Gene, 1998 Jul 17, 215(1), 181 - 9 A novel GFPneo vector designed for the isolation and analysis of enhancer elements in transfected mammalian cells; Primig M et al.; We have designed a new approach to the direct cloning and rapid analysis of mammalian enhancer elements by fusing green fluorescent protein and neomycinphosphotransferase under the control of a thymidine kinase minimal promoter . DNA fragments containing known or potential enhancer elements can be inserted into a polylinker upstream of GFPneo and re-isolated from stably transfected cell lines by a direct transgene-specific polymerase chain reaction (PCR), for further analysis . C2C12 muscle cells were transfected with four vectors containing the GFPneo fusion gene regulated by the cytomegalovirus promoter, the myoD distal core enhancer and myoblast- and myotube-specific enhancers from the desmin gene . GFPneo shows robust epifluorescence by microscopy and flow cytometry and retains sufficient neo activity to permit selection of G418-resistant clones . The fluorescence signal pattern of GFPneo expressed under the control of the desmin enhancers mirrors their transcriptional profile during myogenic differentiation . This finding demonstrates the value of GFPneo as a tool to analyse differentiation stage-specific regulatory DNA elements in stably transfected mammalian cell lines . We were able to re-isolate the myoD enhancer mediating GFPneo expression from a stably transfected C2C12 clone by a transgene-specific PCR reaction, demonstrating the feasibility of using this new vector system for the isolation of regulatory sequences. Laryngoscope, 1998 Jul, 108(7), 1087 - 9 Topical gentamicin and ethacrynic acid: effects on cochlear function; Conlon BJ et al.; OBJECTIVE: To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the aminoglycoside antibiotic gentamicin applied topically on the round window . STUDY DESIGN: The authors studied the effects on cochlear sensitivity of co-administered intracardiac ethacrynic acid (40 mg/kg) and high-dose topical gentamicin solution (100%) applied to the round window . Comparisons were made with animals receiving ethacrynic acid plus systemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gentamicin alone; and intravenous ethacrynic acid alone . METHODS: Experiments were carried out on pigmented guinea pigs weighing 400 to 500 g . Changes in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid . RESULTS: After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demonstrate a significant deterioration in cochlear sensitivity, whereas all animals receiving systemic gentamicin plus ethacrynic acid experienced profound increases in CAP thresholds . CONCLUSIONS: This study supports the contention that ethacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph . In addition, this study answers important clinical concerns regarding the safety of the use of topical aminoglycoside agents in combination with loop diuretics. Drugs, 1998 Jul, 56(1), 73 - 81 Management of travellers' diarrhoea; Caeiro JP et al.; The most common health problem encountered in international travellers to topical and subtropical areas is diarrhoea . Even though it is not a life-threatening condition, it may influence deeply the quality of a vacation or the success of a business trip . The majority of cases of travellers' diarrhoea are due to bacterial pathogens, but viruses have also been implicated in a minority of patients . It is advocated that travellers with diarrhoea provide themselves with sources of salt (crackers or soup) and mineral water, to prevent and treat dehydration . Otherwise, treatment recommendations follow illness severity . For mild cases, symptomatic relief alone can be recommended . Loperamide is an effective agent improving diarrhoea and associated symptoms . For moderate diarrhoea (requiring a forced change in itinerary) combination therapy is advised using a fluoroquinolone together with loperamide . Severe diarrhoea {fever > 38 degrees C, dysentery (bloody stools) or incapacitating symptoms} should prompt the voyager to take an antibiotic alone for 3 to 5 days . Loperamide is relatively contraindicated in these cases . For the minority of patients receiving chemoprophylaxis to prevent travellers' diarrhoea, fluoroquinolones taken once a day while in the area at risk produce the highest protection rate (up to 95%) . However, most authorities do not recommend routine prophylaxis for travellers. Chem Biol, 1998 Jul, 5(7), 373 - 84 Kinetics and regioselectivity of peptide-to-heterocycle conversions by microcin B17 synthetase; Belshaw PJ et al.; BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains four oxazole and four thiazole rings introduced post-translationally in the 69 amino acid McbA gene product, an MccB17 precursor, by the microcin B,C,D enzyme complex . Both monocyclic and 4,2-bis-heterocyclic moieties are generated . The enzymatic cyclization involves 14 of the last 43 amino acids of McbA and requires the presence of the first 26 amino acids that function as a specificity-conferring propeptide . RESULTS: We have constructed maltose-binding protein (MBP)-McbA1-46 fusion proteins and have mutagenized the Gly39-Ser40-Cys41 (GSC) wild-type sequence to assess the regioselectivity and chemoselectivity of MccB17-synthetase-mediated heterocycle formation at the first two loci, residues 40 and 41 of McbA . Four single-site and four double-site substrates showed substantial differences in turnover as assessed by western assays, UV-visible spectroscopy and mass spectrometry . Cysteine-derived thiazoles form at a greater rate than serine-derived oxazoles . Formation of bis-heterocycles is sensitive both to composition and sequence context . CONCLUSIONS: The E . coli McbB,C,D MccB17 synthetase is the first peptide heterocyclization enzyme to be characterized . This study reveals substantial regioselectivity and chemoselectivity (thiazole > oxazole) at the most amino-terminal bis-heterocyclization site of McbA . The heterocyclization of GSS and GCC mutants of McbA1-46 by MccB17 synthetase demonstrates that the complex can efficiently generate tandem bis-oxazoles and bis-thiazoles, moieties not found in MccB17 but present in natural products such as hennoxazole and bleomycin . The observations suggest a common enzymatic mechanism for the formation of peptide-derived heterocyclic natural products. Int J Tuberc Lung Dis, 1998 Jul, 2(7), 531 - 40 Cost-effectiveness of directly observed chemoprophylaxis of tuberculosis among drug users at high risk for tuberculosis; Gourevitch MN et al.; SETTING: A methadone treatment program with on-site medical care in the Bronx, New York . OBJECTIVE: To define whether costs associated with directly observed preventive therapy (DOPT) of tuberculosis are justified by cases and costs of tuberculosis prevented among persons at high risk for active disease . DESIGN: Detailed data were collected on drug users in treatment regarding human immunodeficiency virus (HIV) and tuberculosis infection and disease, and costs of screening, chemoprophylaxis, direct observation and treatment of active disease . The cost-effectiveness of providing DOPT to this population was modeled . RESULTS: We assessed the impact of providing DOPT to 151 eligible persons . Assuming 65% isoniazid effectiveness, and incorporating costs of screening, observed chemoprophylaxis and clinical monitoring, a net savings in tuberculosis-related hospital costs of $285,284 ($563 per person screened) was associated with DOPT ($10,274 per case prevented) . Direct observation of chemoprophylaxis proved cost-effective if associated with even a 10% increment in overall isoniazid effectiveness compared with self-administered chemoprophylaxis . DOPT costs per tuberculosis case averted remained below the in-patient costs of a single case of drug-sensitive disease across a range of parameter values . CONCLUSIONS: Providing DOPT is a highly cost-effective intervention for drug users in treatment . Commitment of additional resources required for DOPT should be given priority in this and other populations at high risk for tuberculosis. Thorax, 1998 Mar, 53(3), 182 - 5 Non-tuberculous mycobacteria in cystic fibrosis; Torrens JK et al.; BACKGROUND: The clinical significance of the presence of non-tuberculous mycobacteria in the sputum of patients with cystic fibrosis is unclear . A retrospective case-control study was performed to assess possible risk factors for non-tuberculous mycobacteria and its impact on clinical status in patients with cystic fibrosis . METHODS: The records of all patients attending the Leeds cystic fibrosis clinics who were positive for non-tuberculous mycobacteria were examined . Each case was matched with two controls for sex, age, and respiratory function at the time of the first non-tuberculous mycobacteria isolate . Details of respiratory function, nutritional status, antibiotic and corticosteroid therapy, Shwachman-Kulczycki (S-K) score, Northern chest radiographic score, and the frequency of isolation of other bacteria and fungi were collected from two years before to two years after the first non-tuberculous mycobacteria isolate . The patients' genotype and the presence of diabetes mellitus were also recorded . RESULTS: Non-tuberculous mycobacteria were isolated from 14 patients out of a cystic fibrosis population of 372 (prevalence = 3.8%) . No significant effect of non-tuberculous mycobacteria was seen on respiratory function, nutritional status, or S-K score . There was a significant association with the number of intravenous antibiotic courses received before the first isolate with cases receiving, on average, twice as many courses as controls (cases 6.64, controls 2.86, 95% CI for difference 1.7 to 5.9) . No significant difference was seen between cases and controls for Northern scores, previous steroid therapy, or the incidence of diabetes mellitus . CONCLUSIONS: Non-tuberculous mycobacteria infection in patients with cystic fibrosis is uncommon and its clinical impact appears to be minimal over a two year period . Frequent intravenous antibiotic usage is a possible risk factor for colonisation with non-tuberculous mycobacteria. Rev Neurol, 1998 Jun, 26(154), 1019 - 20 {Polyneuropathy caused by vitamin B12 deficiency secondary to chronic atrophic gastritis and giardiasis}; Brieva L et al.; INTRODUCTION: In chronic atrophic gastritis atrophy of the stomach glands leads to intrinsic factor deficit, with consequent failure to absorb vitamin B12 and gastric achylia, which predisposes to Giardia infection which in itself leads to depletion of vitamin B12 . We describe the case of a patient with peripheral and central nervous system pathology due to lack of vitamin B12 secondary to the combined effect of these two disorders . CLINICAL CASE: A 54 year old woman consulted us for paraesthesia and weakness of the legs which had been progressive for the previous two years . She presented with tactile hypoaesthesia, hypoparaesthesia, distal hyperreflexia and dysymmetry of the legs, ataxic-spastic gait and a positive Romberg sign . The investigations carried out showed the serum vitamin B12 level to be 3 pg/ml (N: 180-900), hemoglobin 13 g/dl and MCV 111 fl with MCHC 348/dl; neurophysiological studies: compatible with demyelinating motor polyneuropathy . Schilling test: deficit of absorption of vitamin B12 which was corrected on administration of intrinsic factor; gastroscopy; atrophic gastritis which confirmed the morbid anatomy findings . There was also flora containing Helicobacter and massive Giardia infection . Replacement and antibiotic therapy was followed by complete remission of the clinical picture . CONCLUSION: We emphasize the excellent clinical response to treatment in spite of the time elapsed since onset of symptoms. Poult Sci, 1998 Jul, 77(7), 950 - 5 Intervention decision model to prevent spiking mortality of turkeys; Vukina T et al.; Based on the daily records on turkeys' mortalities for the series of flocks placed on different farms in a relatively compact geographical area for the period of approximately 2 yr and other relevant explanatory variables, the goal of the research was to design a decision model to determine whether or not to use the fluorquinolone antibiotic, sarafloxacin, to prevent spiking mortality of turkeys . The core of the designed decision model is the forecasting model that attempts to ex-ante predict the cumulative flock mortality for the period between 8 and 28 d of age . Forecasts were generated with the parameters of the linear regression model where continuous values of daily mortalities served as a dependent variable . The decision variable is a binary (yes/no) choice variable, where "yes" means "go ahead with treatment" and "no" means "do nothing" . If the predicted cumulative mortality for the period between 8 and 28 d of age exceeds 9% of the total initial placement, the model generates a "yes" signal . If the predicted cumulative mortality for the same period is below 9% of the total initial placement, the model generates a "no" signal . The results indicate a reasonable accuracy of the prediction model where the number of correct prediction increases and the number of incorrect predictions falls very fast as the forecasting window shortens . The intervention decision model could help veterinarians in making decisions on whether or not to treat the suspect flocks. Allerg Immunol (Paris), 1998 May, 30(5), 143 - 8 {Postoperative allergic complications: the role of the anesthetist in conducting the immuno-allergic investigation}; Cottineau C et al.; When peri-anaesthesia anaphylactic and/or anaphylactoid reactions occur, anaesthetist is the first investigator: the quality of immuno-allergological investigations depends on these initial investigational procedures . We have used sample kits for several years in order to make easier the immediate investigation . From retrospective analysis of the allergic complications which happened in 1997, the importance of these sample kits as well as the anaesthetist's part in the immuno-allergological management are examined . Nine observations were itemized (0.047%): 3 generalized erythema observations (grade I), in which atracurium was incriminated twice, and propacetamol once; 2 observations of grade II, in which vecuronium (elevated tryptase) and atracurium were incriminated; 4 anaphylactic shocks, in which three neuromuscular blocking drugs (suxamethonium, vecuronium and pancuronium), and one antibiotic (cloxacilline) were incriminated . The use of sample kits allowed an early diagnosis approach, confirmed by skin tests . Diagnosis should be thought closely between anaesthetists and immunologists for investigations. Structure, 1998 Jun 15, 6(6), 783 - 92 The structure and function of antiamoebin I, a proline-rich membrane-active polypeptide; Snook CF et al.; BACKGROUND: Antiamoebin is a member of the peptaibol family of polypeptides and has a unique antibiotic activity: it acts as an antiamoebic agent, but does not effectively haemolyze erythrocytes even though it does exhibit membrane-modifying activity . RESULTS: The structure of antiamoebin I has been determined by X-ray crystallography at 1.4 A resolution . The molecule forms a helical structure, which, as a result of the presence of a number of proline and hydroxyproline residues, has a deep bend in the middle . Circular dichroism spectroscopy, single-channel conductance studies and fluorescence diffusion studies suggest a mode of ion transport that is entirely different from that of the other two members of the peptaibol family (alamethicin and zervamicin) whose structures and functions have been examined in detail . CONCLUSIONS: The structure of the polypeptide has been determined and a functional model for its mode of action in membranes is presented . Although under some conditions antiamoebin may form ion channels, unlike the closely related alamethicin and zervamicin polypeptides, its major membrane-modifying activity appears to be as an ion carrier. Am J Respir Crit Care Med, 1998 Jul, 158(1), 207 - 12 Total sputum nitrate plus nitrite is raised during acute pulmonary infection in cystic fibrosis; Linnane SJ et al.; Nitric oxide (NO) can be detected in exhaled gas in human subjects . It is produced by nitric oxide synthase (NOS) and is rapidly metabolized to nitrite and nitrate (NO2/NO3) . Exhaled NO is reported to be elevated in patients with asthma, bronchiectasis, or upper respiratory tract infection . Recent reports have shown no increase of exhaled NO in stable cystic fibrosis (CF) . We hypothesized that NOS activity is increased in patients with acute pulmonary exacerbation of CF . We therefore measured exhaled NO and sputum NO2/NO3 in three subject categories: patients with acute pulmonary exacerbation of CF, patients with stable CF, and healthy control subjects . Mean +/- SD exhaled NO was significantly higher in control subjects (8.8 +/- 4.9 ppb) than in both acute (3.8 +/- 3.9 ppb) and stable (5.0 +/- 2.5 ppb) patients . Sputum NO2/NO3 was significantly higher in acute patients (774 +/- 307 micromol/L) when compared with both stable patients (387 +/- 203 micromol/L) and control (421 +/- 261 micromol/L) subjects . Sputum NO2/NO3 did not return to normal in a subgroup of patients assessed after 2 wk of intensive antibiotic and glucocorticoid treatment . These results confirm that exhaled NO is not a useful measure of airway inflammation in CF . Elevated levels of sputum NO2/NO3 suggest that NOS is activated during acute pulmonary exacerbations of CF. Am Surg, 1998 Jul, 64(7), 607 - 10 Autologous closure of giant abdominal wall defects; Lucas CE et al.; Split-thickness skin graft coverage of exposed and granulating intestines within large abdominal wall defects provides a life-saving permanent biologic dressing . The resultant abdominal wall defect often is closed with mesh, which may infect and fistulize . This report describes bilateral advancement flaps of the external oblique and recti muscles in 11 patients treated over 3 years . The defects, which averaged 16 x 24 cm, were due to necrotizing fasciitis subsequent to trauma with bowel perforation (3 patients), multiple ventral herniorrhaphies (2 patients), perforated diverticulitis (4 patients), and perforated peptic ulcer (2 patients) . Eight patients were initially treated elsewhere where closure was achieved by split-thickness skin graft in five patients or mesh in 3 patients; 3 developed enterocutaneous fistulae and were transferred for closure while receiving long-term antibiotic and total parenteral nutrition therapy . All 11 patients had successful primary closure . The 8 patients operated on electively had primary healing; 2 developed seromas . Two of the three patients operated on urgently developed superficial wound infections; both healed by second intent without compromise of the primary closure . The following conclusions can be drawn: (1) the linea alba survives despite necrotizing fasciitis, (2) a tension-free primary closure is feasible; (3) morbidity is minimal, and (4) the long-term result is excellent. Acta Otolaryngol, 1998 Jun, 118(3), 362 - 8 Experimental study on the effects of gentamicin injection on the guinea-pig: electrophysiological studies; Hotta S et al.; The inner ear distortion induced by gentamicin (GM), a type of aminoglycoside antibiotic, was examined in guinea-pigs . Previous studies which investigated the function of the eighth cranial nerve and organ of Corti using cochlear microphonics (CM) and compound action potential (CAP) reported ototoxicity following experimental exposure to GM . In this report, the effects of GM on the cochlea and the eighth cranial nerve were investigated systematically by measuring CM, CAP, summating potentials induced by 90 dB (SPL) tone burst, endocochlear potential (EP) and K+ ion concentration of the endolymph . Guinea-pigs were treated with a daily intramuscular injection of GM (60 mg in 1.5 cc) at a dose of 60 mg/kg during different treatment periods . The maximum output voltage of AP was decreased by injection of GM (60 mg/kg x 24) . A decrease in the CM maximum output voltage and the elevation of CM pseudothreshold were typically seen after GM injection at a test frequency of 8 kHz and a decrease in CAP was also observed . Changes in EP during 3 min anoxia were observed, in particular a decrease in the absolute value of the negative potential . The endolymph K+ ion concentration remained unchanged . These findings indicate that the diffusion potentials decreased at the same time as reduction of maximum output voltage in CM induced by GM injection. New Horiz, 1998 May, 6(2 Suppl), S80 - 8 Impact of laparoscopic surgery on stress responses, immunofunction, and risk of infectious complications; Kehlet H et al.; Open laparotomy is followed by profound changes in endocrine metabolic function and various host defense mechanisms, impaired pulmonary function, and hypoxemia, all of which may be important for the development of postoperative infectious complications . Laparoscopic surgery, however, leads to a reduced inflammatory response (C-reactive protein and interleukin-6), a reduced immunomodulatory response, improvement in pulmonary function, and less hypoxemia, whereas classic endocrine metabolic responses are less influenced or not influenced compared with similar open operation . The clinical implications of laparoscopic surgery on postoperative infectious complications have not been assessed in large-scale prospective, randomized studies, except in appendectomy, in which a reduced incidence of wound infection has been demonstrated . Data from cholecystectomy and colorectal surgery suggest a reduction in wound complications, whereas the sparse data on intraperitoneal infections and sepsis are not conclusive . Thus, laparoscopic surgery modifies the injury response and reduces the risk of infectious complications . If integrated into an accelerated rehabilitation program, further improvement may result . The impact of these findings on prophylactic antibiotic regimens cannot be assessed from available data and requires evaluation in prospective clinical studies. FEBS Lett, 1998 May 29, 428(3), 235 - 40 Biochemical characterization of HIV-1 Rev as a potent activator of casein kinase II in vitro; Ohtsuki K et al.; The stimulatory effects of several DNA-binding basic proteins (histone and protamine) and HIV-1 Rev with arginine (Arg)-rich clusters on the activity of casein kinase II (CK-II) were investigated in vitro . It was found that recombinant Rev (rRev) and the synthetic oligo-fragments corresponding to the amino acid sequences of its Arg-rich cluster stimulate CK-II activity in a dose-dependent manner . The activated CK-II phosphorylates several cellular and viral proteins in HIV-1 infected human MOLT-4 cells, and also phosphorylates HIV-1 structural proteins, including recombinant reverse transcriptase (rRT) . These phosphorylations are selectively inhibited by CK-II inhibitors, such as quercetin, oGA (a glycyrrhetinic acid derivative) and NCS-chrom (an enediyne containing antibiotic) . The data presented here suggest that HIV-1 Rev acts as an effective potent activator of CK-II, which may be a cellular mediator promoting HIV-1 replication in virus-infected cells. Eur J Biochem, 1998 Apr 15, 253(2), 406 - 12 Studies on the conformational changes in the bacterial cell wall biosynthetic enzyme UDP-N-acetylglucosamine enolpyruvyltransferase (MurA); Schonbrunn E et al.; The enzyme UDP-N-acetylglucosamine (UDP-GlcNAc) enolpyruvyltransferase (MurA), the target of the antibiotic fosfomycin, was investigated by small-angle X-ray scattering (SAXS) and fluorescence spectroscopy to detect conformational changes that had been proposed on the basis of the crystal structure of unliganded and liganded MurA . The SAXS data indicate that binding of UDP-GlcNAc to free enzyme results in substantial conformational changes, which can be interpreted as the transition from an open to a closed form . Fosfomycin did not affect the structure of free enzyme or sugar-nucleotide-bound MurA . Phosphoenolpyruvate (pyruvate-P) appeared to induce a structural change upon addition to free enzyme, which differed from that observed upon binding of UDP-GlcNAc . Fluorescence experiments were performed using the hydrophobic fluorescence probe 8-anilino-1-naphthalene sulfonate (ANS) . The fluorescence quenching of MurA/ANS solutions upon addition of UDP-GlcNAc or pyruvate-P was concentration dependent in a saturating manner, yielding apparent dissociation constants of K(d(UDP-GlCNAc)) = 59 microM and K(d(pyruvate-P)) = 240 microM . The results suggest that binding of substrates does not exclusively follow an ordered mechanism with UDP-GlcNAc binding first, although binding of UDP-GlcNAc to free enzyme is preferred and possibly influenced by pyruvate-P . The reaction thus appears to follow an induced-fit mechanism, in which the binding site for fosfomycin, and presumably also for pyruvate-P, is created by the interaction of free enzyme with the sugar nucleotide . The methods described here provide a tool for the characterization of site-directed mutants of MurA and the interaction of this enzyme with potential inhibitors. J Infect Dis, 1998 Jul, 178(1), 278 - 81 A guinea pig model for Q fever endocarditis; La Scola B et al.; A new model of experimental endocarditis, using electrocoagulation of native aortic valves, was used for the study of Q fever endocarditis . In the 20 guinea pigs electrocoagulated and inoculated with Coxiella burnetii Nine Mile phase I strain, 10 presented with infective endocarditis . Of these, 7 died spontaneously . All guinea pigs with endocarditis presented with blood cultures positive for C . burnetii, and C . burnetii antigen was found in their cardiac valves . Positive blood cultures or valvular immunopositive cells were not identified in either nonelectrocoagulated or noninoculated controls . This experimental model demonstrates that Q fever in an animal with previously damaged valves results in endocarditis . It could provide a new tool for the investigation of pathophysiology and antibiotic therapy for Q fever endocarditis. Br J Cancer, 1998 May, 77(10), 1689 - 95 Treatment-induced mucositis: an old problem with new remedies; Symonds RP; Mucositis may be a painful, debilitating, dose-limiting side-effect of both chemotherapy and radiotherapy for which there is no widely accepted prophylaxis or effective treatment . The basis of management is pain relief, prevention of dehydration and adequate nutrition . When tested vigorously, most antiseptic mouthwashes and anti-ulcer agents are ineffective . Simple mechanical cleansing by saline is the most effective traditional measure . A variety of new agents are effective . Granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) act outwith the haemopoeitic system and can reduce mucositis, but the best schedule, dosage and method of administration is not known or which is the best growth factor to prevent this side-effect . A placebo-controlled randomized trial of antibiotic pastilles has shown a significant reduction in mucositis and weight loss during radiotherapy for head and neck cancer . Another method to reduce radiation effects in normal tissue is to stimulate cells to divide before radiotherapy by silver nitrate or interleukin 1 . These methods may be particularly effective when given along with hyperfractionated radiation treatment such as CHART. Food Chem Toxicol, 1998 Apr, 36(4), 347 - 63 Review of the biological properties and toxicity of bee propolis (propolis); Burdock GA; Propolis is a multifunctional material used by bees in the construction and maintenance of their hives . Use of propolis by humans has a long history, predated only by the discovery of honey . Use of products containing propolis have resulted in extensive dermal contact and it is now increasingly being used a dietary supplement . Unlike many 'natural' remedies, there is a substantive database on the biological activity and toxicity of propolis indicating it may have many antibiotic, antifungal, antiviral and antitumour properties, among other attributes . Although reports of allergic reactions are not uncommon, propolis is relatively non-toxic, with a no-effect level (NOEL) in a 90-mouse study of 1400 mg/kg body weight/day. Tierarztl Prax Ausg G Grosstiere Nutztiere, 1998 May, 26(3), 110 - 8 {Experiences with a theloresectoscope compared with conventional teat endoscopy in diagnosis and therapy of covered teat lesions}; Seeh C et al.; In 30 dairy-cows, suffering from a covered teat lesion near the papillar duct and, as a result, from milk flow hindrance, two different methods of minimal invasive endoscopy for diagnosis and therapy were performed . In 15 patients (group I) the endoscope was inserted through the papillar duct and additionally through an artificial approach in the teat wall . Avulsions of mucosa could be visualized and resected with special instruments . In further 15 patients (group II) a new Theloresectoscope (teat-endoscope, combined with integrated radiosurgery-unit) was used for performance of endoscopy via papillar duct and lateral endoscopy . Mucosal avulsions were removed under visualization by means of radiosurgery without inserting an additional instrument through the papillar duct . Afterwards, after application of antibiotic drugs intramammarily, a natural teat canal insert (NIT) was administered in the papillar ducts of the 30 treated teats for seven days to keep the teat canal calm and wide . After three days the NIT was replaced and antibiosis refreshed . Eight days after endoscopy the temporary cessation of milking was canceled and the quarters were milked by machine . In two probands out of group I and three cows out of group II six weeks after first intervention lateral endoscopy was performed again for documentation of the healing process . In all 30 cases six weeks after resection of mucosal avulsions inquiries about the milking-quality were made by phoning the owners of patients . In 29 cows, still existing on the farms after six weeks, the milking comfort was considered as being good or, in few cases, satisfactory by the owners . Somatic cell count showed good results, though eight probands in group I and nine cows in group II presented positive results in the California-Mastitis-Test . Comparing the two different endoscopic techniques used in this study, both methods appeared of same value concerning diagnosis of aberrations in bovine teat by means of endoscopy via teat canal . Differences were found in handling of instruments performing endoscopy with lateral, artificial approach: the novel Theloresectoscope is by far more useful in endoscopic surgery, because the surgical intervention can be performed by a single person, whereas using the conventional instruments in most cases a second person as an assistant for operation is required. Arch Intern Med, 1998 Jun 22, 158(12), 1350 - 6 Safely increasing the proportion of patients with community-acquired pneumonia treated as outpatients: an interventional trial; Atlas SJ et al.; BACKGROUND: Patients with community-acquired pneumonia who are at low risk for short-term mortality can be identified using a validated prediction rule, the Pneumonia Severity Index . Such patients should be candidates for outpatient treatment, yet many are hospitalized . OBJECTIVE: To assess a program to safely increase the proportion of low-risk patients with pneumonia treated at home . METHODS: The intervention provided physicians with the Pneumonia Severity Index score and corresponding mortality risk for eligible patients and offered enhanced visiting nurse services and the antibiotic clarithromycin . Prospectively enrolled, consecutive low-risk patients with pneumonia presenting to an emergency department during the intervention period (n = 166) were compared with consecutive retrospective controls (n = 147) identified during the prior year . A second group of 208 patients from the study hospital who participated in the Pneumonia Patient Outcomes Research Team cohort study served as controls for patient-reported measures of recovery . Results: There were no significant baseline differences between patients in the intervention and control groups . The percentage initially treated as outpatients increased from 42% in the control period to 57% in the intervention period (36% relative increase; 95% confidence interval, 8%-72%; P = .01) . However, more outpatients during the intervention period were subsequently admitted to the study hospital (9% vs 0%) . When any admission to the study hospital within 4 weeks of presentation was considered, there was a trend toward more patients receiving all their care as outpatients in the intervention group (42% vs 52%; 25% relative increase; 95% confidence interval -2% to 59%; P = .07) . No patient in the intervention group died in the 4-week follow-up period . Symptom resolution and functional status were not diminished . Satisfaction with overall care was similar, but patients treated in the outpatient setting during the intervention were less frequently satisfied with the initial treatment location than comparable control patients (71% vs 90%; P = .04) . CONCLUSIONS: Use of a risk-based algorithm coupled with enhanced outpatient services effectively identified low-risk patients with community-acquired pneumonia in the emergency department and safely increased the proportion initially treated as outpatients . Outpatients in the intervention group were more likely to be subsequently admitted than were controls, lessening the net impact of the intervention. Antibiot Khimioter, 1998, 43(6), 16 - 9 {Clinical and laboratory study of cefodizime (Modivid) in prophylaxis and treatment of surgical patients}; Khlebnikov EP et al.; The results of the clinical and laboratory study of the efficacy of the prophylactic and therapeutic use of cefodizime (modivid) in patients with chronic calculous cholecystitis and burns are presented . Expediency of the preoperative prophylactic use of the drug and its significance in the treatment of infectious complications of the burn disease were verified . The immunological investigation gave evidence of an increase of the phagocytosis functional activity when cefodizime (modivid) was used prophylactically in cholecystectomy. J Pharm Pharmacol, 1998 May, 50(5), 515 - 9 Metabolism of roxithromycin in the isolated perfused rat liver; Jarukamjorn K et al.; Roxithromycin is a macrolide antibiotic with high clinical potency . N-Demethylation is considered to be one of the main pathways of roxithromycin metabolism in rats . We have studied the hepatic metabolism of roxithromycin in the isolated perfused rat liver . After addition of roxithromycin (30 microM) to the perfusion medium the parent compound and one major metabolite were detected in bile by high-performance liquid chromatography . The metabolite was identified as monodesmethylated roxithromycin by mass spectrometric analysis . Onset of biliary excretion of native roxithromycin was fast, reaching a maximum (130.52 +/- 43.88 pmol g(-1) min(-1)) after only 10 min, whereas excretion of the metabolite was delayed (maximum 75.83 +/- 11.92 pmol g(-1) min(-1) at 30 min) . The cumulative excretion of roxithromycin and its metabolite into bile during the 60 min of application amounted to only 1.09 +/- 0.30 and 0.64 +/- 0.22% of the roxithromycin cleared from the perfusate during the same time . The liver content was 0.48 micromol (g liver)(-1), indicating high retention within the organ . No release of the metabolite into the perfusate was detected . In conclusion, this study has demonstrated the importance of phase-I metabolism for the biliary excretion of roxithromycin in rat liver . These findings might be predictive of roxithromycin biotransformation and biliary excretion in man. J Clin Pediatr Dent, 1998 Winter, 22(2), 159 - 65 Oral manifestations of Ellis-van Creveld syndrome: report of two siblings with unusual dental anomalies; Hattab FN et al.; Ellis-van Creveld syndrome (EvC), also called chondroectodermal dysplasia, is a rare occurrence inherited as an autosomal recessive disease . Despite the fact that oral manifestations play an important role in the diagnosis criteria for EvC, few detailed reports have been published in the dental literature . This articles presents two siblings with EvC, a boy aged 9 years and a girl aged 7 1/2 years, a product of unaffected first cousin parents . The patients manifests: chondrodysplasia of tubular bones resulting in disproportionate dwarfism, polydactyly and syndactyly of hands and feet, severe dystrophic nails, multiple broad labial frenula with abnormal attachments, congenital missing incisors, anomalous teeth, bilateral partial clefts of the alveolar bone, and malocclusion . Other features noted in either cases are: congenital heart defect, median notch of the upper lip, shovel-shaped incisors and taurodontism . Of the unusual dental findings observed in our patients are talon cusp, reduced crown size, supernumerary tooth, and early eruption of teeth . Because half of the cases with EvC have cardiac malformation, dental treatment must be performed under prophylactic antibiotic coverage . Dentists play an important role in early diagnosis and control of dental problem of this condition. Curr Opin Neurol, 1998 Jun, 11(3), 253 - 8 Lyme neuroborreliosis; Haass A; A broad variability in the clinical manifestations is observed in the European and North American borrelioses . This is dependent on bacterial strain differences in virulence and organotropism, and on different immune responses to Borrelia burgdorferi of the host in these areas . Experimental neuroborreliosis has given insights into mediators and molecular mechanisms of inflammation induced by B . burgdorferi . Histopathological investigations have described the different patterns of injury in the peripheral and central nervous systems . The classic symptoms of neuroborreliosis have been supplemented by new clinical syndromes and neuropsychological investigations . In clinical trials, the efficacy and cost effectiveness of recommended oral and intravenous antibiotic therapies have been compared in early Lyme disease, arthritis and acute disseminated Lyme disease. J Refract Surg, 1998 May-Jun, 14(3), 357 - 60 Mycobacterium chelonae keratitis following laser in situ keratomileusis; Reviglio V et al.; Corneal infection after laser in situ keratomileusis (LASIK) is rare . However, surgical trauma or breakdown of epithelium increases the risk of surface infection . We present the case of a 45 year old woman who developed keratitis due to Mycobacterium chelonae 1 month after LASIK with the Mini-Laser Sight 2000 excimer laser . After an initial improvement following antibiotic therapy the infection progressed until it was necessary to perform penetrating keratoplasty, with a successful result. Pediatr Surg Int, 1998 Jul, 13(5-6), 435 - 6 An unusual domestic accident: a penetrating abdominal wound with intestinal evisceration in a child; Sanchez Jarquin MR et al.; We report a penetrating abdominal injury due to a piece of glass, a very unusual domestic accident, in a 2-year-old boy who was admitted to the emergency department with an evisceration through the umbilicus . His mother reported that she was asleep when the boy came to her room, and did not know how it had happened . We primarily suspected child abuse, but the presence of a piece of glass in the boy's heel led us to think of a domestic accident . He had poured himself a glass of water, and then fell on the glass . We could not find a similar case in the literature on domestic accidents. Perfusion, 1998 May, 13(3), 176 - 80 The effects of haemofiltration on cefazolin levels during cardiopulmonary bypass; O'Rullian JJ et al.; Ultrafiltration has been shown to affect cardiac drug concentrations during cardiopulmonary bypass (CPB), based on their respective pharmacological properties . In an attempt to understand the aetiology of sternal wound infections, a study was performed to eliminate the use of ultrafiltration as a possible cause . We compared cefazolin levels at three time intervals during the course of routine CPB with ultrafiltration to those levels in a control group in which ultrafiltration was not used . Our results indicate that there is little difference in the rate of decay of antibiotic levels with or without the use of a haemoconcentrator . This implies that ultrafiltration procedures do not put the patient at any increased risk for infection and that additional measures beyond that which we would normally use at our institution need not be taken. Wiad Lek, 1995 Jan-Jun, 48(1-12), 154 - 6 {A case of Lyell's syndrome caused by carbamazepine}; Urbanowski S et al.; A case is described of Lyell syndrome in a female patient with schizoaffective psychosis which developed several days after addition of carbamazepine to the psychotropic treatment used . After withdrawal of the drug and three weeks of treatment with prednisone in dose 60 mg daily, antibiotic therapy and intensive dermatological-nursing care, full remission of skin lesions and oral mucosa lesions was obtained. Dtsch Med Wochenschr, 1998 May 22, 123(21), 663 - 6 {Sicca symptoms and hearing loss in Behçet's syndrome}; Eichhorn A et al.; HISTORY AND ADMISSION FINDINGS: A 39-year-old woman sustained an irreversible hearing loss in the left ear, followed 6 months later by a left facial paresis . Oral aphthous ulcers frequently recurred with fever of up to 39.5 degrees C . Her general condition was noticeably poor . INVESTIGATIONS: An inflammatory disease was suggested by an increased erythrocyte sedimentation rate (70/100 mm), leucocytosis (18,500/microliter), decreased haemoglobin (10.2 g/l) and leftward shift of the neutrophil granulocytes . Diagnostic tests for an infectious, autoimmune or haemato-oncological disease were negative . TREATMENT AND COURSE: Antibiotic and antimycotic treatment failed to bring lasting improvement . Thrombophlebitis and venous thrombosis developed in both upper limbs and acute episcleritis (scleritis) in the left eye . Behcet's disease with oral, ocular, neurological, cutaneous and vascular involvement was diagnosed and treated with chlorambucil (variable dosage around 7 mg/d orally), with rapid regression of symptoms . 3 months later joint pains set in, and another 18 months later she developed sicca symptoms (xerostomia with dry eyes): both responded to symptomatic treatment . CONCLUSION: The combination of loss of hearing, sicca syndrome and Behcet's syndrome has not been previously reported. J Acoust Soc Am, 1998 Jun, 103(6), 3567 - 80 Auditory perception following hair cell regeneration in European starling (Sturnus vulgaris): frequency and temporal resolution; Marean GC et al.; Behavioral detection thresholds, auditory filter widths, and temporal modulation transfer functions were obtained from four starlings before, during and after 11 days of subcutaneous injections of kanamycin, an aminoglycoside antibiotic . Birds were operantly conditioned to respond to pure tones and amplitude modulated noises ranging in frequency from 0.25 to 7 kHz using adaptive staircase procedures and were tested daily for 92 days after the first injection of aminoglycoside . All birds had threshold shifts of at least -60 dB at frequencies above 4 kHz . Lower frequencies were affected in some birds, although none of the birds had hearing loss below 3 kHz . All four birds had wider auditory filters at 5 kHz immediately after the aminoglycoside series . Any changes in frequency resolution at frequencies below 5 kHz were slight, transitory, and rarely observed . Two of the four birds had permanently wider auditory filters at 5 kHz . Temporal modulation transfer functions were briefly affected in two birds during the time of greatest threshold shift . Recovery of detection thresholds began soon after the injections ceased and continued for approximately 60 days . Recovery in frequency resolution lagged behind auditory threshold by about 10 days . Normal temporal resolution was observed in the context of impaired intensity and frequency resolution . Changes in auditory threshold and frequency resolution were closely associated for all birds at 5 kHz, but were correlated with statistical significance in only two birds . Scanning electron microscopy was performed on all four birds after 90 days of recovery and confirmed that the extent of initial damage was consistent with the pattern of observed hearing loss. Pediatr Cardiol, 1998 Jul-Aug, 19(4), 282 - 8 The use of valved conduits in pediatric cardiac surgery; Stark J; Extracardiac valved conduits were introduced in 1966 . Currently, both aortic and pulmonary homografts, preserved in antibiotic/nutrient solution or cryopreserved, are used . Conduits are implanted between the right ventricle and pulmonary artery, left ventricle and pulmonary artery, right atrium and right ventricle, and left atrium to left ventricle . Several factors can influence longevity of valved conduits: young age at implantation, small size of homograft, and immunological response . In the recent study from our department, we evaluated 405 homografts implanted between 1971 and 1993 in patients who survived 90 days after surgery . Freedom from conduit replacement at 5 and 15 years was 84% and 31% (95% confidence limits: 80-88% and 19-43%), respectively . In multivariate analysis, there were only two predictors of conduit longevity: (1) conduits used at reoperation lasted less well than those used at original operation; and (2) conduits used earlier in the series lasted longer . Conduits may have to be replaced because of obstruction, conduit valve regurgitation, aneurysm/pseudoaneurysm, and endocarditis . Obstructed conduits are either replaced or outflow tract patch is used after removal of the conduit with or without pulmonary valve implantation . Current mortality of conduit insertion is low (5-6%) . The risk of conduit replacement has also decreased in recent years to 2-3.5% Diagn Microbiol Infect Dis, 1998 Jun, 31(2), 411 - 6 Expanding the options for risk-based therapy in febrile neutropenia; Rolston KV; Fever in neutropenic cancer patients is often due to the development of an infection . The standard management of febrile neutropenic patients involves the administration of empiric, hospital-based, parenteral antibiotic therapy . Although this treatment strategy has evolved from experience in high-risk patients with hematological malignancies, in whom bacterial infection can result in substantial morbidity and mortality, it has been adopted for all patients with febrile neutropenia, largely because of the inability of clinicians to reliably distinguish between patients who are at high risk for developing such morbidity/mortality and those who are not . The development of risk-assessment models has facilitated the recognition of high-, moderate-, and low-risk subgroups among febrile neutropenic patients and allows the administration of outpatient antibiotic therapy to the moderate- and low-risk groups, with the same degree of efficacy and safety as hospital-based therapy . Monotherapy with the carbapenems (imipenem/cilastatin and meropenem), with their broad spectrum of activity and established efficacy in high-risk patients, represents realistic options for risk-based treatment of febrile neutropenic patients within and outside the hospital setting. Biochemistry, 1998 May 26, 37(21), 7716 - 24 rRNA chemical groups required for aminoglycoside binding; Blanchard SC et al.; Through an affinity chromatography based modification-interference assay, we have identified chemical groups within Escherichia coli 16S ribosomal RNA sequence that are required for binding the aminoglycoside antibiotic paromomycin . Paromomycin was covalently linked to solid support via a nine atom spacer from the 6"'-amine of ring IV, and chemical modifications to an A-site oligonucleotide that disrupted binding were identified . Positions in the RNA oligonucleotide that correspond to G1405(N7), G1491(N7), G1494(N7), A1408(N7), A1493(N7), A1408(N1), A1492(N1), and A1493(N1), as well as the pro-R phosphate oxygens of A1492 and A1493 in 16S rRNA are chemical groups that are essential for a high-affinity RNA-paromomycin interaction . These data are consistent with genetic, biochemical, and structural studies related to neomycin-class antibiotics and provide additional information for establishing an exact model for their interaction with the ribosome. J Med Chem, 1998 May 21, 41(11), 1883 - 93 Synthesis and structure-activity relationships of bafilomycin A1 derivatives as inhibitors of vacuolar H+-ATPase; Gagliardi S et al.; The macrolide antibiotic bafilomycin A1 is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases) . With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of bafilomycin A1 were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG) . Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A1 . The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues. Blood, 1998 May 15, 91(10), 3607 - 15 A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031); Godwin JE et al.; Older age is a poor prognosis factor in acute myeloid leukemia (AML) . This double-blind trial was designed to test the hypothesis that granulocyte colony-stimulating factor (G-CSF) used as supportive care could improve the treatment of elderly AML patients . Two hundred thirty-four patients 55 or more years of age with a morphologic diagnosis of de novo or secondary AML, French-American-British (FAB) M0-M7, excluding M3, were randomly assigned to a standard induction regimen (daunorubicin at 45 mg/m2 intravenously {IV} on days 1 through 3 and Ara-C at 200 mg/m2 IV continuous infusion on days 1 through 7) plus either placebo or G-CSF (400 microg/m2 IV over 30 minutes once daily) . Results are reported here for 211 centrally confirmed cases of non-M3 AML . The two groups were well balanced in demographic, clinical, and hematological parameters, with median ages of 68 years in the G-CSF and 67 years in the placebo groups . The complete response (CR) rate was not significantly better in the G-CSF group: 50% in the placebo and 41% in the G-CSF group (one-tailed P = .89) . Median overall survival was also similar, 9 months (95% confidence interval {CI}, 7 to 10 months) in the placebo and 6 months (95% CI, 3 to 8 months) in the G-CSF arms (P = .71) . We found a significant 15% reduction in the time to neutrophil recovery in the G-CSF group (P = .014) . G-CSF had no impact on recovery from thrombocytopenia (P = .80) or duration of first hospitalization (P = .27) . When infection complications were evaluated, G-CSF had a beneficial effect on the duration but not on incidence of infection . G-CSF patients had fewer days with fever and shorter duration of antibiotic use . However, there was no difference in the frequency of total documented infections or in the number of fatal infections (19% placebo v 20% G-CSF) . In this study of elderly AML patients, G-CSF improved clinical parameters of duration of neutropenia and antibiotic use, but did not change CR rate or survival or shorten hospitalization. Cutis, 1998 Apr, 61(4), 215 - 6 Solid facial edema as a complication of acne vulgaris; Mahajan PM; A case of persistent solid facial edema in an 18-year-old man from India with papulopustular acne vulgaris is reported . Acne lesions responded well to systemic antibiotic and topical antiacne treatment, whereas there was a moderate reduction in the facial edema with a course of systemic steroid therapy. J Med Chem, 1998 Jun 18, 41(13), 2319 - 32 Comprehensive study on structure-activity relationships of rifamycins: discussion of molecular and crystal structure and spectroscopic and thermochemical properties of rifamycin O; Bacchi A et al.; The mechanism of action of rifamycins against bacterial DNA-dependent RNA polymerase has been explained on the basis of the spatial arrangement of four oxygens which can form hydrogen bonds with the enzyme . Structural descriptors are derived from X-ray diffraction crystal structures of 25 active and nonactive rifamycins . Principal component analysis is used to find the combination of structural parameters which better discriminate between active and nonactive rifamycins . Two possible mechanisms of molecular rearrangement are described which can convert nonactive into active conformations . The energy involved for conformational rearrangements is studied by molecular modeling techniques . Methyl C34 is found to play a key role for determining the geometry of the pharmacophore . Rifamycin O, reported to be active, is obtained by oxidation of rifamycin B and is studied by X-ray single-crystal diffractometry, by solution IR and NMR spectroscopy, and by thermal analysis . Surprisingly the oxidation process is totally stereospecific, and an explanation is given based on solution spectroscopic evidence . The conformation found in the solid state is typical of nonactive compounds, and molecular mechanics calculations show that a molecular rearrangement to the active conformation would require about 15 kcal/mol . Thermal analysis confirms that rifamycin O has a sterically constrained conformation . Therefore, it is likely that the antibiotic activity of rifamycin O is due either to chemical modification prior to reaching the enzyme or to conformational activation. Bone Marrow Transplant, 1998 May, 21(10), 1005 - 10 Early vs delayed administration of G-CSF following autologous peripheral blood stem cell transplantation; Colby C et al.; It is well established that recombinant human G-CSF accelerates neutrophil recovery following autologous peripheral blood stem cell transplantation (PBSCT) . However, the optimal timing of G-CSF following transplantation remains unknown . We have conducted a retrospective analysis of patients treated with either early, day +1 (n = 42) or delayed, day +4 (n = 39) administration of G-CSF following autologous PBSCT for a variety of hematologic malignancies and solid tumors . G-CSF was given at a dose of 5 microg/kg/day i.v . as a 2 h infusion beginning either day +1 or day +4 following PBSC infusion and continued until the total white blood count (WBC) was >10 x 10(9)/l . The numbers of transplanted CD34+ cells were similar in each group . Treatment with early administration of G-CSF resulted in a significantly shorter time to an absolute neutrophil count (ANC) of >0.5 x 10(9)/l (8.5 vs 10.0 days, P < 0.0003) and shorter length of hospitalization (16.3 vs 18.6 days, P < 0.0008), a trend towards a reduced incidence of infection (53 vs 72%) and a significant decrease in the duration of non-prophylactic antibiotic (NPA) therapy for neutropenic fever (4.0 vs 7.5 days, P < 0.009) compared to day +4 administration . Despite the additional cost of G-CSF, the reduction in the hospitalization and NPA therapy with early G-CSF administration resulted in 11% cost savings overall per transplant at our institution. J Am Coll Surg, 1998 Jun, 186(6), 654 - 8 Risk factors for early infection of central venous catheters in pediatric patients; Shaul DB et al.; BACKGROUND: In an effort to avoid infections that can lead to the premature removal of indwelling central venous catheters (CVCs), the surgical technique and host factors present in pediatric recipients of permanent CVCs were reviewed . STUDY DESIGN: All patients receiving CVCs over a 17-month period were identified . Those patients with fever and positive blood cultures drawn through the CVC within 45 days of line placement were labeled as having early infection . A case-control design was used to select two control patients for each infected patient . Charts from both the infection and control groups were reviewed for several factors present at the time of CVC placement, including fever, neutropenia (absolute neutrophil count {ANC} < 500 and ANC < 1,000), use of perioperative antibiotics, diagnosis, CVC site, and type of CVC . Chi-square test with Yates correction was used to compare the groups . Odds ratios (ORs) and 95% confidence intervals were derived . RESULTS: Among the 473 CVCs placed, early infections developed in 53 patients (12%) . The control group consisted of 106 patients . Neutropenia was present in 16 of 53 infected patients versus 8 of 106 controls (p = 0.004, OR = 5.30) . Perioperative antibiotics were given to 25 of 53 infected patients versus 72 of 106 controls (p = 0.02, OR = 0.42) . Fever was present in 12 of 53 infected patients versus 14 of 106 controls (p = 0.19, OR = 1.92) . Factors that were equally prevalent between the groups and that did not appear to influence the CVC infection rate included a diagnosis of malignancy, CVC type, and site of placement . Of the 53 infected catheters, 16 (30%) could not be cleared of infection and were removed . CONCLUSIONS: This study documents that neutropenia and failure to administer prophylactic antibiotics are risk factors for the development of early CVC infection in pediatric patients . To avoid early infection and possible premature CVC removal, we recommend that placement of permanent CVCs be postponed until the ANC is > 1,000 . Perioperative antibiotics should be given . A trend toward higher infection rates was seen in patients with preoperative fever. Oncogene, 1998 May, 16(20), 2639 - 45 Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol; Sharma SV et al.; Radicicol, a macrocyclic anti-fungal antibiotic, has the ability to suppress transformation by diverse oncogenes such as Src, Ras and Mos . Despite this useful property, the mechanism by which radicicol exerts its anti-transformation effects is currently unknown . To understand the transformation-suppressing effects of radicicol, a biotinylated derivative of radicicol was chemically synthesized and used as a probe in a Western-blot format to visualize cellular proteins that interact with radicicol . In transformed and untransformed mouse fibroblasts, the most prominent cellular protein that bound to radicicol had a molecular weight of approximately 90 kDa . Further analysis revealed that this protein was the mouse homologue of the 90 kDa heat shock protein (HSP90) . This was confirmed by demonstrating the ability of radicicol to specifically bind purified human HSP90 . Specificity of binding was demonstrated by the inhibition of binding of biotinylated radicicol by the native drug . Taken together with other studies the present observations suggest that the anti-transformation effects of radicicol may be mediated, at least in part, by the association of radicicol with HSP90 and the consequent dissociation of the Raf/HSP90 complex leading to the attenuation of the Ras/MAP kinase signal transduction pathway. Helicobacter, 1998 Jun, 3(2), 115 - 9 Optimal PPI-based triple therapy for the cure of Helicobacter pylori infection: a single center comparison of four 14-day schedules; Battaglia G et al.; BACKGROUND: Helicobacter pylori eradication is accomplished using a wide array of drugs combined in a multitude of dosage schedules . The aim of the present study was to define the best 14-day eradication schedule using a PPI plus either two antibiotics or one antibiotic and bismuth . MATERIAL AND METHODS: For this study, 367 subjects (198 males, 169 females, age 22-87 years) with document H . pylori infection of the stomach were recruited from out-patients of the Gastroenterology Department of the Venezia Hospital . In all patients, H . pylori infection was identified by histology and the CLO-test . Patients were treated as follows: 1) PPI (P) plus clarithromycin (C) 250 mg plus amoxicillin (A) 1000 mg bid (P + C + A); 2) P plus C plus bismuth subcitrate (B) 120 mg qid (P + C + B); 3) P plus C plus tinidazole (T) 500 mg bid (P + C + T); and 4) P plus A plus T bid (P + A + T) . After two months, an upper gastrointestinal endoscopy was repeated for end point histological evaluation and the CLO- test . Positivity of one of the two methods was considered sufficient to define H . pylori as "not eradicated" . Statistics: Chi-squared test and Fisher exact test . RESULTS: Thirty-three subjects dropped out (six due to adverse events) . P + C + B was proven significantly less effective than P + C + A, P + C + T and P + A + T, eradication rates being, respectively, 75.0%, 90.5%, 87.6%, 92.0%, (p = .005, per protocol analysis) . CONCLUSIONS: All PPI-based triple therapies tested in this study were effective in curing H . pylori infection; however, P + C + B resulted in rates too low (< 85%) to be recommended . P + C + A and P + A + T resulted in the high cure rates and thus may be considered the treatment of choice. Nat Biotechnol, 1996 Apr, 14(4), 499 - 503 Efficient control of gene expression by single step integration of the tetracycline system in transgenic mice; Schultze N et al.; Tetracycline-regulated gene expression in eukaryotic cell lines, plants, and transgenic mice has become a powerful tool for the analysis of eukaryotic gene expression and function . The system consists of two plasmids, one encoding the transactivator protein under control of a viral cytomegalovirus promoter, and the second being the tet-operator minimal promoter driving the gene of interest . Here we show that these control elements, when integrated in cis on a single plasmid, allow efficient and tight control of reporter gene expression in vitro and in vivo . Dependent on the route of administration of tetracycline, gene expression can be partially or fully repressed in transgenic mice, whereas removal of the antibiotic induces the reporter gene in various tissues to levels up to 800-fold more than the two-plasmid system . In addition, crossing and analysis of animals transgenic for the individual components of the system are unnecessary, and genetic segregation of the control elements during breeding is prevented. Nat Biotechnol, 1996 Apr, 14(4), 458 - 67 Directed evolution of a para-nitrobenzyl esterase for aqueous-organic solvents; Moore JC et al.; Through sequential generations of random mutagenesis and screening, we have directed the evolution of an esterase for deprotection of an antibiotic p-nitrobenzyl ester in aqueous-organic solvents . Because rapid screening directly on the desired antibiotic (loracarbef) nucleus p-nitrobenzyl ester was not feasible, the p-nitrophenyl ester was employed . Catalytic performance on the screening substrate was shown to reasonably mimic enzyme activity toward the desired ester . One p-nitrobenzyl esterase variant performs as well in 30% dimethylformamide as the wildtype enzyme in water, reflecting a 16-fold increase in esterase activity . Random pairwise gene recombination of two positive variants led to a further two-fold improvement in activity . Considering also the increased expression level achieved during these experiments, the net result of four sequential generations of random mutagenesis and the one recombination step is a 50-60-fold increase in total activity . Although the contributions of individual effective amino acid substitutions to enhanced activity are small (< 2-fold increases), the accumulation of multiple mutations by directed evolution allows significant improvement of the biocatalyst for reactions on substrates and under conditions not already optimized in nature . The positions of the effective amino acid substitutions have been identified in a pNB esterase structural model developed based on its homology to acetylcholinesterase and triacylglycerol lipase . None appear to interact directly with the antibiotic substrate, further underscoring the difficulty of predicting their effects in a 'rational' design effort. Int J Clin Pharmacol Ther, 1998 May, 36(5), 253 - 7 Pharmacokinetics of ampicillin/sulbactam in patients undergoing spinal microneurosurgical procedures; Warnke JP et al.; The fixed combination of ampicillin (2 g)/sulbactam (1 g) was administered as perioperative prophylaxis at induction of anesthesia in 20 patients undergoing spinal microneurosurgery . It was noteworthy that after the short infusion ampicillin and sulbactam penetrated rapidly from blood into the different tissues affected by the surgical procedures . The following mean concentrations were measured in tissues: muscle 32.3+/-6.5 mg/kg ampicillin and 18.6+/-2.9 mg/kg sulbactam (11.1 min), ligament 39.5+/-11.1 mg/kg ampicillin and 25+/-6.5 mg/kg sulbactam (13.8 min), bone 12+/-3.6 mg/kg ampicillin and 7+/-0.8 mg/kg sulbactam (20.6 min), disk 10.2+/-3.3 mg/kg ampicillin and 7.3+/-1.8 mg/kg sulbactam (44.2 min) . The mean time of sampling is given in brackets . For a period of at least 2 h the levels of both drugs measured in serum and in the different tissues were above the MICs for bacteria involved in postoperative wound infections . The administration of ampicillin/sulbactam apparently achieved sufficiently, high antibiotic concentrations, even in bradytrophic tissues such as ligament, bone, and disk, and seemed to meet the pharmacological criteria for perioperative prophylaxis in spinal microneurosurgery. Andrologia, 1998, 30 Suppl 1, 99 - 101 Influence of bacteria and leukocytes on the outcome of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI); Michelmann HW; The influence of bacteria and/or leukocytes on the outcome of IVF or ICSI is influenced by three factors which have little in common with in vivo conditions: 1) The process of ejaculate preparation (swim-up, Percoll) with antibiotic buffered media; 2) The small amount of inseminated spermatozoa (100,000 per culture); 3) The short cultivation time . From the very beginning, these factors limit whatever the influence of bacteria and leukocytes on fertilization and embryonic development in vivo may be . Despite the contradictory results published so far, the influence of bacteria and/or leukocytes on the functional integrity of spermatozoa during the process of IVF or ICSI can be ignored . Furthermore, during IVF or ICSI the spermatozoon does not act as a vector for the transportation of bacteria into the ooplasm. J Urol, 1998 Jul, 160(1), 210 - 3 Angiogenesis inhibitor TNP-470 inhibits growth and metastasis of a hormone-independent rat prostatic carcinoma cell line; Miki T et al.; PURPOSE: Inhibitory effects of TNP-470, a synthetic analogue of the antibiotic fumagillin secreted by Aspergillus fumigatus, were studied with respect to growth and lung metastasis of the hormone-independent rat prostatic carcinoma cell line AT6.3 . MATERIALS AND METHODS: Rat prostatic carcinoma AT6.3 cells were implanted in nude mice subcutaneously . Antimetastatic and growth-inhibitory effects of TNP-470 in vivo were examined 3 weeks after inoculation of AT6.3 cells . Direct growth-inhibitory effect was examined by MTT assay in vitro . RESULTS: TNP-470 inhibited the growth of AT6.3 cells in vitro . Subcutaneously injected TNP-470 markedly reduced numbers and individual size of lung metastases from AT6.3 cells inoculated percutaneously or intravenously into male BALB/c-nu/nu mice . CONCLUSION: This agent, which acts as an angiogenesis inhibitor, may prove to be clinically useful in preventing metastasis of hormone-independent prostatic cancer. J Altern Complement Med, 1998 Summer, 4(2), 173 - 83 Qigong Yangsheng as a complementary therapy in the management of asthma: a single-case appraisal; Reuther I et al.; OBJECTIVES: Qigong Yangsheng, the health-promoting method of traditional Chinese medicine that combines movement, mental exercise, and breathing technique, is used in China for the therapy of bronchial asthma, and for some time now has been enjoying an ever-widening acceptance in the Western world as well . This pilot study investigates if Qigong Yangsheng could be used as a complementary therapeutic measure to treat asthma patients in a Western industrialized country . DESIGN: Thirty asthma patients, with varying degrees of illness severity, were taught Qigong Yangsheng under medical supervision . They were asked to exercise independently, if possible, on a daily basis and to keep a diary of their symptoms for half a year including peak-flow measurements three times daily, use of medication, frequency and length of exercise as well as five asthma-relevant symptoms (sleeping through the night, coughing, expectoration, dyspnea, and general well-being) . The concept of this study was based on a single-case research design series with baseline, one teaching phase, a phase of self-practice and a refresher teaching course . A 4-week follow-up period was carried out in the same season as the original baseline phase 52 weeks later . RESULTS: An improvement was indicated if subjects showed a decrease of at least 10 percent in peak-flow variability between the 1st and the 52nd week . This occurred more frequently in the group of the exercisers (n = 17) than in the group of nonexercisers (n = 13) (p < 0.01 chi-square with Yates correction) . When comparing the study year with the year before the study, there was improvement also in reduced hospitalization rate, less sickness leave, reduced antibiotic use and fewer emergency consultations resulting in reduced treatment costs . CONCLUSION: Qigong Yangsheng is recommended for asthma patients with professional supervision . An improvement in airway capability and a decrease in illness severity can be achieved by regular self-conducted Qigong exercises. BMJ, 1998 May 30, 316(7145), 1648 - 54 Varying efficacy of Helicobacter pylori eradication regimens: cost effectiveness study using a decision analysis model; Duggan AE et al.; OBJECTIVE: To determine how small differences in the efficacy and cost of two antibiotic regimens to eradicate Helicobacter pylori can affect the overall cost effectiveness of H pylori eradication in duodenal ulcer disease . DESIGN: A decision analysis to examine the cost effectiveness of eight H pylori eradication strategies for duodenal ulcer disease with and without 13C-urea breath testing to confirm eradication . MAIN OUTCOME MEASURES: Cumulative direct treatment costs per 100 patients with duodenal ulcer disease who were positive for H pylori . RESULTS: In model 1 the strategy of omeprazole, clarithromycin, and metronidazole alone was the most cost effective of the four strategies assessed . The addition of the 13C-urea breath test and a second course of omeprazole, clarithromycin, and metronidazole achieved the highest eradication rate (97%) but was the most expensive (62.63 pounds per patient) . The cost of each additional effective eradication was 589.00 pounds (incremental cost per case) when compared with the cost of treating once only with omeprazole, clarithromycin, and metronidazole; equivalent to the cost of a patient receiving ranitidine for duodenal ulcer relapse for more than 15 years . Eradication strategies of omeprazole, amoxycillin, and metronidazole were less cost effective than omeprazole, clarithromycin, and metronidazole alone . In model 2 the addition of the 13C-urea breath test after treatment, and maintenance treatment, increased the cost of all the strategies and reduced the cost advantage of omeprazole, clarithromycin, and metronidazole alone . CONCLUSION: Small differences in efficacy can influence the comparative cost effectiveness of strategies for eradicating H pylori . Of the strategies tested the most cost effective (omeprazole, clarithromycin, and metronidazole alone) was neither the least expensive (omeprazole, amoxycillin, and metronidazole alone) nor the most effective (omeprazole, clarithromycin, and metronidazole with further treatment for patients found positive for H pylori on 13C-urea breath testing) . Cost effectiveness should be an important part of choosing an eradication strategy for H pylori. Am J Gastroenterol, 1998 May, 93(5), 836 - 7 Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone; Longo F et al.; An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone . Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia . These responded to systemic steroids and immunoglobulins . Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics. Anal Chem, 1998 Jun 1, 70(11), 2415 - 20 Assay for cephapirin and ampicillin in raw milk by high-performance liquid chromatography--integrated pulsed amperometric detection; Dasenbrock CO et al.; The FDA has issued guidelines governing the use of antibiotics in cattle and routinely tests for the presence of antibiotics in milk . Unfortunately, these compounds are often difficult to detect by direct methods because they often lack a chromophore or fluorophore . Integrated pulsed amperometric detection (IPAD) following reversed-phase liquid chromatography is well-suited for this analysis because it is selective, sensitive, and direct; i.e., derivatization is not required . This work involves the development of a simple, rapid assay for the determination of beta-lactam antibiotic residues in milk using HPLC-IPAD, specifically, ampicillin and cephapirin . Since the analyst studied here are detectable by UV detection, a comparison between IPAD and UV detection will be made . Sample preparation schemes that involve the extraction of antibiotics of interest from the milk matrix and subsequent cleanup are an important aspect of this project . These procedures will be discussed in detail . In addition, analytical figures of merit and IPAD wave form optimization will be addressed. Clin Infect Dis, 1998 Apr, 26(4), 806 - 10 Effect of prophylaxis on the clinical manifestations of AIDS-related opportunistic infections; Sepkowitz KA; Administration of targeted prophylaxis for AIDS-related opportunistic infections has contributed significantly to the recent decrease in mortality among patients with AIDS in the United States . Most reported prophylaxis trials have focused on determining (a) the percentage of cases prevented and (b) the effect of widespread antibiotic use on drug susceptibility . A third phenomenon that is seldom reported on is the attenuating effect of failed prophylaxis on the clinical presentation of opportunistic infections (OIs) . With the increasingly widespread use of prophylaxis for OIs, more atypical "breakthrough" cases of opportunistic infections will be seen . Reports of clinical changes are reviewed below . Investigators should routinely report the clinical manifestations of breakthrough cases in all articles pertaining to prophylaxis for opportunistic infections in patients with AIDS. Ned Tijdschr Geneeskd, 1997 Jul 19, 141(29), 1424 - 7 {Side effects of minocycline in the treatment of acne vulgaris}; Hoefnagel JJ et al.; Minocycline is the most commonly used systemic antibiotic in the long-term treatment (weeks to months) of severe acne vulgaris . Currently much attention is being paid in the Dutch and international literature to the safety of minocycline, after several reports on serious adverse events . The clinical efficacy of minocycline in the treatment of acne vulgaris is better than that of tetracycline and equal to that of doxycycline . The serious adverse events of minocycline therapy described consist of hyperpigmentation of various tissues, autoimmune disorders (systemic lupus erythematosus, autoimmune hepatitis) and serious hypersensitivity reactions (hypersensitivity syndrome reaction, pneumonitis and eosinophilia, and serum sickness-like syndrome) . In relation to the number of prescriptions, the number of serious adverse events of minocycline described is small . However, it is very important that prescribing doctors should be aware of the possibility of these adverse events occurring during long-term minocycline therapy and able to recognize the characteristic symptoms at an early stage. Jpn J Pharmacol, 1998 Apr, 76(4), 405 - 13 Effects of in vitro and in vivo exposure to doxorubicin (adriamycin) on caffeine-induced Ca2+ release from sarcoplasmic reticulum and contractile protein function in 'chemically-skinned' rabbit ventricular trabeculae; Takahashi S et al.; Doxorubicin is an anthracycline antibiotic that is used widely as a chemotherapeutic agent . However, the usefulness of this agent is limited due to its cardiotoxic effects . The mechanisms associated with this cardiotoxicity remain essentially unknown, despite numerous studies describing a range of structural and functional abnormalities . The purpose of the present study was to determine the in vivo and in vitro effects of doxorubicin exposure on sarcoplasmic reticulum (SR) Ca2+-content and contractile protein function . The Ca2+-content of SR is shown to have a biphasic response to in vivo and in vitro doxorubicin exposure that is time- and dose-dependent . In vitro doxorubicin exposure initially reduces the SR Ca2+-content, but the predominant action to block the SR Ca2+-release channel increases SR Ca2+-content within 60 min . Similar results are observed with in vivo doxorubicin exposure: it leads to Ca2+-overload . These data are consistent with the view that doxorubicin acts in a similar manner to ryanodine and results in cardiomyopathy due to Ca2+-overload. Zentralbl Chir, 1998, 123 Suppl 2, 31 - 3 {Aspects of preoperative management of biliary surgical procedures}; Richter C; Difference between open cholecystectomy and laparoscopic cholecystectomy are described . General preparations and pre-operative work up in Austria, Switzerland, Germany and East German quality assurance study at compared . The importance of antibiotic and thrombembolic prophylaxis increased. Eksp Klin Farmakol, 1998 Mar-Apr, 61(2), 45 - 7 {The immunotropic properties of rifampicin and their correction}; Sakaeva DD et al.; The effect of rifampicin on antibody genesis depends on the dose, duration, and time of its administration in relation to the antigen, as well as on the character of immunosuppression . The antibiotic has no effect on delayed hypersensitivity and stimulates the activity of phagocytes, predominantly that of neutrophils . The effectiveness of rifampicin in experimental infection is maintained in treatment with cyclophosphane and azathioprine . When administered in combination with rifampicin and cytostatics methyluracil possesses a broader spectrum of immunostimulating activity than that of prodigiosin and levamisole. Genetics, 1998 Jun, 149(2), 621 - 31 Selection of T-DNA-tagged male and female gametophytic mutants by segregation distortion in Arabidopsis; Howden R et al.; As a strategy for the identification of T-DNA-tagged gametophytic mutants, we have used T-DNA insertional mutagenesis based on screening for distorted segregation ratios by antibiotic selection . Screening of approximately 1000 transgenic Arabidopsis families led to the isolation of eight lines showing reproducible segregation ratios of approximately 1:1, suggesting that these lines are putative gametophytic mutants caused by T-DNA insertion at a single locus . Genetic analysis of T-DNA transmission through reciprocal backcrosses with wild type showed severe reductions in genetic transmission of the T-DNA through the male and/or female gametes . Direct evidence for mutant phenotypes in these lines was investigated by DAPI staining of mature pollen grains and by the analysis of seed set and embryo sac morphology in cleared ovules . One line, termed limpet pollen, showed a novel pollen phenotype in that the generative cell failed to migrate inward after pollen mitosis I, such that the generative or sperm cells remained against the pollen wall . Two other lines, andarta and tistrya, were defective in female transmission and showed an early arrest of embryo sac development with the viable megaspore not initiating the nuclear division cycles . These data demonstrate the efficacy of a segregation ratio distortion strategy for the identification of T-DNA-tagged gametophytic mutants in Arabidopsis. J Vasc Surg, 1998 May, 27(5), 902 - 8; discussion 908-9 Improved adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in a canine model; Falk J et al.; PURPOSE: A significant limitation to using genetically modified endothelial cells (ECs) to seed prosthetic grafts before implantation has been poor cell adherence to the graft lumen . Methodologic changes to improve cell adherence were evaluated in a canine carotid interposition graft model using 4 mm interior diameter expanded polytetrafluoroethylene . METHODS: ECs harvested from external jugular veins were grown in culture, with 80% of the cells from each culture transduced by incubation with an LXSN-type retroviral vector carrying a gene for human prourokinase and a neomycin resistance gene for selection in antibiotic G418 . Control grafts had passive luminal coating with fibronectin and were seeded with transduced ECs immediately after G418 selection; these grafts were incubated for 2 days before implantation . Experimental grafts had fibronectin forcefully squeezed through the interstices and were seeded with ECs that had recovered in culture for 5 days after G418 selection; these grafts were incubated for 4 days before implantation . For each control (n = 9) and experimental (n = 12) graft, a graft prepared in the same fashion but seeded with the remaining autologous nontransduced cells was placed in the contralateral carotid artery . Grafts were explanted after 30 days and were evaluated for patency, thrombus-free surface area, and cell-free surface area . RESULTS: No significant differences in patency rates were seen between any groups . The thrombus-free surface area was improved for experimental grafts (90%) compared with control grafts (76%), but this improvement did not achieve statistical significance . The cell-free surface area for transduced cells on experimental grafts was 65% compared with 96% for control grafts (p = 0.021) and was comparable with that for nontransduced cells on both control grafts (62%) and experimental grafts (51%; p = 0.201) . CONCLUSIONS: Adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in an in vivo physiologic flow model is significantly improved when cells have a more prolonged recovery from G418 selection, when the graft lumen is more uniformly coated with fibronectin before EC seeding, and when seeded grafts are left longer in culture before implantation to develop cell lining stability . The short-term patency rate of these seeded grafts is not affected by increased cell retention; long-term graft patency data and luminal healing require further evaluation. J Voice, 1998 Mar, 12(1), 91 - 5 Candida laryngitis appearing as leukoplakia and GERD; Forrest LA et al.; The symptoms and physical findings of reflux laryngopharyngitis are characteristic, but the mucosal alterations evident in the larynx are not exclusive to reflux . When conventional reflux management produces an equivocal response, other etiologic factors such as mycotic laryngitis, need consideration . The differential diagnosis of dysphonia in an immunocompromised patient always includes mycotic infections, but mycotic laryngitis can also occur in the immunocompetent host . Laryngeal candidiasis can produce physical findings, such as erythema and leukoplakia, that are similar to reflux laryngopharyngitis . Predisposing factors include previous radiation therapy, antibiotic therapy, corticosteroids, and any alteration in the mucosal barrier . Diagnosis is established by mucosal biopsy with special staining of the tissue to identify the characteristic hyphae . Treatment of mycoses can be difficult and long-term therapy is often required. Cancer Chemother Pharmacol, 1998, 42(1), 31 - 6 FK317: a novel substituted dihydrobenzoxazine with potent antitumor activity which does not induce vascular leak syndrome; Naoe Y et al.; PURPOSE: FK973, a substituted dihydrobenzoxazine, is an antitumor antibiotic which has shown high therapeutic efficacy in a phase I study, but its development has been abandoned because of the side effect of vascular leak syndrome (VLS) in the clinical study . This study was performed to investigate whether or not FK317, a new benzmethoxy derivative of FK973, retains the antitumor activity of FK973 without the side effect of VLS . METHODS: VLS was evaluated by the volume of pleural effusion in rats . Cytotoxic activities were determined by a tetrazolium-based colorimetric assay (MTT assay) against murine (B16, P388) and human (HeLa S3, KB) tumor cell lines . Antitumor activities against murine ascitic leukemia (P388, L1210), murine solid tumors (reticulum cell sarcoma M5076, Colon 38 carcinoma) and human xenografts (mammary carcinoma MX-1, lung carcinoma LX-1) were examined . RESULTS: FK973 (1.8 mg/kg) given i.v . to rats induced pleural effusion, one of the elements of VLS, 36 days after the first dosing, but did not 28 days after dosing . This model reflects clinical VLS delayed-type effusion with high protein concentrations . In contrast, FK317 (1.0-3.2 mg/kg) did not induce pleural effusion at all . FK317 had stronger cytotoxic effects against in vitro cultured B16, P388, HeLa S3 and KB tumor cell lines, and in in vivo experiments, FK317 showed equivalent antitumor activity against P388, M5076 and MX-1, and more potent antitumor activity against L1210, Colon 38 and LX-1 compared with FK973 . CONCLUSION: These results suggest that FK317 retains the antitumor activity of FK973 and does not induce VLS, and FK317 is a drug with high clinical potential for treating tumors in humans. J Struct Biol, 1998, 121(2), 123 - 41 Recent Advances in the High Resolution Structures of Bacterial Channels: Gramicidin A; Wallace BA; Gramicidin is a polypeptide antibiotic which forms dimeric channels specific for the transport of monovalent cations across membranes . It adopts several different conformations, most notably double helical (pore) and helical dimer (channels) forms, which have very different structural and functional characteristics . This review focuses on recent high resolution structure determinations of both the pore and channel forms of the molecule by X-ray crystallographic and/or NMR spectroscopic techniques . It discusses the structural consequences of binding ions and the location of ion binding sites and how the structures are related to the conductance properties of the molecule . This relatively simple molecule is probably the best characterized ion channel (both structurally and functionally) and has, to date, been the principal proving-ground for many of our ideas about the molecular nature of ion conduction in membranes . Minerva Stomatol, 1998 Mar, 47(3), 95 - 101 {Actinomycosis of the tongue . Report of two cases and review of the literature}; Gerbino G et al.; Actinomycosis of the tongue is a rare form of infection whose initial clinical manifestation is a submucosal swelling that may mimic both benign and malignant neoplasias . Two cases are, presented and their clinical features and diagnostic criteria are discussed in the light of twelve cases drawn from the literature . Infection in the tongue is rare, though perhaps underestimated . It is generally located on the anterior two thirds laterally to the median sulcus, and presents as a moderately painful nodule set deep in the extrinsic and intrinsic muscles and poorly mobile on the adjacent planes . In a few weeks the lesion increases in size and painfulness with consequent loss of function in the absence of diagnosis and appropriate antibiotic management . Both our patients, in fact, presented with deep lesions and no apparent involvement of the mucosa, and were investigated by means of fine-needle aspiration biopsy (FNAB) . The aspirated material was used to prepare both routine smears and cell blocks embedded in paraffin . The pathological material provided by this combination of methods proved quantitatively and qualitatively sufficient for the definitive diagnosis of actinomycosis in both cases. Rev Stomatol Chir Maxillofac, 1998 Apr, 99(1), 33 - 9 {Florid cemento-osseous dysplasia: a poorly recognized entity . Apropos of 5 cases}; Lahbabi M et al.; We present five cases of florid osseous dysplasia observed in our department . There has been some confusion as to the terminology of this entity . We present here a review of the literature and outline the histological classification among odontogenic tumors as well as their epidemiology . The orthopantomogam is the mainstay radiological exploration, sometimes in association with a CT-scan . There are three main differential diagnoses: Paget's disease, Gardner's syndrome located in the maxillofacial area and diffuse sclerosing osteomyelitis . Asymtomatic forms motivate therapeutic abstenstion . When inflammatory, infectious or morphological complications appear, treatment relies on surgery in combination with long-term antibiotic regimens. Ann Dermatol Venereol, 1996, 123(10), 647 - 50 {Painful nodular and plantar erythema in children}; Sandraps E et al.; INTRODUCTION: According to our knowledge, only twenty-three similar cases have been reported in the literature . Possible hypotheses for localised painful red nodules on the feet in children include erythema nodosum, neutrophilic eccrine hidradenitis, traumatic plantar urticaria, vasculitis and cold panniculitis . CASE REPORT: We report a typical case of painful erythematous plantar nodules of the child . A 13-yr-old boy was first seen by a paediatrician for intermittent fever . The fever was associated with red, painful nodules on the soles . He was unable to walk . Routine blood chemistry parameters were within normal limits . Histopathologic examination of lesional skin revealed an image of septal and lobular panniculitis with vasculitis . Direct immunofluorescence study was not contributive . With proper antibiotic therapy, pain resolved within one week while fever and nodules cleared within two weeks . DISCUSSION: Briefly, this observation concerns a child disease occurring as painful erythematous plantar nodules . The lesions are spontaneously resolutive and the children are in good health . Our observation should constitute a supplementary group with the same classical symptoms of nodular plantar painful erythema of the child but moreover accompanied by a septal and lobular panniculitis with vasculitis at the histological examination . Further studies are necessary to verify these hypotheses. J Mol Biol, 1998 Mar 27, 277(2), 333 - 45 Paromomycin binding induces a local conformational change in the A-site of 16 S rRNA; Fourmy D et al.; Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site (A-site) cause misreading of the genetic code and inhibit translocation . An A-site RNA oligonucleotide specifically binds to aminoglycoside antibiotics and the structure of the RNA-paromomycin complex was previously determined by nuclear magnetic resonance (NMR) spectroscopy . Here, the A-site RNA structure in its free form has been determined using heteronuclear NMR and compared to the structure of the paromomycin-RNA complex . As in the complex with paromomycin, the asymmetric internal loop is closed by a Watson-Crick base-pair (C1407.G1494) and by two non-canonical base-pairs (U1406.U1495, A1408.A1493) . A1492 stacks below A1493 and is intercalated between the upper and lower stems . The comparison of the free and bound conformations of the RNA shows that two universally conserved residues of the A site of 16 S rRNA, A1492 and A1493, are displaced towards the minor groove of the RNA helix in presence of antibiotic . These changes in the RNA conformation place the N1 positions of A1492 and A1493 on the minor groove side of the A-site RNA and suggest a mechanism of action of aminoglycosides on translation . Glycobiology, 1998 Apr, 8(4), 407 - 14 Spectroscopic studies on the interaction of pradimicin BMY-28864 with mannose derivatives; Fujikawa K et al.; Pradimicin BMY-28864 (Pm) is an antibiotic effective against yeasts and fungi, and is known to bind mannose in the presence of Ca2+ . We examined spectroscopically the mode of interactions among Pm, Ca2+, and glycosides of mannose and mannose oligosaccharides (Manalpha1-OMe, Manalpha1-2Manalpha1-OMe, Manalpha1-3Manalpha1-OMe, Manalpha1-4Manalpha1-OMe, Manalpha1-6Manalpha1-OMe, Manalpha1-6(Manalpha1-3)Manalpha1-OMe, and Man9GlcNAc2-Asn, a high mannose type N-linked oligosaccharide) . All the mannosides interacted with Pm in the presence of Ca2+ and caused absorbance changes . The absorbance changes occurred nonlinearly with respect to the carbohydrate concentration and do not follow a simple binding isotherm equation, suggesting a unique multistep interaction mode . The concentrations that induced half the maximum absorbance change were approximately 10 mM for the mono- and di-mannosides and around 1.5 mM for the trimannoside and Man9GlcNAc2-Asn . Methyl alpha-D-glucopyranoside, methyl alpha-D-galactopyranoside, lactose, and myo-inositol did not affect the absorbance of Pm up to 50 mM . Ca2+ alone also influenced the absorbance of Pm . The absorbance between 200 and 700 nm decreased hypochromically when Ca2+ was added . The concentration that gave half the maximum absorbance decrease caused by Ca2+was around 15 microM . Our results suggest that two Pm molecules bind one C a2+, and each Pm binds two mannosyl residues. Mol Gen Genet, 1998 Apr, 258(1-2), 156 - 65 Transport activity of FhuA, FhuC, FhuD, and FhuB derivatives in a system free of polar effects, and stoichiometry of components involved in ferrichrome uptake; Mademidis A et al.; The Escherichia coli fhu operon, composed of the fhuA, C, D, and B genes, is essential for the utilization of ferric siderophores of the hydroxamate type and for the uptake of the antibiotic albomycin . We have had difficulty studying the effects of missense mutations in individual plasmid-encoded transport genes because appropriate test strains were not found: all isolated chromosomal mutations in either one of the fhu genes (with a complete loss of function) negatively influenced the expression of other fhu genes in the operon . In order to analyze Fhu mutant proteins in a system free of polar effects, we constructed a plasmid-encoded gene cassette system by introducing unique restriction sites that allowed precise cloning of individual fhu genes . The fhu cassette operon expressed in a chromosomal fhu deletion mutant enabled us to evaluate the transport activity of mutated FhuA, FhuC, FhuD or FhuB derivatives . In addition, we found that transport across the outer membrane (via FhuA, TonB, ExbB, D) rather than transport across the cytoplasmic membrane (via FhuC, D, B) was rate limiting . The stoichiometry of the components involved in the uptake of iron(III) hydroxamates seems to be important for proper functioning. Fam Pract, 1998 Apr, 15(2), 99 - 104 Changing attitudes to infection management in primary care: a controlled trial of active versus passive guideline implementation strategies; Onion CW et al.; BACKGROUND AND OBJECTIVES: When attempting to implement evidence-based medicine, such as through clinical guidelines, we often rely on passive educational tactics, for example didactic lectures and bulletins . These methods involve the recipient in relatively superficial processing of information, and any consequent attitude changes can be expected to be short-lived . However, active methods, such as practice-based discussion, should involve recipients in deep processing, with more enduring attitude changes . In this experiment, the aim was to assess the efficacy of an active strategy at promoting deep processing and its effectiveness, relative to a typical passive method, at changing attitudes between groups of GPs over 12 months across an English Health District . METHODS: All 191 GPs operating from 69 practices in the Wirral Health District of Northwest England were assigned, with minimization of known confounding variables, to three experimental groups: active, passive and control . The groups were shown to have similar learning styles . The objective of the study was to impart knowledge of best management of infections as captured in a series of locally developed clinical guidelines . The passive group GPs were given a copy of the guidelines and were invited to an hour-long lecture event . The GPs in the deep group were given a copy of the guidelines and were invited to engage in an hour-long discussion about the guideline content at their own premises . The control group received neither the guidelines nor any educational contact regarding them . Three months before and 12 months after the interventions, all GPs were sent a postal questionnaire on their preferred empirical antibiotic for 10 common bacterial infections . The responses were compared in order to ascertain whether increased knowledge of best clinical practice was evident in each group . Results: Seventy-five per cent (144/191) of GPs responded to the pre-intervention questionnaire, 62 % (119/191) post-intervention . Thirty-four per cent (22/64) of GPs in the passive group attended the lecture; 91% (60/66) of the active group engaged in discussion at meetings with the authors . A significantly higher proportion of the active group participants' speaking time, during a sample of four visits, was devoted to verbal indicators of active processing than the passive group lecture attenders (difference = 55%, Fisher's exact test P = 0.002, OR = 11.5, 95% CI 2.1-113.4) . Inter-observer agreement on the classification of the verbal evidence was highly statistically significant for all classes (Pearson's product moment correlation, P < 0.0005, r = +0.893 to +0.999) except repetition (P > 0.05, r = +0.407) . Median compliance of responses with the guidelines improved by 2.5% within the control group and 4% within the passive, but by 23% within the active . The difference between the changes in the active and control groups was highly statistically significant at 17.5% (Mann-Whitney test, P = 0.004, 95% CI 6-29%) . However, for the 10 infections, the median difference between the changes in the passive and control groups was not significant at 3% (P = 0.75, 95% CI -8 to +12 . The median difference between changes in the active and passive groups was significant at 17% (P = 0.015, 95% CI 7-24%) in favour of the active . DISCUSSION: An active educational strategy attracted more participation and was more effective at generating deep cognitive processing than a passive strategy . A large improvement, lasting for at least 12 months, in attitude-compliance with guidelines on the optimal treatment of infections was imparted by the active processing method . A typical passive method was much less popular and had an insignificant impact on attitudes . The findings suggest that initiatives aiming to implement evidence-based guidelines must employ active educational strategies if enduring changes in attitude are to result. Anesteziol Reanimatol, 1998 Mar-Apr, (2), 71 - 3 {Standards of examination, anesthesia and postoperative care of surgical patients with concomitant cardiovascular diseases}; Gaidenko GV et al.; The authors present the standards for postoperative care of patients with concomitant cardiovascular diseases used at Medical Center No . 122 in St . Petersburg . Special attention is paid to detailed assessment of cardiac function, continuity of the pre-, intra-, and postoperative cardio- and vasotropic therapy, and adequacy of anesthesiological protection as the main guarantee of an uneventful postoperative course . The authors consider it important that preoperative examinations include echocardiography and daily ECG monitoring; preoperative treatment is to include antibiotic prevention of infective endocarditis and heparin prevention of pulmonary artery embolism in the risk group patients . Alternative methods for intraoperative hemodynamic monitoring are pulmonary artery catheterization and integral rheography with the real-time data processing . The importance of regional anesthesia and the hazards of hypercorrection of the globular volume are emphasized. Am J Physiol, 1998 May, 274(5 Pt 1), G931 - 8 Selecting agent hygromycin B alters expression of glucose-regulated genes in transfected Caco-2 cells; Rodolosse A et al.; Incorporation into plasmids of genes conferring resistance to aminoglycoside antibiotics such as hygromycin B is currently utilized for selection in experiments involving gene transfer in eukaryotic cells . Using a subclone of Caco-2 cells stably transfected with an episomal plasmid containing the hygromycin resistance gene, we observed that transformed cells subcultured in the presence of hygromycin B exhibit, compared with the same cells subcultured in antibiotic-free medium, a sixfold increase in the rates of glucose consumption and lactic acid production and dramatic changes, at mRNA and protein level, of the expressions of sucrase-isomaltase and hexose transporter GLUT-2, which are downregulated, contrasting with an upregulation of hexose transporter GLUT-1 . This occurs without significant modifications of the differentiation status of the cells, as demonstrated by the normal expression of villin, ZO-1, dipeptidyl peptidase IV, or Na(+)-K(+)-ATPase . The plasmid copy number is, however, the same, whether or not the cells are cultured in the presence of hygromycin B . These results draw attention to the need to consider antibiotic-dependent alterations of metabolism and gene expression in transfection experiments. Med Tekh, 1998 Mar-Apr, (2), 23 - 8 {Hydrodynamic and technological bases of a new design of the automyoneoventricle in assisted blood circulation}; Roeva LA et al.; The paper presents evidence for and results of development of a new hydrodynamic optimized design of the automyoneoventricle (AMNV) for extracorporeal circulation in critical myocardial lesions . The chosen geometry of externally spirally braided AMNV forms a curled flow that excludes the presence of eddy and stagnant zones which present a risk for thrombogenesis . Moreover, the paper details the original process for manufacturing the prototypes of the AMNV having spiral latex ribs, which has been modified to give its thromboresistant and antibiotic properties . The proposed biomechanical system has been put through tests yielding satisfactory results and it is to undergo clinical trials. Quintessence Int, 1998 Jan, 29(1), 41 - 8 Comparison of the clinical effects of subgingival application of metronidazole 25% gel and scaling in the treatment of adult periodontitis; Awartani FA et al.; OBJECTIVE: Control of subgingival plaque is of paramount importance in the treatment of periodontal diseases . The role of subgingival sustained-release antibiotic therapy needs elucidation . A single-blind clinical trial was carried out in 13 patients with adult periodontitis to compare the effects of subgingival application of metronidazole dental gel with those of subgingival scaling . METHOD AND MATERIALS: A split-mouth design was used so that each patient received all treatments simultaneously . Randomly selected quadrants were treated with application of 25% metronidazole gel, subgingival scaling, or a combination of scaling and gel application . The remaining quadrant in each patient was left untreated as a control . RESULTS: All three treatments were effective in significantly reducing Plaque Index, Gingival Index, and bleeding on probing over the 14-week observation period . No statistically significant differences were found between scaling alone and combined treatment . Scaling and combined treatment were better than metronidazole . Metronidazole produced transient effects, best noted during the first 4 weeks after treatment . No additive effect of metronidazole was noted in the combined treatment . At week 14, only combined treatment sites and scaled sites showed statistically greater probing depth reduction than control sites . CONCLUSION: For the treatment of mild-to-moderate adult periodontitis, subgingival scaling alone is as effective as the combination of scaling and antibiotic therapy. J Emerg Med, 1998 May-Jun, 16(3), 437 - 8 Lyme disease complicated by the Jarisch-Herxheimer reaction; Maloy AL et al.; A 31-year-old woman diagnosed with Lyme disease was treated with amoxicillin . One hour after the first antibiotic dose, the patient became acutely ill . She developed hypertension, fever, and rigors . Shortly afterward, she became hypotensive and required fluid resuscitation . This systemic illness, the Jarisch-Herxheimer reaction, was first noted in association with antibiotic therapy for neurosyphilis . Thus, the institution of antibiotic therapy may be complicated by the Jarisch-Herxheimer reaction. Rev Mal Respir, 1998 Apr, 15(2), 159 - 68 {The sickle cell anemia lung from childhood to adulthood}; Fauroux B et al.; The pulmonary complications remain the prime cause of morbidity and mortality in sickle cell disease . The pathogenetic mechanisms consists both of an alteration of the rheological properties of the blood, the existence of a hypercoagulability state and above all specific interactions between the abnormal sickle cells and the vascular endothelium and a dysregulation of the vascular reactivity in which nitrous oxide intervenes . The acute chest syndrome (ACS) is characterised by chest pain with dyspnoea and recent radiological abnormalities and it is an acute lung complication whose problem is one of aetiology . The infectious pneumonias are rarely documented . On the other hand, alveolar hypoventilation linked to infarcts of the thoracic ribs, thoracoabdominal trauma, subdiaphragmatic pain, the administration of analgesics causing respiratory depression, obesity or sleep disturbance are frequent causes of ACS . Bronchoalveolar lavage has revealed a frequency of fat emboli following infarcts in the long bones . Pulmonary emboli is rarely a cause . Pulmonary thrombosis is a serious complication, the diagnosis is difficult and is seen in a predisposed clinical setting . The treatment of ACS rests on controlled hydration and antibiotic therapy, oxygen therapy and controlled analgesic therapy . The indications for blood transfusion and for exchange transfusion merits a better evaluation . In the long term patients with sickle cell disease present with a failure of normal thoracopulmonary growth with a restrictive ventilatory defect and progressive diminution in the transfer factor of carbon monoxide with age . A history of ACS favours chronic lung disease . Pulmonary arterial hypertension is less frequent. J Pediatr Surg, 1998 May, 33(5), 761 - 3 Splenectomy in a child with chronic Mycobacterium avium complex infection and splenic sequestration; Kaufman HL et al.; Mycobacterium avium complex infections (MAC) are being reported with increasing frequency in immunocompromised patients . When these infections become resistant to standard antibiotic therapy, treatment with interferon-gamma (IFN-gamma) can be helpful . Pain, fever, splenic enlargement, and cytopenias caused by splenic sequestration developed during IFN-gamma treatment in a 9-year-old boy and were successfully treated by splenectomy . The development of IFN-gamma-induced splenic sequestration and cytopenias in MAC-infected patients represents a new indication for splenectomy. Antibiot Khimioter, 1998, 43(3), 22 - 6 {Protective properties of doxycycline, rifampicin and sisomycin in experimental pulmonary tularemia of albino mice}; D'iakov SI et al.; The protective effects of doxycycline, rifampicin and sisomicin were compared in a multifactor experiment with animal infection induced by finally dispersed aerosol of a virulent strain of the European variant of the tularemia causative agent and the optimal regimens for the antibiotic use were determined . By the values of the protective effect rifampicin and sisomicin were shown to provide a high percentage of the animal survival: more than 80 and up to 50-70 per cent of the animals survived when the aerosol infective doses were 100 and 10,000 LD50, respectively . A characteristic feature of doxycycline was its activity only in the infection induced by low doses of the biological agent . The optimal course of the antibiotic therapy in inhalation tularemia was 6 to 8 days . The interval of 1 to 3 days between the infection and the therapy start had no significant effect on the protective efficacies of the antibiotics. Ann Pharmacother, 1998 May, 32(5), 564 - 73 Treatment and prophylaxis of disseminated Mycobacterium avium complex in HIV-infected individuals; Faris MA et al.; OBJECTIVE: To review the pathophysiology, epidemiology, treatment, and prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected individuals . DATA SOURCES: A MEDLINE (January 1966-July 1997) and AIDSLINE (January 1980-July 1997) search of basic science articles pertinent to the MAC infection in HIV-infected patients . STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review . Pertinent information, as judged by the authors, was selected for discussion . DATA SYNTHESIS: The organism, epidemiology, and pathophysiology of disseminated MAC are discussed for background . A review of clinical trials for the treatment and prophylaxis of disseminated MAC are presented, along with unresolved issues concerning these topics . CONCLUSIONS: The incidence of disseminated MAC has increased dramatically with the AIDS epidemic . The infection can lead to increased morbidity and mortality in HIV-infected patients . Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin . Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50/mm3. Ann Pharmacother, 1998 May, 32(5), 549 - 53 Dapsone-induced methemoglobinemia; Ward KE et al.; OBJECTIVE: To report a case of methemoglobinemia in a patient receiving dapsone for prophylaxis of Pneumocystis carinii pneumonia (PCP) . CASE SUMMARY: A 69-year-old white woman was hospitalized to rule out sepsis . Two years prior to this admission, the patient received an orthotopic liver transplant after which she required hemodialysis three times weekly . Because of intolerance to trimethoprim/ sulfamethoxazole and aerosolized pentamidine, she was prescribed dapsone therapy on hospital day 13, that was continued for 11 days . On hospital day 45 the patient received a cadaveric kidney transplant, and dialysis treatments were scheduled only as needed . One week after the transplant, dapsone therapy was resumed . Nine days into this course of dapsone, the patient developed dyspnea and oxygen desaturation of unknown etiology . The patient was evaluated for and diagnosed with methemoglobinemia . She received two doses of intravenous methylene blue and one dose of oral activated charcoal due to fluctuating methemoglobin concentrations . DISCUSSION: The elimination of dapsone is not completely understood . Several case reports of dapsone-induced methemoglobinemia are present in the literature . Most have occurred in patients who have accidentally or deliberately overdosed . Cases of methemoglobinemia in patients receiving therapeutic doses of dapsone are discussed . CONCLUSIONS: The growing numbers of immunosuppressed patients due to transplantation of HIV may result in increased dapsone use for the prevention of PCP . Clinicians should be aware of the adverse effects associated with dapsone therapy, and patients with dyspnea and hypoxemia of unclear etiology should be evaluated for methemoglobinemia. Pedi