose VAS patients to infection . Postoperative bleeding necessitating re-operation is an important contributing factor . Endotracheal tubes, intravascular catheters, and other indwelling tubes necessary for the care of postsurgical patients are also common routes of contamination . Control of infection may be improved with new VAS designs, antibiotic impregnated drivelines, and innovative therapies such as antibiotic beads . The next generation of VASs should be inherently less susceptible to infection because of their smaller size, reduced thrombogenicity, and better flow characteristics . In addition to more effective antibiotics, improved VAS designs that incorporate transcutaneous energy transmission systems may reduce infectious complications and allow safe, long-term VAS support.

Biochem Pharmacol, 2000 Dec 15, 60(12), 1845 - 53
Pharmacodynamic approach to study the gene transfer process employing non-viral vectors; Alino SF et al.; In the present work we set out to apply pharmacodynamic concepts derived from dose-response curves (Potency and Efficacy) to characterize the gene transfer efficiency of a vector:DNA complex . We employed two widely used vectors, the cationic lipid DOTAP (N,N, N-trimethyl 1-2-3-bis (1-oxo-9-octa-decenyl)oxy-(Z, Z)-1-propanaminium methyl sulfate) and the cationic polymer PEI (polyethylenimine, 800 kDa) to transfect several constructions of the green fluorescent protein cDNA . The analysis of dose-response curves indicated that in all cases the goodness-of-fit was > 0.99 . Potency is a measure that provides information on gene activity per amount of DNA . Efficacy is a measure of maximum gene expression achievable using a specific vector:DNA complex, and depends on both the intrinsic efficacy of the gene (evaluated using different vectors to transfer the same gene construct) and on vector efficacy in DNA delivery (evaluated using a single vector to deliver different gene constructs) . The results suggest that Potency and Efficacy are objective parameters for describing and comparing the goodness of vectors, as well as the intrinsic efficacy of a given gene construct . Furthermore, they are useful tools that may contribute to a better understanding of the mechanistic gene transfer process of each vector.

Int Microbiol, 1999 Jun, 2(2), 61 - 8
David Hopwood and the emergence of Streptomyces genetics; Chater K; Streptomyces spp . are unusual among bacteria in growing as mycelial colonies with sporulating aerial hyphae . They are very important as the source of most of the major antibiotics . Pioneering work by David Hopwood in the 1950s and 1960s established Streptomyces coelicolor A3(2) as the model system for the genus . Since then he has led successive key phases of research on this organism . In the 1970s, plasmids were discovered and characterised, and used both to establish conditions for transformation and in the subsequent development of cloning vectors . Protoplasts were exploited in both transformation and highly efficient cell fusion . In the 1980s, the early cloning of resistance genes from antibiotic-producing strains was followed by the cloning of antibiotic biosynthetic gene clusters, and the development of general methods and probes for the cloning of such clusters from diverse species . Analysis of these gene sets led to wide-ranging inferences about the biosynthesis of the important polyketide class of antibiotics, and to the production of hybrid antibiotics, and then, in the last decade, to more sophisticated combinatorial biosynthesis of designer molecules . In parallel, David Hopwood's work has also provided a crucial platform for studies of the regulation of the morphological and physiological differentiation that is manifested by sporulating antibiotic-producing colonies . Most recently, his involvement in the physical mapping of the entire 8 Mb genome of S . coelicolor A3(2) has culminated in its complete DNA sequencing: a project that should be completed under his management during the year 2000.

Ear Nose Throat J, 2000 Nov, 79(11), 884 - 8, 890-2
Clinical experiences with acute mastoiditis--1988 through 1998; Lee ES et al.; The incidence of acute mastoiditis has declined dramatically during the postantibiotic era . Even so, antibiotic-resistant or unusual pathogens can still cause this disease entity . At our hospital, we documented an increase in antibiotic-resistant and atypical pathogens such as Actinomyces spp . and Mycobacterium tuberculosis . In this paper, we discuss the optimal diagnosis and treatment strategy for acute mastoiditis, and we describe our retrospective review of 13 patients with mastoiditis who were treated at our hospital from 1988 through 1998 . Eight of these patients recovered following treatment with intravenous antibiotics, with or without myringotomy, and five who had complications of disease were managed surgically . Among these five, one developed chronic otitis media and one developed cholesteatoma 3 years later . For patients with acute mastoiditis, we emphasize the need to be aware of any unusual pathogens that do not respond to empiric antibiotic therapy.

J Vet Pharmacol Ther, 2000 Oct, 23(5), 281 - 5
Pharmacokinetics and residual behaviour in milk of oxytetracycline in cows following administration of uterine pessaries; Roncada P et al.; The plasma kinetics and residual depletion in milk of cows treated by the intrauterine route with pessaries containing oxytetracycline (OTC) were evaluated . The antibiotic was administered to five healthy Friesian cows at a dosage of 3g/head in the early post partum phase . Blood samples were collected before and at different time intervals (3, 6, 12, 24, 48, 72, 84, and 96 h) after treatment . Milk was drawn before treatment and at 12-h intervals for 4 consecutive days . Samples were analysed by a high-performance liquid chromatography method and the pharmacokinetic parameters were processed using the minimum Akaike information criterion estimation (MAICE) test . The mean values obtained indicated a relatively low area under the concentration time curve (25.19+/-12.61 microg/mg per h) and maximum plasma concentration (Cmax) (0.549+/-0.278 microg/mL) with delayed time to Cmax (11.71+/-4.15 h) and elimination half-life (21.96+/-4.42 h) . A similar pattern could be shown for milk, in which measurable residual levels are found in two out of five animals until the 72nd hour after treatment . Data obtained demonstrate that OTC administered as a solid form is poorly and slowly absorbed from the uterus of cows.

J Chromatogr A, 2000 Oct 20, 895(1-2), 67 - 79
Capillary electrophoresis analysis of gentamicin sulphate with UV detection after pre-capillary derivatization with 1,2-phthalic dicarboxaldehyde and mercaptoacetic acid; Kaale E et al.; A selective, sensitive, and rapid pre-capillary derivatization method for determination of the multicomponent aminoglycoside antibiotic gentamicin is described . The derivatization reagents 1,2-phthalic dicarboxaldehyde and mercaptoacetic acid were used and the thioisoindole derivative was UV detected at 330 nm . A central composite experimental design was performed to optimize selectivity and derivatization conditions . Baseline separation of gentamicin C1, C1a, C2, C2a, C2b, sisomicin and several minor components was achieved with a background electrolyte containing 30 mM sodium tetraborate, 7.5 mM beta-cyclodextrin and 12.5% (v/v) methanol at pH 10 . Quantitative analysis was performed and illustrated the potential use of capillary electrophoresis for the identification and quantitation of gentamicin as an alternative to methods prescribed in the United States Pharmacopeia and European Pharmacopoeia.

J Neurosurg Sci, 2000 Jun, 44(2), 107 - 12
Cranio-orbital missile wound and bullet migration . Case report; Rinaldi A et al.; An unusual case of craniocerebral missile injury, with orbital roof perforation and spontaneous bullet migration into the maxillary sinus, is reported . Emergency treatment consisted in wide craniectomy around the bullet entry point, blood and foreign bodies debridement . Subsequent procedures were necessary for abscess evacuation, transmaxillary bullet removal and later cranial vault reconstruction . Challenging aspects were the treatment of the infectious complications, following cerebrospinal fluid fistula through the wound, and the onset of post-traumatic epilepsy, scarcely responsive to common antiepileptic drugs . The treatment of the abscess by combined systemic and intracavitary antibiotic therapy and of the chronic seizures by progressive adjustment with new protocols of antiepileptic drugs under EEG and brain mapping revealed successful.

J Emerg Nurs, 2000 Dec, 26(6), 549 - 53
ED "hold" patients: is their care also being held?
Sobie JM, Gaves D, Tringali A.
INTRODUCTION: Patient care should be governed by the same standards of care regardless of location within a hospital system . Little is known about adherence to standards of care for admitted patients who are "held" in the emergency department because of an unavailable inpatient bed . For example, is there a difference in the timeliness of nursing assessments and initial antibiotic administration for patients with pneumonia who are held in the emergency department compared with those who are directly admitted to an inpatient bed? METHODS: A descriptive comparison research design with 2 known groups ("ED hold" patients and "ED direct-admit" patients) was used . A convenience sample of 104 closed medical records was obtained from a Midwestern hospital for a retrospective chart audit . RESULTS: Patients held in the emergency department had their blood pressure, pulse, respiratory rate, and oxygen saturation recorded with greater frequency compared with patients who were directly admitted . Directly admitted patients had their intake and output and their temperature noted with greater frequency . Although there was no statistically significant difference in the timeliness of respiratory assessments or antibiotic administration, antibiotics were delivered to the ED direct-admit group an average of 1 hour earlier than to the ED hold group . DISCUSSION: When measuring only the frequency and/or timeliness of taking vital signs, recording intake and output, and administering antibiotics, there were statistical differences between "hold" patients and "direct-admit" patients . In some instances, ED "hold" patients actually received more timely assessment than did "direct-admit" patients . Direct-admit patients received antibiotics an average of 1 hour sooner . More studies are necessary to evaluate other aspects of care that may or may not be compromised when admitted patients are "held" in the emergency department.

Actas Urol Esp, 2000 Sep, 24(8), 677 - 8
{Self-administration of an oil solution in the penis}; Rebassa Llull MJ et al.; We report the case of a patient who has autoinjected himself the penis and the scrotum with a solution constituted by petroleum, vaseline, oxygenated water and ketoconazol gel . Treatment consists in the excision of the injected deposit of lipid material and antibiotic therapy with good result at 4 months . We review the existing literature related with this exceptional pathology.

Actas Urol Esp, 2000 Sep, 24(8), 652 - 8
{Malignant neoplasms of the penis}; Banon Perez VJ et al.; OBJECTIVE: To assess the behaviour and management of these uncommon neoplasias . MATERIAL AND METHODS: Between March 1975 and July 1999, a total of 95 malignant neoplasias of the penis were diagnosed and treated by our unit . Patients mean age was 62 years (28 to 87 years) . A retrospective analysis of any associated lesions, biological behaviour of the various neoplasias, as well as therapies used is carried out . RESULTS: The squamous carcinoma of the penis (SCP) is the most frequent pathohistological entity entailing 78 cases (82%), followed by verrucous carcinoma (VC) 13 cases (13.5%), basal cells carcinoma 1 case, and melanoma, lymphoma and penile metastasis 1 case each . There is a significant presence of associated lesions with marked predominance of phimosis . The most frequent reason for the call is an injury of the penis (74 cases; 78%) . Treatment was mainly partial penectomy (51 patients; 53.7%), followed by conservative treatment in 28 cases (30%) . Inguinal lymphadenectomy was performed in 13 patients (14%), due to either a positive nodular biopsy or a persistent adenopathy following antibiotic therapy . CONCLUSIONS: Neoplasias showing superior biological behaviour are basal cell carcinoma of the penis, and verrucous carcinoma . Prognosis in SCP is based on pathological status and node involvement . Patients with pT1 tumours showed no metastatic adenopathies after follow-up regardless of cytological grading, and are therefore candidates to watchful waiting with regular monitoring . Melanoma of the penis is a highly aggressive tumour due to its high metastatic capacity with a poor prognosis.

Biochemistry, 2000 Dec 5, 39(48), 14968 - 75
DNA binding and alkylation by the "left half" of azinomycin B; Zang H et al.; Azinomycin B (also known as carzinophilin A) contains two electrophilic functional groups-an epoxide and an aziridine residue-that react with nucleophilic sites in duplex DNA to form cross-links at 5'-dGNT and 5'-dGNC sequences . Although the aziridine residue of azinomycin is undoubtedly required for cross-link formation, analogues containing an intact epoxide group but no aziridine residue retain significant biological activity . Azinomycin epoxide analogues (e.g., 5 and 6) are of interest due to their potent biological activity and because there is evidence that azinomycin may decompose in vivo to yield such compounds . To investigate the chemical events underlying the toxicity of azinomycin epoxides, DNA binding and alkylation by synthetic analogues of azinomycin B (6, 8, and 9) that comprise the naphthalene-containing "left half" of the antibiotic have been investigated . The epoxide-containing analogue of azinomycin (6) efficiently alkylates guanosine residues in duplex DNA . DNA alkylation by 6 is facilitated by noncovalent binding of the compound to the double helix . The results of UV-vis absorbance, fluorescence spectroscopy, DNA winding, viscometry, and equilibrium dialysis experiments indicate that the naphthalene group of azinomycin binds to DNA via intercalation . Equilibrium dialysis experiments provide an estimated binding constant of (1.3 +/- 0.3) x 10(3) M(-)(1) for the association of a nonalkylating azinomycin analogue (9) with duplex DNA . The DNA-binding and alkylating properties of the azinomycin epoxide 6 provide a basis for understanding the cytotoxicity of azinomycin analogues which contain an epoxide residue but no aziridine group and may provide insight into the mechanisms by which azinomycin forms interstrand DNA cross-links.

Thorac Cardiovasc Surg, 2000 Oct, 48(5), 290 - 3
Surgical outcome of mycobacterium other than mycobacterium tuberculosis pulmonary disease; Tsunezuka Y et al.; Between January 1995 and May 1999, MOTT were cultured from sputum, bronchoalveolar lavage or resected lung specimens in 110 cases . 17 patients with MOTT pulmonary disease underwent pulmonary resection . Preoperatively, 5 of 17 patients had been diagnosed with MOTT pulmonary disease . The diagnosis of others was based on positive cultures from surgically resected material, and organism identification was successfully performed by the microplate DNA-DNA hybridization procedure . Surgical resections performed included wedge resection in 7, lobectomy in 6, and segmentectomy in 4 . Antibiotics were generally continued for 6 to 24 months postoperatively . However, postoperative antibiotics therapy was not performed for patients who were postoperatively diagnosed with foci localized at the peripheral lung . Resected specimens yielded positive cultures for MOTT in all patients . There were no patients infected with M . konsasii . Regarding postoperative complications, 1 late bronchopleural fistula developed after right upper and middle lobectomy, and was treated with omentopexy . Persistent air leaks (> 7 days) occurred in 5 patients, none of which occurred where linear stapling devices fitted with expanded polytetrafluoroethylene (ePTFE) sleeves were used . One patient diagnosed with M . szulgai postoperatively experienced reactivation 2 years after middle lobectomy despite postoperative antibiotic therapy for 6 months . Other patients have remained free of disease postoperatively . Surgical resection achieve good results for MOTT pulmonary disease, and wedge resection or segmentectomy without postoperative antibiotic therapy was enough for patients whose foci localized at the peripheral lung and whose sputum or BAL cultures revealed no MOTT . Surgical treatment should be performed as early as possible before the pulmonary disease necessitates an extensive operation, and ePTFE sleeves were effective in preventing a postoperative prolonged air leak.

Int Anesthesiol Clin, 2000 Fall, 38(4), 1 - 29
Management of the septic patient in the operating room; Jodka PG et al.; Sepsis, severe sepsis, and septic shock represent the spectrum of physiological response to a variety of infecting pathogens . Multiple-organ dysfunction may result from widespread activation of inflammatory and antiinflammatory mechanisms . Intensive multiorgan support, effective antibiotic therapy, and eradication of the inciting source remain the cornerstones in the care of septic patients . Perioperative planning and management need to ensure the continuation of such care in addition to providing for the requirements of the given surgical procedure.

Curr Opin Pulm Med, 2000 Nov, 6(6), 551 - 7
Outpatient care of the cystic fibrosis patient after lung transplantation; Yankaskas JR et al.; Lung transplantation has become an accepted treatment for respiratory failure due to cystic fibrosis (CF) . Effective means of patient selection, surgical technique, immunosuppression, and post-transplant management permit survival as good as that of transplant patients with other diseases . The new lungs do not acquire the CF ion transport abnormalities but are subject to the usual post-transplant complications . CF problems in other organ systems persist and may be worsened by some of the immunosuppressive regimens . Prolonged survival increases the risk of age-related CF and other complications . Effective medical management requires expert knowledge of CF and lung transplantation and of how their problems interact, and good communications among the participating care teams.

Pediatr Infect Dis J, 2000 Nov, 19(11), 1071 - 4
Clinical sinusitis in children attending primary care centers; Kakish KS et al.; OBJECTIVES: To determine the proportion of children who meet the clinical criteria for the diagnosis of sinusitis among all children attending primary care pediatric practices, to explore the relationship between passive smoking and the occurrence of sinusitis and to study the role of antibiotics in the management of sinusitis . DESIGN: A prospective observational cohort study . SETTING: Outpatient Pediatric Clinics of Jordan University of Science and Technology and Princess Rahma Teaching Hospital . Patients . All children ages 1 to 10 years presenting for any reason to participating practices . METHODS: Physicians participating in this study completed a questionnaire on all children attending the primary care centers, detailing the presence of nasal congestion or discharge, the duration of symptoms, daytime cough and whether symptoms were improving . The presence or absence of smokers in the family was also recorded . Children meeting our clinical criteria for sinusitis were further evaluated for other signs and symptoms including the type of medication prescribed . The severity of symptoms was reassessed at 10-day follow-up after the first visit . RESULTS: The study population was composed of 3001 children, of whom 249 met our clinical criteria for diagnosis of sinusitis (8.3%; 95% confidence interval, 7.3 to 9.3%) . The prevalence rate of clinical sinusitis was greater among children age 5 years and older than among those younger (9.3% vs . 7.2%, P = 0.04) . Children exposed to passive smoking in the household had clinical sinusitis significantly more than those not exposed (68.8% vs . 1.2%, P = 0.00) . Antibiotics were prescribed for 80% of children who fulfilled the clinical criteria for diagnosis of sinusitis . Marked improvement of symptoms at the 10-day follow-up visit was reported among those who received antibiotics compared with those who did not (91% vs . 21.4%, P = 0.00) . CONCLUSIONS: Sinusitis is not an uncommon problem in children, passive smoking might be a contributing factor and a course of antibiotic therapy is beneficial.

Complement Ther Med, 2000 Dec, 8(4), 276 - 9
Effect of Mao-bushi-saishin-to on infection of ofloxacin resistant bacteria and of unknown origin; Kamei T et al.; When seven elderly patients with fever due to bacterial infection failed to respond to ofloxacin 300 mg/day for 3 days, we prescribed Mao-bushi-saishin-to for 7 days . Bushi, one of the components of Mao-bushi-saishin-to, is a complex of various alkaloids, which is known to stimulate the conducting system of the heart, so half of the standard dose was prescribed for these patients . We assessed changes in the patients' body temperatures and serum C-reactive protein concentrations . As a result, the patients' body temperatures all fell to under 37 degrees C and C-reactive protein levels decreased from an average of 3.06 mg/dl to an average of 0.36 mg/dl (P< 0.02) . In cases where a fever does not decrease through dosage of an antibiotic such as ofloxacin after about 3 days, half of the standard dose of Mao-bushi-saishin-to for 7 days should be considered as a complementary therapy .

Folia Microbiol (Praha), 1999, 44(6), 663 - 8
Nikkomycin Z counteracts Rylux BSU and Congo red inhibition of Saccharomyces cerevisiae growth but does not prevent formation of aberrant cell walls; Raclavsky V et al.; Rylux BSU and congo red bind to chitin, interfere with proper cell-wall assembly, and stimulate chitin synthesis by increasing, most probably, chitin synthase 3 (ChS3) levels in Saccharomyces cerevisiae . On the other hand, the antibiotic nikkomycin Z inhibits chitin synthesis competitively . As ChS3 is the critical target of nikkomycin Z, its effect was tested in cells inhibited in growth by Rylux BSU or Congo red . Nikkomycin Z counteracted this inhibition but did not counteract aberrant cell-wall formation . These results indicate that chitin synthesis stimulation is the key step in Rylux BSU and congo red inhibition and support the idea that increase in chitin synthesis represents a compensatory response to damaged cell-wall structure . As Rylux BSU and congo red bind to newly synthesized chitin, further damage is caused in the wall and the response works in this case contrariwise . Nikkomycin Z breaks this vicious circle by counteracting the chitin synthesis stimulation.

Am J Kidney Dis, 2000 Dec, 36(6), 1267 - 70
Successful medical treatment of acute bilateral emphysematous pyelonephritis; Tahir H et al.; Emphysematous pyelonephritis most often presents as an acute medical emergency, typically in a septic diabetic patient with acute renal failure . The management of this condition has traditionally been surgical, with nephrectomy . However, some recent reports have described successful medical interventions . We describe a case of acute bilateral emphysematous pyelonephritis in a frail patient not suitable for bilateral nephrectomy and long-term dialysis . This condition was managed medically, not surgically, with intensive antibiotic and circulatory support . The outcome was complete recovery after months of hospital-based treatment . We discuss the management of this rare but important condition in detail.

Am J Kidney Dis, 2000 Dec, 36(6), 1183 - 92
Factors predicting outcome of fungal peritonitis in peritoneal dialysis: analysis of a 9-year experience of fungal peritonitis in a single center; Wang AY et al.; Fungal peritonitis causes significant morbidity and mortality for patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . We retrospectively reviewed 70 episodes of fungal peritonitis in a single center over the last 9 years in 896 CAPD patients . Seventy percent of the episodes of fungal peritonitis were caused by CANDIDA: species, among which 50% were CANDIDA: parapsilosis . As a result of fungal peritonitis, 44% of the patients died, whereas further peritoneal dialysis failed in 14%, requiring a change to long-term hemodialysis . Only 37% managed to continue CAPD . The remaining 5% either underwent transplantation or were lost to follow-up . We identified the factors associated with poor outcome, namely mortality and technique failure . The presence of abdominal pain, bowel obstruction, and a catheter remaining in situ were significantly associated with greater mortality . Abdominal pain, antibiotic use within 3 months before fungal peritonitis, and complication by bowel obstruction were associated with greater technique failure . In choosing antifungal agents with catheter removal, oral fluconazole alone appears equally as effective as combined oral fluconazole with 5-flucytosine for peritonitis caused by CANDIDA: species . For peritonitis caused by species other than CANDIDA:, the choice of antifungal therapy needs to be individualized, based on fungal species and sensitivities.

Jpn J Clin Oncol, 2000 Sep, 30(9), 401 - 5
Bacterial meningitis observed in a phase I trial of vinorelbine, cisplatin and thoracic radiotherapy for non-small cell lung cancer: report of a case and discussion on dose-limiting toxicity; Sekine I et al.; Although neutropenia increases the risk of life-threatening infections, bacterial meningitis is rarely encountered as a complication during cancer chemotherapy in adults with a solid tumor . A 66-year-old male with adenosquamous carcinoma of the lung, cT2N3M0, stage IIIB, was enrolled in a phase I trial of chemoradiotherapy and treated with cisplatin 80 mg/m2 (122 mg/ body) on day 1, vinorelbine 20 mg/m2 (32 mg/body) on days 1 and 8 and thoracic radiotherapy 30 Gy/15 fractions, beginning on day 2, with dexamethasone administered for antiemesis at a dose of 16 mg on day 1, 8 mg on days 2 and 3, 4 mg on day 4 and 2 mg on day 5 . The patient developed headache and fever on day 6 of the second cycle of the treatment and bacterial meningitis was diagnosed based on the findings of consciousness disturbance, an elevated peripheral blood leukocyte count and numerous leukocytes in the cerebrospinal fluid . In spite of the doctor's delay in establishing the exact diagnosis, the bacterial meningitis in this case was successfully treated with intensive antibiotic therapy . This life-threatening complication, equivalent to a grade 4 non-hematological adverse reaction, was not counted as dose-limiting toxicity in the current phase I trial, because there are only a few reports of bacterial meningitis associated with cancer chemotherapy and it developed in this case without any associated decrease in the peripheral blood leukocyte count.

Chem Biol, 2000 Nov, 7(11), 895 - 905
A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis; Aparicio JF et al.; BACKGROUND: Polyene macrolides are a class of large macrocyclic polyketides that interact with membrane sterols, having antibiotic activity against fungi but not bacteria . Their rings include a chromophore of 3-7 conjugated double bonds which constitute the distinct polyene structure . Pimaricin is an archetype polyene, important in the food industry as a preservative to prevent mould contamination of foods, produced by Streptomyces natalensis . We set out to clone, sequence and analyse the gene cluster responsible for the biosynthesis of this tetraene . RESULTS: A large cluster of 16 open reading frames spanning 84985 bp of the S . natalensis genome has been sequenced and found to encode 13 homologous sets of enzyme activities (modules) of a polyketide synthase (PKS) distributed within five giant multienzyme proteins (PIMS0-PIMS4) . The total of 60 constituent active sites, 25 of them on a single enzyme (PIMS2), make this an exceptional multienzyme system . Eleven additional genes appear to govern modification of the polyketide-derived framework and export . Disruption of the genes encoding the PKS abolished pimaricin production . CONCLUSIONS: The overall architecture of the PKS gene cluster responsible for the biosynthesis of the 26-membered polyene macrolide pimaricin has been determined . Eleven additional tailoring genes have been cloned and analysed . The availability of the PKS cluster will facilitate the generation of designer pimaricins by combinatorial biosynthesis approaches . This work represents the extensive description of a second polyene macrolide biosynthetic gene cluster after the one for the antifungal nystatin.

Chem Biol, 2000 Nov, 7(11), 821 - 31
The NDP-sugar co-substrate concentration and the enzyme expression level influence the substrate specificity of glycosyltransferases: cloning and characterization of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster; Hoffmeister D et al.; BACKGROUND: Streptomyces fradiae is the principal producer of urdamycin A . The antibiotic consists of a polyketide-derived aglycone, which is glycosylated with four sugar components, 2x D-olivose (first and last sugar of a C-glycosidically bound trisaccharide chain at the 9-position), and 2x L-rhodinose (in the middle of the trisaccharide chain and at the 12b-position) . Limited information is available about both the biosynthesis of D-olivose and L-rhodinose and the influence of the concentration of both sugars on urdamycin biosynthesis . RESULTS: To further investigate urdamycin biosynthesis, a 5.4 kb section of the urdamycin biosynthetic gene cluster was sequenced . Five new open reading frames (ORFs) (urdZ3, urdQ, urdR, urdS, urdT) could be identified each one showing significant homology to deoxysugar biosynthetic genes . We inactivated four of these newly allocated ORFs (urdZ3, urdQ, urdR, urdS) as well as urdZ1, a previously found putative deoxysugar biosynthetic gene . Inactivation of urdZ3, urdQ and urdZ1 prevented the mutant strains from producing L-rhodinose resulting in the accumulation of mainly urdamycinone B . Inactivation of urdR led to the formation of the novel urdamycin M, which carries a C-glycosidically attached D-rhodinose at the 9-position . The novel urdamycins N and O were detected after overexpression of urdGT1c in two different chromosomal urdGT1c deletion mutants . The mutants lacking urdS and urdQ accumulated various known diketopiperazines . CONCLUSIONS: Analysis of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster revealed a widely common biosynthetic pathway leading to D-olivose and L-rhodinose . Several enzymes responsible for specific steps of this pathway could be assigned . The pathway had to be modified compared to earlier suggestions . Two glycosyltransferases normally involved in the C-glycosyltransfer of D-olivose at the 9-position (UrdGT2) and in conversion of 100-2 to urdamycin G (UrdGT1c) show relaxed substrate specificity for their activated deoxysugar co-substrate and their alcohol substrate, respectively . They can transfer activated D-rhodinose (instead of D-olivose) to the 9-position, and attach L-rhodinose to the 4A-position normally occupied by a D-olivose unit, respectively.

Curr Treat Options Gastroenterol, 1999 Jun, 2(3), 171 - 182
Helicobacter Pylori; Chey WD; All infected patients with a peptic ulcer should be treated for H . pylori . The role of treating H . pylori in patients with undiagnosed dyspepsia or non-ulcer dyspepsia, those taking nonsteroidal anti-inflammatory medications, or with a family history of gastric cancer remains controversial . Triple therapies consisting of a proton pump inhibitor or ranitidine bismuth citrate and two antibiotics are the current standard of therapy for H . pylori . In general, dual therapies should no longer be used to treat H . pylori . Bismuth triple therapy consisting of bismuth, tetracycline, and metronidazole is a less expensive alternative to proton pump inhibitor-or ranitidine bismuth citrate-based triple therapies . However, bismuth triple therapy is hampered by frequent side effects and the need for qid dosing . In Europe, a 7-day course of therapy appears to be adequate . In the United States, 10-14 days of therapy are currently recommended . Metronidazole resistance in H . pylori strains varies geographically, and negatively influences the effectiveness of therapies containing this antibiotic . Clarithromycin resistance is relatively infrequent at the current time but may be rising in countries where this antibiotic is in use . If a patient remains infected after a course of therapy for H . pylori, the second treatment should avoid the antibiotics used initially.

Curr Treat Options Gastroenterol, 1999 Apr, 2(2), 86 - 90
Pyogenic Liver Abscess; Olivera MA et al.; The percutaneous approach-specifically, ultrasound-guided percutaneous catheter drainage-associated with intravenous administration of antibiotics is the therapy of choice in patients with single or multiple pyogenic liver abscesses . The initial empiric antibiotic therapy should be modified based on results of blood and pus cultures . Surgery should be reserved for patients in whom antibiotic therapy and percutaneous drainage is unsuccessful.

Curr Treat Options Cardiovasc Med, 2000 Aug, 2(4), 343 - 350
Purulent Pericarditis; Goodman LJ; Purulent pericarditis represents a subset of pericardial disease usually due to a nonviral infectious agent . The presentation is often acute, with rapid progression to tamponade unless a drainage procedure is performed . Although several infectious agents account for the majority of infections, the differential diagnosis is broad . Often, patients with more exotic infectious causes have risk factors for these agents that can be identified by careful history-taking . Distinguishing a bacteremic source from infection acquired by contiguous spread is particularly important . Although most infections spread contiguously are a complication of recent surgery or nearby pneumonia and are, therefore, apparent to the physician, others may be less obvious . For example, head and neck space infections may track to the retropharyngeal space and, from there, posteriorly to the so-called "danger" space, which connects inferiorly to the mediastinum and the pericardium . Failing to identify this source of tracking infection may lead to inadequate drainage as well as inappropriate empiric antibiotic therapy . In acute cases, needle drainage with appropriate staining and culturing of the fluid is adequate for diagnosis and initial management of the complications of fluid collection in the closed space of the pericardial sac . Pericardial biopsy may be the sole method of identifying an etiologic agent, particularly in chronic cases in which granulomatous disease is more commonly seen . In select cases, pericardial window or pericardiectomy procedures are needed to limit complications of reaccumulation of fluid.

Curr Infect Dis Rep, 2000 Aug, 2(4), 337 - 344
Bacterial Meningitis: Principles and Practical Aspects of Therapy; Aronin SI; Acute bacterial meningitis continues to be associated with significant morbidity and mortality . Recent research efforts to improve outcome for such patients have focused on antibiotic-cerebrospinal fluid interactions, factors influencing antibiotic selection, indications for cranial imaging, the role of anti-inflammatory agents, and the impact of antibiotic timing on outcome . In this article, I use an illustrative case to review timely data on these topics and provide guidelines for the empiric and pathogen-directed treatment of patients with acute bacterial meningitis.

Curr Infect Dis Rep, 2000 Aug, 2(4), 299 - 301
Update on Lyme Carditis; Bateman H et al.; Lyme carditis is an uncommon manifestation of infection with Borrelia bugdorferi . It is easily treated with standard antibiotic regimens and prognosis is excellent, especially if treatment is prompt . For symptomatic or higher degrees of block, patients may require hospitalization for monitoring and occasionally temporary external pacing . Intravenous antibiotics are warranted for such patients . For less severe conduction disturbances, oral therapy suffices.

Curr Infect Dis Rep, 1999 Aug, 1(3), 267 - 272
Prosthetic Joint Infection; Berendt AR et al.; Total joint replacement has been one of the most remarkable successes of modern medical technology . Once John Charnley had solved the problems of implant design, choice of materials, implant fixation, and infection (initial rates of infection were approximately 10%), the way was clear for the widespread use of this valuable treatment, which is highly effective at removing pain and restoring function . Unfortunately, infection still remains an important, though less common, problem . It is associated with serious morbidity (pain, loss of function, wound breakdown, wound discharge, implant failure) and sometimes mortality . It may be impossible to eradicate or suppress infection in the long term without removal of the prosthesis, and most clinicians would consider it unwise to re-implant a new prosthesis in the presence of infection . Hence, patients with infected prosthetic joints generally require multiple additional operations and prolonged periods of antibiotic therapy . Even radical attempts at cure may fail (in 10% to 15% of cases in most series), requiring further cycles of treatment with progressively deteriorating function . Thus, the treatment of prosthetic joint infection is arduous for the patient and the health care team, with no guarantee of success.

Curr Infect Dis Rep, 1999 Aug, 1(3), 261 - 266
Osteomyelitis; Sax H et al.; Despite significant progress in antibiotic therapy and orthopedic surgery, osteomyelitis remains a difficult-to-treat infection that is often associated with recurrence . In this paper we summarize the most recent developments in understanding the pathogenesis of this complex disease, as well as novel means for its diagnosis and treatment.

Curr Infect Dis Rep, 1999 Apr, 1(1), 22 - 26
Current Concepts of Therapy for Otitis Media; Wientzen RL et al.; The therapy for acute otitis media is currently a topic in evolution . What was once a straightforward approach of matching middle ear pathogens to appropriate antibiotics has become a complex calculus that attempts to balance multiple terms such as spontaneous cure, emergence of resistance, pharmacokinetics-dynamics, antibiotic therapeutic efficacy, suppurative complications, and cost . This review highlights new developments in our understanding of this complex interaction of the issues surrounding a physician's decision to begin antibiotic therapy for acute otitis media.

Acta Crystallogr D Biol Crystallogr, 2000 Dec, 56 Pt 12, 1647 - 51
Crystallization and preliminary X-ray analysis of tetracenomycin A2 oxygenase: a flavoprotein hydroxylase involved in polyketide biosynthesis; Beynon J et al.; The tcm operon in Streptomyces glaucescens encodes a group of enzymes involved in the synthesis of the polyketide tetracenomycin (Tcm) C that exhibits both antitumor and antibiotic activities . Here, the crystallization and preliminary data characterization of the tcmG gene product, Tcm A2 oxygenase, which catalyzes the triple hydroxylation of Tcm A2 to form Tcm C, are reported . Tcm A2 oxygenase crystallizes in two different space groups, both with six monomers per asymmetric unit, resulting in large unit-cell parameters . Synchrotron data have been collected from both the hexagonal and tetragonal crystal forms to 4.5 and 4.2 A, respectively . The self-rotation function searches in both space groups suggest the monomers assemble into a complex with D(3) symmetry.

Cell Mol Life Sci, 2000 Oct, 57(11), 1562 - 9
Cellular and molecular aspects of Lyme arthritis; Gross DM et al.; Lyme disease is a multisystem illness initiated upon infection with the spirochete Borrelia burgdorferi . Whereas the majority of patients who develop Lyme arthritis may be successfully treated with antibiotic therapy, about 10% go on to develop arthritis which persists for months to years, despite antibiotic therapy . Development of what we have termed treatment-resistant Lyme arthritis has previously been associated with both the presence of particular major histocompatibility complex class II alleles and immunoreactivity to the spriochetal outer surface protein A (OspA) . Recently, we showed that patients with treatment-resistant Lyme arthritis, but not patients with other forms of arthritis, generate synovial fluid T cell responses to an immunodominant epitope of OspA and a highly homologous region of the human-lymphocyte-function-associated antigen-1alphaL chain . Identification of a bacterial antigen capable of propagating an autoimmune response against a self-antigen provides a model of molecular mimicry in the pathogenesis of treatment-resistant Lyme arthritis.

J Int Med Res, 2000, 28 Suppl 1, 37A - 47A
How short can courses be in lower respiratory tract infections?
Siegel R.
Prospective clinical studies conducted over the last 10 years provide data on which to base decisions regarding the treatment of community-acquired pneumonia (CAP), including the need for hospitalization, optimal timing of the switch from intravenous to oral antibiotic therapy and the discharge of patients . Validated treatment algorithms, such as the classification of community-acquired pneumonia, now enable decisions to be made on which patients with CAP require hospitalization, as well as identifying those who will benefit from early switch therapy . Generally, unstable CAP patients are suitable candidates for early switch therapy, which consists of rapid initiation of 1 - 2 days' intravenous therapy followed by 5 days' oral therapy, with early discharge from hospital after the receipt of one or two doses of oral antibiotic . Studies with intravenous cefuroxime and followed by oral cefuroxime axetil suggest this regimen is both effective and well tolerated as rapid switch therapy, and has the potential to reduce overall healthcare costs and improve patient satisfaction.

Int J Clin Pract, 2000 Jul-Aug, 54(6), 353 - 5
Ceftriaxone-PMMA beads--a slow release preparation?
Alonge TO, Fashina AN.
The use of various drug delivery systems to achieve high levels of the desired antibiotic(s) at the site of infection has become commonplace in orthopaedic and trauma units the world over . One of these techniques uses the implantation of antibiotic-impregnated beads at operation sites . Commercial antibiotic beads such as the gentamicin bead are available but expensive, especially for patients in developing countries . We have shown that ceftriaxone-polymethylmethacrylate beads can be produced locally and at low cost in a resource-poor environment . We have also shown that such beads elute the antibiotic (ceftriaxone) effectively in vitro, achieving similar or better activity when measured by zones of inhibition against various bacteria species compared with standard antibiotic discs . This technique offers a cost-effective method of treating chronic bone infections in resource-poor settings.

J Hematother Stem Cell Res, 2000 Oct, 9(5), 645 - 9
Clinical and laboratory features predicting a favorable outcome and allowing early discharge in cancer patients with low-risk febrile neutropenia: a literature review; Castagnola E et al.; To value feasibility of early discharge in febrile granulocytopenic patients, 27 original paper published in the last 11 years were analyzed concerning these clinical and therapeutic approaches . A Medline search of English language literature published in the last 11 years (1988-1999) used the key words neutropenia, fever, cancer, home-antibiotic therapy, short course of antibiotic therapy, and early discharge . Twenty-seven original papers fulfilling the study criteria were identified . In these studies, 5208 episodes were evaluated: there were 538 failures with 87 deaths . Features of low-risk patients who developed life-threatening infectious disease were related to general clinical condition, cancer control, bone marrow function, presence of clinical signs of infection, and social features . Careful risk assessment can allow safe recognition of low-risk patients with febrile neutropenia who can be discharged early and can be used to follow outpatient treatment programs to improve patients' quality of life as well as the use of economic resources.

Artif Organs, 2000 Oct, 24(10), 829 - 33
Specific determination of endothelial cell viability in the whole cell fraction from cryopreserved canine femoral veins using flow cytometry; Park JC et al.; Abstract: An efficient method for specifically determining the viability of endothelial cells (EC) from cells dissociated from the human saphenous vein was investigated . Three different methods, trypan blue staining assay, {3H}-proline incorporation assay, and flow cytometry (FCM), combined with the fluorescein isothiocyanate conjugated with Griffonia simplicifolia agglutins (GS1-FITC)/propidium iodide (PI) double staining, were used . Both trypan blue staining and {3H} proline incorporation assays demonstrated less sensitivity to determine viability of EC differentially from the other cells . FITC-GS1 showed prominent binding to the vascular EC and could be counted by FCM including PI on dead cells . Following the cryopreservation process, the GS1-FITC/PI FCM analytical method was adopted to test simultaneously the viability of whole cells and EC from the same tissue, human saphenous veins, and mongrel dogs' femoral veins after harvesting, antibiotic solution treatment, and thawing . The viability of the whole cells from veins decreased with a significant difference (p < 0.05) from that of EC after thawing.

Am J Cardiol, 2000 Dec 1, 86(11), 1279 - 81, A9
Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy; Ishii M et al.; This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals . A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs . The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.

Int J Immunopharmacol, 2000 Nov, 22(11), 935 - 42
Modification of tumor necrosis factor-induced acute toxicity D-galactosamine challenge by polymyxin B, an anti-endotoxin; Sakaguchi S et al.; Polymyxin B (PMB), an antibiotic with anti-endotoxin activity, was used to examine the participation of endogenously produced endotoxin in the enhancement of recombinant human tumor necrosis factor (rhTNF)-induced toxicity in D-galactosamine (GalN)-sensitized mice . GalN-sensitized mice (700 mg/kg, intraperitoneally (i.p.)) injected together with rhTNF (1x10(4) U/mouse, intravenously (i.v.)) exhibited severe symptoms, with 100% mortality at 18 h . However, mice pretreated with PMB (20 mg/kg, i.p.) showed protection against the rhTNF-induced lethality following GalN sensitization . Little or no effects were observed on alanine aminotransferase (ALT) activity or lactate dehydrogenase (LDH) isozyme leakage in serum in mice 7 h after administration of rhTNF alone . Administration of rhTNF to GalN-sensitized mice resulted in marked increases in ALT activity and LDH isozyme leakage relative to those in mice treated with rhTNF alone . In mice pretreated with PMB, the levels of ALT and LDH isozyme leakage 7 h after rhTNF/GalN injection were significant decreased as compared with those in mice treated with rhTNF/GalN . Similarly, injection of PMB markedly decreased lipid peroxide formation in the liver of the GalN-sensitized mice treated with rhTNF . The injection of a low endotoxin dose (0.1 mg/kg, i.p.) markedly increased the lethality in mice treated with rhTNF (5x10(3) U/mouse, i.v.) and GalN, and these animals showed 100% mortality at 8 h . These findings suggested that the extent of TNF-induced toxicity caused by GalN administration may be a result of synergism between TNF and gut-derived endotoxin . It is likely that endogenously produced endotoxin play a significant role in rhTNF/GalN-hypersensitized mice.

Med Pregl, 2000 May-Jun, 53(5-6), 289 - 92
{Therapy of inflammatory changes in Bartholin's glands}; Bulatovic S et al.; INTRODUCTION: Bartholin's glands are bilateral structures whose function begins after puberty, so the diseases of these glands are most common during the reproductive period . Management of the inflammatory changes--abscess and cyst can be invasive and conservative, and quite often the changes become chronic, due to the failure of techniques . The aim of the study was to assess efficacy of various therapeutic approaches in the treatment of the inflammatory changes of Bartholin's glands . MATERIAL AND METHODS: The study was done at the Department of Obstetrics and Gynecology, Clinical Centre in Novi Sad, during the period 1993-1996, at the Dept . of Inflammatory Gynaecological Diseases . The total of 129 patients was treated . The first two years were analyzed retrospectively while during the years 1995 and 1996 a prospective study was done . The analysis of the therapeutic results was done according to the immediate efficacy of the therapeutic approach, incidence of recurrence, length of hospitalization and use of antibiotics . RESULTS: A total of 129 patients was treated, the mean age was 35.4 years . Cysts were treated in 14.7% and abscess in 85.3% of cases . Therapeutic approaches were different during different years . During 1993 and 1994 in majority of cases incision and complete extirpation of the glands were done, and rarely marsupialization, alone or in combination with silver nitrate (AgNO3) . In 1995 and 1996 in a majority of cases incision of the gland was performed, together with the AgNO3 application (94.3% in 1995, 64% in 1996) . In 1995 total gland extirpation was performed (5.7%) while in 1996 in 9 cases (36%) incision was done . The length of hospitalization was longer in earlier years, the shortest being when incision and AgNO3 application was performed (3.1/2.4 days) . The use of antibiotics was significantly lower in the years when incision and AgNO3 were used . DISCUSSION: Our results are in concordance with the results of similar studies except for the fact that in our group the changes were seen more often in the age group 30-39 years . The parity was of no significance . The recurrence of the disease when this method is applied is the same as in other studies--around 3%, whereas the complications were rare . The length of hospitalization and the cost of the antibiotic therapy is of great significance as well, and they can be brought to minimum by employment of this method . CONCLUSION: The therapeutic approach of incision and AgNO3 application in therapy of inflammatory changes of Bartholin's glands is an efficient, safe, simple and cheap method, which can easily be applied in ambulatory conditions.

Arch Intern Med, 2000 Nov 27, 160(21), 3243 - 7
Clinical signs and symptoms predicting influenza infection; Monto AS et al.; BACKGROUND: New antiviral drugs are available for the treatment of influenza type A and type B infections . In clinical practice, antiviral use has rarely been guided by antecedent laboratory diagnosis . Defined clinical predictors of an influenza infection can help guide timely therapy and avoid unnecessary antibiotic use . OBJECTIVE: To examine which clinical signs and symptoms are most predictive of influenza infection in patients with influenza-like illness using a large data set derived from clinical trials of zanamivir . METHODS: This analysis is a retrospective, pooled analysis of baseline signs and symptoms from phase 2 and 3 clinical trial participants . It was conducted in mainly unvaccinated (mean age, 35 years) adults and adolescents who had influenza-like illness, defined as having fever or feverishness plus at least 2 of the following influenza-like symptoms: headache, myalgia, cough, or sore throat who underwent laboratory testing for influenza . Clinical signs and symptoms were evaluated in statistical models to identify those best predicting laboratory confirmation of influenza . RESULTS: Of 3744 subjects enrolled with baseline influenza-like symptoms, and included in this analysis, 2470 (66%) were confirmed to have influenza . Individuals with influenza were more likely to have cough (93% vs 80%), fever (68% vs 40%), cough and fever together (64% vs 33%), and/or nasal congestion (91% vs 81%) than those without influenza . The best multivariate predictors of influenza infections were cough and fever with a positive predictive value of 79% (P< . 001) . The positive predictive value rose with the increase in the temperature at the time of recruitment . CONCLUSION: When influenza is circulating within the community, patients with an influenza-like illness who have both cough and fever within 48 hours of symptom onset are likely to have influenza and the administration of influenza antiviral therapy may be appropriate to consider . Arch Intern Med . 2000;160:3243-3247.

J Cell Biol, 2000 Nov 27, 151(5), 1025 - 34
Dissection of autophagosome biogenesis into distinct nucleation and expansion steps; Abeliovich H et al.; Rapamycin, an antifungal macrolide antibiotic, mimics starvation conditions in Saccharomyces cerevisiae through activation of a general G(0) program that includes widespread effects on translation and transcription . Macroautophagy, a catabolic membrane trafficking phenomenon, is a prominent part of this response . Two views of the induction of autophagy may be considered . In one, up-regulation of proteins involved in autophagy causes its induction, implying that autophagy is the result of a signal transduction mechanism leading from Tor to the transcriptional and translational machinery . An alternative hypothesis postulates the existence of a dedicated signal transduction mechanism that induces autophagy directly . We tested these possibilities by assaying the effects of cycloheximide and specific mutations on the induction of autophagy . We find that induction of autophagy takes place in the absence of de novo protein synthesis, including that of specific autophagy-related proteins that are up-regulated in response to rapamycin . We also find that dephosphorylation of Apg13p, a signal transduction event that correlates with the onset of autophagy, is also independent of new protein synthesis . Finally, our data indicate that autophagosomes that form in the absence of protein synthesis are significantly smaller than normal, indicating a role for de novo protein synthesis in the regulation of autophagosome expansion . Our results define the existence of a signal transduction-dependent nucleation step and a separate autophagosome expansion step that together coordinate autophagosome biogenesis.

J Biol Chem, 2001 Mar 2, 276(9), 6529 - 36 Epub 2000 Nov 20.
Activation of the endothelial nitric-oxide synthase by tumor necrosis factor-alpha . A novel feedback mechanism regulating cell death; Bulotta S et al.; Cell death via apoptosis induced by tumor necrosis factor-alpha (TNF-alpha) plays an important role in many physiological and pathological conditions . The signal transduction pathway activated by this cytokine is known to be regulated by several intracellular messengers . In particular, in many systems nitric oxide (NO) has been shown to protect cells from TNF-alpha-induced apoptosis . However, whether NO can be generated by the cytokine to down-regulate its own apoptotic program has never been studied . We have addressed this question in HeLa Tet-off cell clones stably transfected with the endothelial NO synthase under a tetracycline-responsive promoter . Endothelial NO synthase, induced about 100-fold in these cells by removal of the antibiotic, retained the characteristics of the native enzyme of endothelial cells, both in terms of intracellular localization and functional activity . Expression of the endothelial NO synthase was sufficient to protect from TNF-alpha-induced apoptosis . This protection was mediated by the generation of NO . TNF-alpha itself stimulated endothelial NO synthase activity to generate NO through a pathway involving its lipid messenger, ceramide . Our results identify a novel mechanism of regulation of a signal transduction pathway activated by death receptors and suggest that NO may constitute a built-in mechanism by which TNF-alpha controls its own apoptotic program.

J Gynecol Obstet Biol Reprod (Paris), 2000 Oct, 29(6), 599 - 606
{Premature rupture of the membranes between 28 and 34 weeks of amenorrhea . Retrospective study apropos of 71 cases}; Mehdi A et al.; OBJECTIVE: The aim of our study is to compare the outcome of infants born after preterm premature rupture of the membranes (PPROM) between 28 and 34 weeks gestation . We compare two groups of infants: group A, infants born in hospitals without neonatal intensive care unit, after PPROM with long tocolysis, no maternal prophylactic antibiotic therapy and no systematic maternal steroid therapy . Group B with systematic maternal steroid therapy, maternal prophylactic antibiotic therapy, short tocolysis and born in an hospital with neonatal intensive care unit . The latency period (time from rupture of membranes to the onset of labor) authorized was 15 days in the group B and not limited in the group A . RESULTS: Death (13.8% vs 0%; p=0.022), neonatal infection (66.6% vs 28.6%; p=0.0013), and respiratory distress (63.8% vs 34.3%; p=0.0144) were less frequent in the group B . The group A infants passed more than ten days in intensive care unit (61.1% vs 37.1%; p=0.043) . Neonatal infection was not higher in the corticosteroid therapy group (41.2% vs 70.3%; p=0.0135) . There is more neonatal infection in the group A with long latency period (61.7% vs 24.3%; p=0.0014) and more chorioamnionitis (70.6% vs 24.3%; p<0.0001) . CONCLUSION: The association maternal steroid and antibiotic therapy, short latency period, and hospitalization of the pregnant woman close to a neonatal intensive care unit reduce significantly the neonatal morbidity after preterm premature rupture of the membranes.

Injury, 2000 Nov, 31(9), 687 - 92
Total elbow arthroplasty as primary treatment for distal humeral fractures in elderly patients; Ray PS et al.; Distal humeral fractures are difficult to treat . In the elderly population, the problems are compounded by osteoporosis and gross comminution . Open reduction and internal fixation for such fractures is sometimes difficult and may be associated with poor results . Total elbow arthroplasty has been suggested as a last-ditch effort to salvage functional use for such difficult fractures in the elderly . We followed seven patients (seven elbows) with a mean age of 81.7 years at the time of injury . Open reduction and internal fixation was considered a difficult option for these fractures . They were treated with a total elbow arthroplasty using the semi-constrained Coonrad-Morrey elbow replacement prosthesis . The duration of follow up at present is between 2 and 4 years . At the latest follow up the mean arc of flexion is 20-130 degrees . Six patients have no pain while one complains of mild pain . All elbows are stable . The Mayo elbow performance score for five elbows is excellent and two scored good . All but one patient are satisfied with the result . One patient developed superficial wound infection which resolved after antibiotic therapy . One patient has developed post-operative triceps weakness . There have been no cases of deep infection, ulnar nerve neuritis or component failure . The rarity of this procedure suggests its very narrow spectrum of indication . We feel that the short-term results do suggest an important role for semi-constrained total elbow arthroplasty in managing carefully selected comminuted distal humeral fractures in the elderly, especially those that cannot be treated by conventional open reduction and internal fixation.

Antimicrob Agents Chemother, 2000 Dec, 44(12), 3381 - 8
Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis; Roberts J et al.; The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis . Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls . Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge . Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis . Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues . The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either drug was seen after 6 days of treatment . Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B . Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection.

Org Lett, 2000 Nov 2, 2(22), 3493 - 6
Synthesis of the functionalized tricyclic core of lactonamycin by oxidative dearomatization; Cox C et al.; {reaction: see text} We report in this Letter a synthesis of the densely oxygenated CDEF ring system (27) corresponding to that found in the recently discovered antibiotic lactonamycin . The key steps in the synthesis consist of an intramolecular Wessely oxidative lactonization of acid 18, followed by a hydroxyl-directed epoxidation of enol ether 21.

Gac Med Mex, 2000 Sep-Oct, 136(5), 449 - 54
{Pneumonia complicated with empyema in children, to operate or not? Risk factors for surgery and review of the literature}; Furuya-Meguro ME et al.; The precise indication for surgery for pleural empyema is still a controversy . With the aim of identifying the risk factors associated with surgery in pediatric patients with empyema post-pneumonia, a retrospective case control study was performed . From 1992 to 1996, 18 children underwent surgery (cases) and 12 did not (controls) . The analyzed variables were those mentioned in the literature as risk factors . More than 25 days of evolution, more than three antibiotic schemes, fever, empyema organizing phase, two or more chest tubes lasting more than nine days, multiple loculations, trapped lung and paquipleura were associated with thoracostomy and decortication (p < 0.05) . We conclude that a pediatric patient with a late referral to the hospital, empyema organizing phase, and multiple loculations with large purulent collections no longer susceptible to drainage and complications that impair lung expansion will probably require major surgery.

J Antibiot (Tokyo), 2000 Aug, 53(8), 828 - 36
Production of a new hybrid anthracycline 4-O-methylepelmycin by heterologous expression of dnrK in epelmycin-producing Streptomyces violaceus; Miyamoto Y et al.; A new hybrid anthracycline antibiotic was produced by heterologous expression of dnrK encoding carminomycin 4-O-metyltransferase in an epelmycin-producing Streptomyces violaceus . pMK100 was constructed by insertion of Steptomyces peucetius dnrK gene in Steptomyces-expression vector pIJ6021 and introduced to the epelmycin producer . The transformant produced a hybrid anthracycline antibiotic together with host epelmycins when cultured in antibiotic production medium in the presence of thiostrepton . The hybrid anthracycline was determined to be 7-O-L-rhodosaminyl-4-O-methyl-epsilon-rhodomycinone (4-O-methylepelmycin D) . However, the attempts on production of hybrid 4-O-methylaclarubicin and 4-O-methyl-1-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers with pMK 100 were unsuccessful.

Yonsei Med J, 2000 Oct, 41(5), 556 - 62
Viability of cells in cryopreserved canine cardiovascular organs for transplantation; Park JC et al.; To determine applicability of the cryopreservation procedure for vessel grafts, the viability of endothelial cells (ECs) among the whole cells in three kinds of organs artery, vein, trachea in mongrel dogs was evaluated on the basis of histological analysis . The Griffonia simplicifolia agglutins-fluorescein isothiocyanate (GSA-FITC) and propidium iodide (PI) double staining methods were combined with flow cytometry (FCM), which was able to simultaneously determine the viability of whole cells and ECs from the same tissue, were performed after harvesting, after antibiotic solution treatment, and after cryopreservation and thawing . In most cases, the viability of ECs is lower than that of whole cells from veins and arteries . The viability of whole cells in veins was maintained until the antibiotic solution treatment and then decreased significantly after cryopreservation and thawing, while the ECs began to decrease significantly after the antibiotic solution treatment and more markedly decreased after thawing . The viability of ECs and whole cells from arteries was similar to that of the veins' conditions . The viability of whole cells from the trachea decreased with a similar pattern to that of the ECs from vessels . In consideration of maintaining cell viability among the three kinds of organs, the viability of arteries was better than that of the others . The cells in the trachea demonstrated a lower viability than the vessels . The effect of antibiotic solution treatment on the reduction of cell viability depends on the treatment time and temperature.

J Dent Res, 2000 Oct, 79(10), 1808 - 14
Cytokine responses of oral epithelial cells to Porphyromonas gingivalis infection; Sandros J et al.; Accumulating evidence indicates that epithelia are not merely mechanical barriers but also important elements of the innate immune system . The present study was performed to examine cytokine responses of oral epithelial cells after infection with the periodontal pathogen Porphyromonas gingivalis . The KB-cell line and primary cultures of periodontal pocket epithelium were infected with P . gingivalis for assessment of bacterial invasion by an antibiotic protection assay, and examination of expression of interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha by in situ hybridization and immunohistochemistry . We observed that P . gingivalis induces a strong cytokine response, positively correlated with the adhesive/invasive potential of the infecting strain, in both KB cells and primary cultures . These findings indicate that the epithelial cells of the periodontal pocket are an integral part of the immune system, eliciting cytokine responses to a bacterial challenge . In this context, the adhesive/invasive phenotype of P . gingivalis appears to contribute to pathogenicity.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000 Nov, 90(5), 564 - 6
Intracranial placement of a nasogastric tube after severe craniofacial trauma; Ferreras J et al.; Complications of intracranial placement of a nasogastric tube in patients with complex facial and skull base fractures are infrequent, though the associated morbidity and mortality are high . In such situations some authors advocate craniotomy to allow removal of the tube in several linear segments under direct visualization . Others advise tube removal nasally under antibiotic coverage . We present a case of complex craniofacial fracture in which a nasogastric tube was positioned intracranially 48 hours after admission . The tube was quickly removed through the nose, and the patient was discharged without neurologic problems.

Acta Crystallogr C, 2000 Nov, 56 Pt 11, 1372 - 3
Norfloxacin dihydrate; Florence AJ et al.; The antibiotic norfloxacin recrystallizes from acetonitrile as a dihydrate with the norfloxacin molecule in a zwitterionic form, i.e . 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazin-4-io)-3-quinolinecarboxylate dihydrate, C(16)H(18)FN(3)O(3).2H(2)O.

Acta Crystallogr C, 2000 Nov, 56 Pt 11, 1343 - 5
Tetracycline hydrochloride: a synchrotron microcrystal study; Clegg W et al.; The title compound, {(4S,4aS,5aS,6S,12aS)-2-aminohydroxymethylene-1, 2,3,4,4a,5,5a,6,11,12a-decahydro-6,10,12,12a-tetrahydroxy-6-methyl -1, 3,11-trioxonaphthacen-4-yl}dimethylammonium chloride, C(22)H(25)N(2)O(8)(+).Cl(-), a well known antibiotic, has been structurally characterized from an individual coarse powder grain by use of high-intensity synchrotron radiation, in conjunction with an exercise in ab initio powder diffraction structure solution . Free refinement of all H atoms establishes the major tautomeric form of the protonated tetracycline molecule without prejudice . The molecule has extensive intramolecular hydrogen bonding involving most of the potential donors and acceptors, and all intermolecular hydrogen bonding uses the chloride anion as acceptor.

J Mol Microbiol Biotechnol, 2000 Oct, 2(4), 551 - 6
Application of redD, the transcriptional activator gene of the undecylprodigiosin biosynthetic pathway, as a reporter for transcriptional activity in Streptomyces coelicolor A3(2) and Streptomyces lividans; van Wezel GP et al.; redD encodes the transcriptional activator of the biosynthetic pathway for undecylprodigiosin, a red-pigmented, mycelium-bound antibiotic made by Streptomyces coelicolor A3(2) and Streptomyces lividans . A promoterless version of redD preceded by the efficiently used tuf1 ribosome binding site was inserted into two different plasmid vectors, providing a convenient reporter of transcriptional activity in both species . One plasmid, plJ2587, replicates autonomously in both Escherichia coli and streptomycetes, while the other, plJ2585, replicates in E . coli and can be transferred to streptomycetes by conjugation or transformation, whereupon it integrates stably at the chromosomal attachment site for the temperate phage phiC31 . The utility of the plasmids in detecting not only transcriptional activity, but also its regulation, was confirmed using the rrnAp, ermEp*, and glnRp promoters . The ability to screen visually and spectrophotometrically for red pigmentation should make the vectors particularly attractive for analysing the regulation of gene expression, and for the isolation of mutants, in both S . coelicolor and S . lividans.

Pediatr Radiol, 2000 Oct, 30(10), 677 - 80
Ilio-psoas abscess in neonates: treatment by ultrasound-guided percutaneous drainage; Dib M et al.; Ilio-psoas abscess is rare in neonates and is usually treated by surgical drainage . We report two cases of ilio-psoas abscess in 15- and 21-day-old infants successfully treated by US-guided percutaneous drainage as a supplement to antibiotic therapy . Clinical improvement was observed within 24-48 h of drainage and subsequent imaging demonstrated resolution of the abscess cavity . The analysis of these cases and of those previously reported indicates that imaging is essential for diagnosis . In neonates, US-guided percutaneous drainage may represent the first-choice treatment of this disease in association with antibiotic therapy.

J Biol Chem, 2001 Feb 2, 276(5), 3702 - 8 Epub 2000 Nov 08.
Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90; Xu W et al.; ErbB receptors are a family of ligand-activated tyrosine kinases that play a central role in proliferation, differentiation, and oncogenesis . ErbB2 is overexpressed in >25% of breast and ovarian cancers and is correlated with poor prognosis . Although ErbB2 and ErbB1 are highly homologous, they respond quite differently to geldanamycin (GA), an antibiotic that is a specific inhibitor of the chaperone protein Hsp90 . Thus, although both mature and nascent ErbB2 proteins are down-regulated by GA, only nascent ErbB1 is sensitive to the drug . To reveal the underlying mechanism behind these divergent responses, we made a chimeric receptor (ErbB1/2) composed of the extracellular and transmembrane domains of ErbB1 and the intracellular domain of ErbB2 . The ErbB1/2 protein is functional since its kinase activity was stimulated by epidermal growth factor . The sensitivity of ErbB1/2 to GA was similar to that of ErbB2 and unlike that of ErbB1, indicating that the intracellular domain of the chimera confers GA sensitivity . This finding also suggests that the GA sensitivity of mature ErbB2 depends on cytosolic Hsp90, rather than Grp94, a homolog of Hsp90 that is restricted to the lumen of the endoplasmic reticulum, although both chaperones bind to and are inhibited by GA . Lack of Grp94 involvement in mediating ErbB2 sensitivity to GA is further suggested by the fact that a GA derivative with low affinity for Grp94 efficiently depleted ErbB2 protein in treated cells . To localize the specific region of ErbB2 that confers GA sensitivity, we made truncated receptors with progressive deletions of the cytoplasmic domain and tested the GA sensitivity of these molecules . We found that ErbB2 constructs containing an intact kinase domain retained GA sensitivity, whereas those lacking the kinase domain (ErbB2/DK) lost responsiveness to GA completely . Hsp90 co-immunoprecipitated with all ErbB2 constructs that were sensitive to GA, but not with ErbB2/DK or ErbB1 . Both tyrosine-phosphorylated and non-phosphorylated ErbB2 proteins were similarly sensitive to GA, as was a kinase-dead ErbB2 mutant . These data suggest that Hsp90 uniquely stabilizes ErbB2 via interaction with its kinase domain and that GA stimulates ErbB2 degradation secondary to disruption of ErbB2/Hsp90 association.

Acta Paediatr, 2000 Sep, 89(9), 1068 - 71
Middle ear effusion IL-6 concentration in bacterial and non-bacterial acute otitis media; Barzilaia A et al.; BACKGROUND: The pathogenesis of acute otitis media is complex and multifactorial . It is characterized by inflammation of the middle ear with an infiltration of leukocytes, macrophages and mast cells . The resulting effusion contains a large amount of inflammatory mediators, among which are cytokines . OBJECTIVES: To test the role of IL-6 in the inflammatory process associated with acute otitis media . METHODS: We analyzed 20 middle ear fluid (MEF) sample pairs, obtained by aspiration before initiating antibiotic therapy (day 1) and during treatment (days 4-5), for the presence of IL-6 . IL-6 concentrations were assayed with an ELISA kit (detection limit 5 pg/ml) and were correlated with bacterial etiology and bacterial eradication from the middle ear . RESULTS: IL-6 was detected in all middle ear effusions analyzed . We found decreased IL-6 concentrations in culture negative MEF compared to culture positive MEF on both days I and 4-5 (day 1, 1752.20+/-1001.31 pg/ml vs 1216.20+/-1015.44 pg/ml, p = 0.19; days 4-5, 1049.36+/-472.40 pg/ml vs 800.33+/-676.00 pg/ml, p = 0.23); however, differences did not achieve statistical significance . Overall, a marked and significant decrease in IL-6 concentration occurred following 72-96 h of antibiotic therapy (1618.15+/-1004.88 pg/ml vs 936.85+/-581.05 pg/ml, p = 0.04) . While MEF IL-6 concentrations decreased in ears where bacteria persisted (1468.20+/-858.48 pg/ml vs 1044.80+/-514.16 pg/ml, p = 0.167) or were eradicated (2320.20+/-866.16 pg/ml vs 767.40+/-522.88 pg/ml, p = 0.029), a more prominent decline was demonstrated in the latter . CONCLUSIONS: These results strongly suggest the involvement of IL-6 in the ongoing inflammatory process in both bacterial and non-bacterial acute otitis media . Resolution of inflammation in the middle ear, especially where bacteria were eradicated, is reflected by low IL-6 levels.

Mol Microbiol, 2000 Nov, 38(3), 482 - 92
The quarternary molecular architecture of TetA, a secondary tetracycline transporter from Escherichia coli; Yin CC et al.; TetA, a tetracycline cation/proton antiporter, was expressed in Escherichia coli with a C-terminal tag of six histidines, solubilized in dodecyl maltoside and purified in a single step using Ni2+ affinity chromatography . Two-dimensional crystals were obtained after reconstitution of purified protein with lipids . Electron microscopy of negatively stained crystals revealed a trigonal symmetry, from which we infer that this secondary transporter has a trimeric structure . An overall molecular envelope can be described by a triangle of side approximately 100 A enclosing a central stain-filled depression . These dimensions are consistent with those obtained from projection views of single, isolated TetA particles that also display a trimeric architecture, confirming that the threefold symmetry is not simply a consequence of crystal-packing interactions . These data represent the first direct view of the quarternary arrangement of any antibiotic efflux pump . They are fully consistent with biochemical data on TetA, which indicate that it functions as a multimer and that the monomer consists of two domains, one of which plays the major part in oligomerization interactions.

Can J Microbiol, 2000 Oct, 46(10), 956 - 60
Isolation of a chitinase overproducing mutant of Streptomyces peucetius defective in daunorubicin biosynthesis; Vetrivel KS et al.; Streptomyces peucetius, producer of the antitumor anthracycline antibiotic daunorubicin, was mutagenized, and mutants defective in daunorubicin biosynthesis were screened . One mutant (SPVI), which failed to produce daunorubicin, was found to overproduce an extracellular chitinase . Time course analyses of chitinase production and of the extracellular protein profile showed that the increase in activity is due to increased synthesis of the enzyme protein . The production of chitinase in SPVI was repressed by glucose as in the case of wild-type S . peucetius . PFGE analysis of VspI restriction fragments of S . peucetius and SPVI showed that there was no major alteration in the mutant genome . The hybridization pattern of S . peucetius and SPVI genomic DNA digested with various restriction enzymes was identical when probed with dnrUVJI genes of the S . peucetius daunorubicin cluster and chiA of Streptomyces lividans 66 . The possible step affected in the daunorubicin biosynthetic pathway could be a polyketide synthase, since aklanonic acid, the earliest detectable intermediate in the daunorubicin pathway, was not synthesized in SPVI.

JAMA, 2000 Nov 8, 284(18), 2361 - 7
Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients; Girou E et al.; CONTEXT: Invasive life-support techniques are a major risk factor for nosocomial infection . Noninvasive ventilation (NIV) can be used to avoid endotracheal intubation and may reduce morbidity among patients in intensive care units (ICUs) . OBJECTIVE: To determine whether the use of NIV is associated with decreased risk of nosocomial infections and improved survival in everyday clinical practice among patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) or hypercapnic cardiogenic pulmonary edema (CPE) . DESIGN AND SETTING: Matched case-control study conducted in the medical ICU of a French university hospital from January 1996 through March 1998 . PATIENTS: Fifty patients with acute exacerbation of COPD or severe CPE who were treated with NIV for at least 2 hours and 50 patients treated with mechanical ventilation between 1993 and 1998 (controls), matched on diagnosis, Simplified Acute Physiology Score II, Logistic Organ Dysfunction score, age, and no contraindication to NIV . MAIN OUTCOME MEASURES: Rates of nosocomial infections, antibiotic use, lengths of ventilatory support and of ICU stay, ICU mortality, compared between cases and controls . RESULTS: Rates of nosocomial infections and of nosocomial pneumonia were significantly lower in patients who received NIV than those treated with mechanical ventilation (18% vs 60% and 8% vs 22%; P<.001 and P =.04, respectively) . Similarly, the daily risk of acquiring an infection (19 vs 39 episodes per 1000 patient-days; P =.05), proportion of patients receiving antibiotics for nosocomial infection (8% vs 26%; P =.01), mean (SD) duration of ventilation (6 {6} vs 10 {12} days; P =.01), mean (SD) length of ICU stay (9 {7} vs 15 {14} days; P =.02), and crude mortality (4% vs 26%; P =.002) were all lower among patients who received NIV than those treated with mechanical ventilation . CONCLUSIONS: Use of NIV instead of mechanical ventilation is associated with a lower risk of nosocomial infections, less antibiotic use, shorter length of ICU stay, and lower mortality . JAMA . 2000;284:2361-2367.

Clin Orthop, 2000 Nov, (380), 234 - 40
The anterior T-frame external fixator for high-energy proximal tibial fractures; Bal GK et al.; The authors' experience using anterior T-frame external fixation combined with percutaneous internal fixation for treatment of high-energy proximal tibial fractures is reported . Thirty-six patients (38 fractures) were reviewed who were treated during a consecutive 42-month period . Three patients died and one patient had an amputation for a Type IIIC open injury, leaving 20 males and 12 females with 21 closed and 13 open fractures (two Type II, seven Type IIIA, three Type IIIB, and one Type IIIC) . The average followup was 26 months . Fractures united at a mean of 20 weeks . Ten secondary surgical procedures were planned, including seven antibiotic bead removals with autogenous bone grafting and three soft tissue coverage procedures . Nine (26%) complications were found, including one deep infection (septic arthritis) and three pin tract infections, and one each malunion, nonunion, refracture, knee stiffness requiring manipulation under anesthesia, and deep venous thrombosis . The average Knee Society score was 85 for pain and 83 for function . All patients achieved full knee extension and mean flexion was 125 degrees . The anterior T-frame external fixator with percutaneous internal fixation is a reliable method to stabilize these injuries . It is simple, inexpensive, and effective.

J Clin Pathol, 2000 Oct, 53(10), 770 - 3
Expression of human alpha-defensin 5 (HD5) mRNA in nasal and bronchial epithelial cells; Frye M et al.; BACKGROUND/AIMS: Human defensins are antibiotic peptides expressed in myeloid and epithelial cells . Human alpha-defensin 5 (HD5) has been detected in Paneth cell granules in the crypts of Lieberkuhn and has recently been identified in the female reproductive tract . The aim of this study was to investigate the presence of HD5 mRNA in nasal and bronchial epithelial cells . METHODS/RESULTS: Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis showed that HD5 mRNA was expressed infrequently and to varying degrees in bronchial and nasal epithelial cells . In situ hybridisation resulted in a positive signal in the epithelial layer of nasal polyps . HD5 mRNA was locally restricted to a specific area of epithelial cells and also occurred in submucosal glands . CONCLUSIONS: HD5 mRNA expression in nasal and bronchial epithelial cells is rare and seemed to be locally induced . The results indicate that HD5 might play a role in innate defence in nasal and bronchial epithelia.

Pediatr Emerg Care, 2000 Oct, 16(5), 352 - 4
Pyomyositis of the leg with early neurologic compromise; Bibbo C et al.; Pyomyositis, although uncommon, is being reported with greater frequency in temperate climates . The presentation is similar to a number of infectious processes, and when associated with a traumatic event, the clinical picture may be confused with that of a musculoskeletal injury . This, coupled with an unfamiliarity of the disease, may result in a delay in diagnosis . Early antibiotic therapy may obviate surgery . Progression to the suppurative stage requires surgical drainage along with antibiotics . CT guided drainage may be accomplished in certain cases . In immunocompromised patients, progression to the septicemic stage is associated with high morbidity and mortality.

Harefuah, 2000 Oct, 139(7-8), 278 - 9, 326
{Thrombocytopenic purpura as sole manifestation of brucellosis in children}; Marom R et al.; Thrombocytopenic purpura associated with brucellosis has rarely been described in children . The thrombocytopenic purpura is usually part of the array of manifestations of brucellosis, such as fever, malaise, arthralgia, arthritis, hepatosplenomegaly and lymphadenopathy . We describe a 4-year-old girl in whom severe thrombocytopenic purpura was the only manifestation of brucellosis and resolved after appropriate antibiotic therapy . We conclude that brucellosis should be included in the differential diagnosis of thrombocytopenic purpura in areas endemic for brucellosis, and when there is a history of exposure to infected food products.

J Am Med Inform Assoc, 2000 Nov-Dec, 7(6), 593 - 604
Automatic detection of acute bacterial pneumonia from chest X-ray reports; Fiszman M et al.; OBJECTIVE: To evaluate the performance of a natural language processing system in extracting pneumonia-related concepts from chest x-ray reports . METHODS: DESIGN: Four physicians, three lay persons, a natural language processing system, and two keyword searches (designated AAKS and KS) detected the presence or absence of three pneumonia-related concepts and inferred the presence or absence of acute bacterial pneumonia from 292 chest x-ray reports . Gold standard: Majority vote of three independent physicians . Reliability of the gold standard was measured . Outcome measures: Recall, precision, specificity, and agreement (using Finn's R: statistic) with respect to the gold standard . Differences between the physicians and the other subjects were tested using the McNemar test for each pneumonia concept and for the disease inference of acute bacterial pneumonia . RESULTS: Reliability of the reference standard ranged from 0.86 to 0.96 . Recall, precision, specificity, and agreement (Finn R:) for the inference on acute bacterial pneumonia were, respectively, 0.94, 0.87, 0.91, and 0.84 for physicians; 0.95, 0.78, 0.85, and 0.75 for natural language processing system; 0.46, 0.89, 0.95, and 0.54 for lay persons; 0.79, 0.63, 0.71, and 0.49 for AAKS; and 0.87, 0.70, 0.77, and 0.62 for KS . The McNemar pairwise comparisons showed differences between one physician and the natural language processing system for the infiltrate concept and between another physician and the natural language processing system for the inference on acute bacterial pneumonia . The comparisons also showed that most physicians were significantly different from the other subjects in all pneumonia concepts and the disease inference . CONCLUSION: In extracting pneumonia related concepts from chest x-ray reports, the performance of the natural language processing system was similar to that of physicians and better than that of lay persons and keyword searches . The encoded pneumonia information has the potential to support several pneumonia-related applications used in our institution . The applications include a decision support system called the antibiotic assistant, a computerized clinical protocol for pneumonia, and a quality assurance application in the radiology department.

J Antimicrob Chemother, 2000 Nov, 46(5), 831 - 4
Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits; Ghelardi E et al.; This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics . Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide . Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone . The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.

Adv Skin Wound Care, 2000 Jan-Feb, 13(1), 25 - 9
Osteomyelitis related to pressure ulcers: the cost of neglect; Hirshberg J et al.; Twelve patients with documented chronic osteomyelitis of the pelvis resulting from truncal pressure ulcers were examined retrospectively to identify the cost of treatment for this significant health care problem . The retrospective review of each case spanned an 18-month period--6 months prior to the initial positive bone biopsy to 1 year following bone biopsy . The financial charges associated with treatment of osteomyelitis were identified using the University of Michigan Health System's databases for hospital charges, professional charges, and pharmacy charges . Prior treatment of these patients included surgical debridement of the pressure ulcer, pelvic bone biopsy, and culture-specific antibiotic therapy . The total charges for this group of 12 patients was $715,204, or an average charge of $59,600 per patient . Each patient was hospitalized, with hospitalization charges of $587,212, or an average of $48,934 per patient . Pharmacy charges for culture-specific antibiotics totaled $85,217 for the 12 patients . Six of 8 flap repairs achieved successful surgical closure of the pressure ulcer (75%) postantibiotic therapy . Surgery charges are not included in the totals.

Expert Opin Investig Drugs, 2000 Nov, 9(11), 2505 - 17
The association of infection and coronary artery disease: an update; Davydov L et al.; Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections . This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (cytomegalovirus, Chlamydia pneumoniae and Helicobacter pylori) in atherogenesis and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease . The interactions of cytomegalovirus and the arterial wall have been extensively studied . However, despite the successful preliminary therapeutic trials with the use of macrolides in augmenting possible C . pneumoniae-induced cardiovascular events, the exact mechanisms of how C . pneumoniae enters the arterial wall remains unknown at this point . For H . pylori, regardless of the large number of studies performed to assess the association between H . pylori and coronary artery disease, no definitive conclusion could be made at this time, due to contradictory results . Before one can widely adopt the use of antibiotics or antiviral agents as treatment for atherosclerosis, further studies must be designed to address some important issues . In vivo animal models need to be established to further examine the various hypotheses regarding the interaction of infectious agents and atherosclerosis and restenosis . Large-scale prospective cohort studies should be designed to relate evidence of infection to future risk of cardiovascular diseases . Confounding variables, such as other cardiovascular risk factors and socio-economic status, should be controlled in order to strengthen the association . Further interventional studies are also required to establish the best antibiotic or antiviral regimen to maximise efficacy and minimise side effects.

Expert Opin Investig Drugs, 2000 Feb, 9(2), 273 - 99
Antifungal peptides: potential candidates for the treatment of fungal infections; De Lucca AJ; Many diversely produced natural peptides, as well as those produced semisynthetically and synthetically, have been found to inhibit the growth or even be lethal to a wide range of fungi . Some of these have the potential to aid mankind in combating mycoses caused by emerging pathogens or as a result of the increasing number of antibiotic-resistant fungi . Antifungal peptides may also assist in non-medical fields such as agriculture . For example, introduction by transgenic research of antifungal peptides could improve crop production yields by increasing host resistance to fungal invasion . The aim of this review is to provide information on research on these important peptides.

Surg Today, 2000, 30(10), 914 - 6
Delayed infection of a lymphocele following mastectomy with immediate breast reconstruction: report of a case; Yamada T et al.; We report herein a rare case of delayed infection of a lymphocele following mastectomy with immediate breast reconstruction . A 38-year-old woman presented to our hospital 7 months after undergoing a left-modified radical mastectomy with an immediate breast reconstruction, following the sudden development of a giant mass in the left thoracoabdominal region as well as a high fever and shivering . Ultrasonography and a computed tomographic scan revealed massive fluid retention extending from the left axilla to the lower abdominal region . Puncture drainage was performed three times and the injection of an antibiotic directly into the cyst resulted in resolution of the fluid . This massive retraction of fluid was considered to have resulted from a delayed infection of an axillary lymphocele.

Ugeskr Laeger, 2000 Oct 16, 162(42), 5610 - 4
{Acute pancreatitis}; Olsen O; Acute pancreatitis is a common disease with significant morbidity and mortality . Despite recent improvements in our understanding of the disease process and the development of a range of supportive measures, today's treatment approaches are still less than ideal . Here I present some of the key points from generally accepted guidelines for the management of acute pancreatitis, including the operational classification system approved in Atlanta, USA, 1992 . Moreover, the diagnostic value of magnetic resonance as well as new approaches to treatment, including data on prophylactic antibiotics, selective digestive decontamination, and enteral nutrition in acute pancreatitis, are discussed in more detail.

Can Respir J, 2000 Sep-Oct, 7(5), 401 - 4
Surgical management of lung gangrene; Krishnadasan B et al.; OBJECTIVE: To review the outcomes of five cases of pulmonary resection for lung gangrene . DESIGN: A retrospective chart review . SETTING: A tertiary referral centre . POPULATION STUDIED: Five patients who underwent pulmonary resection for lung gangrene between April and December 1999 . MAIN RESULTS: Pathological confirmation of lung gangrene was obtained in all cases . Three patients were ventilator dependent . All five patients had ongoing sepsis despite antibiotic therapy . Additional indications for resection included bronchopleural fistula (two patients), empyema (three patients) and hemoptysis (one patient) . In two cases, there was evidence of bilateral, diffuse necrotizing pneumonia, while in three cases the process was localized to one side . Computed tomography revealed cavitation in four cases and the absence of blood supply to the affected lung in one case . Surgical resection included wedge resection (one patient), lobectomy (two patients), bilobectomy (one patient) and pneumonectomy (one patient) . In all cases, the bronchial stump was reinforced with an intercostal flap . Postoperative empyema occurred in two cases, one treated by thoracoscopic decortication, the other by percutaneous drainage . There were no instances of stump leak and no deaths . One patient remains ventilator dependent . CONCLUSIONS: Resection for lung gangrene is possible even in the setting of diffuse parenchymal changes and ventilator dependency . A computed tomography scan of the chest is important to make the diagnosis of lung gangrene and to plan operative management . Reinforcement of the bronchial stump is critical.

J Qual Clin Pract, 2000 Jun-Sep, 20(2-3), 56 - 9
An audit of open and laparoscopic inguinal hernia repair; Eno LM et al.; A retrospective case review to describe current practices and outcomes of patients undergoing inguinal hernia repair was undertaken in a principal referral hospital (John Hunter Hospital, Newcastle, New South Wales) . The participants were patients who had elective laparoscopic or open inguinal hernia repair between 1 June 1997 and 31 May 1998 . The main outcome measures were duration of surgery, type of anaesthesia, use of antibiotics, length of stay, postoperative complications, analgesic administration, and costs . Laparoscopic repair was advantageous in terms of length of stay and use of analgesia, but at a higher in theatre financial cost . Low rates of day stay surgery and use of local anaesthesia, and a high rate of antibiotic administration were apparent . It was concluded that local surgical practice has adopted some but not all advances described in the literature . Performance of a more expensive hernia repair in some patients may mitigate against performance of any repair in others.

Eur J Gastroenterol Hepatol, 2000 Oct, 12(10), 1129 - 34
Isolation of a single strain of Helicobacter pylori from the antrum and body of individual patients; Hua J et al.; OBJECTIVES: This study aimed to determine intra-patient colonization patterns of Helicobacter pylori strains based on DNA fingerprinting and antibiotic susceptibility . METHODS: Two biopsies, one from the antrum and one from the body of the stomach, were taken from 97 patients . Prior informed consent was obtained . The status of cagA gene of H . pylori strains was analysed by using the polymerase chain reaction (PCR) technique, while DNA fingerprints were generated by PCR-based, random amplified polymorphic DNA (RAPD) fingerprinting . The antibiotic susceptibility of the H . pylori isolates was examined by the disk diffusion method . RESULTS: A total of 51 pairs of H . pylori strains were isolated from both antrum and body specimens of 51 patients . This included two patients who were endoscoped twice because of treatment failure . All strains were positive for cagA gene by PCR . These 51 patients were found to harbour a single strain of H . pylori with identical or highly similar DNA profiles by PCR-based RAPD fingerprinting . In four of the 51 pairs, the DNA patterns of H . pylori from antrum and body showed minor differences, while three pairs of strains with different metronidazole sensitivities showed identical DNA fingerprints . Interestingly, the two treatment failure patients remained colonized with the strains that had the same RAPD fingerprinting patterns before and after treatment . CONCLUSION: The present study demonstrates that a single H . pylori strain colonizes a single stomach . However, this single genotypic strain may exhibit different metronidazole susceptibility in different parts of stomach.

Crit Care, 2000, 4(5), 314 - 8 Epub 2000 Aug 21.
Do steroids prevent reintubation in children with laryngotracheobronchitis?
Rajah J, Riera-Fanego J, Keeton J, Ramjee A, Bhana R, Lasersohn L, Hon H.
BACKGROUND: Classic laryngotrachoebronchitis (LTB) is an inflammatory process, with oedema and secretions that involve the entire laryngotracheobronchial tree . The severity of lower airway disease in African children with LTB has previously been documented . The aim of the present study was to determine whether steroids prevent reintubation in African children with classic LTB . METHOD AND RESULTS: The study was a retrospective analysis from January 1993 to December 1996 . Eighty-two black children with LTB were mechanically ventilated in the intensive care unit (ICU) . By univariate regression, the estimated B coefficients for variables such as age, pneumonia, days of intubation, arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) ratio, atelectasis and antibiotic use were not statistically significant (P > 0.05) as predictors for reintubation . Using multiple regression (all independent variables in combination), none of the variables acted as predictors of reintubation (P = 0.25) . Steroids were shown to have no effect alone or in association with other variables in altering reintubation rates . An increase in the days of intubation showed a tendency towards reintubation (P = 0.06) in the univariate analysis (odds ratio 1.00-1.14), but showed no statistically significant difference in multivariate analysis . Of the variables used as predictors of reintubation, none acted either as a preventive factor or as a risk factor . CONCLUSION: The present results suggest that steroids should not be recommended at any stage in treatment of intubated patients with classic LTB . Prospective studies should evaluate the major risk factors for reintubation: duration of intubation, trauma to the airway at intubation and during ICU stay, and dose and timing of steroids . They should also evaluate whether upper airway disease is present alone or in association with lower airway disease.

Crit Care Med, 2000 Oct, 28(10 Suppl), N174 - 80
Emergencies related to implantable cardioverter-defibrillators; Pinski SL; Implantable cardioverter-defibrillators (ICDs) have become the dominant therapeutic modality for patients with life-threatening ventricular arrhythmias . ICDs are implanted using techniques similar to standard pacemaker implantation . They not only provide high-energy shocks for ventricular fibrillation and rapid ventricular tachycardia, but also provide antitachycardia pacing for monomorphic ventricular tachycardia and antibradycardia pacing . Devices incorporating an atrial lead allow dual-chamber pacing and better discrimination between ventricular and supraventricular tachyarrhythmias . Intensivists are increasingly likely to encounter patients with ICDs . Electrosurgery can be safely performed in ICD patients as long as the device is deactivated before the procedure and reactivated and reassessed immediately afterward . Prompt and skilled intervention can prove to be life-saving in patients presenting with ICD-related emergencies, including lack of response to ventricular tachyarrhythmias, pacing failure, and multiple shocks . Recognition and treatment of tachyarrhythmia can be temporarily disabled by placing a magnet on top of an ICD . The presence of an ICD should not deter standard resuscitation techniques . Multiple ICD discharges in a short period of time constitute a serious situation . Causes include ventricular electrical storm, inefficient defibrillation, nonsustained ventricular tachycardia, and inappropriate shocks caused by supraventricular tachyarrhythmias or oversensing of signals . ICD system infection requires hardware removal and intravenous antibiotic therapy . Deactivation of an ICD with the consent of the patient or relatives is reasonable and ethical in terminally ill patients.

Pediatr Infect Dis J, 2000 Oct, 19(10), 979 - 83
Cross-sectional survey of trachoma in school age children in the region of Thiès (Senegal); Moalic E et al.; BACKGROUND: Trachoma is a leading cause of blindness in West Africa . In Senegal previous studies have shown that the endemicity is high . AIMS: To verify the extent of the pathology and to study the epidemiologic characters of this infectious disease in a population of school age children in a rural zone, located in the Thies region (Senegal) . METHODS: A cross-sectional survey in six villages in the region of Thies was performed in a population of school age children (5 to 15 years old) . Sixty variables (individual, family, village, etc.) with morbidity indicators for trachoma cases were collected and analyzed . RESULTS: The cross-sectional survey confirmed the extent of the prevalence of trachoma in the childhood population; 208 of the 388 children (mean age, 9.19 years) included had trachoma (53.6%) . Significant statistical correlations were found among the occurrence of trachoma and ethnic origins, the village of residence, the father's profession and the daily quantity of water ingested and its origin . Inversely no correlation could be found between the occurrence of trachoma and sex, age (except for florid trachoma), the size of the sibship, whether the mother washes the child, washing their hands before eating, the number of cospouses and the number of children per mother . CONCLUSIONS: The data obtained confirmed the extent of this endemic disease in the region of Thies, because dispensing antibiotic eye drop has limited efficacy over time . Information should be provided to the population on the extent of the disease and its epidemiologic characteristics and more widespread well drilling, and use of that water should be encouraged.

Biopolymers, 2000, 57(6), 365 - 72
Chemiluminescent method for determination of tetracycline, chlortetracycline, minocycline, doxycycline, and demeclocycline; Marczynski S; A chemiluminescent method is described for the determination of tetracycline, chlortetracycline, minocycline, doxycycline, and demeclocycline . The method is based on the photon counting technique and the spline functions approximation . The simple formula S = b + Ax(2) is proposed for the observed dependency of the integrated number of countings S on the concentration x of a given antibiotic . The correlation between S and the half-life of a drug in the human body is proved .

Gene, 2000 Oct 17, 257(1), 57 - 65
Puromycin resistance (pac) gene as a selectable marker in vaccinia virus; Sanchez-Puig JM et al.; The antibiotic puromycin, an inhibitor of protein synthesis, was shown to inhibit vaccinia virus (VV) replication . We evaluated the use of puromycin-resistance (pac) gene as a selectable marker in VV . A recombinant vaccinia virus expressing pac (VV-pac) under the control of a viral early/late promoter was constructed and characterized . VV-pac grew in the presence of puromycin at concentrations that were inhibitory for the parental VV and toxic for the cells . Isolation of recombinant VV usually relies on plaque purification under selective conditions . Because virus plaquing was not feasible under inhibitory puromycin concentration, a protocol based on serial passage of virus was devised . The usefulness of this procedure in selecting pac expressing viruses was tested by isolating a recombinant VV.

Ophthalmologica, 2000, 214(6), 429 - 32
Effective treatment with topical cyclosporin A of a patient with Cogan syndrome; Shimura M et al.; The purpose of this report is to describe the effective treatment of severe anterior segment inflammation due to Cogan syndrome through the use of topical administration of cyclosporin A . A 47-year-old female patient had been experiencing headaches and difficulties with her vision . Subsequent examination revealed the sudden onset of bilateral conjunctival injection and swelling of bilateral auricles . Despite the multiple treatment (systemic and topical corticosteroid and antibiotic therapy), necrotizing scleritis had appeared bilaterally and the scleral wall was thinning . Topical administration of 1% cyclosporin A was applied to both eyes 4 times a day . After 2 months of this therapy, the epithelial tissue covered the necrotizing tissue and her symptom of ocular pain was relieved and her corrected visual acuity was improved . This is the first case exhibiting that topical cyclosporin A is an effective treatment for severe anterior segment inflammation associated with Cogan syndrome .

Int J Antimicrob Agents, 2000 Oct, 16(2), 169 - 71
Out-patient management of febrile neutropenia; Talcott JA; Fever and neutropenia commonly complicated cytotoxic cancer therapy . Although standard therapy is empirical in-patient broad-spectrum intravenous antibiotic therapy until fever and neutropenia resolve, different treatments based on patient risk have been reported over the last decade . The data identifying low risk patients, treatment strategies for low risk patients, and additional information required before recommending out-patient management of fever and neutropenia widely are described.

Biophys J, 2000 Nov, 79(5), 2322 - 30
Calculations suggest a pathway for the transverse diffusion of a hydrophobic peptide across a lipid bilayer; Kessel A et al.; Alamethicin is a hydrophobic antibiotic peptide 20 amino acids in length . It is predominantly helical and partitions into lipid bilayers mostly in transmembrane orientations . The rate of the peptide transverse diffusion (flip-flop) in palmitoyl-oleyl-phosphatidylcholine vesicles has been measured recently and the results suggest that it involves an energy barrier, presumably due to the free energy of transfer of the peptide termini across the bilayer . We used continuum-solvent model calculations, the known x-ray crystal structure of alamethicin and a simplified representation of the lipid bilayer as a slab of low dielectric constant to calculate the flip-flop rate . We assumed that the lipids adjust rapidly to each configuration of alamethicin in the bilayer because their motions are significantly faster than the average peptide flip-flop time . Thus, we considered the process as a sequence of discrete peptide-membrane configurations, representing critical steps in the diffusion, and estimated the transmembrane flip-flop rate from the calculated free energy of the system in each configuration . Our calculations indicate that the simplest possible pathway, i.e., the rotation of the helix around the bilayer midplane, involving the simultaneous burial of the two termini in the membrane, is energetically unfavorable . The most plausible alternative is a two-step process, comprised of a rotation of alamethicin around its C-terminus residue from the initial transmembrane orientation to a surface orientation, followed by a rotation around the N-terminus residue from the surface to the final reversed transmembrane orientation . This process involves the burial of one terminus at a time and is much more likely than the rotation of the helix around the bilayer midplane . Our calculations give flip-flop rates of approximately 10(-7)/s for this pathway, in accord with the measured value of 1.7 x 10(-6)/s.

Semin Respir Infect, 2000 Sep, 15(3), 227 - 33
Empiric therapy of community-acquired pneumonia; Green DS et al.; Community-acquired pneumonia (CAP) remains a common and serious clinical problem despite the availability of potent antibiotics and aggressive supportive measures . The management of CAP begins with recognition of the likely pathogens causing the illness in the individual patient; identification of several simple clinical clues allows the organization of the broad variety of possible organisms into a more manageable list of likely pathogens . Once the most likely pathogens are identified, then initial antibiotics may be chosen to cover those possibilities . A number of treatment guidelines have been introduced in the past 10 years, most of which share more similarities than differences . We review 2 of the more established guidelines, those published by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) . We also review the likely modifications of the ATS guidelines and discuss the impact of bacterial resistance on antibiotic choices.

Mil Med, 2000 Oct, 165(10), 796 - 9
Radiographic osseous regeneration after initial therapy with systemic doxycycline; Fowler EB et al.; Early-onset periodontal diseases are often diagnosed in the military as a result of the requirements for annual dental examinations and the youthful population served . A young soldier diagnosed with rapidly progressive periodontitis completed initial therapy of root planing with the systemic antibiotic doxycycline but was poorly compliant with additional treatment . During a subsequent mandatory dental examination, new radiographs demonstrated a significant improvement in the quantity and quality of alveolar bone, illustrating the regeneration potential of the young patient with early-onset periodontal disease.

Aliment Pharmacol Ther, 2000 Oct, 14 Suppl 3, 59 - 66
A systematic review of Helicobacter pylori eradication treatment schedules in children; Oderda G et al.; METHODS: We systematically reviewed all available data in the paediatric literature on treatment for Helicobacter pylori infection to determine overall efficacy of different schedules . A comprehensive search of all published articles and letters from 1987, and of abstracts presented at three main meetings on this topic between 1997 and 1999, was carried out . Results from all English and French papers, letters and abstracts were extracted and analysed . RESULTS: Only 30 full articles and 16 abstracts were found, with results on eradication of H . pylori in 870 and 1552 children, respectively . Monotherapy or dual therapy with an antisecretory drug plus one antibiotic showed a very low efficacy . Dual therapies with bismuth plus one antibiotic (either amoxycillin or a nitro- imidazole) or two antibiotics when administered for 2 or more weeks were as effective as either bismuth-based or proton pump inhibitor-based triple therapies . Triple therapies were less effective than in adults, and while bismuth-based triple therapies were more effective when given for 2 weeks than for one week, proton pump inhibitor-based triple therapies have a similar efficacy irrespective of the duration . CONCLUSION: In children dual therapies seemed as effective as triple therapies, and longer courses of proton pump inhibitor-base triple therapies are not better than shorter ones.

J Hosp Infect, 2000 Oct, 46(2), 135 - 40
A prospective, randomized, double-blind studyof single high dose versus multiple standard dose gentamicin both in combination withmetronidazole for colorectal surgicalprophylaxis; Zelenitsky SA et al.; Single, high dose regimens of gentamicin plus metronidazole for colorectal surgical prophylaxis have not been adequately studied . Patients received single high dose gentamicin (4.5 mg/kg) plus metroni-dazole (500 mg) preoperatively or multiple standard dose gentamicin (1.5 mg/kg) plus metronidazole (500 mg) preoperatively and every 8h for 24h postoperatively . The deep surgical site infection (SSI) rates were 8.1% (6/74) and 6.9% (5/72) in the single high dose and multiple standard dose groups, respectively (P= 0.94) . There was a trend towards fewer superficial SSIs in the single high dose group with infection rates of 18.9% (14/74) vs . 30.6% (22/72) (P= 0.05) . Diabetes mellitus (odds ratio = 7.04) and surgery duration of longer than 3h (odds ratio = 5.46) were independent risk factors for the development of SSIs . A subset analysis of prolonged operations found significantly fewer superficial SSIs in the single high dose group than in the multiple standard dose group with rates of 22.2% (6/27) vs . 55% (11/20), respectively (P= 0.021) . Single high dose gentamicin plus metronidazole preoperatively was at least as effective as the multiple standard dose regimen and may be more effective for prolonged operations .

J Dairy Sci, 2000 Oct, 83(10), 2285 - 8
Pasteurization of discard mycoplasma mastitic milk used to feed calves: thermal effects on various mycoplasma; Butler JA et al.; Discard milk from sick or antibiotic-treated cows is often used as an economical alternative to milk replacer at dairy farms . This practice poses a health risk to calves if the discard milk is from cows with mycoplasma mastitis . Mycoplasma bovis, Mycoplasma californicum, and Mycoplasma canadense are among the agents known to cause contagious mastitis in cattle and occasionally pneumonia, otitis media, or arthritis in calves . This report describes a recent outbreak of calf polyarthritis and respiratory disease on a midwest dairy farm . The farm fed discard mycoplasma mastitic milk to its calves . On-the-farm pasteurization of the discard milk to 65 degrees C for 1 h before feeding prevented additional illness in the calves . Discard milk samples were collected before and after heating and tested for mycoplasma by culture . Only samples collected before pasteurization yielded live cultures . Common mastitic mycoplasma agents were also tested for sensitivity to heat . It was determined that 65 degrees C killed M . bovis and M . californicum after 2 min of exposure, while M . canadense remained viable for up to 10 min . Exposure to 70 degrees C inactivated M . bovis and M . californicum after 1 min, but M . canadense samples were positive for up to 3 min . Thus, M . canadense appears to be more heat resistant than M . bovis and M . californicum . Heat treatment that results in the destruction of M . canadense should be used for the pasteurization of discard mycoplasma mastitic milk.

J Biol Chem, 2001 Mar 2, 276(9), 6551 - 9 Epub 2000 Oct 24.
Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin . Structure and mechanism; Price AC et al.; The beta-ketoacyl-acyl carrier protein (ACP) synthases are key regulators of type II fatty acid synthesis and are the targets for two natural products, thiolactomycin (TLM) and cerulenin . The high resolution structures of the FabB-TLM and FabB-cerulenin binary complexes were determined . TLM mimics malonyl-ACP in the FabB active site . It forms strong hydrogen bond interactions with the two catalytic histidines, and the unsaturated alkyl side chain interaction with a small hydrophobic pocket is stabilized by pi stacking interactions . Cerulenin binding mimics the condensation transition state . The subtle differences between the FabB-cerulenin and FabF-cerulenin (Moche, M., Schneider, G., Edwards, P., Dehesh, K., and Lindqvist, Y . (1999) J . Biol . Chem . 244, 6031-6034) structures explain the differences in the sensitivity of the two enzymes to the antibiotic and may reflect the distinct substrate specificities that differentiate the two enzymes . The FabB{H333N} protein was prepared to convert the FabB His-His-Cys active site triad into the FabH His-Asn-Cys configuration to test the importance of the two His residues in TLM and cerulenin binding . FabB{H333N} was significantly more resistant to both antibiotics than FabB and had an affinity for TLM an order of magnitude less than the wild-type enzyme, illustrating that the two-histidine active site architecture is critical to protein-antibiotic interaction . These data provide a structural framework for understanding antibiotic sensitivity within this group of enzymes.

Photochem Photobiol, 2000 Oct, 72(4), 451 - 7
A laser flash photolysis and pulse radiolysis study of primary photochemical processes of flumequine; Bazin M et al.; The 355 nm laser flash photolysis of argon-saturated pH 8 phosphate buffer solutions of the fluoroquinolone antibiotic flumequine produces a transient triplet state with a maximum absorbance at 575 nm where the molar absorptivity is 14,000 M(-1) cm(-1) . The quantum yield of triplet formation is 0.9 . The transient triplet state is quenched by various Type-1 photodynamic substrates such as tryptophan (TrpH), tyrosine, N-acetylcysteine and 2-deoxyguanosine leading to the formation of the semireduced flumequine species . This semireduced form has been readily identified by pulse radiolysis of argon-saturated pH 8 buffered aqueous solutions by reaction of the hydrated electrons and the CO2*- radicals with flumequine . The absorption maximum of the transient semireduced species is found at 570 nm with a molar absorptivity of 2,500 M(-1) cm(-1) . In argon-saturated buffered solutions, the semireduced flumequine species formed by the reaction of the flumequine triplet with TrpH stoichiometrically reduces ferricytochrome C (Cyt Fe3+) under steady state irradiation with ultraviolet-A light . In the presence of oxygen, O2*- is formed but the photoreduction of Cyt Fe3+ by O2*- competes with an oxidizing pathway which involves photo-oxidation products of TrpH.

Br J Neurosurg, 2000 Aug, 14(4), 326 - 30
Traumatic cranial empyemas: a review of 55 patients; Nathoo N et al.; A 15-year (1983-1997) review of our unit's computed tomographic experience with traumatic cranial empyema (TCE) is reported . Fifty-five patients with documented history and clinical evidence of neurotrauma with secondary cranial empyema at surgery were identified . The clinical records and CT scans were analysed . TCE {four extradural and 51 subdural collections (SDE)} accounted for 7.86% of the total cranial empyemas seen during the study period . Most of the patients were young males (44 patients) and neurological deficits on admission were found only in the SDE group . Forty-one of 53 patients presented with septic compound skull fractures . Fifty-four patients had urgent surgical drainage . Eighty per cent of patients experienced a good outcome (GOS 4 or 5) . A morbidity of 16.4% (including postoperative seizures) was noted and eight patients died (mortality rate 14.5%) . Urgent surgical drainage, removal of osteitic bone, wound debridement and high dose intravenous antibiotic therapy form the mainstay of treatment.

Trop Med Int Health, 2000 Sep, 5(9), 640 - 7
Cost-effectiveness of management strategies for acute urethritis in the developing world; Crabbe F et al.; OBJECTIVE: To recommend a cost-effective approach for the management of acute male urethritis in the developing world, based on the findings of a theoretical study . METHODS: A model was developed to assess the cost-effectiveness of three urethritis management strategies in a theoretical cohort of 1000 men with urethral syndrome . (1) All patients were treated with cefixime and doxycycline for gonococcal urethritis (GU) and nongonococcal urethritis (NGU), respectively, as recommended by WHO . (2) All patients were treated with doxycycline for NGU; treatment with cefixime was based on the result of direct microscopy of a urethral smear . (3) All patients were treated with cotrimoxazole or kanamycin for GU and doxycycline for NGU . Cefixime was kept for patients not responding to the first GU treatment . Strategy costs included consultations, laboratory diagnosis (where applicable) and drugs . The outcome was the rate of patients cured of urethritis . Cost-effectiveness was measured in terms of cost per cured urethritis . RESULTS: Strategy costs in our model depended largely on drug costs . The first strategy was confirmed as the most effective but also the most expensive approach . Cefixime should cost no more than US$ 1.5 for the strategy to be the most cost-effective . The second strategy saved money and drugs but proved a valuable alternative only when laboratory performance was optimal . The third strategy with cotrimoxazole was the least expensive but a low follow-up visit rate, poor treatment compliance or lower drug efficacy limited effectiveness . Maximizing compliance by replacing cotrimoxazole with single-dose kanamycin had the single greatest impact on the effectiveness of the third strategy . CONCLUSION: Our model suggested that a cost-effective approach would be to treat gonorrhoea with a single-dose antibiotic selected from locally available products that cost no more than US$ 1.5.

Ann Thorac Cardiovasc Surg, 2000 Aug, 6(4), 271 - 4
Ruptured sinus valsalva with infectious endocarditis: a technique of defect closure with an autologous-xenologous pericardial sandwich patch; Okada K et al.; We report a case of ventricular septal defect with acquired rupture of sinus Valsalva induced by infectious endocarditis . After irrigati on of all infectious tissues, the defect was closed twice using two different patches . One was an autologous pericardial patch from the right ventricle and the other was a composite patch made of an autologous pericardium and axenologous pericardium from the left ventricle . As a result, the xenologous pericardium was sandwiched between autologous pericardiums . We thought that this "sandwiched patch" would compensate for the shortcomings of each type of pericardium and resist left ventricular pressure and infection . Despite the development of antibiotic therapy, infectious endocardit is (IE) is still one of the most difficult disease to cure . In the case of a rupture of sinus Valsalva, because of the rapid spread of infection into any of the cardiac chambers, surgical intervention is necessary . In this report, we describe a case treated successfully.

Bone Marrow Transplant, 2000 Sep, 26(6), 663 - 6
Economic analysis of a phase III study of G-CSF vs placebo following allogeneic blood stem cell transplantation; Stinson TJ et al.; Hematopoietic colony-stimulating factors (CSF) decrease the duration of neutropenia following stem cell transplantation (SCT) . With CSF-mobilized allogeneic blood SCT (alloBSCT), the yields of CD34+ cells are several-fold higher than in other SCT settings, raising concern that post-transplant CSF use may be unnecessary . In this study, we estimate the resource and cost implications associated with CSF use following alloBSCT . A cost identification analysis was conducted for 44 patients on a randomized, double-blind placebo-controlled trial of G-CSF following alloBSCT . Study drug was given daily until an absolute neutrophil count (ANC) > or = 1000 cells/microl . Billing information from the time of transplant to day +100 was analyzed . The median number of days to an ANC > or = 500 cells/microl was shorter in the G-CSF arm, 10.5 days vs 15 days (P < 0.001), while platelet recovery and rates of acute graft-versus-host disease (GVHD) and survival were similar . Resource use was similar, including days hospitalized, days on antibiotics, blood products transfused and outpatient visits . Total median post-transplant costs were $76577 for G-CSF patients and $78799 for placebo patients (P = 0.93) . G-CSF following allogeneic blood SCT decreased the median duration of absolute neutropenia and did not incur additional costs, but did not result in shorter hospitalizations, or less frequent antibiotic use.

Ann R Coll Surg Engl, 2000 Sep, 82(5), 352 - 4
Pyomyositis mimicking right iliac fossa mass: review of the literature; Iwuagwu OC et al.; Pyomyositis is a pyogenic infection of skeletal muscle . Its incidence in temperate countries though low is rising . Most cases from the temperate region involve immuno-compromised patients . The onset is usually insidious with progression to large purulent collections . Because of its low incidence in temperate countries, it is often initially misdiagnosed . A high index of suspicion with appropriate imaging techniques, aggressive surgical intervention and adjunctive antibiotic therapy are the keys to prompt resolution . A case of pyomyositis mimicking right iliac fossa (RIF) mass is described with a review of the literature.

Biofizika, 2000 Jul-Aug, 45(4), 586 - 99
{Study of the complex formation of daunomycin with deoxytetranucleotides with bases of differing sequence in an aqueous solution by 1H-NMR spectroscopy}; Eaton RJ et al.; The complex formation of the antibiotic daunomycin with deoxytetranucleotides of different base sequence in the chain, 5'-d(GpCpGpC), 5'-d(CpGpCpG), and 5'-d(TpGpCpA) in aqueous salt solution was studied by 1D and 2D (2M-TOCSY and 2M-NOESY) 1H-NMR spectroscopy . Concentration and temperature dependences of proton chemical shifts of molecules were measured . Based on these dependences, reaction equilibrium constants, relative content of various complexes depending on concentration and temperature, limiting values of chemical shifts of protons of daunomycin incorporated in various complexes, and the thermodynamic parameters delta H and delta S of complex formation were calculated . The analysis of the results enables the conclusion that the sites of predominant intercalation of daunomycin are triplet nucleotide sequences, the binding sites of the antibiotic with three consecutive GC pairs in the tetranucleotide duplex being more preferential . Daunomycin exhibits no sequence specificity upon binding to the single-stranded deoxynucleotide sequence . From the calculated values of induced chemical shifts of daunomycin protons and 2M-NOE data, the most probable spatial structures of complexes (1:2) of the antibiotic with deoxytetranucleotides were constructed . The binding of the second daunomycin molecule to both the single-stranded and duplex form of tetramers is of pronounced anticooperative mode, which is explained by the presence in the antibiotic of a positively charged amino sugar residue, which poses considerable steric constraints for the insertion of the second antibiotic molecule into the short tetranucleotide sequence . The results were compared with the data obtained under identical experimental conditions for typical intercalators proflavine and ethidium bromide.

Epidemiol Mikrobiol Imunol, 2000 Aug, 49(3), 115 - 22
{Skin manifestations of Lyme borreliosis in patients at the 1st Dermato-venereologic Clinic of Comenius University Medical School in Bratislava 1996-1998}; Svecova D et al.; 60-70% of Lyme borreliosis is formed by early manifestations, in particular erythema migrans (EM) . All vegetative forms of the tick Ixodes ricinus (e.g . full grown tick, nymphae and larvae) transmit the causal organism, the spirochete Borrelia burgdorferi sensu stricto and Borrelia burgdorferi sensu lato (B . garinii, B . afzelii) . The objective of the work was to evaluate clinical and epidemiological parameters and to contribute by testing and investigating in greater detail criteria to the early and exact diagnosis of the disease . In a group of 50 patients the time of development of EM was evaluated, the mode of transmission, the incubation period, localization, symptoms of dissemination of B . burgdorferi, the period of treatment and the antibiotic used . The dynamics of the antibody titre against B . burgdorferi (IFA test) were assessed in 21 patients with EM for a period of 1 to 22 months and in 5 patients with acrodermatitis chronic atrophicans (ACA) for 3 to 55 months . In 50% EM developed during the summer months . 66% reported as the vector a tick, 14% insects and 20% did not know . An incubation of 1 and 2 weeks was reported in 34%, the lower extremities were affected in 52% . Manifestations of dissemination were found in 6 patients, in 2 patients EM relapsed . Antibodies (Ab) against B . burgdorferi were present in 38 patients . In 21 patients the dynamics of the antibody titre were followed up for 1 to 22 months and no substantial changes were found . Serum positivity in patients with ACA persisted without change of the titre for several years . In the treatment of EM most frequently doxycycline was administered for two weeks . EM as the early stage of LB is a seasonal disease with a natural focus . If treatment is started in the early stage of infection, antibodies against B . burgdorferi need not develop . There is no correlation between clinical complaints and serological results and the type of treatment . The prognosis of the disease is favourable in the majority of patients . Vaccination offers new possibilities in active protection against Borrelia infection, in particular in endemic areas . For European countries at present a recombined vaccine is being prepared from the surface lipoprotein A (OspA) made from prevalent strains of B . afzelii and B . garinii.

J Vet Med Sci, 2000 Sep, 62(9), 971 - 5
Differential toxic effects of gentamicin on cultured renal epithelial cells (LLC-PK1) on application to the brush border membrane or the basolateral membrane; Kiyomiya K et al.; Aminoglycoside antibiotics are generally accepted to accumulate in renal proximal tubule cells from the luminal surface and show toxic effects on the cells . The binding affinity and membrane permeability of aminoglycoside antibiotics are different at the brush border membrane (BBM) and the basolateral membrane (BLM) of proximal tubule cells . This study was performed, therefore, to investigate the differential effects of the aminoglycoside antibiotic gentamicin (GM) on cultured LLC-PK1 cells, a pig kidney proximal epithelial cell line, after addition to the BBM or the BLM side . LLC-PK1 cells were cultured on microporous membranes until forming confluent monolayers, and then GM was added to either the BBM or the BLM side . GM caused release of enzymes from the organelles, with a higher level of release observed following addition to the BBM side than that to the BLM side . Patterns of {3H}GM uptake by the cells differed in a manner dependent on whether it was added to the BBM or the BLM side . That is, the cellular uptake from the BBM side increased with incubation time, while that from the BLM side showed rapid saturation . These results suggested that aminoglycoside antibiotics show differential effects on cultured proximal epithelial cells and have differential patterns of cellular uptake when added to the BBM or the BLM side.

Pancreas, 2000 Oct, 21(3), 290 - 5
Long-term effects of nafamostat and imipenem on experimental acute pancreatitis in rats; Naruse S et al.; Long-term effects of nafamostat mesylate, a protease inhibitor, and imipenem, an antibiotic, on trypsintaurocholate-induced acute pancreatitis were studied in rats . Sham-operated rats infused with a buffer solution into the pancreatic duct served as controls . Nafamostat (1 mg/kg), imipenem (10 mg/kg), or imipenem + nafamostat in saline was injected subcutaneously 0.25, 3, 24, and 48 hours after the induction of pancreatitis . In untreated rats and control rats, saline was injected at the same intervals as in the treated rats . All rats in an untreated group died within 3.5 days (median survival, 1.25 day) after the induction of pancreatitis . The 2-week survival rate was significantly (p < 0.05) improved by a combination of nafamostat and imipenem (42%), but not by nafamostat (17%), or imipenem (8%) alone . Bacterial culture at 24 hours revealed infection of necrotic pancreatic tissues and ascites by intestinal bacteria in all untreated rats but not in control rats . Bacterial counts were significantly reduced by imipenem, but not by nafamostat . In conclusion, bacterial infection occurred within 24 hours after the induction of trypsintaurocholate pancreatitis in rats . Early treatment with nafamostat + imipenem, but not nafamostat or imipenem alone, improves long-term survival.

Food Chem Toxicol, 2000 Oct, 38(10), 925 - 38
An assessment of chloramphenicol and thiamphenicol in the induction of aplastic anaemia in the BALB/c mouse; Turton JA et al.; The potential of the antibiotics chloramphenicol succinate (CAPS) and thiamphenicol (TAP) to induce aplastic anaemia in the female BALB/c mouse was investigated . CAPS was administered at 2000 mg/kg, and TAP at 850 mg/kg, daily by gavage, for 17 days . At 1, 13, 22, 41, 98 and 179 days after the final dose of each antibiotic, mice (n = 4 or 5) were sampled for haematological examination and haematopoietic stem cell assays . Both CAPS and TAP induced significant reductions in red blood cell count, haematocrit and haemoglobin values at day 1 post dosing; counts of colony-forming units-erythroid and colony-forming units-granulocyte-macrophage, were similarly significantly decreased at this time . All these reduced parameters returned towards normal at days 13 and 22 . At days 41, 98 and 179, results for all haematological values and stem cell assays in both CAPS- and TAP-treated mice compared with the controls; there was no evidence of a reduction in peripheral blood values or bone marrow parameters at the later sampling points, as would be expected in a developing or overt bone marrow aplasia . We therefore consider that the administration of CAPS and TAP, which have been associated with the development of aplastic anaemia in man, induce a reversible anaemia, but not a chronic bone marrow aplasia, when given at haemotoxic dose levels for 17 days in the BALB/c mouse.

Unfallchirurg, 2000 Sep, 103(9), 795 - 801
{Fatal soft tissue infections after arthroscopy of the knee joint . A diagnostic or therapeutic problem?}; Esenwein SA et al.; After detection of a bacterial infection of the joint, an absolute indication for intervention is given . Systemic antibiotic drug therapy is indicated and drainage of the joint has to be performed immediately . The following therapeutic algorithm regimen is a proven remedy in treating pyoarthrosis of the knee joint: During the initial period, the infection can be controlled by arthroscopic irrigation and systemic antibiotic therapy . Depending on the progredient findings or if the symptoms persist, curing the joint by open synovectomy is the next step of treatment . If open joint revision including synovectomy is not performed or is performed too late, there will be a threat of irreversible damage of the afflicted joint up to septic spread endangering the patient's life . We report on two patients suffering from generalized sepsis resulting in death after delayed therapy for knee joint infection . Regarding the presented cases, it can be concluded that indication to early surgical joint debridement including open synovectomy of the knee is still rarely seen after development of pyoarthritis.

Chang Gung Med J, 2000 Aug, 23(8), 492 - 7
Fatal and non-fatal chromobacterial septicemia: report of two cases; Chou YL et al.; Chromobacterium violaceum is frequently found in soil and water in tropical and subtropical regions . The organism rarely causes infection in humans, but is associated with a high mortality rate when it occurs . Septicemia associated with abscess in multiple organs such as the liver, skin, lungs, spleen, lymph nodes, and brain has been reported . We report on 2 patients with systemic infections with Chromobacterium violaceum . One presented with a fulminant course with multiple organ involvement and died 78 days later . The other presented with a milder course and survived after antibiotic therapy . In conclusion, infection with Chromobacterium violaceum is rare but its course is usually fulminant with high mortality especially in patients with sepsis and multiple organ involvement . We hope this report will provide additional information to physicians in the treatment of this disease.

Proc Natl Acad Sci U S A, 1997 Mar 18, 94(6), 2117 - 2121
Selection of marker-free transgenic plants using the isopentenyl transferase gene; Ebinuma H et al.; We have developed a new plant vector system for repeated transformation (called MAT for multi-auto-transformation) in which a chimeric ipt gene, inserted into the transposable element Ac, is used as a selectable marker for transformation . Selectable marker genes conferring antibiotic or herbicide resistance, used to introduce economically valuable genes into crop plants, have three major problems: (i) the selective agents have negative effects on proliferation and differentiation of plant cells; (ii) there is uncertainty regarding the environmental impact of many selectable marker genes; (iii) it is difficult to perform recurrent transformations using the same selectable marker to pyramid desirable genes . The MAT vector system containing the ipt gene and the Ac element is designed to overcome these difficulties . When tobacco leaf segments were transformed and selected, subsequent excision of the modified Ac produced marker-free transgenic tobacco plants without sexual crosses or seed production . In addition, the chimeric ipt gene could be visually used as a selectable marker for transformation of hybrid aspen (Populus sieboldii x Populus grandidentata) . The chimeric ipt gene, therefore, is an attractive alternative to the most widely used selectable marker genes . The MAT vector system provides a promising way to shorten breeding time for genetically engineered crops . This method could be particularly valuable for fruit and forest trees, for which long generation times are a more significant barrier to breeding and genetic analysis.

Drug Metab Dispos, 2000 Nov, 28(11), 1267 - 9
Chronic nifedipine dosing enhances cephalexin bioavailability and intestinal absorption in conscious rats; Berlioz F et al.; Cephalexin, a beta-lactam antibiotic, is rapidly absorbed via the di-and tripeptide intestinal transporters, as for many peptidomimetic drugs . Acute nifedipine has been shown to increase intestinal absorption of several beta-lactams: amoxicillin and cefixime in humans, and cephalexin in the rat . We showed previously that the nervous system was involved in the increasing effect of nifedipine on cephalexin intestinal absorption in anesthetized rats . The aim of the present study was 2-fold: 1) to investigate whether the effect of nifedipine is maintained in conscious rats, and 2) to determine whether the nifedipine effect will persist during chronic nifedipine administration . Acute and chronic oral administration of nifedipine significantly increased oral cephalexin area under the plasma concentration-time curve (34 and 25%, respectively) and maximum concentration in plasma (57 and 51%, respectively), while the distribution and elimination parameters of intra-arterial cephalexin were not affected by acute or chronic nifedipine administration . In conclusion, acute nifedipine effect on intestinal absorption of cephalexin is independent of anesthesia in rats . Since nifedipine could still enhance cephalexin intestinal absorption after a 7-day b.i.d . treatment, it can be envisaged to apply this effect to increase bioavailability of poorly absorbed peptidomimetic drugs in man.

J Microencapsul, 2000 Sep-Oct, 17(5), 615 - 24
Labile conjugation of a hydrophilic drug to PLA oligomers to modify a drug delivery system: cephradin in a PLAGA matrix; Ustariz-Peyret C et al.; The physical entrapment of a hydrophilic drug within degradable microspheres is generally difficult because of poor entrapment yield and/or fast release, depending on the microsphere fabrication method . In order to counter the effects of drug hydrophilicity, it is proposed to covalently attach the drug to lactic acid oligomers, with the aim of achieving temporary hydrophobization and slower release controlled by the separation of the drug from the degradable link within the polymer matrix . This strategy was tested on microspheres of the antibiotic cephradin . As the prodrug form, the entrapment of the drug was almost quantitative . The prodrug did degrade in an aqueous medium, modelling body fluids, but cleavage did not occur at the drug-oligomer junction and drug molecules bearing two lactyl residual units were released . When the prodrug is entrapped within a PLAGA matrix, no release was observed within the experimental time period . However, data suggest that conjugation via a bond more sensitive to hydrolysis than the main chain PLA ester bonds should make the system work as desired.

Equine Vet J, 2000 Sep, 32(5), 386 - 91
Anaemia, diarrhoea and opportunistic infections in Fell ponies; Richards AJ et al.; This report summarises clinical and pathological observations on Fell pony foals with a range of signs that included ill thrift, anaemia, respiratory infection, glossal hyperkeratosis and diarrhoea . Some of the foals had normochromic, normocytic anaemia and some had low levels of plasma proteins, including immunoglobulin G . Antibiotic and supportive treatment was ineffective and all affected foals died or were killed on humane grounds . Postmortem examination of 12 foals and tissues from 2 other foals revealed a range of lesions that included glossal hyperkeratosis, typhlocolitis, intestinal cryptosporidiosis, granulomatous enteritis, proliferative and necrotising bronchiolitis consistent with adenovirus infection; lesions similar to those in the respiratory tract were present in the salivary gland and pancreas of individual foals . Lymphoid tissue was judged to be smaller than expected . These observations suggest the possibility of opportunistic infections secondary to some form of undefined immunocompromised state.

J Am Geriatr Soc, 2000 Oct, 48(10), 1292 - 9
Outcome of nursing home-acquired pneumonia: derivation and application of a practical model to predict 30 day mortality; Naughton BJ et al.; OBJECTIVES: To derive a prediction model of 30 day mortality for nursing home-acquired pneumonia (NHAP) based on factors that can be readily identified by nursing home staff at the time of diagnosis and to apply the model to management issues related to NHAP including clarifying the importance of prepneumonia functional status as a predictor of outcome of NHAP . DESIGN: This was a retrospective chart review of 378 episodes of NHAP treated in the nursing home or hospital during two periods: November 1997 to April 1998 and November 1998 to April 1999 . SETTING: Eleven nursing homes in the greater Buffalo, NY region . PARTICIPANTS: Nursing home residents with radiographically proven pneumonia who had at least one of the following signs/symptoms: cough, fever, purulent sputum, respiratory rate > or =25 breaths/minute, localized auscultatory findings, or pleuritic pain . MEASUREMENTS: Status (alive or dead) of each resident at 30 days (30 day mortality) after diagnosis of NHAP was the dependent variable . Factors predicting 30 day mortality were identified by logistic regression analysis . A scoring system was developed based on the results of the logistic model . Each episode of NHAP in the derivation cohort was scored using the model and the cohort was stratified by the model score into six categories or risk for mortality (0-5) . The predictability of the model in the derivation cohort was measured using receiver operator characteristics curve analysis . RESULTS: Of 378 episodes of NHAP, 74% were treated initially in the nursing home and 26% were hospitalized initially for treatment . The overall 30 day mortality was 21.4%; however, the mortality rate was significantly higher for those treated initially in the hospital (29.6% vs 16.6%; P = .012) . Logistic regression analysis identified four predictors of 30 day mortality: (1) respiratory rate >30 breaths/minute (2 points), (2) pulse > 125 beats/minute (1 point), (3) altered mental status (1 point), and (4) a history of dementia (1 point) . Applying the scoring system to each episode in the derivation cohort demonstrated increasing mortality with increasing score . The c statistic for the model in the derivation cohort was .74 . Based on the severity of NHAP, model episodes treated initially in the hospital were more acutely ill than those who were treated initially in the nursing home, and episodes treated with a parenteral antibiotic in the nursing home were more acutely ill than those who were treated with an oral agent . Functional status was not a predictor of 30 day mortality although there was a trend of higher mortality in the most dependent group (P = .065) . The severity of NHAP model was able to define low and high risk mortality groups within a functional status category . CONCLUSIONS: A severity of NHAP model was derived from a large cohort of episodes in multiple facilities . The model had reasonable discriminatory power in the derivation cohort . The model may aid clinicians in making treatment decisions in the nursing home setting and in making hospitalization decisions . Although prepneumonia functional status provides a reasonable estimate of NHAP severity and prognosis, the severity of NHAP model permitted further refinement of these estimates . The severity of NHAP model requires validation before it can be recommended for general use.

J Am Geriatr Soc, 2000 Oct, 48(10), 1219 - 25
Physician orders for life-sustaining treatment (POLST): outcomes in a PACE program . Program of All-Inclusive Care for the Elderly; Lee MA et al.; OBJECTIVES: To evaluate whether terminal care was consistent with Physician Orders for Life-Sustaining Treatment (POLST), a preprinted and signed doctor's order specifying treatment instructions in the event of serious illness for CPR, levels of medical intervention, antibiotics, IV fluids, and feeding tubes . DESIGN: Retrospective chart review . SETTING: ElderPlace, a Program of All-Inclusive Care for the Elderly (PACE) site in Portland, Oregon . PARTICIPANTS: All ElderPlace participants who died in 1997 were eligible (n = 58) . Reasons for exclusion were no POLST (1), missing POLST (1), and insufficient documentation of care (2) . MEASUREMENTS: POLST instructions for each participant and whether or not each of the treatments addressed by the POLST was administered in the final 2 weeks of life . RESULTS: The POLST specified "do not resuscitate" for 50 participants (93%); CPR use was consistent with these instructions for 49 participants (91%) . "Comfort care" was the designated level of medical intervention in 13 cases, "limited interventions" in 18, "advanced interventions" in 18, and "full interventions" in 5 . Interventions administered were at the level specified in 25 cases (46%); at a less invasive level in 18 (33%), and at a more invasive level in 11 (20%) . Antibiotic administration was consistent with POLST instructions for 86% of 28 subjects who had infections in the last 2 weeks of life, and less invasive for 14% . Care matched POLST instructions in 84% of cases for IV fluids and 94% for feeding tubes . CONCLUSIONS: POLST completion in ElderPlace exceeds reported advance directive rates . Care matched POLST instructions for CPR, antibiotics, IV fluids, and feeding tubes more consistently than previously reported for advance directive instructions . Medical intervention level was consistent with POLST instructions for less than half the participants, however . We conclude that the POLST is effective for limiting the use of some life-sustaining interventions, but that the factors that lead physicians to deviate from patients' stated preferences merit further investigation.

Dtsch Tierarztl Wochenschr, 2000 Aug, 107(8), 332 - 4
{Substances with pharmacological effects including hormonally active substances in the environment: identification of tetracyclines in soil fertilized with animal slurry}; Hamscher G et al.; Many drugs used in human medicine are detectable in surface waters from the low to the very low microgram/L concentration range . In drinking waters only some of these substances were detected, the concentrations are usually an order of magnitude below the concentrations found in surface waters . A risk assessment of long time effects caused by a permanent intake of these low concentrations of drug residues cannot be done at this time . Hormonally active substances in surface waters may present an ecotoxicological risk, there are many investigations currently under way to assess this problem . Our investigations show for the first time that residues of the commonly used veterinary drugs tetracycline and chlortetracycline can be detected in the surface of soil (0-40 cm) fertilized with animal slurry . The maximum concentrations found were 32.3 micrograms/kg and 26.4 micrograms/kg respectively . Leaching of these compounds into seeping water sampled at a depth of 80-140 cm could not be detected with the methods employed . The significance of the detected antibiotic residues in soil samples for the quality of food of animal origin or any ecotoxicological consequences needs further investigations . The knowledge about the concentrations of veterinary drug residues resulting from animal husbandry in the environment is the first step for such a risk assessment.

Presse Med, 2000 Sep 9, 29(25), 1425 - 31
{Impact of Chlamydia pneumoniae infections on asthma}; Jebrak G et al.; VIRUSES AND BACTERIA: The fact that the airways are exposed to a large number of infectious agents could explain the frequency of respiratory infections and their causal effect in bronchial inflammation . Viruses are most often the causal agent, but the frequency of bacterial infections make them potential candidates in certain respiratory diseases . Chlamydia are particularly important due to their capacity to provoke immune dysfunction and chronic inflammation . EFFECT ON ASTHMA: It is not surprising to find biological evidence of Chlamydia pneumoniae infection in a large number of subjects who experience major degradation of their asthma because asthmatic subjects are particularly susceptible to respiratory infections and Chlamydia pneumoniae is a frequent cause of such infections . PATHOGENIC EFFECT: Finding Chlamydia pneumoniae as the causal agent in asthma is however much more surprising, with a much different consequence . There are however many epidemiological and clinical findings and case observations (Chlamydia pneumoniae asthma associations, prolonged favorable course in certain obstructive bronchial diseases after a short antibiotic regimen) as well as provocative pathophysiological data favoring this particular form of "infectious asthma" . FURTHER INFORMATION: Large-scale studies with rigorous methodology remain to be performed . The would be needed to determine the exact relationship between Chlamydia pneumoniae infections and certain types of asthma, particularly when wheezing occurs after a respiratory infection and when chronic obstruction develops . The could also determine the role of anti-Chlamydia pneumoniae antibiotics in case of obstructive respiratory failure and also determine their efficacy on long-term outcome.

Presse Med, 2000 Sep 9, 29(25), 1401 - 4
{Severe chronic renal failure subsequent to acute pyelonephritis in alcoholic patients}; Ladriere M et al.; BACKGROUND: Chronic alcoholism and malnutrition are uncommon causes of complicated acute pyelonephritis (APN) . CASE REPORTS: Since 1997, we have seen 5 patients with chronic alcoholism (3 women and 2 men, mean age 53.4 +/- 13 years) without cirrhosis, diabetes or renal failure who developed severe APN in a state of malnutrition (albumin 22 +/- 3 g/l, total cholesterol 0.86 +/- 0.2 g/l) . Diagnosis was made 14.6 +/- 9 days after onset of atypical symptoms which the patients neglected . There was a major bacterial inoculum: Escherichia coli 10(6.2 +/- 2) (3 multisusceptible and 2 amoxicillin-resistant strains); positive blood cultures in 3 cases . The imaging study showed bilateral diffuse lesions with focal swelling and kidney enlargement, without obstacle, abscess, or papillary necrosis . All patients had severe acute renal failure (maximum serum creatinine: 582 +/- 210 mumol/l; 3 patients underwent dialysis) . Mean duration of antibiotic therapy was 40 +/- 7 days (i.v.: 22 +/- 3 d) . Renal scarring occurred since creatinine clearance was 33 +/- 22 ml/min 2 months after the initial episode . One patient progressed to end-stage renal failure . CONCLUSION: In malnourished alcoholic patients, APN may be unusually severe due to late diagnosis leading to the risk of irreversible renal damage and severe chronic renal failure.

Antimicrob Agents Chemother, 2000 Nov, 44(11), 3040 - 8
Identification of the coumermycin A(1) biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489; Wang ZX et al.; The biosynthetic gene cluster of the aminocoumarin antibiotic coumermycin A(1) was cloned by screening of a cosmid library of Streptomyces rishiriensis DSM 40489 with heterologous probes from a dTDP-glucose 4,6-dehydratase gene, involved in deoxysugar biosynthesis, and from the aminocoumarin resistance gyrase gene gyrB(r) . Sequence analysis of a 30.8-kb region upstream of gyrB(r) revealed the presence of 28 complete open reading frames (ORFs) . Fifteen of the identified ORFs showed, on average, 84% identity to corresponding ORFs in the biosynthetic gene cluster of novobiocin, another aminocoumarin antibiotic . Possible functions of 17 ORFs in the biosynthesis of coumermycin A(1) could be assigned by comparison with sequences in GenBank . Experimental proof for the function of the identified gene cluster was provided by an insertional gene inactivation experiment, which resulted in an abolishment of coumermycin A(1) production.

Antimicrob Agents Chemother, 2000 Nov, 44(11), 3012 - 6
In vitro efficacy of nikkomycin Z against the human isolate of the microsporidian species Encephalitozoon hellem; Bigliardi E et al.; Since 1985 microsporidia have been recognized as a cause of emerging infections in humans, mainly in immunocompromised human immunodeficiency virus-positive subjects . As chitin is a basic component of the microsporidian infective stage, the spore, we evaluated in vitro the susceptibility of a human-derived strain of Encephalitozoon hellem to nikkomycin Z, a peptide-nucleoside antibiotic known as a competitive inhibitor of chitin synthase enzymes . Transmission electron microscopy showed that this drug, at 25 microgram/ml, reduced the number of parasitic foci by about 35% +/- standard deviation after 7 days of culture (P < 0.0001) and induced cell damage of both mature and immature spores and also other sporogonic and merogonic stages . In particular, an irregular outline of the cell shape and an abnormally condensed cytoplasm in meronts and sporonts were documented . Also, the polar tubule and the polaroplast membranes appeared disarrayed in the sporoblast stage . The spore wall showed an enlarged endospore and delaminated exospore . Mature spores had a complete cytoplasmic disorganization and a swollen and delaminated cell wall . No ultrastructural cell damage was observed in uninfected control cultures treated with the drug.

Arch Pathol Lab Med, 2000 Oct, 124(10), 1502 - 5
Actinomyces and actinobacillus actinomycetemcomitans-Actinomyces-associated lymphadenopathy mimicking lymphoma; Amrikachi M et al.; We present 2 unusual cases of long-standing, extensive reactive lymphadenopathy secondary to Actinomyces infection, 1 of which was also accompanied by Actinobacillus actinomycetemcomitans-Actinomyces complex infection . To our knowledge, histologic features of lymph node involvement by these organisms have not been previously reported in the literature . One patient had extensive cervical, posterior mediastinal, and abdominal lymphadenopathy . The second patient presented with a submandibular mass and cervical lymphadenopathy . Clinical features strongly suggested lymphoma . The histologic examination of the lymph nodes from both patients revealed reactive follicular hyperplasia, marked interfollicular and capsular fibrosis, and multiple interfollicular microabscesses . Characteristic Actinomyces colonies were identified at the center of the microabscesses in deep sections . Cultures were obtained from the lymph nodes of 1 patient, and were positive for A actinomycetemcomitans . Both patients had poor dental hygiene . Lymphadenopathy subsided with antibiotic therapy and appropriate dental care.

Am J Obstet Gynecol, 2000 Oct, 183(4), 847 - 52
Timing of cerclage removal after preterm premature rupture of membranes: maternal and neonatal outcomes; Jenkins TM et al.; OBJECTIVE: Our aim was to evaluate immediate versus delayed removal of cerclage for women with preterm premature rupture of membranes with respect to maternal and neonatal outcomes . STUDY DESIGN: We retrospectively analyzed women with preterm premature rupture of membranes at <34 weeks' gestation with prior cerclage placement . Exclusion criteria included presentation with chorioamnionitis, active labor, or nonreassuring fetal status . Timing of cerclage removal, immediate (<24 hours) or delayed (>24 hours), was compared . RESULTS: There were 25 women in the delayed-removal group and 37 in the immediate-removal group . Average times to removal were 206.8 +/- 7.4 and 5.4 +/- 0.2 hours, respectively . Use of betamethasone was similar for both groups; however, antenatal antibiotic use (100% vs 80%; P =.03) and short-term tocolytic use (20% vs 3%; P =.04) were higher in the delayed-removal group . Duration of latency was significantly longer with delayed removal (10.1 vs 5.0 days; P < . 001) . Delivery occurred >48 hours from preterm premature rupture of membranes in 96% (24/25) versus 54% (20/37; P <.001) and >7 days from rupture in 56% (14/25) versus 24% (9/37; P =.02), respectively . Rates of neonatal sepsis (at <10 days) and maternal infection were not statistically different . Neonatal outcomes did not significantly differ regarding mortality, respiratory distress syndrome, birth weight, or duration of stay in the intensive care nursery . CONCLUSION: With the current management scheme for preterm premature rupture of membranes, cerclage retention significantly increases duration of latency without significantly altering maternal or neonatal outcomes.

Diagn Microbiol Infect Dis, 2000 Oct, 38(2), 127 - 9
Mycobacterium intracellulare as a cause of a recurrent granulomatous tenosynovitis of the hand; Lefevre P et al.; We report a case of recurrent granulomatous tenosynovitis with M . intracellulare in a 55-year-old HIV negative diabetic woman . Identification of the causative agent further than belonging to the M . avium-intracellulare complex is provided by specific PCR-amplification of genomic DNA and sequencing of an hypervariable region within its 16S RNA gene . Sixteen months antibiotic regimen of rifabutin and clarithromycin led to a complete resolution of the tenosynovitis.

Cochrane Database Syst Rev . 2000;(4):CD002180.
Surgery vs non-surgical treatment for bronchiectasis; Corless JA et al.; BACKGROUND: Standard treatment for bronchiectasis comprises postural drainage and various regimes of antibiotic therapy . If the disease is confined to localised areas of lung, surgical resection of the affected segments is often performed . OBJECTIVES: To assess the benefit of surgical resection compared with standard ("conservative") treatment . SEARCH STRATEGY: The Cochrane Airways Group trials register derived from MEDLINE, EMBASE and hand searching of major journals was searched using the terms {bronchiect* AND surg* OR resection OR lobect* OR pneumonect* OR segementect*} . SELECTION CRITERIA: Only randomised, controlled trials were considered DATA COLLECTION AND ANALYSIS: The titles, abstracts and citations were independently reviewed by the two reviewers to assess potential relevance for full review . STATISTICAL CONSIDERATIONS Not applicable MAIN RESULTS: No randomised or controlled clinical trials were found, other than case series or case-controlled studies . REVIEWER'S CONCLUSIONS: Surgical treatment of bronchiectasis is widely used, but there appear to be no randomised controlled trials . It is not possible to provide an unbiased estimate of its benefit compared to conservative therapy.

Cochrane Database Syst Rev . 2000;(4):CD001935.
Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children; Butler CC et al.; BACKGROUND: OME is common and may cause hearing loss with associated developmental delay . Treatment remains controversial . The effect of both systemic and intra-nasal steroids on effusions has been assessed by randomised controlled trials . OBJECTIVES: To examine evidence for or against treating children with hearing loss associated with OME with systemic or topical nasal steroids . SEARCH STRATEGY: Searches were conducted in February 2000 . We searched the Cochrane Controlled Trials Register using the terms 'otitis-media', 'otitis media with effusion', 'glue ear', or 'OME', and 'steroids', 'glucocorticoids, synthetic', 'glucocorticoids, topical', 'anti-inflammatory agents, steroidal' . EMBASE and MEDLINE were also searched for additional information . SELECTION CRITERIA: Randomised controlled trials of oral and topical nasal steroids, either alone or in combination with another agent such as an antibiotic, were included . Exclusions: publications in abstract form only since adequate appraisal was not possible; uncontrolled, non-randomised or retrospective studies; studies reporting outcomes with ears (rather than children) as the unit of analysis . DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by the two authors independently (CCB and JH van der V) using standardised data extraction forms and methodology . The methodological quality of the included studies were independently assessed by the two authors using the scheme described in the Cochrane Handbook . Dichotomous results were expressed as an odds ratio using a fixed effects model together with the 95% confidence intervals . Continuous data were analysed using the weighted mean difference in a fixed effects model . Tests for heterogeneity between studies were performed using a Mantel-Haenszel approach . In trials with a cross over design, post-crossover treatment data were not used . MAIN RESULTS: No study prospectively documented hearing loss associated with OME prior to randomisation . Follow up was short term . No serious or lasting side effects were reported in the four studies that did mention side effects . Most comparisons involved small numbers of subjects . The odds ratio for OME persisting after short term follow up for children treated with oral steroids plus antibiotic compared to control plus antibiotic was 0.32 (95% CI 0.20 to 0.52) . However there was significant heterogeneity between studies (p<0.01) . Trends favoured steroids for most other comparisons, but confidence intervals included unity . There was no evidence of benefit for steroid treatment in the longer term, and no study assessed effect of steroid treatment on language development . REVIEWER'S CONCLUSIONS: There is evidence that steroids combined with an antibiotic lead to a quicker resolution of OME in the short term . However, there is not evidence for long term benefit from treating hearing loss associated with OME with either oral or topical nasal steroids . These treatments are therefore not recommended at the present time . Future studies should document hearing loss associated with OME before the start of study treatment . Follow up should be longer and ideally include symptom, audiometry and developmental outcomes . Data should not be presented with ears as the unit of analysis.

Ann Med Interne (Paris), 2000 Sep, 151(5), 339 - 44
{Mycobacterium ulcerans infection}; Dega H et al.; Mycobacterium ulcerans infection, or Buruli ulcer, is the third most common mycobacterial disease of the immunocompetent host in the tropical areas . M . ulcerans reservoir is aquatic . Infection occurs in children and young adults . The lesion begins with an indolent subcutaneous nodule, principally located on the limbs, that progressively changes into a deep indolent extensive ulcer . M . ulcerans produces a lipidic necrotic and immunosuppressive toxin, named mycolactone, that causes the clinical lesions . In endemic areas, clinical diagnosis is confirmed by microscopic examination . Spontaneous healing occurs after several months or years, causing retractile scars . Surgical excision and grafting is the treatment of choice . Antibiotic therapy is of limited value.

Mol Cell Biol Res Commun, 2000 Jun, 3(6), 329 - 37
Cellular responses to sodium butyrate exhibit the dominance of one parental phenotype in somatic cell hybrids; Cox GS; The glycoprotein hormone alpha-subunit (GPHalpha) gene is inducible by sodium butyrate (NaBtr) in nontrophoblastic tumor cell lines such as HeLa (cervical carcinoma) but not in trophoblastic tumor cell lines such as JEG-3 (choriocarcinoma) . The studies summarized in this report examined the ability of NaBtr to induce GPHalpha expression in somatic cell hybrids between HeLa SR3(hyg) and JEG-3(neo) . The hybrid cells, pooled clones resistant to both hygromycin B and G418 sulfate, have been named JELA and were indistinguishable from the SR3 parent with regard to induction of the GPHalpha gene . The effects of NaBtr on cell proliferation were also similar in HeLa and JELA but different from those in JEG-3 . The GPHalpha gene could be induced by NaBtr in the JEG-3 parent only when they were simultaneously treated with cycloheximide (CHX) . The ability of NaBtr to induce GPHalpha in CHX-treated JEG-3 cells occurred concomitantly with a change in the electrophoretic mobility of enhancer binding proteins as determined in gel shift assays . The DNA-protein complexes generated between a trophoblast specific element (TSE) and nuclear proteins in HeLa SR3 and JELA migrated significantly more slowly than the complex generated by JEG-3 nuclear proteins . However, when nuclear extracts were prepared from CHX-treated JEG-3 cells, the complex generated with the TSE oligonucleotide migrated more slowly than the complex from untreated JEG-3 cells and coincident with the complexes produced with nuclear extracts from HeLa SR3 and JELA cells . Together, these data demonstrate that inducibility of the GPHalpha gene by NaBtr in JELA cell hybrids resembles that of the HeLa SR3 parent and that its inducibility in the JEG-3 parent parallels the status of an enhancer binding protein (TSEB) as judged from changes in electrophoretic mobility . The results are consistent with a model in which the status of TSEB has a profound influence on the gene's response to NaBtr .

Radiats Biol Radioecol, 2000 Jul-Aug, 40(4), 420 - 4
{Cytokines as agents for the early pathogenetic therapy of radiation injuries . Their efficacy and mechanism of action}; Legeza VI et al.; It has been shown in experiments with three species of laboratory animals that an early administration (during the first hours following irradiation) of human recombinant interleukins 1 alpha and 1 beta separately (to mice, rats) or in combination with antibiotic therapy (dogs) substantially increases survivability, favours a more rapid regeneration of the cellular content of the bone marrow and peripheral blood, intensifies the processes of endogenous colony formation and DNA synthesis in the bone marrow and liver and lowers the expressivity of radiation-induced endotoxemia . The significance of using cytokines in the system of remedial measures in radiation pathology is discussed.

Microb Pathog, 2000 Nov, 29(5), 301 - 9
Intracellular DNA replication and long-term survival of pathogenic mycoplasmas; Dallo SF et al.; We examined intracellular survival and growth of pathogenic mycoplasmas (Mycoplasma penetrans, Mycoplasma pneumoniae and Mycoplasma genitalium) in cultured human cells . By using the eukaryotic nuclear DNA synthesis inhibitor, aphidicolin, we detected the selective synthesis of mycoplasma (My) and mitochondria (Mt) DNA, which could be further differentiated by restriction enzyme analyses . Also, intracellular M . pneumoniae and M . penetrans infectivity of human cells was detected over 6 months using subfractionation of infected cells and determination of mycoIplasma colony forming units (cfu) . For M . genitalium, which we failed to re-grow from infected cells, species-specific PCR primers were used to implicate long-term mycoplasma survivability . Data indicated that pathogenic mycoplasmas reside and replicate intracellularly over extended periods in human cells, consistent with the ability of mycoplasmas to circumvent antibiotic therapy and immune surveillance and establish chronic infections .

Arch Dermatol, 2000 Oct, 136(10), 1231 - 6
Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide; Jick SS et al.; BACKGROUND: It has been suggested that there is a causal association between isotretinoin therapy and the risk of depression, psychotic symptoms, suicide, and attempted suicide . OBJECTIVE: To further investigate the proposed association between isotretinoin therapy and the risk of depression, psychotic symptoms, suicide, and attempted suicide using a formal study design . DESIGN: Large population-based cohort studies . SETTING: The Canadian Saskatchewan Health Database and the United Kingdom General Practice Research Database . PATIENTS: Data were analyzed for 7195 isotretinoin users and 13,700 oral antibiotic users with acne from the Canadian Saskatchewan Health Database and for 340 isotretinoin users and 676 oral antibiotic users with acne from the United Kingdom General Practice Research Database . All subjects had computer-recorded histories of between 6 months and 5 years before, and at least 12 months after, their first isotretinoin or antibiotic prescription . OUTCOME MEASURE: Prevalence rates of neurotic and psychotic disorders, suicide, and attempted suicide were compared between isotretinoin and antibiotic users and within isotretinoin users as their own comparison (pretreatment vs posttreatment) . The results were expressed as relative risks, calculated using multiple logistic regression analyses . RESULTS: Relative risk estimates, comparing isotretinoin use and oral antibiotic use with nonexposure to either drug for newly diagnosed depression or psychosis, were approximately 1.0 regardless of the data source . Similarly, relative risk estimates were all around 1.0 when comparing before with after isotretinoin use . The relative risk estimate for suicide and attempted suicide was 0.9 (95% confidence interval, 0.3-2.4) when comparing current isotretinoin exposure with nonexposure . CONCLUSION: This study provides no evidence that use of isotretinoin is associated with an increased risk for depression, suicide, or other psychiatric disorders.

Appl Microbiol Biotechnol, 2000 Sep, 54(3), 326 - 30
Growth of Photorhabdus luminescens in batch and glucose fed-batch culture; Jeffke T et al.; Photorhabdus luminescens, a bacterial symbiont of entomopathogenic biocontrol nematodes, was grown in batch and glucose fed-batch culture . The cell density, bioluminescence, production of antibiotic substances, number of cells with inclusion bodies, glucose concentration and oxygen uptake rate were recorded . The addition of 12.4 g 1(-1) glucose prolonged the growth, and the yield almost doubled, from 6.85 g 1(-1) to 12.45 g 1(-1) dry mass . The production of antibiotic substances increased by 140% . Bioluminescence was higher in the batch culture . A shift of P . luminescens to phase II variants was not detected.

J Bacteriol, 2000 Nov, 182(21), 6259 - 63
Identification by gene deletion analysis of a regulator, VmsR, that controls virginiamycin biosynthesis in Streptomyces virginiae; Kawachi R et al.; Virginiae butanolide (VB)-BarA of Streptomyces virginiae is one of the newly discovered pairs of a butyrolactone autoregulator and a corresponding receptor protein of Streptomyces species and regulates the production of the antibiotic virginiamycin (VM) in S . virginiae . The gene vmsR was found to be situated 4.7 kbp upstream of the barA gene, which encodes the VB-specific receptor . The vmsR product was predicted to be a regulator of VM biosynthesis based on its high homology to some Streptomyces pathway-specific transcriptional regulators for the biosynthetic gene clusters of polyketide antibiotics, such as Streptomyces peucetius DnrI (47.5% identity, 84 . 3% similarity), which controls daunorubicin biosynthesis . A vmsR deletion mutant was created by homologous recombination . Neither virginiamycin M(1) nor virginiamycin S was produced in the vmsR mutant, while amounts of VB and BarA similar to those produced in the wild-type strain were detected . Reverse transcription-PCR analyses confirmed that the vmsR deletion had no deleterious effects on the transcription of the vmsR-surrounding genes, indicating that VmsR is a positive regulator of VM biosynthesis in S . virginiae.

Food Addit Contam, 2000 Aug, 17(8), 675 - 7
The effect of storage at 4 degrees C on the stability of ampicillin residues in raw milk; Schenck FJ et al.; Raw milk samples collected from tanker trucks are routinely screened for beta-lactam antibiotic drug residues using rapid screening tests . If drug residues are detected, the milk may be shipped on ice blocks to a laboratory for further analysis . A study was conducted to determine the stability of ampicillin in raw milk stored at +4 degrees C in order to predict if shipping the milk would result in the degradation of ampicillin residues . Milk samples were spiked with 20 ppb ampicillin, stored at +4 degrees C and -70 degrees C for 1-6 days, and then analysed by HPLC with fluorescence detection . No loss of ampicillin residues was found in milk stored at +4 degrees C for 1-6 days.

Hong Kong Med J, 2000 Sep, 6(3), 322 - 4
Acute epiglottitis presenting as the sensation of a foreign body in the throat; Chung CH; A 49-year-old man presented with dysphagia and the sensation of a foreign body in the throat, after he had swallowed chicken meat that contained bones during the previous evening . There were no respiratory symptoms . A plain lateral soft-tissue X-ray of the neck and oesophagogastroduodenoscopy showed a grossly swollen epiglottis . His condition improved rapidly with intravenous antibiotic therapy . As acute epiglottitis may be a sudden life-threatening condition, a high index of suspicion should be maintained for patients who present with an obstructive sensation in the throat.

Biophys J, 2000 Oct, 79(4), 1718 - 30
Atomic detail peptide-membrane interactions: molecular dynamics simulation of gramicidin S in a DMPC bilayer; Mihailescu D et al.; Molecular dynamics simulations have been performed of the sequence-symmetric cyclic decapeptide antibiotic gramicidin S (GS), in interaction with a hydrated dimyristoylphosphatidylcholine (DMPC) bilayer, and the results compared with a "control" simulation of the system in the absence of GS . Following experimental evidence, the GS was initially set in a single antiparallel beta-sheet conformation with two Type II' beta-turns in an amphiphilic interaction with the membrane . This conformation and position remained in the 6.5 ns simulation . Main-chain dihedrals are on average approximately 26 degrees from those determined by NMR experiment on GS in dimethylsulfoxide (DMSO) solution . Sequence-symmetric main-chain and side-chain dihedral angle pairs converge to within approximately 5 degrees and approximately 10 degrees, respectively . The area per lipid, lipid tail order parameters, and quadrupole spin-lattice relaxation times of the control simulation are mostly in good agreement with corresponding experiments . The GS has little effect on the membrane dipole potential or water permeability . However, it is found to have a disordering effect (in agreement with experiment) and a fluidifying effect on lipids directly interacting with it, and an ordering effect on those not directly interacting.

Blood, 2000 Oct 15, 96(8), 2703 - 11
Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation; Thomson BG et al.; Unrelated cord blood (UCB) is being used as a source of alternative hematopoietic stem cells for transplantation with increasing frequency . From November 1994 to February 1999, 30 UCB transplant procedures were performed for both malignant and nonmalignant diseases in 27 children, aged 0.4 to 17.1 years . Patients received either HLA-matched (n = 3) or 1- or 2-antigen-mismatched (n = 27) UCB following 1 of 2 standardized preparative and graft-versus-host disease regimens (hyperfractionated total body irradiation, cyclophosphamide, and antithymocyte globulin {ATG} with cyclosporine A and methotrexate; or busulfan, melphalan, and ATG with cyclosporine A and prednisone) . The median time to neutrophil and platelet engraftment was 27 days (12-60 days) and 75 days (33-158 days) posttransplantation, respectively . No correlation was noted between neutrophil and platelet engraftment and nucleated cells per kilogram, CD34(+) cells per kilogram infused, or cytomegalovirus status of recipient . The cumulative probability of acute grade 2 or greater graft-versus-host disease (GVHD) was 37.2%, and of grade 3 or greater GVHD was 8.8% . No patients developed chronic GVHD . CD4, CD19, and natural killer cell recovery was achieved at a median of 12, 6, and 2 months, respectively . CD8 recovery was delayed at a median of 9 months . Normal mitogen response was achieved at 6 to 9 months . The probability of survival, disease-free survival, and event-free survival at 1 year was 52.3% (34.1%-70.5%), 54.7% (34.5%-74.9 %) and 49.6% (29.9%-69.4%), respectively . This series of 30 UCB transplants suggests that although CD8 cell recovery is delayed, the pattern of immune reconstitution with UCB is similar to that reported for other stem cell sources . (Blood . 2000;96:2703-2711)

Bone Marrow Transplant, 2000 Sep, 26(5), 533 - 8
Utility of obtaining blood cultures in febrile neutropenic patients undergoing bone marrow transplantation; Serody JS et al.; Infection remains an important cause of morbidity and mortality after bone marrow or stem cell transplantation . To evaluate the role of obtaining blood cultures for intermittent or persistent fever in neutropenic patients on antibiotic therapy, we performed a retrospective chart review of 196 consecutive patients admitted to the Bone Marrow Transplant Unit at the University of North Carolina Hospitals from 1995 to 1998 . From the cohort of 196 patients, 154 patients developed neutropenic fever . The initial blood culture was positive in 16 of 145 patients during the first fever episode giving a prevalence of 11% . From the total of 109 patients that had blood cultures drawn after day 1 of fever, five patients had blood cultures positive for a pathogen, a prevalence of 4.6% . In only one patient, did blood cultures drawn after day 1 identify an organism not present on day 1 (prevalence 0.9%) . After reviewing the results in the first 105 patients, we changed our timing of collection of blood cultures . Forty-nine patients were treated in this manner and we found that the mean number of blood cultures decreased from 9.2 to 4.7 per patient without a change in the frequency of infectious complications or length of hospitalization.

J Natl Cancer Inst, 2000 Oct 4, 92(19), 1573 - 81
Immunoconjugates of geldanamycin and anti-HER2 monoclonal antibodies: antiproliferative activity on human breast carcinoma cell lines; Mandler R et al.; BACKGROUND: HER2 is a membrane receptor whose overexpression is strongly associated with poor prognosis in breast carcinomas . Inhibition of HER2 activity can reduce tumor growth, which led to the development of Herceptin, an anti-HER2 monoclonal antibody (MAb) that is already in clinical use . However, the objective response rate to Herceptin monotherapy is quite low . HER2 activity can also be inhibited by the highly cytotoxic antibiotic geldanamycin (GA) . However, GA is not used clinically because of its adverse toxicity . Our purpose was to enhance the inhibitory activity of anti-HER2 MAb by coupling it to GA . METHODS: We synthesized 17-(3-aminopropylamino)GA (17-APA-GA) and conjugated it to the anti-HER2 MAb e21, to form e21 : GA . The noninternalizing anti-HER2 MAb AE1 was used as a control . Internalization assays and western blot analyses were used to determine whether the anti-HER2 MAbs and their immunoconjugates were internalized into HER2-expressing cells and reduced HER2 levels . All statistical tests were two-sided . RESULTS: The immunoconjugate e21 : GA inhibited the proliferation of HER2-overexpressing cell lines better than unconjugated e21 (concentration required for 50% inhibition = 40 versus 1650 microg/mL, respectively) . At 15 microg/mL, e21 : GA reduced HER2 levels by 86% within 16 hours, whereas unconjugated e21, 17-APA-GA, or AE1 : GA reduced HER2 levels by only 20% . These effects were not caused by release of 17-APA-GA from the immunoconjugate because immunoconjugates containing {(3)H}GA were stable in serum at 37 degrees C . Furthermore, e21 : GA did not significantly inhibit proliferation of the adult T-cell leukemia cell line HuT102, which is HER2 negative yet highly sensitive to GA . CONCLUSIONS: Our findings suggest that conjugating GA to internalizing MAbs enhances the inhibitory effect of the MAbs . This approach might also be applied in cellular targeting via growth factors and may be of clinical interest.

J Clin Microbiol, 2000 Oct, 38(10), 3896 - 9
Mycobacterium branderi from both a hand infection and a case of pulmonary disease; Wolfe J et al.; Mycobacterium branderi, a potential human pathogen first characterized in 1995, has been isolated from respiratory tract specimens . We report here a case in which M . branderi was the only organism isolated upon culture from a hand infection . This isolate, along with a second isolate from a bronchial specimen, was subjected to conventional identification tests for mycobacterial species . Further analysis by high-performance liquid chromatography (HPLC) of mycolic acids and 16S rRNA gene sequencing was performed, and the antibiotic susceptibility profile was determined for both strains . Biochemical tests and the HPLC pattern were consistent with that of M . branderi and M . celatum, which are very similar . The 16S rRNA gene sequence of both strains corresponded to that of M . branderi and enabled us to confidently differentiate this organism from other closely related species such as M . celatum . This contributes to a further understanding of the status of this species as a potential human pathogen as well as illustrating the need for molecular diagnostics as a complementary method for the identification of rare mycobacterial species.

J Clin Microbiol, 2000 Oct, 38(10), 3715 - 7
Evaluation of the Etest method for determining voriconazole susceptibilities of 312 clinical isolates of Candida species by using three different agar media; Pfaller MA et al.; Performance of the Etest for voriconazole susceptibility testing of 312 isolates of Candida spp . was assessed against that of the National Committee for Clinical Laboratory Standards (NCCLS) microdilution broth method . The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C . Etest MICs were determined with RPMI agar containing 2% glucose (RPG), Casitone agar (CAS), and antibiotic medium 3 (AM3) agar and were read after incubation for 48 h at 35 degrees C . The Candida spp . isolates included C . albicans (n = 174), C . glabrata (n = 55), C . tropicalis (n = 31), C . parapsilosis (n = 39), C . krusei (n = 5), C . lusitaniae (n = 2), and C . guilliermondii (n = 6) . The Etest results obtained using RPG correlated well with the reference MICs . Overall agreement ranged from 91% for C . glabrata to 100% for C . tropicalis, C . parapsilosis, C . guilliermondii, C . krusei, and C . lusitaniae . When CAS was used, agreement ranged from 80% for C . krusei to 100% for C . parapsilosis, C . guilliermondii, and C . lusitaniae . With AM3, agreement ranged from 58% for C . glabrata to 100% for C . lusitaniae and C . guilliermondii . The Etest method using RPG appears to be a useful method for determining voriconazole susceptibilities of Candida species.

Acad Emerg Med, 2000 Oct, 7(10), 1083 - 8
Development of a histomorphologic scale to quantify cutaneous scars after burns; Singer AJ et al.; OBJECTIVE: Cutaneous wound healing in adults invariably results in scarring; however, there are few scales to quantify the degree of such scarring . The authors developed a histomorphologic scale for quantifying scarring after cutaneous burn injury . METHODS: As part of a randomized trial comparing a variety of burn therapies, 40 partial-thickness burns were created on the backs and flanks of anesthetized pigs and treated with a tissue adhesive, antibiotic ointment, occlusive dressing, or dry gauze . Gross scar appearance was independently assessed by two investigators at 90 days on a 100-mm visual analog scale (VAS) marked "best appearance" at the high end . One of the investigators repeated the observation 30 days later . Full-thickness biopsies were taken 90 days after injury and evaluated histologically by a dermatopathologist for the presence of hyperkeratosis, epidermal hyperplasia, presence and depth of scar (defined as abnormally oriented collagen under polarized light), fibroplasia, vascular proliferation, and absence of adnexa, including hair follicles, apocrine glands, and smooth muscles . One point was assigned for each category in the presence of a normal finding, whereas an abnormal finding was assigned a score of zero . The normal dermis (absence of abnormal collagen) was given a score of 3, while decreasing scores of 2 to 0 were given for progressively deeper scars (i.e., 2 for papillary dermis, 1 for upper half of reticular dermis, and 0 for deep dermal lower half) . The total histomorphologic score was derived by adding the scores on the individual items . The score ranges from 0 to 10 from worst scarring to absence of scarring, respectively . A subset of observations was evaluated a second time by one of the observers one month later . Intraobserver reliability of the histomorphologic scale was assessed with Spearman's correlation . Inter- and intraobserver Pearson's correlations for the gross scar VAS were calculated, and the correlation between gross and histomorphologic scores was assessed . RESULTS: Intraobserver correlation for individual histomorphologic categories ranged from 0.19 to 1.00 . Intraobserver correlation for the total histologic score was 0.95 . Inter- and intraobserver correlations for the gross scar VAS were 0.8 each . Correlation between the histomorphologic scale and the gross scar VAS was 0.38 . CONCLUSIONS: A new reliable histomorphologic method for quantifying and scoring cutaneous scars is described together with a reliable scar VAS . However, these two scales are not highly correlated.

Ugeskr Laeger, 2000 Sep 18, 162(38), 5070 - 3
{Bite wounds and infection prophylaxis . Evidence-based therapeutic recommendations}; Modrau IS et al.; Infections are common complications of bite wounds, changing in severity from local cellulitis to life-threatening septicaemia . Treatment recommendations are often contradictory and rarely reflect evidence-based medicine . Risk factors associated with higher rates of infection include localization on the hands, puncture wounds and age older than 50 years . The literature is critically reviewed for evidence-based treatment of bite wounds . The results are discussed with respect to common practice in Denmark.

Commun Dis Public Health, 2000 Sep, 3(3), 184 - 7
Limitations of national guidelines in the management of an outbreak of tuberculosis; Freudenstein U et al.; National guidelines offer no clear definition of a close (non-household) contact of tuberculosis . The resulting lack of distinction between close and casual contacts may lead to excessive screening in outbreaks of pulmonary tuberculosis in the United Kingdom . Poor compliance with chemoprophylaxis suggests that priority should be given to the follow up of high risk contacts, who should be more clearly defined . A review of the management of a family outbreak of tuberculosis illustrates the problem . Fifty-nine out of 213 non-household contacts screened for infection had grade 3 and 4 Heaf reactions and none developed clinical tuberculosis within one year . Three of the 59 did not attend for chest radiography and a further 11 patients did not attend the outpatients appointment offered . Twenty-three took chemoprophylaxis for three months, 14 did not complete chemoprophylaxis, six (11%) declined it and two were offered x-ray follow up.

Commun Dis Public Health, 2000 Sep, 3(3), 181 - 3
Outbreak of tuberculosis associated with a church; Cook SA et al.; Investigation of an outbreak of tuberculosis (TB) in a West Midlands health district in 1999 revealed spread in an extended family network and to church contacts . Within the family four cases of smear positive TB, four cases of smear negative infection, and 14 cases requiring chemoprophylaxis were identified . One of the infectious cases visited a local church on two occasions, which resulted in a further 16 cases of infection including one case of tuberculous meningitis . DNA fingerprinting of isolates from five culture positive cases indicated that the same strain of Mycobacterium tuberculosis was responsible . This outbreak is a reminder that while outbreaks of TB usually arise within households or family networks, where close contact over extended periods provides more opportunity for exposure, community outbreaks of TB can occur after only causal contact.

Can Fam Physician, 2000 Sep, 46, 1780 - 2, 1785-8
Referral of children with otitis media . Do family physicians and pediatricians agree?
McIsaac WJ, Coyte P, Croxford R, Harji S, Feldman W.
OBJECTIVE: To determine factors influencing family physicians' and pediatricians' decisions to refer children with recurrent acute otitis media (RAOM) and otitis media with effusion (OME) to otolaryngologists for an opinion about tympanostomy tube insertion . DESIGN: Mailed survey . SETTING: Physicians' practices in Ontario . PARTICIPANTS: Random sample of 1459 family physicians and all 775 pediatricians in the province . MAIN OUTCOME MEASURES: Physicians' reports of the influence of 17 factors on decisions to refer (more likely, no influence, less likely to refer) and number of episodes of otitis media, months with effusion, level of hearing loss, or months of continuous antibiotics without improvement prompting referral . RESULTS: Physicians agreed (> 80% concordance) on six out of 17 factors as indications for referring children with RAOM or OME . Opinions about the importance of other factors varied widely . Family physicians would refer children with otitis media after fewer episodes of illness, fewer months of effusion, lower levels of hearing loss, and fewer months of prophylactic antibiotic therapy than pediatricians (all P < .001) . Pediatricians would prescribe continuous antibiotics longer (11.8 weeks) than family physicians (8.9 weeks, P < .0001), which correlated with lower referral thresholds for family physicians . CONCLUSION: Family physicians' and pediatricians' self-reported referral practices for surgical opinions on children with otitis media varied considerably . These observations raise questions about the consistency of care for children with otitis media and whether revised clinical guidelines would be helpful.

Br J Neurosurg, 1998 Apr, 12(2), 131 - 5
The preoperative skin shave in neurosurgery: is it justified?
Siddique MS, Matai V, Sutcliffe JC.
Shaving the scalp prior to surgery is a very common practice . Out of 105 cases operated upon without skin shave at the Royal London Hospital, only one became infected (0.95%) . A search into the history of aseptic surgery shows that there are no scientific grounds for the practice of shaving . An examination of contemporary practices worldwide shows that there is a greater realization that preoperative skin shaving does not confer any benefit against postoperative wound infection and that, paradoxically, it may lead to higher rates of wound infection due to the epidermal injury that it inflicts.

Am J Perinatol, 2000, 17(3), 127 - 30
Association between epidural analgesia and intrapartum fever; Gonen R et al.; The objective of this paper is to determine whether or not epidural analgesia is an independent risk factor for intrapartum fever . Maternal temperature was measured every 4 h during labor to 1004 consecutive women in term labor . Women with fever or on antibiotics were excluded . Epidural analgesia was administered upon patients' request . Of the 406 (40%) women who received epidural analgesia, 11.8% (n = 48) developed a fever > or = 37.8 degrees C during labor compared with only 0.2% (n = 1) of women not receiving epidural analgesia . Women who received epidural analgesia were more likely to have one or more risk factors for intrapartum infection . Their labor and ruptured membranes were longer, they were more likely to have internal monitoring and have more vaginal examinations . Compared with women who received epidural analgesia and did not develop intrapartum fever, women that did develop fever had longer epidurals and more risk factors for infection . However, in a logistic regression analysis with fever as dependent variable, only the duration of epidural was significantly associated with the occurrence of fever . The rate of fever increased with longer labors, from 5% with labor < 3 h to 28% with labor > 6 h . In 90% of women the fever resolved within a few hours after delivery . Sepsis evaluation was negative in all of the newborns to mother who had intrapartum fever . Our data support a noninfectious etiology for intrapartum fever in the vast majority of our patients . However, infection must be ruled out before a decision is made to withhold antibiotic therapy.

Biochem Cell Biol, 2000, 78(4), 477 - 85
The ZF87/MAZ transcription factor functions as a growth suppressor in fibroblasts; Stubbs MC et al.; ZF87/MAZ is a zinc finger transcription factor that activates expression of tissue-specific genes and represses expression of the c-myc proto-oncogene . Infection of NIH3T3 fibroblasts with a retrovirus expressing ZF87/MAZ leads to a significant reduction in G418-resistant colonies, compared to cells infected with a retroviral control . Further, only a small fraction of the G418-resistant colonies express ZF87/MAZ . When the ZF87/MAZ-expressing colonies are expanded, they demonstrate a slow growth phenotype, a delayed transit through G1 phase and a decrease in endogenous c-myc gene expression and cyclin A and cyclin E protein levels . Consistent with a partial G1 arrest, the ZF87/MAZ-expressing cells show a reduced sensitivity to the S phase specific chemotherapeutic agent camptothecin . These data indicate that ZF87/MAZ is a growth suppressor protein in nontransformed cells, in part, by affecting the levels of key cell cycle regulatory proteins.

Br J Oral Maxillofac Surg, 2000 Oct, 38(5), 496 - 504
Isolated orbital blowout fractures: survey and review; Courtney DJ et al.; The management of orbital blowout fractures is controversial . The continuing debate includes the use of antibiotics and steroids, imaging, the surgical approach, and the choice of implant material for repair of the bony defect.A cross-sectional study was undertaken to assess current practice in treating orbital blowout fractures in the UK, in the form of a tick-box questionnaire . The questionnaire contained 9 closed and 2 open questions, and was forwarded to 256 practising fellows of the British Association of Oral and Maxillofacial Surgery . The response rate to the questionnaire was 73% (187/256).There was no consensus about the use of prophylactic antibiotics . However, 91% prescribed post-operative antibiotics and over half the respondents prescribed steroids . The most common imaging techniques used were computed tomography (CT, 88%) and plain radiograph (83%), 60% routinely sought an ophthalmic opinion and 65% assessed visual acuity . The most common surgical approaches were the subciliary (41%) and the infraorbital (37%), over half the respondents preferred to operate 6-10 days after the injury, and silicone elastomer was the preferred implant material of 66% .

Adv Ther, 2000 Mar-Apr, 17(2), 103 - 16
Treatment of recurrent respiratory tract infections with a polyvalent bacterial lysate: results of an open, prospective, multinational study; Grevers G et al.; This multicenter, open study, carried out in 14 countries in Europe, Latin America, and Asia, recruited 4965 patients suffering from recurrent respiratory tract infections to investigate the safety and acceptability of the oral bacterial lysate immunomodulator LW 50020 . Patients remained in the study for 4 months (two 4-week courses of LW 50020 separated by a 28-day treatment-free interval and follow-up) . The incidence of all adverse events was 7.2%; that of adverse drug reactions was 0.6% . Adverse drug reactions were mild to moderate and not more frequent in the large subgroup of patients (77%) with a known history of allergies or underlying respiratory diseases; however, the incidence of adverse events in this subgroup was twofold higher than in the study population as a whole, probably indicating a generally increased vulnerability to disease . No clinically relevant changes in laboratory variables followed treatment . Comparison of the first study period (first course of LW 50020 and drug-free interval) with the second study period (second course of LW 50020 and follow-up) showed an overall reduction of at least 50% in the number, severity, and duration of respiratory tract infections, the number of antibiotic and symptomatic treatments, and the number of days absent from school or work . Tolerability and acceptability were assessed as good or very good in 99% of patients who completed the study.

J Comput Aided Mol Des, 2000 Oct, 14(7), 689 - 703
Conformational properties of amphotericin B amide derivatives--impact on selective toxicity; Resat H et al.; Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug . To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives . It was found that the extended conformation with torsional angles (phi,psi)=(290 degrees,180 degrees) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives . The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration . Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel . The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity . Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer . Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives . In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity . This model successfully explains our results . To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before . Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model.

J Pediatr Orthop, 2000 Sep-Oct, 20(5), 585 - 7
Total hip arthroplasty after childhood septic hip in patients younger than 25 years of age; Dudkiewicz I et al.; Childhood septic hip should usually be treated immediately by arthrotomy and antibiotic . Even if treated correctly, the affected hip may become osteoarthritic and functionally disabling . Usually the literature is not in favor of total hip arthroplasty in young patients, and the reports are on patients older than 32 years of age . We present here a unique group of very young patients with early coxarthrosis caused by septic hip in childhood, with an average age of 19.14 years (range, 14-25) at the time of the arthroplasty . The Harris hip score improved from a preoperative mean of 58.43 to a postoperative mean of 94.14 . The follow-up period ranged between 2 and 24 years, with an average of 8.14 years . We conclude that total hip arthroplasty in young people with early coxarthrosis caused by septic hip in childhood provides good functional results.

Clin Pediatr (Phila), 2000 Sep, 39(9), 529 - 33
Syndrome of hypokalemic metabolic alkalosis and hypomagnesemia associated with gentamicin therapy: case reports; Shetty AK et al.; Nephrotoxicity, as evidenced by renal insufficiency is a well-known consequence of gentamicin therapy . We report two patients with gentamicin-induced syndrome of hypokalemic metabolic alkalosis and hypomagnesemia . Both had complete recovery of renal tubular function after cessation of antibiotic therapy . These cases emphasize the need to routinely monitor patients receiving gentamicin therapy for electrolyte abnormalities to avoid potential morbidity.

J Bacteriol, 2000 Oct, 182(20), 5653 - 62
ssgA is essential for sporulation of Streptomyces coelicolor A3(2) and affects hyphal development by stimulating septum formation; van Wezel GP et al.; The role of ssgA in cell division and development of streptomycetes was analyzed . An ssgA null mutant of Streptomyces coelicolor produced aerial hyphae but failed to sporulate, and ssgA can therefore be regarded as a novel whi gene . In addition to the morphological changes, antibiotic production was also disturbed, with strongly reduced actinorhodin production . These defects could be complemented by plasmid-borne ssgA . In the wild-type strain, transcription of ssgA was induced by nutritional shift-down and was shown to be linked to that of the upstream-located gene ssgR, which belongs to the family of iclR-type transcriptional regulator genes . Analysis of mycelium harvested from liquid-grown cultures by transmission electron microscopy showed that septum formation had strongly increased in ssgA-overexpressing strains in comparison to wild-type S . coelicolor and that spore-like compartments were produced at high frequency . Furthermore, the hyphae were significantly wider and contained irregular and often extremely thick septa . These data underline the important role for ssgA in Streptomyces cell division.

An Esp Pediatr, 2000 Apr, 52(4), 398 - 400
{Cervical spondylodiscitis in an infant}; Oliveira T et al.; Spondylitis in childhood is rare, presenting a great variety of symptoms that are related to the child s age and to the site of the inflammatory process . We present the case of a nine-month-old infant, who presented to the emergency department with a torticollis of six weeks evolution . The diagnosis of spondylitis (C6-C7) was confirmed by MRI . Intravenous antibiotic therapy was administered . The patient showed complete regression of symptoms and imaging tests were normal . The rarity of this disease in patients in this age group, as well as the site and form of presentation are emphasised as is the importance of diagnosing this disease to prevent permanent neurological injuries or bone deformities.

Chemistry, 2000 Sep 1, 6(17), 3095 - 115
Total synthesis of everninomicin 13,384-1--Part 1: retrosynthetic analysis and synthesis of the A1B(A)C fragment; Nicolaou KC et al.; In this first of a series of four articles we introduce everninomicin 13,384-1 (1), a powerful antibiotic effective against drug resistant bacteria, as a target for total synthesis and discuss its retrosynthetic analysis . From the three defined fragments required for the synthesis (2: A1B(A)C fragment; 4: DE fragment; 5: FGHA2 fragment), we describe herein two approaches to the A1B(A)C block . The first strategy relied on an olefin metathesis reaction to construct a common intermediate for rings B and C, but was faced with final protecting group problems . The second, and successful approach, involved a 1,2-phenylsulfeno migration and a sulfur directed glycosidation procedure to link rings B and C, as well as an acyl fluoride intermediate to install the sterically hindered aryl ester moiety (ring A1) . The final stages of the synthesis of the required 2-phenylseleno glycosyl fluoride 2 required introduction of a phenylseleno group at C-1 of ring C followed by a novel, DAST-promoted 1,2-migration to produce the desired 2-beta-phenylseleno glycosyl fluoride moiety.

J Pharm Sci, 1987 Sep, 76(9), 753 - 6
Self-consistent field-molecular orbital (SCF-MO) calculations and nuclear magnetic resonance measurements for fosfomycin and related compounds; Smeyers YG et al.; In the present work, the mechanism of action of fosfomycin {(-)-(1R,2S)-(1,2-epoxypropyl)phosphonic acid} as an antibiotic agent is studied by "ab initio" quantum mechanical calculations and by 1H, 13C, and 31P NMR measurements . Attention is focused on the relative charge density and chemical shift of the C(2) atom of the epoxy ring, which seems to be closely related with the activity of this antibiotic . The theoretical results suggest that the sulfhydryl addition should be preceded by a necessary anchoring of the phosphonate moiety on a positive group of the receptor.

Jpn J Thorac Cardiovasc Surg, 2000 Aug, 48(8), 534 - 5
Minimally invasive removal of infected pacemaker lead; Hirata N et al.; A 37-year-old woman with sick sinus syndrome suffered complications with recurring local infection at the generator pocket . Repeated debridement and antibiotic therapy was ineffective . Several attempts to remove leads via the implantation vein by direct traction were unsuccessful . We operated using cardiopulmonary bypass and applied a minimally invasive lower ministernotomy to obtain pleasing cosmetic results . After a right atriotomy, leads were removed . The minimally invasive approach gave satisfactory results, especially cosmetically.

Anticancer Drugs, 2000 Jul, 11(6), 479 - 85
Cytotoxicity of aphidicolin and its derivatives against neuroblastoma cells in vitro: synergism with doxorubicin and vincristine; Michaelis M et al.; Disseminated neuroblastoma diseases are still indicated by a poor outcome despite treatment regimens including radiation therapy and high-dose chemotherapy with stem cell rescue . Therefore, new substances and treatment regimens are of interest . Aphidicolin (APH), a tetracyclic diterpene antibiotic produced by Cephalosporium aphidicola, has a specific toxicity for neuroblastoma cells . Furthermore, it was shown to enhance the effects of X-ray radiation and chemotherapy on malignant cells . To find new substances, 20 APH derivatives were tested for their anti-neuroblastoma efficacy in vitro in UKF-NB-2 cells . Five derivatives had antitumoral activity in neuroblastoma cells . A relationship between the structure and the antitumoral efficacy showed that the hydroxyl groups at C-3 and C-18 are essential for the antitumoral effects . Furthermore, antitumoral effects of APH in combination with doxorubicin and vincristine, both part of commonly used treatment regimens for disseminated neuroblastoma diseases, were tested in the neuroblastoma cell line UKF-NB-2 . APH was found to act synergistically with vincristine and synergistically to additive with doxorubicin depending on the molecular ratio of the substances in combination . This may offer the chance to use APH and its derivatives as additional tools in the treatment of neuroblastomas.

Pediatr Infect Dis J, 2000 Sep, 19(9), 822 - 7
Persistently positive cultures and outcome in invasive neonatal candidiasis; Chapman RL et al.; BACKGROUND: A persistently positive culture >24 h after starting antibiotic therapy has been correlated with adverse outcome in several invasive bacterial infections, but few reports address persistent positivity and outcome in infections caused by fungi and other pathogens that replicate more slowly and therefore may succumb less quickly to therapy . METHODS: To assess whether positive culture >24 h after achieving target doses (amphotericin > or =0.5 mg/kg/day or fluconazole > or =6 mg/kg/day) of systemic antifungal therapy predicts focal infectious complication(s) or death from infection, we compared neonatal intensive care unit infants who had persistent (P+) or nonpersistent (P-) positive cultures with invasive candidiasis (clinical signs of infection and recovery of Candida from a normally sterile site) at this center from January 1, 1981, through June 30, 1999 . Infants who died < or = 24 h after attaining target dosing, recovered without therapy, had a focal infectious complication already present at the time target dosing was achieved or were diagnosed with invasive candidiasis only postmortem were excluded . RESULTS: We identified 58 P+ (29, 12 and 7 had positive cultures for >7, >14 and > or =21 days, respectively) and 38 P- infants . No differences were found between P+ and P- for birth weight; gestational age; gender; onset age; central vascular catheters; necrotizing enterocolitis, surgery or bacterial sepsis; or duration of parenteral nutrition, antibiotics, tracheal intubation or postnatal steroids . P+ were more likely to have blood or cerebrospinal fluid involvement (68 vs . 45%, P = 0.03) . Distribution of Candida species was similar (albicans in 53 vs . 63% for P+ vs . P-) . P+ were significantly more likely to develop later "fungus ball" uropathy (16 of 56 vs . 2 of 32, P = 0.01), to develop renal infiltration (11 of 56 vs . 1 of 32, P = 0.03) and to die from invasive candidiasis (11 of 58 vs . 0 of 38, P = 0.003) than P- . P+ were also more likely to develop endocarditis, abscess, ventriculitis and invasive dermatitis, although P > 0.05 . Focal complication increased as duration of P+ increased (48, 55, 67 and 71% at >1, >7, >14 and > or =21 days, P = 0.06) . When comparing only those with positive blood and/or cerebrospinal fluid culture, similar patterns were observed, although only death and focal complication or death from invasive candidiasis attained significance . CONCLUSIONS: These observations suggest that in neonatal invasive candidiasis: (1) cultures usually remain positive >24 h after attaining target antifungal doses; (2) aggressive imaging for focal complications may be reserved for infants with persistently positive cultures after several days of antifungal therapy at target doses or have signs strongly suggestive of focal complication; (3) focal complications and/or death from candidiasis increase with persistence; (4) focal complications increase with duration of persistence; (5) serial culture of infected site(s) helps predict outcome and the need for aggressive surveillance and intervention for focal complications.

Nature, 2000 Sep 14, 407(6801), 215 - 8
Peptide cyclization catalysed by the thioesterase domain of tyrocidine synthetase; Trauger JW et al.; In the biosynthesis of many macrocyclic natural products by multidomain megasynthases, a carboxy-terminal thioesterase (TE) domain is involved in cyclization and product release; however, it has not been determined whether TE domains can catalyse macrocyclization (and elongation in the case of symmetric cyclic peptides) independently of upstream domains . The inability to decouple the TE cyclization step from earlier chain assembly steps has precluded determination of TE substrate specificity, which is important for the engineered biosynthesis of new compounds . Here we report that the excised TE domain from tyrocidine synthetase efficiently catalyses cyclization of a decapeptide-thioester to form the antibiotic tyrocidine A, and can catalyse pentapeptide-thioester dimerization followed by cyclization to form the antibiotic gramicidin S . By systematically varying the decapeptide-thioester substrate and comparing cyclization rates, we also show that only two residues (one near each end of the decapeptide) are critical for cyclization . This specificity profile indicates that the tyrocidine synthetase TE, and by analogy many other TE domains, will be able to cyclize and release a broad range of new substrates and products produced by engineered enzymatic assembly lines.

J Assoc Physicians India, 1996 Feb, 44(2), 90 - 2
Dexamethasone in adults with bacterial meningitis; Gupta A et al.; Seventy five patients of acute bacterial meningitis, aged 12 to 70 years, were randomized to two treatment groups . In addition to standard antibiotic therapy, one group received dexamethasone in a dose of 8 mg, 6 hourly for 7 days . The main outcome measures used were (a) Rapidity of recovery parameters, namely, time to defervesence, disappearance of neck rigidity and return of consciousness (b) Incidence of neurological complications during hospitalization and follow-up (c) Mortality . There were no significant differences in outcome between the two treatment groups in any of the clinical parameters assessed . The use of dexamethasone as an adjunct does not speed recovery from acute illness and does not reduce the incidence of neurological complications or death in adult patients with acute bacterial meningitis.

Ann Oncol, 2000 Jul, 11(7), 885 - 6
Paradoxical emboli after central venous catheter removal; Zuha R et al.; Central venous catheters are widely used in intensive medicine to provide blood product, nutritional and antibiotic support . A 45-year-old man with an unsuspected patent foramen ovale underwent a bone marrow allograft for poor-risk acute lymphoblastic leukaemia . His venous line was removed because of probable infection, and he simultaneously sustained a myocardial infarct and a cerebrovascular accident . He made a good recovery from both, but subsequently died of relapsed disease . Appropriate pre-transplant screening investigations are discussed, and the differential diagnosis of this complication in the bone marrow transplant setting.

Clin Neurol Neurosurg, 2000 Sep, 102(3), 163 - 5
Diabetes insipidus in neurobrucellosis; Trifiletti RR et al.; Brucellosis is an infection due to Brucella species and is characterized by acute febrile illness, chilly sensations, sweats, weakness, generalized malaise, body aches and headache . The involvement of the nervous system is rare . A few cases have been reported with symptoms and sign of optic neuritis, meningoencephalitis, meningomyelitis and cranial nerve palsy . We report a case with culture proven neurobrucellosis who presented with diabetes insipidus along with systemic signs . Neuroimaging revealed multiple lesions in brain parenchyma, including the suprasellar region . Both diabetes and suprasellar lesions improved markedly with specific antibiotic therapy.

Cardiovasc Surg, 2000 Oct, 8(6), 463 - 5
A novel technique for intraaortic balloon pump placement via the left axillary artery in patients awaiting cardiac transplantation; H'Doubler PB Jr et al.; In order to circumvent the problems associated with long-term femoral intraaortic balloon pump (IABP) placement we have developed and used a new technique of IABP placement . Over the past three years 13 patients awaiting cardiac transplantation have had placement of IABP via a vein cuff sewn to the left axillary artery . Thirteen patients have undergone IABP placement using this technique . The average duration of IABP support was 37 days (range 10-86 days) . Ten patients were successfully transplanted . All patients were allowed to sit, stand and ambulate with assistance . No neurologic complications occurred . There were no episodes of sepsis related to balloon or insertion site . No patient had limb ischemia during IABP counterpulsation . Left axillary artery IABP insertion via a vein cuff portal is a straightforward technique with minimal complications . This method serves as a bridge to cardiac transplantation in a gravely ill group of patients while preserving patient mobility during the waiting period for a donor heart.

Trop Med Int Health, 2000 Aug, 5(8), 515 - 27
Review of the evidence base for the 'F' and 'E' components of the SAFE strategy for trachoma control; Emerson PM et al.; Community control of trachoma as a blinding disease is based on the SAFE strategy of Surgery, Antibiotic therapy, Facial cleanliness and Environmental improvement . Surgery and antibiotic therapy currently dominate most programmes . Blindness from trachoma results from frequent infections repeated over many years, so ultimate success requires the reduction of transmission . This is only likely to be sustainable through the F and E components of SAFE . Environmental improvement with access to water, enhanced hygiene and better sanitation reduces trachoma transmission and the blinding sequelae eventually disappear . Transmission routes and factors that cause this are not known and consequently no single specific tool for F and E is in place . Evidence from intervention studies shows that the promotion of face-washing gave modest gains for intense effort and a pilot study showed that trachoma transmission was reduced in the absence of eye-seeking flies . Other studies have shown that latrines and improved access to water are associated with a lower prevalence of active trachoma . There is likely to be a long-term beneficial effect of a combination of improved water supplies, provision of latrines, facial hygiene promotion through established infrastructure and control of eye-seeking flies . Each of these interventions offers additional public health and other benefits in its own right . Further research on the routes of transmission, the role of hygiene and means of sustainable fly control should be a priority.

J Clin Gastroenterol, 2000 Sep, 31(2), 169 - 71
Helicobacter pylori eradication and remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma: a long-term follow-up study; Papa A et al.; Helicobacter pylori infection plays a crucial role not only in the pathogenesis but also in the treatment of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma . The aim of the present study was to evaluate whether H . pylori eradication provides a definite cure in the early stage of this neoplasia by means of a prolonged follow-up . All patients affected by low-grade gastric MALT lymphoma in stage IE that were referred to our department from January 1995 to June 1999 were enrolled in a prospective study . Diagnosis was histologically proved and H . pylori status was evaluated . Staging was performed according to a modified Ann Arbor classification . All patients who proved positive for H . pylori infection were treated with eradicating therapy, and a prolonged clinical and histologic follow-up was carried out . Until June 1999, seven low-grade gastric MALT lymphomas in stage IE were diagnosed (four men and three women; mean age, 56 years) . All patients were H . pylori-positive and eradication was obtained in all of them after the first cycle of antibiotic therapy . Complete histologic regression of lymphoma was observed in all cases in a period variable between 3 and 6 months . The mean follow-up period was 42 months (range, 20-54) . Only one patient showed a recurrence of lymphoma 22 months after treatment associated with H . pylori reinfection . Our results show the high efficacy of H . pylori eradication in determining a prolonged remission of low-grade gastric MALT lymphomas in stage IE . Thus, this therapeutic approach may avoid or delay the indication for more aggressive therapies, such as surgical resection.

Cleve Clin J Med, 2000 Sep, 67(9), 673 - 80
Long-term medical complications of heart transplantation: information for the primary care physician; Yamani MH et al.; As heart transplantation becomes much more common primary care physicians will play a key role in preventing, detecting, and treating the short-term and long-term complications of this procedure . These complications include chiefly graft rejection and accelerated coronary artery disease, but also dyslipidemia, hypertension, diabetes mellitus, kidney failure, gout, osteoporosis, and malignancy.

J Biomol Screen, 2000 Aug, 5(4), 255 - 62
Development of a functional reporter gene HTS assay for the identification of mGluR7 modulators; Terstappen GC et al.; For the identification of modulators of the metabotropic glutamate receptor mGluR7, a functional cell-based high throughput screening (HTS) assay was developed . This assay utilizes the signal transduction pathway of mGluR7, which is negatively coupled to adenylyl cyclase . A cAMP-responsive luciferase reporter gene and rat mGluR7 cDNA were cotransfected into CHO-K1 cells by electroporation . Stable recombinant cells were selected by resistance to the antibiotic G418 . Functional selection was carried out by analyzing the effect of the agonist glutamate to reduce elevated cAMP levels after forskolin stimulation . Out of 83 G418-resistant cell clones, the clone with the best functional characteristics was selected . This clone displayed the strongest reduction of forskolin-stimulated cAMP levels . Glutamate (10 mM) decreased cAMP levels, as monitored by luciferase expression, by about 50%, and the more potent agonist L-2-amino-4-phosphonobutyrate resulted in nearly complete reduction, exhibiting an EC(50) of 0.9 mM . The functional response of the clone did not change during cell passages, indicating the stability of this novel recombinant cell line . The luciferase reporter gene assay, which allows easy nonradioactive luminescence detection of mGluR7 activity, was optimized for its application in automated HTS.

Arch Dermatol, 2000 Sep, 136(9), 1133 - 8
Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid; Ozog DM et al.; BACKGROUND: Immunosuppressive medications typically used to treat the immunobullous disorders pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid can have serious adverse effects . The tetracycline family of antibiotic drugs has been shown to be effective in the treatment of these conditions with a more favorable side effect profile . Minocycline hydrochloride use has been associated with various forms of hyperpigmentation, and its incidence is well reported in acne vulgaris and rheumatoid arthritis . We examined a series of 9 patients treated with minocycline for pemphigus or pemphigoid, most of whom have developed cutaneous hyperpigmentation . OBSERVATIONS: Seven of 9 patients treated with minocycline, 50 mg daily (1 patient) or 100 mg twice daily (8 patients), for pemphigus vulgaris, pemphigus foliaceous, or bullous pemphigoid developed hyperpigmentation, which necessitated discontinuing therapy . Five of these patients had experienced notable clinical improvement of their immunobullous disease with minocycline therapy . The average duration of treatment was 8.2 months (range, 1-25 months) . The second most common adverse effect in our group was oral candidiasis, which occurred in 2 patients . CONCLUSIONS: We found a favorable response to minocycline therapy in 5 of 9 patients . However, 7 patients developed localized hyperpigmentation as early as 1 month after starting medication use . This incidence of minocycline-induced hyperpigmentation is significantly higher in immunobullous disease than in acne vulgaris or rheumatoid arthritis . This increased incidence may be related to an increase in pigment deposition complexed with collagen during the remodeling process, subclinical inflammation, or glucocorticosteroid-induced skin fragility . The hyperpigmentation process was reversible, as most of our patients had fading of their pigmentation after minocycline cessation.

Clin Infect Dis, 2000 Aug, 31(2), 554 - 60 Epub 2000 Sep 14.
Human granulocytic ehrlichiosis; Bakken JS et al.; Human granulocytic ehrlichiosis is a recently recognized tick-borne infectious disease, and to date >600 patients have been identified in the United States and Europe . Most patients have presented with a non-specific febrile illness occurring within 4 weeks after tick exposure or tick bite . The risk for serious illness or death increases with advancing age and delayed onset of therapy . Routine laboratory testing may reveal reduced white blood cell and platelet concentrations and mildly elevated hepatic transaminase activity in peripheral blood . A high index of suspicion is necessary to arrive at a timely clinical diagnosis . Patients suspected of having human granulocytic ehrlichiosis (HGE) should be treated with a tetracycline-class antibiotic while awaiting the outcome of confirmatory laboratory testing.

Bioorg Med Chem Lett, 2000 Sep 4, 10(17), 1963 - 5
Some selective reactions of moenomycin A; Vogel S et al.; A number of new moenomycin A derivatives have been prepared . Their antibiotic properties highlight the very specific recognition of moenomycin A at the transglycosylase binding site which is the basis of the transglycosylase inhibiting property of moenomycin A (4a).

J Mol Biol, 2000 Sep 22, 302(3), 565 - 79
The bicyclomycin sensitivities of 38 bicyclomycin-resistant mutants of transcription termination protein rho and the location of their mutations support a structural model of rho based on the F(1) ATPase; Moyse KA et al.; A total of 38 bicyclomycin-resistant mutants of Escherichia coli transcription termination protein Rho have been isolated . The locations of their mutations identify the ATP-binding region as the functional domain inhibited by bicyclomycin . Strains containing the S266C, S266A and L208R Rho mutations are very resistant to bicyclomycin in vivo . In a similar way, the mutant Rho proteins containing these mutations are very resistant to bicyclomycin in vitro . These data suggest that Ser266 and Leu208 might make direct contact with the antibiotic . These two residues are close to each other in the tertiary structure of a model of Rho based on the alpha and beta subunits of the F(1) ATPase, supporting the validity of the model . The strain containing the G337S Rho mutation also has high bicyclomycin resistance, and the proximity of L208, S266 and G337 in the quaternary structure of the Rho model has enabled a candidate bicyclomycin-binding pocket to be delineated . As a whole, the bicyclomycin sensitivities of the mutants are consistent with the locations of their respective mutations in the model of Rho based on the F(1) ATPase, therefore supporting the emerging consensus model of Rho structure .

Biochemistry, 2000 Sep 19, 39(37), 11508 - 13
Redox potential measurements of the Mycobacterium tuberculosis heme protein KatG and the isoniazid-resistant enzyme KatG(S315T): insights into isoniazid activation; Wengenack NL et al.; Mycobacterium tuberculosis KatG is a multifunctional heme enzyme responsible for activation of the antibiotic isoniazid . A KatG(S315T) point mutation is found in >50% of isoniazid-resistant clinical isolates . Since isoniazid activation is thought to involve an oxidation reaction, the redox potential of KatG was determined using cyclic voltammetry, square wave voltammetry, and spectroelectrochemical titrations . Isoniazid activation may proceed via a cytochrome P450-like mechanism . Therefore, the possibility that substrate binding by KatG leads to an increase in the heme redox potential and the possibility that KatG(S315T) confers isoniazid resistance by altering the redox potential were examined . Effects of the heme spin state on the reduction potentials of KatG and KatG(S315T) were also determined . Assessment of the Fe(3+)/Fe(2+) couple gave a midpoint potential of ca . -50 mV for both KatG and KatG(S315T) . In contrast to cytochrome P450s, addition of substrate had no significant effect on either the KatG or KatG(S315T) redox potential . Conversion of the heme to a low-spin configuration resulted in a -150 to -200 mV shift of the KatG and KatG(S315T) redox potentials . These results suggest that isoniazid resistance conferred by KatG(S315T) is not mediated through changes in the heme redox potential . The redox potentials of isoniazid were also determined using cyclic and square wave voltammetry, and the results provide evidence that the ferric KatG and KatG(S315T) midpoint potentials are too low to promote isoniazid oxidation without formation of a high-valent enzyme intermediate such as compounds I and II or oxyferrous KatG.

Arch Pediatr, 2000 Aug, 7(8), 825 - 32
{Pediatric drug preparations in French hospitals . Pediatric Group of the French Clinical Pharmacy Society}; Fontan JE et al.; AIMS: Drug formulations that are specifically intended for pediatric use have not been widely developed in France and do not adequately meet therapeutic needs, particularly as regards hospital requirements . A multicenter study was therefore carried out to evaluate the situation . MATERIALS AND METHODS: A questionnaire was sent out in June 1998 to all French university hospital pharmacies and also to those public and private hospitals known to be involved in pediatric care . Of the 78 questionnaires mailed, 63 answers were received . The information requested concerned all the drug formulations prepared in 1997 . RESULTS: Ten out of the 63 hospitals that replied stated that the questionnaire was not relevant in their particular case . Fifty-three answers were therefore evaluated, i.e., corresponding to data from 35 university hospitals, 15 public general hospitals, and three private hospitals . For 7,022 pediatric beds, 1,155,544 units were prepared consisting of 968,520 capsules prepared from 220 active substances, 33,493 liquid preparations for oral intake, 87,592 parenteral nutrition bags, 48,225 injectable antibiotic drugs, 10,663 injectable anticancer agents, and 7,051 miscellaneous sterile preparations . The most frequently prescribed active substances were, in decreasing order of importance, as follows: diphemanil, captopril, fludrocortisone, ranitidine, spironolactone, and ursodesoxycholic acid . A marked heterogeneity was displayed in galenic forms and drug dosages . CONCLUSION: In conclusion, this study has shown the most commonly prescribed drugs and the most frequently prepared dosages for pediatric use . Drug manufacturing companies may find it an useful source of information on the limited pediatric market; it may also encourage pediatricians to homogenize and optimize their therapeutic strategies, and pharmacists to establish specific quality-control procedures . The authors recommend that national guidelines be set up, and it is suggested that the health authorities could participate in organizing the means whereby drugs for pediatric use are made more readily available.

Int J Clin Pharmacol Ther, 2000 Aug, 38(8), 402 - 7
A controlled multicenter pediatric study in the treatment of acute respiratory tract diseases with the aid of a new specific compound, erdosteine (IPSE, Italian Pediatric Study Erdosteine); Titti G et al.; INTRODUCTION: Erdosteine is an original drug which has been suggested as secretolytic compound and promoter of respiratory ventilation in the treatment of acute and chronic respiratory diseases . Moreover, the drug possesses also scavenging, antioxidant, and bacterial anti-adhesivity properties . From a clinical point of view the best results have been obtained by combined treatment with an antibiotic agent of useful spectrum activity . Aim of the present study was to evaluate the improvement induced in the risk/benefit ratio by erdosteine on the broad-spectrum antibiotic (ampicillin) in the treatment of acute lower respiratory tract diseases in the pediatric field . MATERIAL AND METHODS: A controlled multicenter double-blind parallel group trial was planned comparing erdosteine, supplied as syrup 3.5% or as sachets 225 mg, versus the relevant placebo . The tested compounds were administered in association with ampicillin . Two-hundred (n = 200) subjects entered the trial, randomly selected among patients monitored by the different centers, and were assigned to one of the treatments under evaluation, i.e . active compound or placebo with the aim to constitute two comparative homogeneous groups of 100 subjects each . Subsequently each group was again divided according to age in two equivalent subgroups of 50 patients each and treated with the syrup 3.5% (age from 2 to 4 years) or the sachet form (age from 5 to 10 years) . The treatments administered in the two comparison groups were erdosteine (syrup 3.5% and 225 mg sachets) or the relevant placebo . The erdosteine posologies were adapted according to age . The lower dosage of the 5-10 years range in comparison with the 2-4 years range was established on the base of bioavailability characteristics of the two pharmaceutical forms . In all groups ampicillin was administered at the dosage of 100 mg/kg/day, according to a b.i.d . time schedule . The primary efficacy criterion was the cough score evaluated in a subjective way and expressed with the following scores: 1 = absent; 2 = mild; 3 = moderate; 4 = severe . The secondary efficacy end-points were: body temperature (expressed in degrees C); the polypnea, ronchi and rales estimation with a rating scale similar to that previously mentioned . These parameters were determined before starting of the treatment (VO); at the 3rd +/- 1 (V1) and at the 7th +/- 2 (V2) day of treatment . The body temperature was measured orally in the morning at awakening time with a mercury thermometer . Obtained data expressed in Celsius degrees are recorded by the investigator in the patient file during control visits.The safety of adopted treatments was evaluated with two different approaches . The clinical part was determined with the adverse drug reactions (ADRs) estimate . The biological safety was estimated at admission day (day 0) and at the final visit by means of a sophisticated statistical approach . RESULTS: The final results were the following: Erdosteine syrup 3.5%: concerning cough (primary end-point) in the group of patients (n = 50) treated with erdosteine it has been possible to point out a reduction of 23.8% at V1, i.e . after 3+/-1 days, and of 59.8% at V2, i.e . after 7+/-2 days . In the group of patients treated with placebo (n = 50) the reduction has been of 20.1% at V1 and of 36.6% at V2 . The statistical analysis evidenced p values < 0.01 for times, treatments, time x treatments . The relevant results are summarized in Table 2 . Erdosteine sachets 225 mg: concerning cough (primary end-point) in the group of patients (n = 50) treated with erdosteine it has been possible to point out a reduction of 17.6% at V1, i.e . after 3+/-1 days, and of 56.8% at V2, i.e . after 7+/-2 days . In the group of patients treated with placebo (n = 50) the reduction has been of 15.6% at V1 and of 31.8% at V2 . The statistical analysis evidenced p values < 0.01 for times, treatments, time x treatments . (ABSTRACT TRUNCATED)

J Biol Chem, 2000 Dec 22, 275(51), 39900 - 6
Release of the neocarzinostatin chromophore from the holoprotein does not require major conformational change of the tertiary and secondary structures induced by trifluoroethanol; Sudhahar GC et al.; Neocarzinostatin is a potent enediyne antitumor antibiotic complex in which a chromophore is noncovalently bound to a carrier protein . The protein regulates availability of the drug by proper release of the biologically active chromophore . To understand the physiological mechanism of the drug delivery system, we have examined the trifluoroethanol (TFE)-induced conformational changes of the protein with special emphasis on their relation to the release of the chromophore from holoneocarzinostatin . The effect of the alpha helix-inducing agent, TFE, on all the beta-sheet neocarzinostatin proteins was studied by circular dichroism, fluorescence, and (1)H NMR studies . By using binding of anilinonaphthalene sulfonic acid as a probe, we observed that the protein exists in a stable, partially structured intermediate state around 45-50% TFE, which is consistent with the results from tryptophan fluorescence and circular dichroism studies . The native state is stable until 20% TFE and is half-converted into the intermediate state at 30% TFE, which starts to collapse beyond 50% . High pressure liquid chromatographic analysis of the release of the chromophore caused by TFE treatment at 0 degrees C suggests that the release process, which occurs below 20% TFE, does not result from an observable conformational change in the protein . Kinetic measurements of the release of chromophore at 25 degrees C reveal that TFE does stimulate the rate of release, which increases sharply at 15% and reaches a maximum at 20% TFE, although no major secondary or tertiary structural change of the carrier protein is observed under these same conditions . Our data suggest that chromophore release results from a fluctuation of the protein structure that is stimulated by TFE . Complete release of the chromophore occurs at TFE concentrations where no overall observable unfolding of the apoprotein is seen . Thus, the results suggest that denaturation of the protein by TFE is not a necessary step for release of the tightly bound chromophore.

J Pharm Sci, 2000 Oct, 89(10), 1262 - 70
Control of gentamicin release from a calcium phosphate cement by admixed poly(acrylic acid); Bohner M et al.; The aim of this work was to develop a calcium phosphate cement (CPC) providing controlled release of the antibiotic gentamicin sulfate (GS) over at least 1 week . The CPC was made of beta-tricalcium phosphate {beta-TCP; beta-Ca(3)(PO(4))(2)}, monocalcium phosphate monohydrate {MCPM; Ca(H(2)PO(4))(2) . H(2)O} and water . Release of GS was controlled by admixture of poly(acrylic acid) (PAA) . The effects on the GS release kinetics of the molecular weight of PAA, of the amount of admixed PAA, and of the pH of the release medium were investigated . A typical cement sample weighed 3.6 g and contained 100 mg of GS and between 0 and 150 mg of PAA . In the following, PAA content is expressed as the weight ratio, lambda, with respect to GS . At a low PAA content in the CPC (lambda < 0.7), GS was released over 1-2 days according to a square-root-of-time kinetics, but not all GS was released . The unreleased GS fraction increased from 0 to 58% with an increase of PAA content (up to lambda = 0.7) . At high PAA content (lambda > 0.7), GS was released over a period of up to 8 days according to a combination of a square-root-of-time and a zero-order kinetics . The total GS fraction released increased again from 58 to 100% with an increase of the amount of PAA (up to lambda = 1.5) . These observations were explained by molecular interaction between PAA and GS resulting in gel formation . The maximum fraction of GS released from the cement was indeed a function of the solubility of the PAA-GS (coacervate) complex in the release medium . Thus, GS release was controlled by two mechanisms: (1) diffusion of free GS molecules through the porous cement (square-root-of-time kinetics); and (2) dissociation of GS from the PAA-GS complex (zero-order kinetics) . The first mechanism was predominant at low lambda, whereas the second mechanism became important at high lambda and later release times . As the solubility of the PAA-GS complex decreased with an increase in PAA molecular weight, the higher molecular weight PAA yielded more prolonged release periods of up to 8 days . Interestingly, the use of 450 kDa PAA at lambda = 1.00 provided an almost constant release profile over a period of 7 days . Gel formation between PAA and GS was explained in terms of hydrogen bonding of PAA carboxyl groups with GS amino groups . The molar ratio between carboxyl groups and amino groups in the gel was estimated to be approximately 1.9 . In conclusion, admixture of PAA into calcium phosphate cement appeared to be a very elegant tool to control the release of the antibiotic over a period of 7 to 8 days .

Blood, 2000 Sep 15, 96(6), 2284 - 91
Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential G(1) phase accumulation against chronic myelogenous leukemia cells through destabilization of Bcr-Abl with Hsp90 complex; Shiotsu Y et al.; Chronic myelogenous leukemia (CML) is a clonal disorder of a pluripotent hematopoietic stem cells characterized by a chimeric bcr-abl gene giving rise to a p210(Bcr-Abl) protein with dysregulated tyrosine kinase activity . Radicicol, a macrocyclic antifungal antibiotic, binds to the N-terminal of heat shock protein 90 (Hsp90) and destabilizes Hsp90-associated proteins such as Raf-1 . This study investigated the effect of radicicol, novel oxime derivatives of radicicol (KF25706 and KF58333), and herbimycin A (HA), a benzoquinoid ansamycin antibiotic, on the growth and differentiation of human K562 CML cells . Although KF25706 and KF58333 induced the expression of glycophorin A in K562 cells, radicicol and HA caused erythroid differentiation transiently . Cell cycle analysis showed that G(1) phase accumulation was observed in K562 cells treated with KF58333 . KF58333 treatment depleted p210(Bcr-Abl), Raf-1, and cellular tyrosine phosphorylated proteins in K562 cells, whereas radicicol and HA showed transient depletion of these proteins . KF58333 also down-regulated the level of cell cycle-dependent kinases 4 and 6 and up-regulated cell cycle-dependent kinase inhibitor p27(Kip1) protein without an effect on the level of Erk and Hsp90 proteins . Immunoprecipitation analysis showed that p210(Bcr-Abl) formed multiple complexes with Hsp90, some containing p23 and others Hsp70; KF58333 treatment dissociated p210(Bcr-Abl) from Hsp90/p23 chaperone complexes . Furthermore, KF58333 induced apoptosis in K562 cells and administration of KF58333 prolonged the survival time of SCID mice inoculated with K562 cells . These results suggest that KF58333 may have therapeutic potential for the treatment of CML that involves abnormal cellular proliferation induced by p210(Bcr-Abl).

Blood, 2000 Sep 15, 96(6), 2108 - 15
Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model; Rhoades KL et al.; As reported previously, AML1-ETO knock-in mice were generated to investigate the role of AML1-ETO in leukemogenesis and to mimic the progression of t(8;21) leukemia . These knock-in mice died in midgestation because of hemorrhaging in the central nervous system and a block of definitive hematopoiesis during embryogenesis . Therefore, they are not a good model system for the development of acute myeloid leukemia . Therefore, mice were generated in which the expression of AML1-ETO is under the control of a tetracycline-inducible system . Multiple lines of transgenic mice have been produced with the AML1-ETO complementary DNA controlled by a tetracycline-responsive element . In the absence of the antibiotic tetracycline, AML1-ETO is strongly expressed in the bone marrow of AML1-ETO and tet-controlled transcriptional activator double-positive transgenic mice . Furthermore, the addition of tetracycline reduces AML1-ETO expression in double-positive mice to nondetectable levels . Throughout the normal murine lifespan of 24 months, mice expressing AML1-ETO have not developed leukemia . In spite of this, abnormal maturation and proliferation of progenitor cells have been observed from these animals . These results demonstrate that AML1-ETO has a very restricted capacity to transform cells . Either the introduction of additional genetic changes or the expression of AML1-ETO at a particular stage of hematopoietic cell differentiation will be necessary to develop a model for studying the pathogenesis of t(8;21).

J Infect Dis, 2000 Oct, 182(4), 1192 - 8 Epub 2000 Sep 08.
Sulfa or sulfone prophylaxis and geographic region predict mutations in the Pneumocystis carinii dihydropteroate synthase gene; Huang L et al.; To determine factors associated with mutations in the Pneumocystis carinii dihydropteroate synthase (DHPS) gene, a prospective study of human immunodeficiency virus (HIV)-infected patients with confirmed P . carinii pneumonia was conducted in Atlanta, Seattle, and San Francisco . Clinical information was obtained from patient interview and chart abstraction . DHPS genotype was determined from DNA sequencing . Overall, 76 (68.5%) of 111 patients had a mutant DHPS genotype, including 22 (81.5%) of 27 patients from San Francisco . In multivariate analysis, sulfa or sulfone prophylaxis and study site were independent predictors of a mutant genotype . Fourteen (53.8%) of 26 patients who were newly diagnosed with HIV infection and had never taken prophylaxis had a mutant genotype . The significance of geographic location as a risk factor for mutant genotype and the high proportion of mutant genotypes among persons never prescribed prophylaxis, including those newly diagnosed with HIV infection, provide indirect evidence that these mutations are transmitted from person to person either directly or through a common environmental source.

Harefuah, 2000 Jun 15, 138(12), 1032 - 4, 1086
{Minocycline pneumonitis and eosinophilia}; Fink N et al.; Pneumonitis with eosinophilia is one of the less common and severe adverse effects of minocycline . The disease evolves in days or weeks from the beginning of treatment, and is usually characterized by dyspnea, fever and bilateral infiltrates in the chest X-ray . With cessation of the antibiotic, and sometimes adding cortico-steroids, clinical and roentgenological resolution follow . We present a case given minocycline for folliculitis and 3 weeks later fever, cough and shortness of breath developed . The clinical and roentgenological course was consistent with minocycline pneumonitis accompanied by eosinophilia.

Hear Res, 2000 Oct, 148(1-2), 1 - 8
Calcification processes in the chick otoconia and calcium binding proteins: patterns of tetracycline incorporation and calbindin-D28K distribution; Balsamo G et al.; In order to clarify the otoconia formation and turnover, tetracycline, an antibiotic that precipitates at calcifying fronts and serves as a fluorescent marker, was injected into eggs at different stages of chick embryonic development, as well as into postnatal chicken and into adult animals . The changes in the intensity, location patterns and time course of fluorescent labelling in each examined stage in the otolithic organs was studied . The presence and distribution of calbindin (CB)-D28K, one of the calcium-binding proteins constantly found in the mammalian and chicken cochlea and also in otolithic membrane of some adult mammals, was studied . Results in embryonal stages, postnatal and adult animals allow us to postulate that otoliths are mainly produced during the embryonal phase, but they may also be produced throughout the whole life span . Results also indicate that otoconia are dynamic structures which undergo turnover . The correspondence between the patterns of CB-D28K immunoreactivity and tetracycline fluorescence may indicate that CB-D28K participates in the formation of otoconia.

Biochemistry, 2000 Sep 5, 39(35), 10739 - 46
A novel mycothiol-dependent detoxification pathway in mycobacteria involving mycothiol S-conjugate amidase; Newton GL et al.; Mycothiol, 1-D-myo-inosityl-2-(N-acetylcysteinyl)amido-2-deoxy-alpha-D-glucopyranoside (MSH), is composed of N-acetylcysteine (AcCys) amide linked to 1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside (GlcN-Ins) and is the major thiol produced by most actinomycetes . When Mycobacterium smegmatis was treated with the alkylating agent monobromobimane (mBBr), the cellular mycothiol was converted to its bimane derivative (MSmB) . The latter was rapidly cleaved to produce GlcN-Ins and the bimane derivative of N-acetylcysteine (AcCySmB), a mercapturic acid that was rapidly exported from the cells into the medium . The other product of cleavage, GlcN-Ins, was retained in the cell and utilized in the resynthesis of mycothiol . The mycothiol S-conjugate amidase (amidase) responsible for cleaving MSmB was purified to homogeneity from M . smegmatis . A value of K(m) = 95 +/- 8 microM and a value of k(cat) = 8 s(-)(1) was determined for the amidase with MSmB as substrate . Activity with 100 microM mycothiol or with the monobromobimane derivative of 1-D-myo-inosityl-2-(L-cysteinyl)amido-2-deoxy-alpha-D-glucopyra nos ide (CySmB-GlcN-Ins) or of 2-(N-acetyl-L-cysteinyl)amido-2-deoxy-(alpha, beta)-D-glucopyranoside (AcCySmB-GlcN) was at least 10(3) lower than with 100 microM MSmB, demonstrating that the amidase is highly specific for S-conjugates of mycothiol . Conjugates of mycothiol with the antibiotic cerulenin, N-ethylmaleimide, 3-(N-maleimidopropionyl)-biocytin, and 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin also exhibited significant activity . The sequence of the amino-terminal 20 residues was determined, and an open reading frame (Rv1082) coding for 288 residues having an identical predicted amino-terminal amino acid sequence was identified in the Mycobacterium tuberculosis genome . The Rv1082 gene (mca) from M . tuberculosis was cloned and expressed in Escherichia coli, and the expressed protein was shown to have substrate specificity similar to the amidase from M . smegmatis . These results indicate that mycothiol and mycothiol S-conjugate amidase play an important role in the detoxification of alkylating agents and antibiotics.

Bull Exp Biol Med, 2000 May, 129(5), 445 - 8
Involvement of bone marrow fibroblasts in the recovery of granulocytopoiesis after cytostatic-induced myelosuppression; Dygaii AM et al.; The effects of anticancer drugs whose action is mediated by different mechanisms on activity of bone marrow fibroblasts and their role in the regulation of granulocytopoiesis recovery after cytostatic treatment were studied . The antimetabolite 5-fluorouracil strongly suppressed, while the anthracycline antibiotic adriamycin and the alkylating agent cyclophosphamide stimulated function of stromal cells . This largely accounted for different dynamics of recovery of the bone marrow neutrophil lineage.

Am J Manag Care, 2000 Mar, 6(5 Suppl), S247 - 54
Advances in the prophylaxis and treatment of influenza illness . Based on a presentation by Frederick G . Hayden, MD; Effectiveness of a comprehensive diabetes lower-extremity amputation prevention program in a predominantly low-income African-American population; Diabetes Foot Program, Louisiana State University Health Sciences Center, Baton Rouge 70806, USA . cpatou@lsuhsc.edu

OBJECTIVE: To compare patient outcomes 1 year before and 1 year after enrollment in a comprehensive diabetes lower-extremity amputation prevention program . RESEARCH DESIGN AND METHODS: Outcome data were obtained on 197 patients enrolled in the Louisiana State University Health Sciences Center Diabetes Foot Program, which provides foot care to a predominantly low-income African-American population in Louisiana . Data were obtained using a structured interview administered by a registered nurse . Recordings were made of number of days with an open foot ulcer, number of times hospitalized for a foot problem, number of days spent in the hospital for a foot problem, number of visits to the emergency room for a foot problem, number of times an antibiotic was prescribed for a foot problem, number of all foot operations, number of lower-extremity amputations, and number of missed workdays for a foot problem . Data were obtained on all patients at the initial visit and at the 1-year follow-up . RESULTS: Analysis of data showed a reduction in foot-related ulcer days (-49%), hospitalizations, (-89%), hospital days (-90%), emergency room visits (-81%), antibiotic prescriptions, (-57%), foot operations (-87%), lower-extremity amputations (-79%), and missed workdays (-70%) after 1 year of comprehensive foot care compared with the 1-year period before treatment . CONCLUSIONS: This single cohort outcome study showed a large reduction in foot-related complications after the first year of comprehensive preventive foot care.

Microb Ecol, 2000 Jul, 40(1), 64 - 73
Sensitivity of Two Disjunct Bacterioplankton Communities to Exudates from the Cyanobacterium Microcystis aeruginosa Kützing; Casamatta DA et al.; Microcystis aeruginosa Kutzing releases a variety of bioactive compounds during growth . This study determined whether bacteria from communities co-occurring (M+) or not (M-) with this cosmopolitan cyanobacterium respond similarly to its products . Fifty M+ bacteria from a M . aeruginosa bloom site (Western Basin of Lake Erie) and 50 M- bacteria from a Microcystis-free site (East Twin Lake, Portage Co., OH) were isolated and grown on Standard Methods Agar . Three levels of testing were performed: chemotaxis, antibiotic response, and 48-h cell abundance . Chemotaxis was compared using capillary tubes placed in contact with bacterial, Standard Methods Broth (SMB) suspensions . The capillary choices were conditioned SMB, M . aeruginosa exudate, and BG-11 . M+ bacteria showed significantly greater (Tukey's test, p < 0.005) positive chemotaxis to M . aeruginosa exudate compared to control conditions and to M-strains . The latter showed a negative chemotactic response to M . aeruginosa exudate compared to control conditions . Antibiotic response was tested by sensitivity disk assays, first using M . aeruginosa exudates, whole cells, and homogenized cells, and then placing the disks on bacterial lawns of each strain . M+ bacteria were significantly more resistant to inhibition than M- bacteria (chi-square test, p < 0.01) . M . aeruginosa exudate, BG-11 algal medium, SMB, and distilled water effects on 48-h abundance of the strains were compared . The M- community bacteria exhibited significantly lower growth yields (Tukey's comparison of means test, p < 0.005) in M . aeruginosa exudate than did the M+ strains . It is evident that those bacteria co-occurring with M . aeruginosa are more likely to be attracted to it, able to withstand exposure to it, and able to utilize its products without inhibition than are bacteria from communities without previous exposure to this cyanobacterium.

Mol Microbiol, 2000 Aug, 37(4), 811 - 20
The tylosin resistance gene tlrB of Streptomyces fradiae encodes a methyltransferase that targets G748 in 23S rRNA; Liu M et al.; tlrB is one of four resistance genes encoded in the operon for biosynthesis of the macrolide tylosin in antibiotic-producing strains of Streptomyces fradiae . Introduction of tlrB into Streptomyces lividans similarly confers tylosin resistance . Biochemical analysis of the rRNA from the two Streptomyces species indicates that in vivo TlrB modifies nucleotide G748 within helix 35 of 23S rRNA . Purified recombinant TlrB retains its activity and specificity in vitro and modifies G748 in 23S rRNA as well as in a 74 nucleotide RNA containing helix 35 and surrounding structures . Modification is dependent on the presence of the methyl group donor, S-adenosyl methionine . Analysis of the 74-mer RNA substrate by biochemical and mass spectrometric methods shows that TlrB adds a single methyl group to the base of G748 . Homologues of TlrB in other bacteria have been revealed through database searches, indicating that TlrB is the first member to be described in a new subclass of rRNA methyltransferases that are implicated in macrolide drug resistance.

Med J Malaysia, 1999 Jun, 54(2), 270 - 2
Adult varicella pneumonia that responded to combined acyclovir and steroid therapy; Lau LG; We describe a case of adult chickenpox which was complicated by severe varicella pneumonia, mild hepatitis and thrombocytopenia . The hepatitis and the thrombocytopenia were asymptomatic clinically and were diagnosed on biochemistry and blood count results . These eventually improved without specific interventions . The pneumonia, however, deteriorated rapidly despite the early commencement of oxygen supplementation, acyclovir and antibiotic . Subsequently, systemic corticosteroid therapy was initiated and the patient was ventilated in the intensive care unit . The patient eventually recovered.

Med J Malaysia, 1999 Jun, 54(2), 175 - 9
Treating high risk childhood solid tumours with autologous peripheral blood stem cell transplantation--early experience in University Hospital, Kuala Lumpur; Chan LL et al.; Although survival rates for childhood cancers have improved steadily over the past two decades, the outcome for advanced stage solid tumours remains poor . Many of these tumours are chemosensitive but most chemotherapeutic regimens are limited by their haematological toxicities . Much attention is now focused on mega-dose chemotherapy followed by stem cell rescue in the treatment of disseminated neuroblastoma, rhabdomyosarcoma, germ cell tumour and brain tumours . There is a preferential shift towards peripheral blood stem cell transplantation instead of bone marrow transplantation because of its advantages of faster engraftment, decreased transfusion and antibiotic usage and shortened hospitalisation . This mode of therapy is dependent on technologies including peripheral blood stem cell harvesting, cell cryopreservation and thawing . These technologies were recently made available in Malaysia and we report our early experience.

Med J Malaysia, 1999 Mar, 54(1), 47 - 51
Outpatient procedures for cervical dysplasia: a 3 year review of laser vaporisation and LEEP; Lee KE et al.; A 3 year retrospective review (1995 to 1997) of 127 patients with cervical dysplasia who underwent Laser Vaporisation of the cervix and LEEP at the Gynaecological Cancer Centre, KK Women's & Children's Hospital, Singapore, was undertaken . Amongst the patients in the Laser Vaporisation group, the mean age was 37.7 years (SD 8.8), the mean operating time was 14.8 minutes (SD 8.5), 63.6% were given prophylactic antibiotics and the mean follow up period was 15.3 months (SD 12.0), whilst in the LEEP group, mean age was 40.3 years (SD 8.4), mean operating time, 11.8 minutes (SD 4.9), prophylactic antibiotic rate, 53.8% and mean follow up period was 19.1 months (SD 9.3) . Mild and moderate haemorrhage post procedure were the only complications encountered, 10.2% (5/49) in the Laser group and 3.8% (3/78) in the LEEP group . 98% (48/49) and 97.4% (76/78) of the Laser and LEEP groups, respectively, were free of disease on follow up . None of the 3 patients with persistent or recurrent disease were diagnosed as having invasive cancer . Overall, there were no significant differences in the patient characteristics, histopathology, operating times, follow up period, the use of prophylactic antibiotics, and complications in the 2 groups . The low complication rate, high disease-free rate and the relatively short operating time of Laser Vaporisation and LEEP in our study suggests that, indeed, both the procedures can be done safely and efficiently in the outpatient setting . However the discrepancy between the histology of colposcopically directed biopsy and that of LEEP specimens suggests that colposcopically directed biopsy may not be as accurate as one might believe, and further studies analysing the concordance between colposcopically directed biopsy and LEEP biopsy histologies are needed.

Schweiz Med Wochenschr, 2000 Jul 25, 130(29-30), 1078 - 83
{Sulfasalazine-induced pulmonary infiltrates and Legionella pneumonia}; Bielecki JW et al.; After 2 weeks' treatment with sulfasalazine (SASP) and mesalazine enema, a 32-year-old female with recently diagnosed ulcerative colitis developed bilateral pulmonary infiltrates with peripheral eosinophilia . Both drugs were discontinued . In view of a high-positive antibody titre (1:4096) against Legionella pneumophila serogroups 1-5, legionnaires' disease was assumed and empirical antilegionella therapy with macrolid antibiotic was started . The patient's condition improved within days . Three months later SASP was given again in view of exacerbation of the inflammatory bowel disease . Three days after initiation of therapy acute pulmonary symptoms again developed with bilateral, confluent opacities and blood eosinophilia . The abnormalities resolved completely after the drug was discontinued and prophylactic antibiotic therapy was given . Peripheral lung infiltrates with blood eosinophilia are a rare side effect of SASP therapy . The prognosis of the illness after the drug has been discontinued is generally good, usually with complete recovery of pulmonary function . The risk factors for sulfasalazine pulmonary toxicity are not well known . We describe the first case of SASP-induced hypersensitivity lung disease with simultaneous Legionella pneumophila infection.

Br J Cancer, 2000 Oct, 83(7), 914 - 20
Carcinogenic effects of ptaquiloside in bracken fern and related compounds; Potter DM et al.; Consumption of the bracken fern Pteridium aquilinum by cattle has been shown to induce bladder and intestinal carcinomas in cattle and to cause a number of diseases in other farm animals . An unstable glucoside named ptaquiloside, containing a reactive cyclopropane ring, has been isolated from the fern and its potent carcinogenicity proven . Nineteen of 31 ferns tested by chemotaxonomic methods in Japan have been found to contain potentially carcinogenic ptaquilosides as have Cheilanthes sieberi and Pteridium esculentum . Hydrolysis of ptaquilosides leads to pterosins; under milder conditions a dienone which is believed to be the primary carcinogen is obtained . Hypacrone, a sesquiterpine containing a reactive cyclopropane ring, has been isolated from Hypolepis punctata and its structure proved by synthesis . Illudins, structurally similar to ptaquiloside, have been isolated from the basidiomycete Omphalotus illudens . These give anti-tumour activity and similar reactivity with nucleophiles to ptaquiloside . Compound CC-1065, a highly toxic antibiotic also containing a cyclopropane ring, has been isolated from Streptomyces zelensis . The mechanism of its reactivity with DNA has been compared to that of ptaquiloside and the small structural differences between carcinogenic and anti-tumour activity discussed . Both CC-1065 and adozelesin, a synthetic analogue with anti-tumour activity, have been shown to alkylate the N-3 atom of adenine in a certain sequence of DNA . The reactivity of cysteine with ptaquilosides and illudins is discussed, as is the role of cysteine alkylating agents in apoptosis .

Assist Inferm Ric, 1999 Jan-Mar, 18(1), 14 - 9
{Medicated intravascular catheters . Review of the literature}; Rasero L et al.; Central Venous Catheters (CVC) are widely used in the setting of intensive care units, but they are associated with an increased risk of CVC-related infections . To prevent infections originated from CVC, a number of devices have been more recently produced, that are characterized by the presence of antiseptic/antibiotic substances in the matrix of the CVC itself ("impregnated" CVC) . In this brief review, more recent studies on the topic are discussed, especially in the light of guidelines from the CDC . Although from these studies many suggestions about the efficacy of impregnated CVC in the prevention of CVC-related infections can be derived, notwithstanding the critical role of preventive measures during CVC procedures must be recognized as the principal factor in reducing CVC infections.

Ear Nose Throat J, 2000 Aug, 79(8), 650 - 2, 654-7
Laser-assisted myringotomy for otitis media: a feasibility study with short-term followup; Reilly JS et al.; Intermediate-duration middle ear ventilation appears to be a good treatment option for selected children with otitis media . Laser-assisted myringotomy is one way to provide such ventilation . It can provide prompt pain relief and resolution of middle ear effusion and effusion-related hearing loss, and it can provide an opportunity for surveillance of antibiotic-resistant organisms . We performed laser-assisted myringotomy on 97 ears of 54 children over a 5-month period . All children had acute or recurrent otitis media or persistent middle ear effusions . Our experience suggests that laser-assisted myringotomy is a feasible treatment option for selected patients . Practitioner experience and patient and family considerations will contribute to the decision whether to use general or topical anesthesia.

Bull Cancer, 2000 Jul, 87(7-8), 557 - 91
{Standards, Options and Recommendations (SOR) for the surveillance and the prevention of cross infections in oncology . Fédération Nationale des Centres de Lutte Contre le Cancer}; Pottecher B et al.; CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics . The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients . The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery . OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the prevention and the surveillance of cross infection in oncology . METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups . Once the guidelines were defined, the document was submitted for review to 106 independent reviewers, and to the medical committees of the 20 French Cancer Centres . RESULTS: 1) Criteria of infection status and nosocomiality defined by the Centers for Infectious Diseases (CDC) and Prevention and the Superior Council of Public Hygiene (CSHPF) are not adapted and have to be redefined in oncology . 2) The epidemiology of nosocomial infections in oncology is not well known but their incidence seems to be higher . Numerous risk factors of cross infections coexist in cancer patients, among which the duration and depth of neutropenia . 3) Surveillance and prevention of cross infection are compulsory and were taken into account in the accreditation of hospitals . Obligation is expressed in terms of means and results . 4) The objectives of the cross infection surveillance are to detect major problems and critic situations, to guide probabilistic antibiotic therapy and to assess the effectiveness of the infections control . The surveillance means consist in prevalence and incidence survey, punctually and continuously conducted . 5) The three specific behaviors to be adopted to prevent cross infections are to control: all the patients, infected patients carrying multiresistant bacteria, immunodepressed patients . 6) Standards of care have to be applied to a/l patients with cancer . 7) It is necessary to add particular septic cares for the patients infected with micro-organisms indicated on reference lists or carrying multiresistant bacteria . 8) The only objective of the protective isolation of immunodepressed cancer patients is to reduce the cross infection . There is no standard behavior for the indications and the modalities of protective isolation . The prevention behaviors to be taken are defined by expert agreements.

Bioorg Med Chem, 2000 Jan, 8(1), 173 - 9
Monoalkylation of DNA by reductively activated FR66979; Paz MM et al.; The antitumor antibiotic FR66979 has previously been shown to form interstrand cross-links in duplex DNA at the sequence {5'-d(CG)}2, linking the exocyclic amino groups (N2) of deoxyguanosine (dG) residues . During the reaction of reductively activated FR66979 with DNA . products are formed which have electrophoretic mobility in denaturing polyacrylamide gels which is intermediate between that of unmodified and interstrand cross-linked DNA . We show here that these products are monoadducts between FR66979 and DNA and provide strong evidence for the site of alkylation being N2 of dG . Moreover, the sequence selectivity of monoalkylation reactions between FR66979 and DNA containing either 5'-d(CG).5'-d(CI) or {5'-d(CG)}2 was observed to be ca . 5-fold less than for the related antitumor antibiotic mitomycin C (MC) . The mechanistic implications of this result are discussed . Furthermore, it was demonstrated that contrary to a previous report, FR66979 requires DNA to be in duplex form for efficient monoadduct formation.

Med J Malaysia, 1998 Sep, 53 Suppl A, 83 - 5
A review of haematogenous osteomyelitis in children in Kuala Lumpur Hospital; Razak M et al.; We review 81 cases of acute haematogenous osteomyelitis from 1983 to 1990 to establish current pattern of clinical presentation, modes of treatment and success of therapy . Majority of the patient (70%) presented within a week of symptom and significant number of them came with fever and swelling of the affected limb . Sedimentation rate was found to be raised in all of them . Fifty-four (55%) of them were treated surgically . The average antibiotic time was one week by intravenous administration followed by additional oral therapy for period up to four weeks . Average follow-up was 9 months . Six of them (7.5%) end up with various complication which was believed to be due to delay in getting medical treatment.

Med J Malaysia, 1998 Sep, 53(3), 302 - 10
Management of Helicobacter pylori infection--a Working Party Report of the Malaysian Society of Gastroenterology and Hepatology; Goh KL et al.; The Working Party Report on the Management of Helicobacter pylori serves as a clinical practice guideline for Malaysian doctors . H . pylori is not uncommon in the Malaysian population . Marked racial differences and the consistently low prevalence rates amongst Malays are noted . The working party recommends that if endoscopy is to be performed, a rapid urease test should be used for diagnosis . Where suspicion of the infection is strong and the urease test is negative, histology should be performed on gastric biopsies . Culture should be used to monitor resistance patterns to antibiotics and regional laboratories should assume this responsibility . The urea breath tests are highly accurate tests for diagnosis of H . pylori but is as yet not widely available in Malaysia . The working party strongly recommends that all peptic ulcer patients infected with H . pylori whether active, in remission and complicated ulcers should be treated for the infection . Patients with low-grade gastric mucosal lymphoid tissue lymphoma should also be treated for H . pylori infection . It is considered advisable that patients on long term nonsteroidal antinflammatory drug (NSAID) treatment with a history of peptic ulcers or dyspepsia and patients following resection of early gastric cancer or those with a family history of gastric cancer should also be tested and treated for H . pylori . The working party recommends, as first line treatment a 7-day combination therapy of a proton pump inhibitor, clarithromycin and metronidazole or amoxicillin . High metronidazole resistance rates locally may adversely affect regimens containing the antibiotic . It should also be noted that regimens that yield lower eradication rates may result in higher long term expenditure.

Med J Malaysia, 1998 Mar, 53(1), 16 - 21
The prevalence of Chlamydia trachomatis in patients with pelvic inflammatory disease; Ravindran J et al.; Chlamydia trachomatis is recognized as the most prevalent sexually transmitted organism in many parts of the world . Most complications associated with chlamydial infection in women and their infants can be avoided by appropriate treatment . However, treatment is often not initiated because infections are frequently asymptomatic . The identification of at risk patients and treatment of these patients is a practical clinical approach in the reduction of transmission and prevention of complications . The prevalence of chlamydial infection among patients with pelvic inflammatory disease admitted to Seremban General Hospital was 22.7% . The difference in seropositivity between PID patients (20.5%) and antenatal controls (2.3%) was statistically significant . The corresponding cervical antigen detection rates were 6.8% and 2.3% respectively . Chlamydial infection should be screened for in gynaecological patients and antibiotic policies should take cognizance of the aetiological role played by this organism in pelvic inflammatory disease.

Med J Malaysia, 1996 Dec, 51(4), 437 - 41
Mortality in Malaysians with systemic lupus erythematosus; Paton NI et al.; One hundred and two patients attending the systemic lupus erythematosus (SLE) clinic of the Department of Medicine, Universiti Kebangsaan Malaysia, were studied retrospectively to determine their survival rates and causes of death . There were 21 deaths . The 1, 5, and 10 year survival rates were 93%, 86% and 70% respectively . There was a bimodal pattern of mortality with more patients dying in the first 2 years or after 5 years of disease . Infection was the direct cause of death in 52% and contributed to a further 19% of deaths . Patients with lupus nephritis had a higher relative risk (RR) of death (RR = 4.34, p < 0.02) although there was no significant increase in risk with any particular histological type on biopsy . Cerebral lupus (RR = 3.08, p < 0.001) and methylprednisolone treatment (RR = 6.24, p < 0.001) were also associated with increased risk of death . Increased awareness of infection and earlier use of antibiotic therapy may improve survival of patients suffering from SLE.

Emerg Med Clin North Am, 2000 Aug, 18(3), 481 - 519
The swollen face . Severe odontogenic infections; Flynn TR; Owing to the widespread availability of preventive dental care and the development of effective antibiotics for the treatment of orofacial infection, the incidence of serious odontogenic infections has decreased dramatically over the past 50 years . Serious dental infections still occur, however, and their occasionally severe complications or even mortality warrant serious study of the clinical presentation, anatomy, and pathophysiology of orofacial infections . The goal of this review is to provide the emergency practitioner with a concise description of the clinical presentation, relevant anatomy, and treatment principles of odontogenic infection in the patient who presents to the ED with a swollen face or difficulty in opening the mouth widely . Prompt institution of surgical therapy for the infection, aided by appropriate antibiotic therapy enables the healthcare professions to continue their remarkable progress in treating these once-dreaded infections.

Rays, 2000 Jan-Mar, 25(1), 75 - 88
Combined imaging in spondylodiscitis; Guglielmi G et al.; At present, in spite of the advancement in antibiotic therapy no significant decrease in the incidence of spinal infections is observed: most likely, this is correlated to the increased immigration flows, high risk behaviors (drug addiction, alcoholism), immunosuppressive diseases (AIDS, leukemia, lymphoma), interventional procedures (iatrogenic causes) . Early diagnosis, at times difficult and often misunderstood, is facilitated by the use of a correct diagnostic algorithm, supported by blood culture, needle aspiration and biopsy . Aim of this report was to evaluate the role of the different imaging procedures, CT and MRI in particular, for prompt correct therapeutic management.

Hum Reprod, 2000 Sep, 15(9), 1978 - 84
Semen granulocyte elastase: its relevance for the diagnosis and prognosis of silent genital tract inflammation; Zorn B et al.; Elastase-inhibitor complex was assessed by immunoassay in the seminal plasma of 312 men attending the outpatient infertility clinic . Using receiver operating characteristic (ROC) curve analysis, elastase at the cut-off value of > or =290 ng/ml was shown to be efficient (sensitivity 79.5%, specificity 74.4%) in the detection of genital tract inflammation as defined by leukocytospermia (>1x10(6) leukocytes/ml) . The prevalence of increased elastase in 292 infertile men was significantly higher (34%) as compared with that (5%) observed in 20 fertile men (P: = 0.02) . Moreover, high elastase concentration (> or =290 ng/ml) was observed in 66 of the 264 men (25%) without leukocytospermia . A significant positive correlation was found between elastase concentration and patient age (r = 0.202, P: < 0.0001) and the number of leukocytes (r = 0.330, P: < 0.0001) . A negative correlation was found between elastase concentration and semen volume (r = -0.146, P: = 0.01) and the percentage of spermatozoa with single-stranded DNA (r = -0.194, P: = 0.024), but there was no correlation between elastase and sperm reactive oxygen species production . A higher seminal elastase concentration was significantly associated with tubal damage in female partners (P: < 0.001) . After norfloxacine antibiotic therapy, decrease in elastase concentration was observed in 15 (25%) of the 60 treated patients . Tubal damage in the partner negatively affected the response to antibiotic therapy . In conclusion, granulocyte elastase is a reliable screening test for silent genital tract inflammation of the couple . The elastase-inhibitor complex may have a protective effect in reducing sperm DNA denaturation.

Am J Physiol Renal Physiol, 2000 Sep, 279(3), F584 - 91
Functional and pharmacological characterization of human Na(+)-carnitine cotransporter hOCTN2; Wagner CA et al.; L-Carnitine is essential for the translocation of acyl-carnitine into the mitochondria for beta-oxidation of long-chain fatty acids . It is taken up into the cells by the recently cloned Na(+)-driven carnitine organic cation transporter OCTN2 . Here we expressed hOCTN2 in Xenopus laevis oocytes and investigated with two-electrode voltage- clamp and flux measurements its functional and pharmacological properties as a Na(+)-carnitine cotransporter . L-carnitine transport was electrogenic . The L-carnitine-induced currents were voltage and Na(+) dependent, with half-maximal currents at 0.3 +/- 0.1 mM Na(+) at -60 mV . Furthermore, L-carnitine-induced currents were pH dependent, decreasing with acidification . In contrast to other members of the organic cation transporter family, hOCTN2 functions as a Na(+)-coupled carnitine transporter . Carnitine transport was stereoselective, with an apparent Michaelis-Menten constant (K(m)) of 4.8 +/- 0.3 microM for L-carnitine and 98.3 +/- 38.0 microM for D-carnitine . The substrate specificity of hOCTN2 differs from rOCT-1 and hOCT-2 as hOCTN2 showed only small currents with classic OCT substrates such as choline or tetraethylammonium; by contrast hOCTN2 mediated transport of betaine . hOCTN2 was inhibited by several drugs known to induce secondary carnitine deficiency . Most potent blockers were the antibiotic emetine and the ion channel blockers quinidine and verapamil . The apparent IC(50) for emetine was 4.2 +/- 1.2 microM . The anticonvulsant valproic acid did not induce a significant inhibition of carnitine transport, pointing to a different mode of action . In summary, hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity transport of L-carnitine and Na(+) . hOCTN2 displays transport properties distinct from other members of the OCT family and is directly inhibited by several substances known to induce systemic carnitine deficiency.

Genomics, 2000 Sep 1, 68(2), 118 - 26
Modular bacterial artificial chromosome vectors for transfer of large inserts into mammalian cells; Frengen E et al.; To facilitate the use of large-insert bacterial clones for functional analysis, we have constructed new bacterial artificial chromosome vectors, pPAC4 and pBACe4 . These vectors contain two genetic elements that enable stable maintenance of the clones in mammalian cells: (1) The Epstein-Barr virus replicon, oriP, is included to ensure stable episomal propagation of the large insert clones upon transfection into mammalian cells . (2) The blasticidin deaminase gene is placed in a eukaryotic expression cassette to enable selection for the desired mammalian clones by using the nucleoside antibiotic blasticidin . Sequences important to select for loxP-specific genome targeting in mammalian chromosomes are also present . In addition, we demonstrate that the attTn7 sequence present on the vectors permits specific addition of selected features to the library clones . Unique sites have also been included in the vector to enable linearization of the large-insert clones, e . g., for optical mapping studies . The pPAC4 vector has been used to generate libraries from the human, mouse, and rat genomes . We believe that clones from these libraries would serve as an important reagent in functional experiments, including the identification or validation of candidate disease genes, by transferring a particular clone containing the relevant wildtype gene into mutant cells or transgenic or knock-out animals .

Otolaryngol Head Neck Surg, 2000 Sep, 123(3), 328 - 33
Factors affecting wound infection rates in head and neck surgery; Coskun H et al.; PURPOSE: This study was planned with 2 goals in mind: to evaluate the efficacy of prolonged and 1-day antibiotic regimens for prophylaxis and to evaluate the effect of various factors such as neck dissection, localization and stage of tumor, type of laryngectomy, and history of prior radiotherapy, tracheotomy, and diabetes mellitus on postoperative wound infection rates . Methods and Material: In this study, 408 head and neck procedures (201 clean and 207 clean-contaminated) performed at our institution were retrospectively reviewed . RESULTS: Prolonged and 1-day antibiotic regimens for both clean and clean-contaminated procedures were similar in efficacy (7% vs 3% for clean procedures {P = 0.165} and 30% vs 28% for clean-contaminated procedures {P = 0.777}) . The wound infection rate was higher (13%) after clean radical neck dissections versus other clean procedures (1%) (P = 0.001) . For clean-contaminated procedures, factors affecting postoperative wound infection rates were performance of bilateral neck dissections (P = 0.014), disease stage (P = 0.002), type of laryngectomy (P = 0.002), and history of prior tracheotomy (P = 0.006).

J Bone Joint Surg Br, 2000 Jul, 82(5), 689 - 94
Two-stage uncemented revision hip arthroplasty for infection; Haddad FS et al.; We treated 50 consecutive patients with infected total hip arthroplasties according to a standard protocol . Previous surgery to eradicate the infection had been attempted in 13 patients and discharging sinuses were present in 20 . Aspiration arthrography was routinely carried out before our interventions . The first stage was a meticulous removal of all foreign and potentially infected material . Samples were taken for culture and a thorough lavage carried out . Antibiotic-loaded beads were placed in the femoral shaft and an antibiotic-loaded cement ball in the acetabulum . At the second stage an uncemented arthroplasty was introduced . Bone allograft was used in 18 patients . The interval between procedures was usually three weeks, but this was extended if the wound was slow to heal or there was extensive bony destruction . Appropriate antibiotics were given for three months . At a mean follow-up of 5.8 years the rate of reinfection was 8% (4 patients) . Two of these patients have had another, successful, two-stage revision . At this medium-term review, a satisfactory clinical and radiological outcome was obtained in all except two patients.

J Thorac Cardiovasc Surg, 2000 Sep, 120(3), 450 - 8
Homograft mitral valve replacement: five years' results; Kumar AS et al.; OBJECTIVE: Results of mitral valve replacement with a mitral homograft were evaluated at 5 years to assess the suitability of the procedure . METHODS: Thirty-seven patients (25 male subjects) aged 10 to 49 years (mean, 32 +/- 10 years) with rheumatic mitral valve disease underwent total (n = 35) or partial (n = 2) mitral valve replacement with a fresh antibiotic-preserved (n = 23) or cryopreserved (n = 14) mitral homograft . The predominant lesion was mitral stenosis (n = 30) . RESULTS: There were 5 early deaths . Operative survivors were followed up for 1 to 60 months (mean, 26.6 +/- 12 months) . Among these, 21 patients had severe mitral regurgitation during the follow-up period; 3 died and 8 underwent reoperation . The homograft failure rate was not affected by preoperative physiologic lesion (stenosis vs regurgitation, P =.4), type of homograft (antibiotic-preserved vs cryopreserved homograft, P =.9), papillary muscle pretreatment (yes vs no, P =.9), or addition of posterior collar annuloplasty (yes vs no, P =.2) . Among the remaining patients, 5 had moderate mitral regurgitation, 4 had either trivial or mild mitral regurgitation, and 2 were lost to follow-up . Study of the explanted mitral homografts (n = 8) revealed that disruption of one of the donor papillary muscles was responsible for early failures (n = 2), whereas cuspal and chordal degeneration was responsible for late failures (n = 6) . Microscopically, the explanted valve lacked any viable cellular elements, and there was no evidence of immunologic injury to the homografts . CONCLUSION: The mitral homograft did not fulfill our expectations as a suitable substitute for the diseased mitral valve.

Acta Biochim Pol, 2000, 47(1), 121 - 31
N-Methyl-N-D-fructosyl amphotericin B methyl ester (MF-AME), a novel antifungal agent of low toxicity: monomer/micelle control over selective toxicity; Cybulska B et al.; Rational chemical modification of amphotericin B (AMB) led to the synthesis of sterically hindered AMB derivatives . The selected optimal compound, N-methyl-N-D-fructosyl amphotericin B methyl ester (MF-AME) retains the broad spectrum of antifungal activity of the parent antibiotic, and exhibits a two orders of magnitude lower toxicity in vivo and in vitro against mammalian cells . Comparative studies of MF-AME and AMB comprising the determination of the spectroscopic properties of monomeric and self-associated forms of the antibiotics, the investigation of the influence of self-association on toxicity to human red blood cells, and of the antibiotic-sterol interaction were performed . On the basis of the results obtained it can be assumed that the improvement of the selective toxicity of MF-AME could in part be a consequence of the diminished concentration of water soluble oligomers in aqueous medium, and the better ability to differentiate between cholesterol and ergosterol.

Diabetes Res Clin Pract, 2000 Oct, 50(2), 87 - 95
Cost and resource utilization for prevention and treatment of foot lesions in a diabetic foot clinic in Belgium; Van Acker K et al.; This prospective observational study was carried out to assess the annual preventive and curative treatment costs for diabetic foot problems . Measures of resource use over the 1-year study period were taken for 151 patients whose lesions covered the entire Wagner classification . Treatment was provided under the current protocols of a multidisciplinary team . The 1993 market prices for health services were used to convert units of health service utilization to expenditures by the social insurance system and the patients . The severity of the foot problems determined the medical cost . Preventive care (47 cases), represented an average cost per case of US$ 880 (1US$ 1993=BEF 30.65) . Curative care (120 cases), including diagnostic tests, wound dressings, antibiotic therapy, revascularization and off loading techniques resulted in a mean cost of US$ 5227 per ulcer . Care for the 16 most severe wounds and amputations involved hospitalization and surgery at a mean cost per ulcer of US$ 31716 . The most important cost contributers were hospitalizations (72%), drugs (11%) and diagnostic examinations (4%) . Preventive treatment for diabetic foot problems can represent a significant saving for the social insurance system as well as for the patients.

Plant Sci, 2000 Aug 22, 157(2), 201 - 207
Transgenic expression of the TRI101 or PDR5 gene increases resistance of tobacco to the phytotoxic effects of the trichothecene 4,15-diacetoxyscirpenol; Muhitch MJ et al.; Mycotoxins are fungal secondary compounds that are toxic to vertebrates . Their presence in food and feeds, as the result of fungal disease in crops, can present a danger to animal or human health . Many mycotoxins have also been shown to be phytotoxic and in some cases, such as with trichothecenes produced by the wheat head blight fungus Fusarium graminearum, mycotoxins may act as virulence factors . Antibiotic-producing organisms, including fungi, protect themselves from their own toxins by metabolic alteration of the compound, modification of the target site of action or by exporting the compound to the extracellular space . We have tested the effectiveness of adapting two of these strategies, metabolic alteration and extracellular transport, to protect plant cells from the deleterious effects of the trichothecene 4,15-diacetoxyscirpenol (DAS) . Tobacco plants were transformed with either the Saccharomyces cerevisiae gene PDR5, which encodes a multi-drug transporter, or with the Fusarium sporotrichioides gene TRI101, which encodes a trichothecene 3-O-acetyltransferase . Both genes conferred significant increased tolerance to DAS as measured by a sensitive seed germination assay . Expression of PDR5 or TRI101 in a seed-specific manner in crop plants such as wheat could lower the incidence of head blight as well as reduce mycotoxin levels within the seed.

Harefuah, 1999 Jul, 137(1-2), 28 - 30, 87, 86
{Mesalamine-induced hypersensitivity pneumonitis}; Zamir D et al.; A 23-year-old woman was admitted with a history of 2 weeks of cough, fever and bilateral lung infiltrates . She had been diagnosed 2 months before as having ulcerative proctitis and was treated with mesalamine, which induced a full remission, but 3 antibiotic regimens failed to improve her lung disease . Since computerized tomography revealed bilateral peripheral lung infiltrates and her eosinophile count was elevated, the diagnosis of drug-induced eosinophilic pneumonia was suggested . Mesalamine and antibiotics were stopped and oral corticosteroids begun . She became almost asymptomatic a week after mesalamine withdrawal, and the x-ray became normal.

Ophthalmologe, 2000 Jul, 97(7), 487 - 90
{Haze and regression after photoreactive keratectomy (PRK)}; Katlun T et al.; According to the recommendations of the German Ophthalmological Society (DOG), PRK in myopic patients between -1.0 dpt and -6.0 dpt is a scientific acknowledge treatment . The risks of the treatment, however, increase in myopia above -6.0 dpt . MATERIAL AND METHODS: Between june 1994 and october 1997 we performed PRK on 338 eyes from 212 myopic patients in the ALZ Eye Clinic Hamburg . Myopia ranged between -1.25 and -11.25 diopters . All treatments were performed with the Keracor 116 (Fa . Chiron Technolas) . The procedure was the same in all cases: mechanical abrasion, excimer laser treatment, antibiotic and nonsteroidal antiphlogistic drops for three days followed by a corticosteroid therapy for 5 months . RESULTS: Out of these 338 eyes, 17 eyes after 12 months had a persistent haze grade 1-2 or more according to Stein, Cheskes and Stein . These 17 eyes had also an average regression of -1.67 diopters (SD 1.8) and lost at least in minimum two lines of the best corrected visual acuity 12 months postoperatively . The refraction of the 17 eyes was more than -6 dpt preoperatively . CONCLUSION: Haze after PRK is in most cases only transient . Haze of grade 1-2 or more after 12 months postoperatively is correlated with regression and a loss of best corrected visual acuity . PRK below -6 dpt in our hands never showed haze grade 1-2 or more 12 months postoperatively . Therefore patients with a refraction of more than -6 dpt before PRK should be informed about this potential risks . In these cases LASIK should be taken into consideration.

J Urol, 2000 Sep, 164(3 Pt 2), 1067 - 9
The prevalence of persistent vesicoureteral reflux after 1 negative nuclear medicine cystogram; Neel KF et al.; PURPOSE: Radionuclide cystography is a widely used test for the diagnosis or indication of resolution of vesicoureteral reflux . The recurrence or persistence of reflux after 1 negative radionuclide cystogram has been previously reported . We examined the value of a second radionuclide cystogram in patients who were believed to be cured on 1 previous study and tried to identify variables that could explain the false-negative result on the initial cystogram . MATERIALS AND METHODS: The study included 85 patients with primary vesicoureteral reflux, treated conservatively between 1991 and 1996 who had 1 negative radionuclide cystogram . A repeat radionuclide cystogram was done 12 to 18 months after the negative study . Patients were divided into those with and without reflux recurrence identified, and compared in regard to sex distribution, age at presentation and reflux resolution, time between presentation and first negative radionuclide cystogram, change in reflux grade between presentation and just before resolution, side of reflux at presentation and grade before resolution . The differences between both groups were statistically analyzed . RESULTS: Of the 85 patients 25 (29%) had reflux recurrence, including 18 (72%) with grade 2 or greater recurrent reflux and 15 (60%) with persistent reflux 12 months after the second positive radionuclide cystogram . There was no observed association between the 2 groups in any of the variables (p >0.05) . CONCLUSIONS: This study emphasizes the importance of a second negative radionuclide cystogram to indicate the absence or resolution of reflux as 1 negative cystogram alone would have missed persistent reflux in 25 of 85 patients at 1 year and 15 of 85 patients at 2 . Whether absence or resolution of reflux is a variable of the disease or an unknown factor inherent in the test is unknown as there was no statistical difference in the parameters studied between our 2 groups.

J Basic Microbiol, 2000, 40(3), 157 - 66
Optimization of the cultivation medium for natamycin production by Streptomyces natalensis; Farid MA et al.; The effects of certain nutrients on natamycin production by Streptomyces natalensis in submerged batch culture were studied . The production of this antibiotic required glucose in the cultivation medium with a concentration of 20 g/l . On the other hand, the highest antibiotic production was obtained in a cultivation medium containing 0.05 g/l of potassium dihydrogen phosphate . Further increase in phosphate concentration resulted in a significant increase in biomass concomitant with lower antibiotic production . Among different N-sources tested, only ammonium sulphate, sodium nitrate and beef extract were the suitable nitrogen sources in supporting the antibiotic production . Furthermore, a mixture of beef extract and yeast extract (8 g/l and 2 g/l, respectively) exhibited a synergistic effect in enhancing the natamycin production reaching about 1.5 g/l.

Mil Med, 2000 Aug, 165(8), 638 - 40
Lemierre syndrome: magnetic resonance imaging and computed tomographic appearance; Auber AE et al.; Lemierre syndrome consists of septic thrombophlebitis of the internal jugular vein secondary to oropharyngeal infection, usually with Fusobacterium necrophorum . Septic metastatic emboli and distant infection are characteristic . We describe the imaging appearance of Lemierre syndrome in an adolescent female by both magnetic resonance imaging and computed tomography . This case illustrates the rapid onset and characteristic progression of the rare syndrome of Lemierre . In addition, we used magnetic resonance imaging to effectively distinguish between inflammatory venous thrombosis and abscess, thus avoiding surgery in our patient . Early directed antibiotic therapy is mandatory to ensure good outcome.

Pediatr Nephrol, 2000 Aug, 14(8-9), 707 - 9
Obstructive airway disease caused by Moraxella catarrhalis after renal transplantation; Seidemann K et al.; We report a case of severe acute obstructive airway disease 2 months after renal transplantation in a 16-year-old patient with Biedl-Bardet syndrome who was transplanted for end-stage renal failure secondary to cystic kidney disease . Symptoms of severe obstructive airway disease developed 2 months after transplantation under immunosuppression with prednisone, azathioprine, and tacrolimus . The patient did not develop signs of infection; progressive shortness of breath remained the only symptom for several weeks . After extensive diagnostic evaluation, bronchoalveolar lavage revealed Moraxella catarrhalis as the single infectious agent . After 3 weeks of appropriate antibiotic therapy, symptoms of obstructive airway disease were completely relieved . This atypical presentation of Moraxella infection in an immunocompromised host represents a rare complication of renal transplantation, especially in young patients . Special aspects such as frequency, diagnosis, differential diagnosis, and management of this rare complication of renal transplantation in a pediatric patient are discussed.

J Gastroenterol, 2000, 35(8), 641 - 5
Inflammatory pseudotumor of the liver diagnosed by needle liver biopsy under ultrasonographic tomography guidance; Nakama T et al.; Inflammatory pseudotumor of the liver is a rare benign lesion, but exploratory laparotomy and a hepatectomy are often performed unnecessarily after various misdiagnoses, including liver abscess, hepatocellular carcinoma, metastatic liver tumor, and cholangiocarcinoma . We present a case of hepatic inflammatory pseudotumor in a 17-year-old man in whom diagnosis was confirmed by liver needle biopsy under ultrasonographic tomography (UST) guidance . He had complained of fever and right hypochondralgia 2 months after being operated for appendicitis . He was admitted to our hospital because of the persistence of these symptoms and the presence of a hepatic mass lesion detected by UST . He had hepatomegaly, with tenderness; leukocytosis and elevated erythrocyte sedimentation rate and C-reactive protein level were noted . UST showed a hypoechoic mass in the liver and pre-contrast computerized tomography (CT) revealed a low-density area with an ill defined margin, which was barely enhanced by the contrast medium . On the basis of the patient's clinical symptoms and the laboratory data and imaging studies, the presence of a liver abscess was suspected and antibiotics were administered . One month after the initiation of the antibiotic therapy, UST demonstrated that the portal vein had dilated serpiginously and penetrated into the mass . As the heterogeneous appearance displayed by post-enhanced CT indicated the need for a differential diagnosis of the hepatic mass lesion to rule out hepatocellular carcinoma, percutaneous needle biopsy was performed, under UST guidance . Histopathological examination demonstrated marked infiltration of plasma cells and fibrosis, findings which were consistent with those of hepatic inflammatory pseudotumor . There was a spontaneous reduction of the hepatic pseudotumor without continuous antibiotics and this reduction was documented on follow-up UST and CT.

Harefuah, 1999 Jun 1, 136(11), 855 - 7, 915
{Superficial skin necrosis--an uncommon manifestation of short bowel syndrome}; Eisenman A et al.; Short bowel syndrome causes a complex of symptoms due to compromise of small intestinal nutrient absorption . A 60-year-old woman underwent major resection of the small intestine due to a road accident 3 years ago . The sole manifestation of short-bowel-syndrome was superficial skin necrosis due to vitamin K deficiency . She was asymptomatic for a long time, until treatment with antibiotics further intensified initially subclinical malabsorption . It is not clear why there had been no other symptoms and why the main impact was on the fibrinolytic system rather than the coagulation system, as is usually the case . It is recommended that patients after major resection of the small intestine be closely monitored for coagulation function if an oral antibiotic is prescribed.

AJNR Am J Neuroradiol, 2000 Aug, 21(7), 1327 - 30
Incidence and clinical significance of frontal sinus or orbital entry during pterional (frontotemporal) craniotomy; Patel RS et al.; BACKGROUND AND PURPOSE: Frontal sinus entry, orbital entry, or both may occur during pterional craniotomy for microsurgical clipping of aneurysms . We sought to determine the incidence and clinical significance of these findings on postoperative CT scans . METHODS: Eighty-two postoperative CT scans of the head obtained from 81 patients (64 women, 17 men; age range, 25-80 years) were retrospectively reviewed over a 1-year period . These scans were reviewed independently by two blinded neuroradiologists for the presence and degree of orbit and frontal sinus entry that may have occurred during craniotomy . Clinical charts, operative notes, and discussions with the patients' neurosurgeons were reviewed to determine the clinical management and significance of these findings . RESULTS: Of the total 82 craniotomies reviewed, 77 (94%) had been performed via the pterional approach (43 right, 34 left) . Twenty-three (30%) of these 77 studies revealed some evidence of penetration into the orbit or frontal sinus (orbit=65.2% {15/23}; frontal sinus=30.4% {7/23}; both=4.4% {1/23}) . Only five of 16 patients with radiographic orbital penetration had evidence of involvement of intraorbital contents (ie, thickened lateral rectus, fat herniation, intraorbital air) . Chart review revealed no complication or change in management . Of the seven patients with frontal sinus entry, three had mucosal exenteration and packing with antibiotic-coated gelfoam . No delayed complications (ie, persistent fever, mucocele, cerebrospinal fluid leak, air leak, or meningitis) were identified (follow-up period, 18-29 months) . CONCLUSION: Frontal sinus or orbital entry is not uncommon after pterional craniotomy, but the incidence of immediate complications is rare.

Clin Nutr, 2000 Aug, 19(4), 253 - 8
Comparison of the efficacy of medium chain triglycerides with long chain triglycerides in total parenteral nutrition in patients with hematologic malignancies undergoing peripheral blood stem cell transplantation; Demirer S et al.; BACKGROUND AND AIMS: The purpose of this randomized study was to compare the efficacy of medium chain triglycerides (MCT) plus long chain triglycerides (LCT) with LCT alone in total parenteral nutrition (TPN) solutions in patients with various hematologic malignancies who underwent a hematopoietic peripheral blood stem cell (PBSC) transplantation . METHODS: Of 36 patients entering into this study, 18 received MCT + LCT (group I) and the remaining 18 received LCT alone (group II) in TPN solutions . Patients were comparable regarding age, gender, donor-recipient gender, diagnosis, body weights, blood group differences and number of infused CD34(+) cells/kg . Post - transplant parameters such as duration of platelet and neutrophil engraftment, coagulation parameters, number of days of febrile neutropenia and antibiotic administration, plasma glucose, triglyceride, cholesterol and albumin levels, graft-versus-host disease (GVHD) and first 100 day mortality were compared in both groups . RESULTS: Median days of neutrophil >0.5 x 10(9)/l and platelet of >20 x 10(9)/l in group I and group II were 15 (range, 8-21), 11 (10-29) and 14 (range, 9-31), 13 (9-18) respectively (P>0.05) . Median days of febrile neutropenia in group I and II were 10 (range, 4-23) and 7 (2-13) respectively (P=0.01) . Median days of antibiotic administration in group I and II were 12 (range, 6-22) and 8 (4-25) respectively (P=0.04) . Pre, peri- and post-transplant coagulation parameters such as PT, aPTT, and fibrinogen did not differ significantly between two groups (P>0.05), as well as plasma glucose, triglyceride, cholesterol, albumin levels, GVHD and first 100 day mortality . CONCLUSION: There was no difference between patients receiving MCT + LCT (group I) and LCT alone (group II) in TPN solutions regarding duration of engraftment and coagulation parameters, but numbers of median days of febrile neutropenia and days of antibiotic administration were significantly shorter in patients receiving LCT alone (group II) than those receiving MCT + LCT (P<0.01 and 0.04 respectively) .

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2492 - 7
Enhanced reduction of Helicobacter pylori load in precolonized mice treated with combined famotidine and urease-binding polysaccharides; Icatlo FC Jr et al.; The present study investigated the effect of a model urease-binding polysaccharide in combination with a histamine H(2) receptor antagonist on Helicobacter pylori colonization in vivo . Euthymic hairless mice were treated daily with dextran sulfate via drinking water and/or famotidine via intragastric gavage starting at 1 week postchallenge with a CagA(+) VacA(+) (type 1) strain of H . pylori . Treatment of precolonized mice for 2 weeks with dextran sulfate combined with famotidine yielded a group mean bacterial load (per 100 mg of gastric tissue) of log(10) 1.04 CFU, which was significantly lower than those of the famotidine (log(10) 3.35 CFU, P < 0.01) and dextran sulfate (log(10) 2.45 CFU, P < 0.05) monotherapy groups and the infected nontreated group (log(10) 3.64 CFU, P < 0.01) . Eradication was achieved after 2 weeks of treatment in 50% or more of the test mice using drug combinations (1 or 2 weeks of famotidine plus 2 weeks of dextran sulfate) versus none in the monotherapy and positive control groups . The enhanced activity of the drug combination may be related to the daily pattern of transient acid suppression by famotidine inducing periodic bacterial convergence to superficial mucus sites penetrated by dextran sulfate from the lumen . Increased urease-dextran sulfate avidity was observed in vitro in the presence of famotidine and may partly account for the enhanced activity . With potential utility in abbreviating treatment time and eradication of antibiotic-resistant strains, the use of urease-targeted polysaccharides concurrently with a gastric acid inhibitor warrants consideration as an additional component of the standard multidrug chemotherapy of H . pylori infection.

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2424 - 30
Therapeutic efficacy of liposomal rifabutin in a Mycobacterium avium model of infection; Gaspar MM et al.; Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied . The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of infection with a virulent Mycobacterium avium strain (strain P1581) and was compared with that of free rifabutin . The influences of the size of the liposomal rifabutin formulation, the administered doses, and the treatment schedules on the evolution of infection were studied . Two types of treatment schedules were assayed: therapeutic and prophylactic . The therapeutic treatment started 2 weeks after infection, while the prophylactic treatment began 1 day before the experimental infection with mycobacteria . Incorporation of rifabutin in liposomes resulted in a significant enhancement of activity against M . avium infection compared to that of rifabutin in the free form in both schedules . These results demonstrate that liposomal formulations of antibiotics such as rifabutin may be effective for the treatment or prophylaxis of infectious diseases.

Antimicrob Agents Chemother, 2000 Sep, 44(9), 2259 - 62
Prophylactic effect of FK463, a novel antifungal lipopeptide, against Pneumocystis carinii infection in mice; Ito M et al.; The prophylactic effect of FK463, a new water-soluble echinocandin-like lipopeptide with inhibitory activity against 1, 3-beta-D-glucan synthase, against Pneumocystis carinii infection was investigated with the severe combined immunodeficient (SCID) mouse model . Treatment with FK463, pentamidine, and saline only was performed for 6 weeks from the day after the SCID mice were inoculated intranasally with infected lung homogenates . FK463 at 0.2 or 1.0 mg/kg of body weight, pentamidine at 4 mg/kg, or saline was subcutaneously administered daily into the backs of the SCID mice . The effects of the drugs were evaluated by detection of P . carinii cysts in mouse lung homogenates by toluidine blue O staining, lung histology, and PCR amplification of a P . carinii-specific DNA fragment from the lungs . P . carinii cysts were detected in the lungs of all mice administered saline . In contrast, no cysts were detected in mice administered both doses of FK463 and pentamidine . A specific DNA fragment was amplified from all mice administered saline and at least half or more of the mice administered FK463 and pentamidine . These results indicate that FK463 acts on cyst wall formation but not on trophozoite proliferation and is extremely effective in preventing P . carinii-associated pneumonia . These results suggest that FK463 is potentially useful as a prophylactic agent against P . carinii infection.

Vet Q, 2000 Jul, 22(3), 157 - 62
Prevention of pleuropneumonia in pigs by in-feed medication with sulphadimethoxine and sulphamethoxazole in combination with trimethoprim; Mengelers MJ et al.; The prophylactic effect of in-feed medication of conventional pigs with sulphadimethoxine (SDM), sulphamethoxazole (SMX), and trimethoprim (TMP) was tested by using an Actinobacillus pleuropneumoniae infection model . In each of five experiments, six pigs were given medicated feed twice daily and three pigs received antibiotic-free feed and served as positive (unmedicated, infected) controls . The following drugs or drug combinations were tested (in mg per kg feed): 500 SDM + 100 TMP, 500 SMX + 100 TMP, 125 SMX + 25 TMP, 125 SMX (alone) and 25 TMP (alone) . After six days of feed medication, all animals were endobronchially inoculated with A . pleuropneumoniae in a dose of 1-3.10(4) colony-forming units (CFU) . The response to the challenge in all control pigs was characterized by fever, lethargy, anorexia, reduced water consumption, and laboured breathing . At autopsy all controls manifested a fibrinous haemorrhagic pleuropneumonia . In-feed medication with 500 SDM + 100 TMP, 500 SMX + 100 TMP as well as 125 SMX + 25 TMP resulted in an effective protection against the challenge in all treated animals . After consumption of feed medicated with 125 mg per kg SMX or 25 mg per kg TMP, pleuropneumonia was evident in all challenged pigs . The results of this study indicate an in vivo potentiation of SMX and TMP in pigs against this respiratory tract pathogen.

Rev Mal Respir, 2000 Jun, 17(3), 700 - 3
{Lipid pneumonia and pleural-pulmonary atypical mycobacteriosis}; Dorion I et al.; We report a case of fat deposit pneumonia extending to the parietal pleura with a granulomatous reaction centered on the fat vaculoles . This case was complicated by an atypical and fatal mycobacterial infection caused by Mycobacterium chelonae . The severity of Mycobacterium chelonae infection in fat deposit pneumonia warrants early empirical antibiotic therapy.

J Med Primatol, 2000 Apr, 29(2), 85 - 7
Chemotherapy of haemobartonellosis in squirrel monkeys (Saimiri sciureus); Michel JC et al.; Splenectomised Saimiri sciureus squirrel monkeys are being used increasingly as an experimental host for human malarial studies, notably for the assessment of candidate vaccines against Plasmodium falciparum blood-stage infection . Recently, we have reported that colony-reared S . sciureus monkeys are asymptomatic carriers of Haemobartonella sp . and that patent Haemobartonella infection, activated following splenectomy, may interfere with the course of P . falciparum parasitaemia in these animals . For several years, splenectomised S . sciureus monkeys were routinely submitted to oxytetracycline therapy before their use in malarial studies in order to prevent a possible spontaneous Heamobartonella infection . However, we report here that such antibiotic therapy is often ineffective and that neoarsphenamine chemotherapy may be considered as an alternative to cure both latent and patent haemobartonellosis in S . sciureus monkeys.

J Foot Ankle Surg, 2000 Jul-Aug, 39(4), 244 - 8
Necrotizing fasciitis in the lower extremity: a review and case presentation; Lombardi CM et al.; Necrotizing fasciitis is a rare but potentially fatal disease which is often confused with cellulitis . By examining the pathogenesis, clinical presentation, treatment, and a representative case study, this article proposes to lend a broader perspective to this infection . Emphasis is placed on the necessity of surgical debridement in combination with antibiotic therapy to minimize the possible morbidity associated with this condition.

J Reprod Med, 2000 Jul, 45(7), 572 - 6
Conservative management of isolated posthysterectomy fever; McNally CG et al.; OBJECTIVE: To demonstrate that an isolated fever in the absence of other signs or symptoms of infection following hysterectomy does not require empiric antibiotics and laboratory tests . METHODS: Retrospective analysis of all the charts of patients who had a hysterectomy from July 1995 to December 1996 at our institution . Patients with a postoperative temperature > 38 degrees C had a physical examination . If the examination was normal, no studies were ordered, and antibiotic therapy was not initiated . If a patient was febrile after 72 hours postoperatively, laboratory studies and radiographic tests were ordered . If the results were negative, the patient did not appear septic, and physical examination was normal, no antibiotics were given . Outcomes were measured by comparing patients with postoperative infections and fever to those without infections . RESULTS: Of 132 patients, 112 were included in the study . Seventy-two hysterectomies were abdominal and 40 vaginal . Postoperative fever during the first 72 hours following hysterectomy occurred in 51/112 (46%) patients . Clinically significant infection was documented in seven patients, all of whom manifested signs and symptoms of infection > 72 hours postoperatively . CONCLUSION: Postoperative fever in the first 72 hours after hysterectomy is common and nonspecific . If a febrile patient does not show any other signs or symptoms of infection, it is safe to forego routine laboratory and imaging studies as well as therapeutic antibiotics.

Arch Environ Contam Toxicol, 2000 Oct, 39(3), 386 - 91
Development of a bioassay to test the possible role of thiamine disturbance as a mechanism behind pollution-induced reproductive failures in birds; de Roode DF et al.; A test system was developed to examine the effects of environmental contaminants on thiamine homeostasis in bird embryos . This system employs fresh chicken egg yolk lipids as a vehicle for use in egg injection studies . Furazolidone, an antibiotic suspected to interfere with thiamine metabolism, was used as a positive control to evaluate the utility of the test system . It was determined that fresh chicken egg yolk lipids were preferable over chemical vehicles as it resulted in lower mortality rates (16% versus 23-62%) and did not induce any observable effects in the embryo . Injection of 1 mg/egg of furazolidone at day 0 of development resulted in decreased respiration followed by death, with mortality rates being twice as high as in carrier controls . In addition, transketolase activity, which was measured as an indicator of thiamine availability in the body, was decreased 25% in brains of 19-day-old embryos . This mechanism may be of importance for effects of environmental contaminants in wild bird populations.

Infect Immun, 2000 Sep, 68(9), 5416 - 9
Invasion of human vascular endothelial cells by Actinobacillus actinomycetemcomitans via the receptor for platelet-activating factor; Schenkein HA et al.; Strains of the periodontal pathogen Actinobacillus actinomycetemcomitans are variable with respect to display of phosphorylcholine (PC)-bearing antigens . We have examined strains of A . actinomycetemcomitans with and without PC to assess their ability to invade endothelial cells via the receptor for platelet-activating factor (PAF) . Results of antibiotic protection assays indicate that PC-bearing A . actinomycetemcomitans invade human vascular endothelial cells by a mechanism inhibitable by CV3988, a PAF receptor antagonist, and by PAF itself . The invasive phenotype was verified by transmission electron microscopy . A PC-deficient strain of this organism was not invasive . This property, in addition to the established ability of A . actinomycetemcomitans to invade epithelial cells, may provide this organism with access to the systemic circulation . The ability of PC-bearing oral bacteria to access the circulation may also explain the elevated levels of anti-PC antibody in serum found in patients with periodontitis.

Infect Immun, 2000 Sep, 68(9), 5412 - 5
Regulation of human beta-defensins by gastric epithelial cells in response to infection with Helicobacter pylori or stimulation with interleukin-1; O'Neil DA et al.; Gastric epithelial cells in vitro and in vivo are shown to constitutively express the peptide antibiotic human beta-defensin type 1 (hBD-1) . In contrast, hBD-2 expression is regulated in gastric epithelial cells and increases in response to infection with Helicobacter pylori or stimulation with the proinflammatory cytokine interleukin-1 . These data suggest that hBD-2 is a component of the regulated host gastric epithelial cell response to H . pylori infection and proinflammatory mediators.

J Vet Med Sci, 2000 Jul, 62(7), 681 - 6
Intramammary application of ozone therapy to acute clinical mastitis in dairy cows; Ogata A et al.; The infusion of ozone into the inflamed quarter of cows with clinical mastitis was performed and the efficacy of ozone therapy was evaluated . Ozone was infused into the inflamed quarter via a teat canal using ozone gas generating equipment . Nineteen Holstein cows with acute clinical mastitis were divided into two groups: 15 cows treated with ozone therapy, and 4 cows treated with antibiotic therapy . Systemic and local clinical signs, California Mastitis Test scores, the mastitis causing pathogens, electronic conductivity of milk, and somatic cell counts in milk from ozone- and antibiotic-treated quarters, were compared between the groups . Sixty percent (9/15) of cows with acute clinical mastitis treated with ozone therapy, did not require any antibiotics for recovery . This newly developed ozone therapy method was proven to be effective, safe, and cost effective, and carries no risk of drug residues in milk.

RNA, 2000 Aug, 6(8), 1174 - 84
Mutations in helix 27 of the yeast Saccharomyces cerevisiae 18S rRNA affect the function of the decoding center of the ribosome; Velichutina IV et al.; A dynamic structural rearrangement in the phylogenetically conserved helix 27 of Escherichia coli 16S rRNA has been proposed to directly affect the accuracy of translational decoding by switching between "accurate" and "error-prone" conformations . To examine the function of helix 27 in eukaryotes, random and site-specific mutations in helix 27 of the yeast Saccharomyces cerevisiae 18S rRNA have been characterized . Mutations at positions of yeast 18S rRNA corresponding to E . coli 886 (rdn8), 888 (rdn6), and 912 (rdn4) increased translational accuracy in vivo and in vitro, and caused a reduction in tRNA binding to the A-site of mutant ribosomes . The double rdn4rdn6 mutation separated the killing and stop-codon readthrough effects of the aminoglycoside antibiotic, paromomycin, implicating a direct involvement of yeast helix 27 in accurate recognition of codons by tRNA or release factor eRF1 . Although our data in yeast does not support a conformational switch model analogous to that proposed for helix 27 of E . coli 16S rRNA, it strongly suggests a functional conservation of this region in tRNA selection.

Jpn Circ J, 1999 May, 63(5), 400 - 3
Hemolytic anemia in native valve infective endocarditis: a case report and literature review; Huang HL et al.; Hemolytic anemia is a rare manifestation of infective endocarditis . A 19-year-old man with a small ventricular septal defect developed right-sided infective endocarditis with huge vegetations involving the tricuspid valve, the ventricular septal defect, and the pulmonary valve . Intravascular hemolysis was suggested by the presence of numerous fragmented erythrocytes, giant platelets and polychromasia of the red blood cells . The direct Coombs test was positive, and there were spherocytes and splenomegaly, findings that suggested an immune-mediated mechanism also played a role in the hemolysis . The hematological picture persisted despite antibiotic therapy and recovered only after surgical removal of the vegetations, tricuspid and pulmonary valvectomy, and patch closure of the ventricular septal defect.

Rev Med Interne, 2000 Jul, 21(7), 580 - 5
{Do hematopoietic growth factors have a role in the treatment of drug-induced agranulocytosis?}; Andres E et al.; PURPOSE: Our study was aimed at determining the role of hematopoietic growth factor in drug-induced agranulocytosis . METHODS: Fifty-five cases of drug-induced agranulocytosis were reviewed and subdivided retrospectively into a G-CSF group (n = 15) and an untreated group (n = 40) . Mortality and hematological recovery (number of days required for neutrophil counts to exceed 1.5 x 10(9)/L) were studied in the two groups . RESULTS: The mean granulocyte count was 0.09 x 10(9)/L . All patients presented infection . In the G-CSF group, no mortality (0% versus 5%, P = 0.85) and a shorter recovery time (8.1 versus 9.5 days P = 0.39) were observed . No significant difference between the two groups was observed in either the duration of antibiotic therapy (9.3 days in the G-CSF group versus 10.1 days in the untreated group, P = 0.51) or duration of hospitalization (10 days in the treated group versus 11 days in the G-CSF group, P = 0.46) . CONCLUSION: Our results as well as a literature review indicate that G-CSF could decrease the time to hematological recovery and perhaps reduce mortality . However, the exact role of hematopoietic growth factors requires further investigations.

Ann Oncol, 2000 Jun, 11(6), 743 - 7
Acute deterioration of Charcot-Marie-Tooth disease IA (CMT IA) following 2 mg of vincristine chemotherapy; Hildebrandt G et al.; BACKGROUND: Severe up to life-threatening neuropathy has been observed in patients with hereditary neuropathies receiving vincristine . CASE REPORT: A 52-year-old female painter suffering from high-grade non-Hodgkin's lymphoma (stage IVB) was treated with a total of 4 mg of vincristine during two courses of CHOP chemotherapy (cyclophosphamide, vincristine, adriamycin, prednisone) . At onset of treatment no neurological problems were reported . There was good lymphoma response to chemotherapy . At the same time, however, the patient gradually developed dysphagia, dysarthria, muscular weakness of both lower and upper extremities, areflexia, paraesthesia of the fingertips and bilateral sensory impairment of feet and lower legs . These symptoms continually worsened over a period of seven weeks until she was unable to walk or to perform her work . Electrophysiological studies showed peripheral axonal and demyelinative sensorimotor neuropathy in correlation to histological findings . Molecular analysis revealed 17p11.2 duplication typical for Charcot-Marie-Tooth disease IA . While continuing chemotherapy without the use of vincristine the patient's neurologic symptoms slowly recovered within six months . CONCLUSION: Prior to administration of vincristine family and patient history as well as physical examination should be performed carefully to look for underlying hereditary neuropathy . For those patients with a clinical history or symptoms suggestive for CMT nerve conduction velocity studies and on an individual base even molecular genetic analysis are necessary to prevent serious neurologic complications . worsened significantly resulting in dependency on a wheelchair and inability to perform her work as a painter . Finally she consulted a neurologist and was admitted to hospital for further diagnostic studies and continuation of treatment for her lymphoma in March 1998 with a provisional diagnosis of severe vincristine-induced neuropathy . Medical history at time of admission included hyperthyroidism, that was currently treated with propylthiouracil, a MALT lymphoma 1983, that was treated surgically only, and a meningoencephalitis in 1968 . No further medication was taken . In addition she had a history of Lyme disease since 1993 with positive IgM-titer until December 1997, when antibiotic therapy with doxycycline and ceftriaxone was administered successfully . Family history obtained on admission revealed that her mother had non-specific neuropathic symptoms as well as a poorly defined foot deformities of the mother's father . The patient's brother does not show any neurologic impairment and is in good physical health.

Ann Oncol, 2000 Jun, 11(6), 735 - 41
Phase I open study of the effects of ascending doses of the cytotoxic immunoconjugate CMB-401 (hCTMO1-calicheamicin) in patients with epithelial ovarian cancer; Gillespie AM et al.; PURPOSE: We have performed a phase I study of the cytotoxic immunoconjugate CMB-401 in women with epithelial ovarian cancer (EOC) . CMB-401 is a directed chemotherapy that comprises a genetically engineered human antibody against polymorphic epithelial mucin, to which is attached covalently two to three molecules, on average, of the cytotoxic antibiotic calicheamicin . The primary objectives of this two-centre study were to identify end-organ toxicities and to establish the maximum tolerated dose (MTD) . PATIENTS AND METHODS: Thirty-four patients aged 37-75 years with progressive EOC not amenable to platinum/standard therapy, and with satisfactory WHO performance status (0-2) were recruited . Patients had received a mean of 3.2 previous chemotherapeutic regimens with a median interval since last chemotherapy of 182 days (range 34-1217) . Patients received up to four cycles of a dual infusion of 35 mg/m2 hCTMO1 'predose' followed by doses of CMB-401 which were increased for each cohort--a regimen which minimises drug uptake in normal tissues whilst enhancing delivery to the ovarian tumour . CMB-401 dosing commenced at 2 mg/m2 and progressed via seven cohorts to 16 mg/m2 . RESULTS: CMB-401 was generally well tolerated . However, transient fever and emesis occurred, necessitating routine prophylaxis, and increasingly significant malaise was reported as the dose increased . WHO grade 3-4 toxicities, irrespective of causality, included: anaemia 21%, granulocytopenia 9%, thrombocytopenia 9%, liver transaminases 3%, sepsis 3%, haemorrhage 6%, nausea/vomiting 76%; pulmonary 6%, and conscious state/somnolence 6% . The MTD was reached at 16 mg/m2 . During the study four patients had a greater than 50% reduction in CA125, and three patients had radiological evidence of reduction in tumour bulk . CONCLUSIONS: CMB-401 appears to have an acceptable toxicity profile with demonstrable activity against EOC.

Arch Pediatr, 2000 Jun, 7 Suppl 3, 517s - 522s
{Lyme disease in Upper Normandy: report of a hospital survey}; Marguet C et al.; This study presents the results of a hospital survey on Lyme disease in children living in upper Normandy, a region that is quite densely wooded (with 18% forest areas and woods) . The aim of this survey was to assess the prevalence of this disease in children from the Seine-Maritime and L'Eure, hospitalized in pediatric wards in the Seine-Maritime department, which includes Rouen, Dieppe, Fecamp, Elbeuf, and Le Havre . Fifteen cases of Lyme disease were diagnosed between September 1988 and June 1997 . The children (6 girls and 9 boys) were aged between 5 and 14 years old . Only 7 subjects showed primary symptoms, while secondary symptoms were observed in 12 children . In the study population, a high prevalence (11 out of the 15 children) of neurological disorders was found . The following secondary symptoms were noted: 5 cases of erythema migrans, 2 cases of non-malignant cutaneous lymphocytoma, and 4 cases which in fact had previously displayed primary clinical signs (3 subjects with erythema migrans and 1 subject with non-malignant cutaneous lymphocytoma); 7 cases of uni- or bilateral facial paralysis, the most frequent neurological manifestation with or without lymphocytic meningitis; 1 case of central vestibular syndrome with a hyperalgesic meningoradicular reaction in the vicinity of the tick bite; 1 case of peripheral radicular involvement and intense pain in the left lower limb; 4 cases of ocular disorders (3 diplopias, 1 bilateral conjunctivitis complicated by kerato-uveitis, 1 bilateral complete cecitis) . Only 10 child had rheumatological symptoms, i.e., Lyme arthritis of the right knee . Treatment consisted of amoxicillin (10 children) administered at a dosage of 50 to 100 mg/kg/d over a period ranging from 10 days to 1 month, or ceftriaxone (7 children) at a dosage of 50 to 100 mg/kg/d administered intravenously over a period ranging from 8 days to 3 weeks . Two of the children received combined antibiotic therapy, and 5 subjects had adjunct corticotherapy.

Respiration, 2000, 67(4), 467 - 70
Organizing pneumonia related to common variable immunodeficiency . case report and literature review; Wislez M et al.; A 68-year-old woman suffering from common variable immunodeficiency (CVI) developed a typical picture of organizing pneumonia . Causative factors other than CVI were eliminated . Several antibiotic regimens failed to improve the patient's condition, while the clinical manifestations rapidly disappeared under steroid therapy, with complete radiological recovery, but relapsed after steroid withdrawal . Finally, organizing pneumonia was definitely demonstrated by pathological findings obtained by open lung biopsy . Interestingly, pathological examination exhibited two other well-known CVI-associated lesions, i.e . benign lymphoid hyperplasia and noncaseating granuloma . In view of reports in the literature, we speculate that these different histological patterns could have resulted in a spectrum of symptomatic CVI-associated pulmonary disorders that improved under steroid therapy .

Surg Neurol, 2000 Jun, 53(6), 573 - 8; discussion 578-9
Diagnostic pitfalls in osteomyelitis of the odontoid process: case report; Noguchi S et al.; BACKGROUND: Pyogenic osteomyelitis of the odontoid process is a very rare disease associated with a variety of clinical symptoms, and previous reports have stressed the difficulties inherent in making the diagnosis . The authors present a case of osteomyelitis of the odontoid process with epidural abscess in which magnetic resonance imaging (MRI) was used in the diagnosis, assessment of the extent of concomitant epidural abscess, treatment effect, and long-term follow-up.CASE DESCRIPTION: A 68-year-old male was admitted to our hospital with cervical pain, neck stiffness, and fever . Although the diagnosis was missed at the beginning, the patient was diagnosed with osteomyelitis of the odontoid process with a paravertebral epidural abscess by MRI . The patient became asymptomatic after 3 months of antibiotic therapy.CONCLUSION: Pyogenic osteomyelitis of the odontoid process is a rare condition requiring a high index of suspicion for diagnosis . MRI examination should be considered in the diagnosis in patients with neck pain combined with fever . Serial MRI during and after antibiotic therapy provided an objective assessment of the healing rate of the lesions.

J Bacteriol, 2000 Sep, 182(17), 4979 - 86
Developmental control of stress stimulons in Streptomyces coelicolor revealed by statistical analyses of global gene expression patterns; Vohradsky J et al.; Stress-induced regulatory networks coordinated with a procaryotic developmental program were revealed by two-dimensional gel analyses of global gene expression . Four developmental stages were identified by their distinctive protein synthesis patterns using principal component analysis . Statistical analyses focused on five stress stimulons (induced by heat, cold, salt, ethanol, or antibiotic shock) and their synthesis during development . Unlike other bacteria, for which various stresses induce expression of similar sets of protein spots, in Streptomyces coelicolor heat, salt, and ethanol stimulons were composed of independent sets of proteins . This suggested independent control by different physiological stress signals and their corresponding regulatory systems . These stress proteins were also under developmental control . Cluster analysis of stress protein synthesis profiles identified 10 different developmental patterns or "synexpression groups." Proteins induced by cold, heat, or salt shock were enriched in three developmental synexpression groups . In addition, certain proteins belonging to the heat and salt shock stimulons were coregulated during development . Thus, stress regulatory systems controlling these stimulons were implicated as integral parts of the developmental program . This correlation suggested that thermal shock and salt shock stress response regulatory systems either allow the cell to adapt to stresses associated with development or directly control the developmental program.

J Bacteriol, 2000 Sep, 182(17), 4951 - 8
Halocin S8: a 36-amino-acid microhalocin from the haloarchaeal strain S8a; Price LB et al.; Halocin S8 is a hydrophobic microhalocin of 36 amino acids (3,580 Da) and is the first microhalocin to be described . This peptide antibiotic is unique since it is processed from inside a much larger, 33,962-Da pro-protein . Halocin S8 is quite robust, as it can be desalted, boiled, subjected to organic solvents, and stored at 4 degrees C for extended periods without losing activity . The complete amino acid sequence of halocin S8 was obtained first by Edman degradation of the purified protein and verified from the halS8 gene: H(2)N-S-D-C-N-I-N-S-N-T-A-A-D-V-I-L-C-F-N-Q-V-G-S-C-A-L-C-S-P-T-L-V-G -G-P-V-P-COOH . The halS8 gene is encoded on an approximately 200-kbp megaplasmid and contains a 933-bp open reading frame, of which 108 bp are occupied by halocin S8 . Both the halS8 promoter and the "leaderless" halS8 transcript are typically haloarchaeal . Northern blot analysis revealed three halS8 transcripts: two abundant and one minor . Inspection of the 3' end of the gene showed only a single, weak termination site (5'-TTTAT-3'), suggesting that some processing of the larger transcripts may be involved . Expression of the halS8 gene is growth stage dependent: basal halS8 transcript levels are present in low concentrations during exponential growth but increase ninefold during the transition to stationary phase . Initially, halocin activity parallels halS8 transcript levels very closely . However, when halocin activity plateaus, transcripts remain abundant, suggesting inhibition of translation at this point . Once the culture enters stationary phase, transcripts rapidly return to basal levels.

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