Aliment Pharmacol Ther, 2000 Dec, 14(12), 1605 - 11 One-week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease; Veldhuyzen Van Zanten S et al.; BACKGROUND: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases . METHODS: Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d . (n=224), in combination with amoxicillin 1 g b.d . and clarithromycin 500 mg b.d . for 1 week (EAC and OAC, respectively) . A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H . pylori eradication . RESULTS: Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185) . Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%) . Between-group differences in eradication rates were not statistically significant . Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy . CONCLUSIONS: Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H . pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated. Clin Exp Pharmacol Physiol, 2000 Dec, 27(12), 980 - 6 Changes in absorptive function of rat intestine injured by methotrexate; Naruhashi K et al.; 1 . Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine . The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino-beta-lactam antibiotic cephalexin (CEX) . Time-dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg) . 2 . Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration-time curve of CEX (AUC(CEX)) following oral administration of 20 mg/kg tended to decrease . Thereafter, the AUC(CEX) increased significantly and the histopathological changes diminished within 5 days . 3 . Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day . Methotrexate-induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUC(CEX), but did not correlate with mucosal DAO and ALP activity . 4 . These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX . In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function. Rev Prat, 2000 Oct 1, 50(15), 1665 - 71 {Infectious endocarditis}; Delahaye F et al.; The incidence of infective endocarditis has not decreased over the last years . Infective endocarditis remains severe: the mortality rate during the initial hospital stay is 15%, and a surgical intervention is needed in 25% of the cases . Stricter application of prophylaxis guidelines and better diagnostic and therapeutic management should decrease the frequency and severity of infective endocarditis. Indian J Exp Biol, 2000 Jun, 38(6), 617 - 20 Nitrosomethylurea induced streptomycin resistance in Lycopersicon esculentum Mill; Rao AV et al.; High frequency of streptomycin resistant variants of Lycopersicon esculentum were isolated on selective shoot regeneration medium supplemented with IAA (0.5 mg/L), zeatin (1.5 mg/L) and streptomycin sulphate (500 mg/L) . Nonmutagenized (controls) and NMU treated cotyledons were placed on shoot regeneration medium supplemented with antibiotic streptomycin . Resistant shoots appeared at a high frequency in mutagenized cotyledons, whereas in controls morphogenesis was suppressed, accompanied by bleaching . Shoot regeneration occurred from the nodular tissues developed at the cut ends of cotyledons . Resistant shoots developed into complete plantlets on rooting medium containing selective concentration of antibiotic . Stability of streptomycin resistance was confirmed by leaf assay and reciprocal crosses between streptomycin-resistant and sensitive plants. Arch Fam Med, 2000 Nov-Dec, 9(10), 997 - 1001 Does drug treatment of patients with acute bronchitis reduce additional care seeking? Evidence from the Practice Partner Research Network; Hueston WJ et al.; BACKGROUND: Considerable discussion has focused on treatment methods for patients with acute bronchitis . OBJECTIVE: To examine whether antibiotic or bronchodilator treatment is associated with differences in follow-up visit rates for patients with acute bronchitis . METHODS: A retrospective medical chart review was conducted for patients with a new episode of acute bronchitis over a 3-year period in the Practice Partner Research Network (29,248 episodes in 24,753 patients) . Primary outcomes of interest were another visit in the next 14 days (early follow-up) or 15 to 28 days after initial treatment (late follow-up) . RESULTS: Antibiotics were used more commonly in younger patients (<18 years), whereas older patients (>65 years) were more likely to receive no treatment . Younger patients treated with antibiotics were less likely to return for an early follow-up visit, but no differences were seen in adults and older patients . Late follow-up rates were not affected by the initial treatment strategy . When patients did return for a follow-up visit, no new medication was prescribed to most (66% of younger patients and 78% of older adults) . However, compared with patients who did not receive an antibiotic at their first visit, patients initially treated with an antibiotic were about 50% more likely to receive a new antibiotic at their second visit . CONCLUSIONS: Initial prescribing of an antibiotic reduces early follow-up for acute bronchitis in younger patients but seems to have no effect in adults . However, reductions in future follow-up visits might be outweighed by increases in antibiotic consumption because patients who return for a follow-up visit seem to receive additional antibiotic prescriptions . Arch Fam Med . 2000;9:997-1001 Int J Androl, 2000 Dec, 23(6), 357 - 9 Penile prosthesis surgery under local penile block anaesthesia via the infrapubic space; Ghanem H et al.; The aim of this study was to evaluate the effectiveness and patient tolerance to local penile block anaesthesia via the infrapubic space with penile prosthesis implantation . Local anaesthesia was administered using a 23-guage 1.5-inch needle . A 50-50 mixture of 0.5% bupivicaine (Marcaine) and 0.5% lidocaine (Xylocaine) without adrenaline was injected into the infrapubic space with additional subcutaneous penile ring infiltration at the level of the penile root . A total number of 159 patients underwent this technique, mean age 57 years (range 34-86) . In 148 (93%) patients, no booster sedation was needed; eight (5%) patients needed a boost of the pre-operative sedative during crural dilatation; three (1.8%) patients required general anaesthesia owing to insufficiently effective local anaesthesia and unexpectedly difficult dilatation . It is concluded that local anaesthesia was effective and safe to produce a pain-free procedure in 93% of cases . However, as the need for booster sedation or general anaesthesia exists, the procedure should be performed under monitored anaesthetic care and pre-operative evaluation should be performed as for general anaesthesia. J Mass Spectrom, 2000 Nov, 35(11), 1342 - 50 Determination of gentamicin in swine and calf tissues by high-performance liquid chromatography combined with electrospray ionization mass spectrometry; Cherlet M et al.; Gentamicin is a broad-spectrum aminoglycoside antibiotic widely used in veterinary medicine for the treatment of serious infections . The purpose of this study was to develop and validate a method to determine gentamicin residues in edible tissues of swine and calf . Extraction of gentamicin was performed using a liquid extraction with phosphate buffer containing trichloroacetic acid, followed by a solid-phase clean-up procedure on a CBA weak cation-exchange column . Tobramycin was used as the internal standard . After drying of the eluate, the residue was redissolved and further analyzed by reversed-phase liquid chromatography/electrospray ionization tandem mass spectrometry (MS/MS) . Chromatographic separation of the internal standard tobramycin and the gentamicin components was achieved on a Nucleosil (5 microm) column using a mixture of 10 mM pentafluoropropionic acid in water and acetonitrile as the mobile phase . The gentamicin components C1a, C2 + C2a and C1 could be identified with the MS/MS detection, and subsequently quantified . The method was validated according to the requirements of the EC at the maximum residue limit (MRL) (100 ng g(-1) for muscle and fat, 200 ng g(-1) for liver and 1000 ng g(-1) for kidney), half the MRL and double the MRL levels . Calibration graphs were prepared for all tissues and good linearity was achieved over the concentration ranges tested (r > 0.99 and goodness of fit <10%) . Limits of quantification of 25.0 ng g(-1) were obtained for the determination of gentamicin in muscle, fat, liver and kidney tissues of swine and calf, which correspond in all cases to at least half the MRLs . Limits of detection ranged between 0.5 and 2.5 ng g(-1) for the tissues . The within-day and between-day precisions (RSD) and the results for accuracy fell within the ranges specified . The method was successfully used for the determination of gentamicin in tissue samples of swines and calves medicated with gentamicin by intramuscular injection . J Pediatr, 2000 Dec, 137(6), 856 - 64 The burden of influenza illness in children with asthma and other chronic medical conditions; Neuzil KM et al.; OBJECTIVE: Although influenza immunization is recommended for children with high-risk medical conditions, the majority of such children do not receive influenza vaccine . This study was designed to measure the burden of influenza among children with asthma and other chronic medical conditions . STUDY DESIGN: We performed a retrospective cohort study of children younger than 15 years with medically treated asthma or other chronic medical conditions enrolled in the Tennessee Medicaid program from 1973 to 1993 . We determined rates of hospitalization for acute cardiopulmonary disease, outpatient visits, and antibiotic courses throughout the year . Annual differences between event rates when influenza virus was circulating and event rates during winter months when there was no influenza in the community were used to calculate influenza-attributable morbidity . RESULTS: Influenza accounted for an average of 19, 8, and 2 excess hospitalizations for cardiopulmonary disease yearly per 1000 high-risk children aged <1 year, 1 to <3 years, and 3 to <15 years, respectively . For every 1000 children, an estimated 120 to 200 outpatient visits and 65 to 140 antibiotic courses were attributable to influenza annually . CONCLUSIONS: Children younger than 15 years with asthma and other chronic medical conditions experience substantial morbidity requiring inpatient and outpatient care during influenza season . More effective targeting of this population for annual influenza immunization is warranted. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000 Dec, 90(6), 746 - 9 Paresthesia of the mental nerve induced by periapical infection: a case report; Di Lenarda R et al.; Paresthesia can be a rare complication of infections of dental origin . This article presents a case of anesthesia/paresthesia caused by a periapical infection of the right mandibular second premolar . The sensory disturbance disappeared 2 weeks after conventional endodontic treatment associated with antibiotic therapy . Twelve months later, the tooth was still asymptomatic . The possible mechanisms responsible for paresthesia associated with periapical infection are discussed. J Org Chem, 2000 Dec 15, 65(25), 8595 - 607 Total synthesis of (-)-mniopetal E, a novel biologically intriguing drimane sesquiterpenoid; Suzuki Y et al.; We have achieved the total synthesis of (-)-mniopetal E, a drimane sesquiterpenoid which inhibits the reverse transcriptase of human immunodeficiency virus (HIV)-1 . Our enantiospecific total synthesis of this target molecule in naturally occurring form commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using the Sharpless asymmetric epoxidation strategy . The key steps of our total synthesis were as follows: (1) a combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations for construction of a butenolide tethering a 1,2,4, 9-functionalized nona-5,7-diene moiety at the beta-carbon, (2) stereoselective thermal intramolecular Diels-Alder reaction of the thus-formed trienic compound, providing preferentially an endo-cycloadduct with the desired pi-facial selection, and (3) efficient transformation of the gamma-lactone moiety in the major cycloadduct to the gamma-hydroxy-gamma-lactone part in mniopetal E . Our total synthesis of (-)-mniopetal E established the unsettled absolute stereochemistry of the antibiotic. J Arthroplasty, 2000 Dec, 15(8), 990 - 3 Patient satisfaction and outcome after septic versus aseptic revision total knee arthroplasty; Barrack RL et al.; A consecutive series of revision total knee arthroplasties performed at 3 university-affiliated centers by 3 surgeons was prospectively studied . The same implant was used in all cases . The evaluation included a Knee Society clinical score (KSCS); SF-36; satisfaction survey; and radiographs preoperatively, at 6 and 12 months postoperatively, and annually thereafter . Follow-up averaging 36 months (range, 24-60 months) was obtained in 125 of 138 knees (91%) . Twenty-eight knees were infected, and 26 of 28 knees were treated successfully with 2-stage exchange with an interval of 4 to 6 weeks using an antibiotic-impregnated spacer block and intravenous antibiotics . The remaining 99 knees were revised for reasons other than infection, including aseptic component loosening, progressive osteolysis, and component instability . Preoperatively, patients with infection had a significantly decreased arc of motion compared with patients without infection (79 degrees vs 92 degrees; P<.05) . There was a strong trend for the infected knees to have a lower preoperative KSCS than the noninfected knees, although this trend did not achieve statistical significance (76 vs . 92; P =.11) . Postoperatively, patients with infection continued to have a significantly decreased range of motion (89 degrees vs . 99 degrees; P =.05) . The postoperative KSCS was markedly lower in the septic versus aseptic revisions (115 vs . 135; P =.02) . Patients with infection had a significantly lower function score (44 vs . 57; P =.03) . A significantly higher percentage of patients stated that they were unable to return to normal activities of daily living after septic versus aseptic revision total knee arthroplasty (24% vs . 7%; P<.05) . Despite the inferior functional result, patients expressed an equal degree of satisfaction with the results of their treatment in septic versus aseptic revision cases. ASAIO J, 2000 Nov-Dec, 46(6), S41 - 6 Infection in patients after implantation of an orthopedic device; Stocks G et al.; During the last several decades, the use of appropriate antibiotics has significantly improved our ability to prevent and treat infection that occurs after implantation of an orthopedic device . Despite improved prevention and treatment of this condition, patients who develop an infection secondary to implantation of an orthopedic device face increased mortality, morbidity, and/or delayed recovery . The presence of an orthopedic device significantly reduces the number of bacteria required to produce colonization and decreases the ability of the body's own defense mechanism and antibiotics to resolve this condition . Efforts devoted to prevention of infection are much more effective than those spent treating the condition once it has developed . Pretreatment of patients with antibiotics and the use of ultra clean surgical rooms have been shown effective . Prevention will become increasingly important as antibiotic resistant strains of bacteria become more prevalent and the number of arthroplasty procedures performed also increases. ASAIO J, 2000 Nov-Dec, 46(6), S28 - 36 Infectious complications associated with ventricular assist systems; Myers TJ et al.; Infectious complications during support with a ventricular assist system (VAS) can cause severe morbidity and mortality, affecting nearly one-half of all VAS recipients . Because of the lack of a uniform definition of infection, the incidence of this complication is hard to determine accurately . It is approximately 50% for patients being supported by an implantable VAS as a bridge to heart transplantation and 28% for patients supported by an external, short-term VAS . Infections can be classified according to the involvement or noninvolvement of the implanted device and according to the severity of the infection . Severe infections involving the implanted device may preclude heart transplantation for some patients, but numerous patients with milder infections have undergone successful transplantation . Numerous factors predispose VAS patients to infection . Postoperative bleeding necessitating re-operation is an important contributing factor . Endotracheal tubes, intravascular catheters, and other indwelling tubes necessary for the care of postsurgical patients are also common routes of contamination . Control of infection may be improved with new VAS designs, antibiotic impregnated drivelines, and innovative therapies such as antibiotic beads . The next generation of VASs should be inherently less susceptible to infection because of their smaller size, reduced thrombogenicity, and better flow characteristics . In addition to more effective antibiotics, improved VAS designs that incorporate transcutaneous energy transmission systems may reduce infectious complications and allow safe, long-term VAS support. Biochem Pharmacol, 2000 Dec 15, 60(12), 1845 - 53 Pharmacodynamic approach to study the gene transfer process employing non-viral vectors; Alino SF et al.; In the present work we set out to apply pharmacodynamic concepts derived from dose-response curves (Potency and Efficacy) to characterize the gene transfer efficiency of a vector:DNA complex . We employed two widely used vectors, the cationic lipid DOTAP (N,N, N-trimethyl 1-2-3-bis (1-oxo-9-octa-decenyl)oxy-(Z, Z)-1-propanaminium methyl sulfate) and the cationic polymer PEI (polyethylenimine, 800 kDa) to transfect several constructions of the green fluorescent protein cDNA . The analysis of dose-response curves indicated that in all cases the goodness-of-fit was > 0.99 . Potency is a measure that provides information on gene activity per amount of DNA . Efficacy is a measure of maximum gene expression achievable using a specific vector:DNA complex, and depends on both the intrinsic efficacy of the gene (evaluated using different vectors to transfer the same gene construct) and on vector efficacy in DNA delivery (evaluated using a single vector to deliver different gene constructs) . The results suggest that Potency and Efficacy are objective parameters for describing and comparing the goodness of vectors, as well as the intrinsic efficacy of a given gene construct . Furthermore, they are useful tools that may contribute to a better understanding of the mechanistic gene transfer process of each vector. Int Microbiol, 1999 Jun, 2(2), 61 - 8 David Hopwood and the emergence of Streptomyces genetics; Chater K; Streptomyces spp . are unusual among bacteria in growing as mycelial colonies with sporulating aerial hyphae . They are very important as the source of most of the major antibiotics . Pioneering work by David Hopwood in the 1950s and 1960s established Streptomyces coelicolor A3(2) as the model system for the genus . Since then he has led successive key phases of research on this organism . In the 1970s, plasmids were discovered and characterised, and used both to establish conditions for transformation and in the subsequent development of cloning vectors . Protoplasts were exploited in both transformation and highly efficient cell fusion . In the 1980s, the early cloning of resistance genes from antibiotic-producing strains was followed by the cloning of antibiotic biosynthetic gene clusters, and the development of general methods and probes for the cloning of such clusters from diverse species . Analysis of these gene sets led to wide-ranging inferences about the biosynthesis of the important polyketide class of antibiotics, and to the production of hybrid antibiotics, and then, in the last decade, to more sophisticated combinatorial biosynthesis of designer molecules . In parallel, David Hopwood's work has also provided a crucial platform for studies of the regulation of the morphological and physiological differentiation that is manifested by sporulating antibiotic-producing colonies . Most recently, his involvement in the physical mapping of the entire 8 Mb genome of S . coelicolor A3(2) has culminated in its complete DNA sequencing: a project that should be completed under his management during the year 2000. Ear Nose Throat J, 2000 Nov, 79(11), 884 - 8, 890-2 Clinical experiences with acute mastoiditis--1988 through 1998; Lee ES et al.; The incidence of acute mastoiditis has declined dramatically during the postantibiotic era . Even so, antibiotic-resistant or unusual pathogens can still cause this disease entity . At our hospital, we documented an increase in antibiotic-resistant and atypical pathogens such as Actinomyces spp . and Mycobacterium tuberculosis . In this paper, we discuss the optimal diagnosis and treatment strategy for acute mastoiditis, and we describe our retrospective review of 13 patients with mastoiditis who were treated at our hospital from 1988 through 1998 . Eight of these patients recovered following treatment with intravenous antibiotics, with or without myringotomy, and five who had complications of disease were managed surgically . Among these five, one developed chronic otitis media and one developed cholesteatoma 3 years later . For patients with acute mastoiditis, we emphasize the need to be aware of any unusual pathogens that do not respond to empiric antibiotic therapy. J Vet Pharmacol Ther, 2000 Oct, 23(5), 281 - 5 Pharmacokinetics and residual behaviour in milk of oxytetracycline in cows following administration of uterine pessaries; Roncada P et al.; The plasma kinetics and residual depletion in milk of cows treated by the intrauterine route with pessaries containing oxytetracycline (OTC) were evaluated . The antibiotic was administered to five healthy Friesian cows at a dosage of 3g/head in the early post partum phase . Blood samples were collected before and at different time intervals (3, 6, 12, 24, 48, 72, 84, and 96 h) after treatment . Milk was drawn before treatment and at 12-h intervals for 4 consecutive days . Samples were analysed by a high-performance liquid chromatography method and the pharmacokinetic parameters were processed using the minimum Akaike information criterion estimation (MAICE) test . The mean values obtained indicated a relatively low area under the concentration time curve (25.19+/-12.61 microg/mg per h) and maximum plasma concentration (Cmax) (0.549+/-0.278 microg/mL) with delayed time to Cmax (11.71+/-4.15 h) and elimination half-life (21.96+/-4.42 h) . A similar pattern could be shown for milk, in which measurable residual levels are found in two out of five animals until the 72nd hour after treatment . Data obtained demonstrate that OTC administered as a solid form is poorly and slowly absorbed from the uterus of cows. J Chromatogr A, 2000 Oct 20, 895(1-2), 67 - 79 Capillary electrophoresis analysis of gentamicin sulphate with UV detection after pre-capillary derivatization with 1,2-phthalic dicarboxaldehyde and mercaptoacetic acid; Kaale E et al.; A selective, sensitive, and rapid pre-capillary derivatization method for determination of the multicomponent aminoglycoside antibiotic gentamicin is described . The derivatization reagents 1,2-phthalic dicarboxaldehyde and mercaptoacetic acid were used and the thioisoindole derivative was UV detected at 330 nm . A central composite experimental design was performed to optimize selectivity and derivatization conditions . Baseline separation of gentamicin C1, C1a, C2, C2a, C2b, sisomicin and several minor components was achieved with a background electrolyte containing 30 mM sodium tetraborate, 7.5 mM beta-cyclodextrin and 12.5% (v/v) methanol at pH 10 . Quantitative analysis was performed and illustrated the potential use of capillary electrophoresis for the identification and quantitation of gentamicin as an alternative to methods prescribed in the United States Pharmacopeia and European Pharmacopoeia. J Neurosurg Sci, 2000 Jun, 44(2), 107 - 12 Cranio-orbital missile wound and bullet migration . Case report; Rinaldi A et al.; An unusual case of craniocerebral missile injury, with orbital roof perforation and spontaneous bullet migration into the maxillary sinus, is reported . Emergency treatment consisted in wide craniectomy around the bullet entry point, blood and foreign bodies debridement . Subsequent procedures were necessary for abscess evacuation, transmaxillary bullet removal and later cranial vault reconstruction . Challenging aspects were the treatment of the infectious complications, following cerebrospinal fluid fistula through the wound, and the onset of post-traumatic epilepsy, scarcely responsive to common antiepileptic drugs . The treatment of the abscess by combined systemic and intracavitary antibiotic therapy and of the chronic seizures by progressive adjustment with new protocols of antiepileptic drugs under EEG and brain mapping revealed successful. J Emerg Nurs, 2000 Dec, 26(6), 549 - 53 ED "hold" patients: is their care also being held? Sobie JM, Gaves D, Tringali A. INTRODUCTION: Patient care should be governed by the same standards of care regardless of location within a hospital system . Little is known about adherence to standards of care for admitted patients who are "held" in the emergency department because of an unavailable inpatient bed . For example, is there a difference in the timeliness of nursing assessments and initial antibiotic administration for patients with pneumonia who are held in the emergency department compared with those who are directly admitted to an inpatient bed? METHODS: A descriptive comparison research design with 2 known groups ("ED hold" patients and "ED direct-admit" patients) was used . A convenience sample of 104 closed medical records was obtained from a Midwestern hospital for a retrospective chart audit . RESULTS: Patients held in the emergency department had their blood pressure, pulse, respiratory rate, and oxygen saturation recorded with greater frequency compared with patients who were directly admitted . Directly admitted patients had their intake and output and their temperature noted with greater frequency . Although there was no statistically significant difference in the timeliness of respiratory assessments or antibiotic administration, antibiotics were delivered to the ED direct-admit group an average of 1 hour earlier than to the ED hold group . DISCUSSION: When measuring only the frequency and/or timeliness of taking vital signs, recording intake and output, and administering antibiotics, there were statistical differences between "hold" patients and "direct-admit" patients . In some instances, ED "hold" patients actually received more timely assessment than did "direct-admit" patients . Direct-admit patients received antibiotics an average of 1 hour sooner . More studies are necessary to evaluate other aspects of care that may or may not be compromised when admitted patients are "held" in the emergency department. Actas Urol Esp, 2000 Sep, 24(8), 677 - 8 {Self-administration of an oil solution in the penis}; Rebassa Llull MJ et al.; We report the case of a patient who has autoinjected himself the penis and the scrotum with a solution constituted by petroleum, vaseline, oxygenated water and ketoconazol gel . Treatment consists in the excision of the injected deposit of lipid material and antibiotic therapy with good result at 4 months . We review the existing literature related with this exceptional pathology. Actas Urol Esp, 2000 Sep, 24(8), 652 - 8 {Malignant neoplasms of the penis}; Banon Perez VJ et al.; OBJECTIVE: To assess the behaviour and management of these uncommon neoplasias . MATERIAL AND METHODS: Between March 1975 and July 1999, a total of 95 malignant neoplasias of the penis were diagnosed and treated by our unit . Patients mean age was 62 years (28 to 87 years) . A retrospective analysis of any associated lesions, biological behaviour of the various neoplasias, as well as therapies used is carried out . RESULTS: The squamous carcinoma of the penis (SCP) is the most frequent pathohistological entity entailing 78 cases (82%), followed by verrucous carcinoma (VC) 13 cases (13.5%), basal cells carcinoma 1 case, and melanoma, lymphoma and penile metastasis 1 case each . There is a significant presence of associated lesions with marked predominance of phimosis . The most frequent reason for the call is an injury of the penis (74 cases; 78%) . Treatment was mainly partial penectomy (51 patients; 53.7%), followed by conservative treatment in 28 cases (30%) . Inguinal lymphadenectomy was performed in 13 patients (14%), due to either a positive nodular biopsy or a persistent adenopathy following antibiotic therapy . CONCLUSIONS: Neoplasias showing superior biological behaviour are basal cell carcinoma of the penis, and verrucous carcinoma . Prognosis in SCP is based on pathological status and node involvement . Patients with pT1 tumours showed no metastatic adenopathies after follow-up regardless of cytological grading, and are therefore candidates to watchful waiting with regular monitoring . Melanoma of the penis is a highly aggressive tumour due to its high metastatic capacity with a poor prognosis. Biochemistry, 2000 Dec 5, 39(48), 14968 - 75 DNA binding and alkylation by the "left half" of azinomycin B; Zang H et al.; Azinomycin B (also known as carzinophilin A) contains two electrophilic functional groups-an epoxide and an aziridine residue-that react with nucleophilic sites in duplex DNA to form cross-links at 5'-dGNT and 5'-dGNC sequences . Although the aziridine residue of azinomycin is undoubtedly required for cross-link formation, analogues containing an intact epoxide group but no aziridine residue retain significant biological activity . Azinomycin epoxide analogues (e.g., 5 and 6) are of interest due to their potent biological activity and because there is evidence that azinomycin may decompose in vivo to yield such compounds . To investigate the chemical events underlying the toxicity of azinomycin epoxides, DNA binding and alkylation by synthetic analogues of azinomycin B (6, 8, and 9) that comprise the naphthalene-containing "left half" of the antibiotic have been investigated . The epoxide-containing analogue of azinomycin (6) efficiently alkylates guanosine residues in duplex DNA . DNA alkylation by 6 is facilitated by noncovalent binding of the compound to the double helix . The results of UV-vis absorbance, fluorescence spectroscopy, DNA winding, viscometry, and equilibrium dialysis experiments indicate that the naphthalene group of azinomycin binds to DNA via intercalation . Equilibrium dialysis experiments provide an estimated binding constant of (1.3 +/- 0.3) x 10(3) M(-)(1) for the association of a nonalkylating azinomycin analogue (9) with duplex DNA . The DNA-binding and alkylating properties of the azinomycin epoxide 6 provide a basis for understanding the cytotoxicity of azinomycin analogues which contain an epoxide residue but no aziridine group and may provide insight into the mechanisms by which azinomycin forms interstrand DNA cross-links. Thorac Cardiovasc Surg, 2000 Oct, 48(5), 290 - 3 Surgical outcome of mycobacterium other than mycobacterium tuberculosis pulmonary disease; Tsunezuka Y et al.; Between January 1995 and May 1999, MOTT were cultured from sputum, bronchoalveolar lavage or resected lung specimens in 110 cases . 17 patients with MOTT pulmonary disease underwent pulmonary resection . Preoperatively, 5 of 17 patients had been diagnosed with MOTT pulmonary disease . The diagnosis of others was based on positive cultures from surgically resected material, and organism identification was successfully performed by the microplate DNA-DNA hybridization procedure . Surgical resections performed included wedge resection in 7, lobectomy in 6, and segmentectomy in 4 . Antibiotics were generally continued for 6 to 24 months postoperatively . However, postoperative antibiotics therapy was not performed for patients who were postoperatively diagnosed with foci localized at the peripheral lung . Resected specimens yielded positive cultures for MOTT in all patients . There were no patients infected with M . konsasii . Regarding postoperative complications, 1 late bronchopleural fistula developed after right upper and middle lobectomy, and was treated with omentopexy . Persistent air leaks (> 7 days) occurred in 5 patients, none of which occurred where linear stapling devices fitted with expanded polytetrafluoroethylene (ePTFE) sleeves were used . One patient diagnosed with M . szulgai postoperatively experienced reactivation 2 years after middle lobectomy despite postoperative antibiotic therapy for 6 months . Other patients have remained free of disease postoperatively . Surgical resection achieve good results for MOTT pulmonary disease, and wedge resection or segmentectomy without postoperative antibiotic therapy was enough for patients whose foci localized at the peripheral lung and whose sputum or BAL cultures revealed no MOTT . Surgical treatment should be performed as early as possible before the pulmonary disease necessitates an extensive operation, and ePTFE sleeves were effective in preventing a postoperative prolonged air leak. Int Anesthesiol Clin, 2000 Fall, 38(4), 1 - 29 Management of the septic patient in the operating room; Jodka PG et al.; Sepsis, severe sepsis, and septic shock represent the spectrum of physiological response to a variety of infecting pathogens . Multiple-organ dysfunction may result from widespread activation of inflammatory and antiinflammatory mechanisms . Intensive multiorgan support, effective antibiotic therapy, and eradication of the inciting source remain the cornerstones in the care of septic patients . Perioperative planning and management need to ensure the continuation of such care in addition to providing for the requirements of the given surgical procedure. Curr Opin Pulm Med, 2000 Nov, 6(6), 551 - 7 Outpatient care of the cystic fibrosis patient after lung transplantation; Yankaskas JR et al.; Lung transplantation has become an accepted treatment for respiratory failure due to cystic fibrosis (CF) . Effective means of patient selection, surgical technique, immunosuppression, and post-transplant management permit survival as good as that of transplant patients with other diseases . The new lungs do not acquire the CF ion transport abnormalities but are subject to the usual post-transplant complications . CF problems in other organ systems persist and may be worsened by some of the immunosuppressive regimens . Prolonged survival increases the risk of age-related CF and other complications . Effective medical management requires expert knowledge of CF and lung transplantation and of how their problems interact, and good communications among the participating care teams. Pediatr Infect Dis J, 2000 Nov, 19(11), 1071 - 4 Clinical sinusitis in children attending primary care centers; Kakish KS et al.; OBJECTIVES: To determine the proportion of children who meet the clinical criteria for the diagnosis of sinusitis among all children attending primary care pediatric practices, to explore the relationship between passive smoking and the occurrence of sinusitis and to study the role of antibiotics in the management of sinusitis . DESIGN: A prospective observational cohort study . SETTING: Outpatient Pediatric Clinics of Jordan University of Science and Technology and Princess Rahma Teaching Hospital . Patients . All children ages 1 to 10 years presenting for any reason to participating practices . METHODS: Physicians participating in this study completed a questionnaire on all children attending the primary care centers, detailing the presence of nasal congestion or discharge, the duration of symptoms, daytime cough and whether symptoms were improving . The presence or absence of smokers in the family was also recorded . Children meeting our clinical criteria for sinusitis were further evaluated for other signs and symptoms including the type of medication prescribed . The severity of symptoms was reassessed at 10-day follow-up after the first visit . RESULTS: The study population was composed of 3001 children, of whom 249 met our clinical criteria for diagnosis of sinusitis (8.3%; 95% confidence interval, 7.3 to 9.3%) . The prevalence rate of clinical sinusitis was greater among children age 5 years and older than among those younger (9.3% vs . 7.2%, P = 0.04) . Children exposed to passive smoking in the household had clinical sinusitis significantly more than those not exposed (68.8% vs . 1.2%, P = 0.00) . Antibiotics were prescribed for 80% of children who fulfilled the clinical criteria for diagnosis of sinusitis . Marked improvement of symptoms at the 10-day follow-up visit was reported among those who received antibiotics compared with those who did not (91% vs . 21.4%, P = 0.00) . CONCLUSIONS: Sinusitis is not an uncommon problem in children, passive smoking might be a contributing factor and a course of antibiotic therapy is beneficial. Complement Ther Med, 2000 Dec, 8(4), 276 - 9 Effect of Mao-bushi-saishin-to on infection of ofloxacin resistant bacteria and of unknown origin; Kamei T et al.; When seven elderly patients with fever due to bacterial infection failed to respond to ofloxacin 300 mg/day for 3 days, we prescribed Mao-bushi-saishin-to for 7 days . Bushi, one of the components of Mao-bushi-saishin-to, is a complex of various alkaloids, which is known to stimulate the conducting system of the heart, so half of the standard dose was prescribed for these patients . We assessed changes in the patients' body temperatures and serum C-reactive protein concentrations . As a result, the patients' body temperatures all fell to under 37 degrees C and C-reactive protein levels decreased from an average of 3.06 mg/dl to an average of 0.36 mg/dl (P< 0.02) . In cases where a fever does not decrease through dosage of an antibiotic such as ofloxacin after about 3 days, half of the standard dose of Mao-bushi-saishin-to for 7 days should be considered as a complementary therapy . Folia Microbiol (Praha), 1999, 44(6), 663 - 8 Nikkomycin Z counteracts Rylux BSU and Congo red inhibition of Saccharomyces cerevisiae growth but does not prevent formation of aberrant cell walls; Raclavsky V et al.; Rylux BSU and congo red bind to chitin, interfere with proper cell-wall assembly, and stimulate chitin synthesis by increasing, most probably, chitin synthase 3 (ChS3) levels in Saccharomyces cerevisiae . On the other hand, the antibiotic nikkomycin Z inhibits chitin synthesis competitively . As ChS3 is the critical target of nikkomycin Z, its effect was tested in cells inhibited in growth by Rylux BSU or Congo red . Nikkomycin Z counteracted this inhibition but did not counteract aberrant cell-wall formation . These results indicate that chitin synthesis stimulation is the key step in Rylux BSU and congo red inhibition and support the idea that increase in chitin synthesis represents a compensatory response to damaged cell-wall structure . As Rylux BSU and congo red bind to newly synthesized chitin, further damage is caused in the wall and the response works in this case contrariwise . Nikkomycin Z breaks this vicious circle by counteracting the chitin synthesis stimulation. Am J Kidney Dis, 2000 Dec, 36(6), 1267 - 70 Successful medical treatment of acute bilateral emphysematous pyelonephritis; Tahir H et al.; Emphysematous pyelonephritis most often presents as an acute medical emergency, typically in a septic diabetic patient with acute renal failure . The management of this condition has traditionally been surgical, with nephrectomy . However, some recent reports have described successful medical interventions . We describe a case of acute bilateral emphysematous pyelonephritis in a frail patient not suitable for bilateral nephrectomy and long-term dialysis . This condition was managed medically, not surgically, with intensive antibiotic and circulatory support . The outcome was complete recovery after months of hospital-based treatment . We discuss the management of this rare but important condition in detail. Am J Kidney Dis, 2000 Dec, 36(6), 1183 - 92 Factors predicting outcome of fungal peritonitis in peritoneal dialysis: analysis of a 9-year experience of fungal peritonitis in a single center; Wang AY et al.; Fungal peritonitis causes significant morbidity and mortality for patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . We retrospectively reviewed 70 episodes of fungal peritonitis in a single center over the last 9 years in 896 CAPD patients . Seventy percent of the episodes of fungal peritonitis were caused by CANDIDA: species, among which 50% were CANDIDA: parapsilosis . As a result of fungal peritonitis, 44% of the patients died, whereas further peritoneal dialysis failed in 14%, requiring a change to long-term hemodialysis . Only 37% managed to continue CAPD . The remaining 5% either underwent transplantation or were lost to follow-up . We identified the factors associated with poor outcome, namely mortality and technique failure . The presence of abdominal pain, bowel obstruction, and a catheter remaining in situ were significantly associated with greater mortality . Abdominal pain, antibiotic use within 3 months before fungal peritonitis, and complication by bowel obstruction were associated with greater technique failure . In choosing antifungal agents with catheter removal, oral fluconazole alone appears equally as effective as combined oral fluconazole with 5-flucytosine for peritonitis caused by CANDIDA: species . For peritonitis caused by species other than CANDIDA:, the choice of antifungal therapy needs to be individualized, based on fungal species and sensitivities. Jpn J Clin Oncol, 2000 Sep, 30(9), 401 - 5 Bacterial meningitis observed in a phase I trial of vinorelbine, cisplatin and thoracic radiotherapy for non-small cell lung cancer: report of a case and discussion on dose-limiting toxicity; Sekine I et al.; Although neutropenia increases the risk of life-threatening infections, bacterial meningitis is rarely encountered as a complication during cancer chemotherapy in adults with a solid tumor . A 66-year-old male with adenosquamous carcinoma of the lung, cT2N3M0, stage IIIB, was enrolled in a phase I trial of chemoradiotherapy and treated with cisplatin 80 mg/m2 (122 mg/ body) on day 1, vinorelbine 20 mg/m2 (32 mg/body) on days 1 and 8 and thoracic radiotherapy 30 Gy/15 fractions, beginning on day 2, with dexamethasone administered for antiemesis at a dose of 16 mg on day 1, 8 mg on days 2 and 3, 4 mg on day 4 and 2 mg on day 5 . The patient developed headache and fever on day 6 of the second cycle of the treatment and bacterial meningitis was diagnosed based on the findings of consciousness disturbance, an elevated peripheral blood leukocyte count and numerous leukocytes in the cerebrospinal fluid . In spite of the doctor's delay in establishing the exact diagnosis, the bacterial meningitis in this case was successfully treated with intensive antibiotic therapy . This life-threatening complication, equivalent to a grade 4 non-hematological adverse reaction, was not counted as dose-limiting toxicity in the current phase I trial, because there are only a few reports of bacterial meningitis associated with cancer chemotherapy and it developed in this case without any associated decrease in the peripheral blood leukocyte count. Chem Biol, 2000 Nov, 7(11), 895 - 905 A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis; Aparicio JF et al.; BACKGROUND: Polyene macrolides are a class of large macrocyclic polyketides that interact with membrane sterols, having antibiotic activity against fungi but not bacteria . Their rings include a chromophore of 3-7 conjugated double bonds which constitute the distinct polyene structure . Pimaricin is an archetype polyene, important in the food industry as a preservative to prevent mould contamination of foods, produced by Streptomyces natalensis . We set out to clone, sequence and analyse the gene cluster responsible for the biosynthesis of this tetraene . RESULTS: A large cluster of 16 open reading frames spanning 84985 bp of the S . natalensis genome has been sequenced and found to encode 13 homologous sets of enzyme activities (modules) of a polyketide synthase (PKS) distributed within five giant multienzyme proteins (PIMS0-PIMS4) . The total of 60 constituent active sites, 25 of them on a single enzyme (PIMS2), make this an exceptional multienzyme system . Eleven additional genes appear to govern modification of the polyketide-derived framework and export . Disruption of the genes encoding the PKS abolished pimaricin production . CONCLUSIONS: The overall architecture of the PKS gene cluster responsible for the biosynthesis of the 26-membered polyene macrolide pimaricin has been determined . Eleven additional tailoring genes have been cloned and analysed . The availability of the PKS cluster will facilitate the generation of designer pimaricins by combinatorial biosynthesis approaches . This work represents the extensive description of a second polyene macrolide biosynthetic gene cluster after the one for the antifungal nystatin. Chem Biol, 2000 Nov, 7(11), 821 - 31 The NDP-sugar co-substrate concentration and the enzyme expression level influence the substrate specificity of glycosyltransferases: cloning and characterization of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster; Hoffmeister D et al.; BACKGROUND: Streptomyces fradiae is the principal producer of urdamycin A . The antibiotic consists of a polyketide-derived aglycone, which is glycosylated with four sugar components, 2x D-olivose (first and last sugar of a C-glycosidically bound trisaccharide chain at the 9-position), and 2x L-rhodinose (in the middle of the trisaccharide chain and at the 12b-position) . Limited information is available about both the biosynthesis of D-olivose and L-rhodinose and the influence of the concentration of both sugars on urdamycin biosynthesis . RESULTS: To further investigate urdamycin biosynthesis, a 5.4 kb section of the urdamycin biosynthetic gene cluster was sequenced . Five new open reading frames (ORFs) (urdZ3, urdQ, urdR, urdS, urdT) could be identified each one showing significant homology to deoxysugar biosynthetic genes . We inactivated four of these newly allocated ORFs (urdZ3, urdQ, urdR, urdS) as well as urdZ1, a previously found putative deoxysugar biosynthetic gene . Inactivation of urdZ3, urdQ and urdZ1 prevented the mutant strains from producing L-rhodinose resulting in the accumulation of mainly urdamycinone B . Inactivation of urdR led to the formation of the novel urdamycin M, which carries a C-glycosidically attached D-rhodinose at the 9-position . The novel urdamycins N and O were detected after overexpression of urdGT1c in two different chromosomal urdGT1c deletion mutants . The mutants lacking urdS and urdQ accumulated various known diketopiperazines . CONCLUSIONS: Analysis of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster revealed a widely common biosynthetic pathway leading to D-olivose and L-rhodinose . Several enzymes responsible for specific steps of this pathway could be assigned . The pathway had to be modified compared to earlier suggestions . Two glycosyltransferases normally involved in the C-glycosyltransfer of D-olivose at the 9-position (UrdGT2) and in conversion of 100-2 to urdamycin G (UrdGT1c) show relaxed substrate specificity for their activated deoxysugar co-substrate and their alcohol substrate, respectively . They can transfer activated D-rhodinose (instead of D-olivose) to the 9-position, and attach L-rhodinose to the 4A-position normally occupied by a D-olivose unit, respectively. Curr Treat Options Gastroenterol, 1999 Jun, 2(3), 171 - 182 Helicobacter Pylori; Chey WD; All infected patients with a peptic ulcer should be treated for H . pylori . The role of treating H . pylori in patients with undiagnosed dyspepsia or non-ulcer dyspepsia, those taking nonsteroidal anti-inflammatory medications, or with a family history of gastric cancer remains controversial . Triple therapies consisting of a proton pump inhibitor or ranitidine bismuth citrate and two antibiotics are the current standard of therapy for H . pylori . In general, dual therapies should no longer be used to treat H . pylori . Bismuth triple therapy consisting of bismuth, tetracycline, and metronidazole is a less expensive alternative to proton pump inhibitor-or ranitidine bismuth citrate-based triple therapies . However, bismuth triple therapy is hampered by frequent side effects and the need for qid dosing . In Europe, a 7-day course of therapy appears to be adequate . In the United States, 10-14 days of therapy are currently recommended . Metronidazole resistance in H . pylori strains varies geographically, and negatively influences the effectiveness of therapies containing this antibiotic . Clarithromycin resistance is relatively infrequent at the current time but may be rising in countries where this antibiotic is in use . If a patient remains infected after a course of therapy for H . pylori, the second treatment should avoid the antibiotics used initially. Curr Treat Options Gastroenterol, 1999 Apr, 2(2), 86 - 90 Pyogenic Liver Abscess; Olivera MA et al.; The percutaneous approach-specifically, ultrasound-guided percutaneous catheter drainage-associated with intravenous administration of antibiotics is the therapy of choice in patients with single or multiple pyogenic liver abscesses . The initial empiric antibiotic therapy should be modified based on results of blood and pus cultures . Surgery should be reserved for patients in whom antibiotic therapy and percutaneous drainage is unsuccessful. Curr Treat Options Cardiovasc Med, 2000 Aug, 2(4), 343 - 350 Purulent Pericarditis; Goodman LJ; Purulent pericarditis represents a subset of pericardial disease usually due to a nonviral infectious agent . The presentation is often acute, with rapid progression to tamponade unless a drainage procedure is performed . Although several infectious agents account for the majority of infections, the differential diagnosis is broad . Often, patients with more exotic infectious causes have risk factors for these agents that can be identified by careful history-taking . Distinguishing a bacteremic source from infection acquired by contiguous spread is particularly important . Although most infections spread contiguously are a complication of recent surgery or nearby pneumonia and are, therefore, apparent to the physician, others may be less obvious . For example, head and neck space infections may track to the retropharyngeal space and, from there, posteriorly to the so-called "danger" space, which connects inferiorly to the mediastinum and the pericardium . Failing to identify this source of tracking infection may lead to inadequate drainage as well as inappropriate empiric antibiotic therapy . In acute cases, needle drainage with appropriate staining and culturing of the fluid is adequate for diagnosis and initial management of the complications of fluid collection in the closed space of the pericardial sac . Pericardial biopsy may be the sole method of identifying an etiologic agent, particularly in chronic cases in which granulomatous disease is more commonly seen . In select cases, pericardial window or pericardiectomy procedures are needed to limit complications of reaccumulation of fluid. Curr Infect Dis Rep, 2000 Aug, 2(4), 337 - 344 Bacterial Meningitis: Principles and Practical Aspects of Therapy; Aronin SI; Acute bacterial meningitis continues to be associated with significant morbidity and mortality . Recent research efforts to improve outcome for such patients have focused on antibiotic-cerebrospinal fluid interactions, factors influencing antibiotic selection, indications for cranial imaging, the role of anti-inflammatory agents, and the impact of antibiotic timing on outcome . In this article, I use an illustrative case to review timely data on these topics and provide guidelines for the empiric and pathogen-directed treatment of patients with acute bacterial meningitis. Curr Infect Dis Rep, 2000 Aug, 2(4), 299 - 301 Update on Lyme Carditis; Bateman H et al.; Lyme carditis is an uncommon manifestation of infection with Borrelia bugdorferi . It is easily treated with standard antibiotic regimens and prognosis is excellent, especially if treatment is prompt . For symptomatic or higher degrees of block, patients may require hospitalization for monitoring and occasionally temporary external pacing . Intravenous antibiotics are warranted for such patients . For less severe conduction disturbances, oral therapy suffices. Curr Infect Dis Rep, 1999 Aug, 1(3), 267 - 272 Prosthetic Joint Infection; Berendt AR et al.; Total joint replacement has been one of the most remarkable successes of modern medical technology . Once John Charnley had solved the problems of implant design, choice of materials, implant fixation, and infection (initial rates of infection were approximately 10%), the way was clear for the widespread use of this valuable treatment, which is highly effective at removing pain and restoring function . Unfortunately, infection still remains an important, though less common, problem . It is associated with serious morbidity (pain, loss of function, wound breakdown, wound discharge, implant failure) and sometimes mortality . It may be impossible to eradicate or suppress infection in the long term without removal of the prosthesis, and most clinicians would consider it unwise to re-implant a new prosthesis in the presence of infection . Hence, patients with infected prosthetic joints generally require multiple additional operations and prolonged periods of antibiotic therapy . Even radical attempts at cure may fail (in 10% to 15% of cases in most series), requiring further cycles of treatment with progressively deteriorating function . Thus, the treatment of prosthetic joint infection is arduous for the patient and the health care team, with no guarantee of success. Curr Infect Dis Rep, 1999 Aug, 1(3), 261 - 266 Osteomyelitis; Sax H et al.; Despite significant progress in antibiotic therapy and orthopedic surgery, osteomyelitis remains a difficult-to-treat infection that is often associated with recurrence . In this paper we summarize the most recent developments in understanding the pathogenesis of this complex disease, as well as novel means for its diagnosis and treatment. Curr Infect Dis Rep, 1999 Apr, 1(1), 22 - 26 Current Concepts of Therapy for Otitis Media; Wientzen RL et al.; The therapy for acute otitis media is currently a topic in evolution . What was once a straightforward approach of matching middle ear pathogens to appropriate antibiotics has become a complex calculus that attempts to balance multiple terms such as spontaneous cure, emergence of resistance, pharmacokinetics-dynamics, antibiotic therapeutic efficacy, suppurative complications, and cost . This review highlights new developments in our understanding of this complex interaction of the issues surrounding a physician's decision to begin antibiotic therapy for acute otitis media. Acta Crystallogr D Biol Crystallogr, 2000 Dec, 56 Pt 12, 1647 - 51 Crystallization and preliminary X-ray analysis of tetracenomycin A2 oxygenase: a flavoprotein hydroxylase involved in polyketide biosynthesis; Beynon J et al.; The tcm operon in Streptomyces glaucescens encodes a group of enzymes involved in the synthesis of the polyketide tetracenomycin (Tcm) C that exhibits both antitumor and antibiotic activities . Here, the crystallization and preliminary data characterization of the tcmG gene product, Tcm A2 oxygenase, which catalyzes the triple hydroxylation of Tcm A2 to form Tcm C, are reported . Tcm A2 oxygenase crystallizes in two different space groups, both with six monomers per asymmetric unit, resulting in large unit-cell parameters . Synchrotron data have been collected from both the hexagonal and tetragonal crystal forms to 4.5 and 4.2 A, respectively . The self-rotation function searches in both space groups suggest the monomers assemble into a complex with D(3) symmetry. Cell Mol Life Sci, 2000 Oct, 57(11), 1562 - 9 Cellular and molecular aspects of Lyme arthritis; Gross DM et al.; Lyme disease is a multisystem illness initiated upon infection with the spirochete Borrelia burgdorferi . Whereas the majority of patients who develop Lyme arthritis may be successfully treated with antibiotic therapy, about 10% go on to develop arthritis which persists for months to years, despite antibiotic therapy . Development of what we have termed treatment-resistant Lyme arthritis has previously been associated with both the presence of particular major histocompatibility complex class II alleles and immunoreactivity to the spriochetal outer surface protein A (OspA) . Recently, we showed that patients with treatment-resistant Lyme arthritis, but not patients with other forms of arthritis, generate synovial fluid T cell responses to an immunodominant epitope of OspA and a highly homologous region of the human-lymphocyte-function-associated antigen-1alphaL chain . Identification of a bacterial antigen capable of propagating an autoimmune response against a self-antigen provides a model of molecular mimicry in the pathogenesis of treatment-resistant Lyme arthritis. J Int Med Res, 2000, 28 Suppl 1, 37A - 47A How short can courses be in lower respiratory tract infections? Siegel R. Prospective clinical studies conducted over the last 10 years provide data on which to base decisions regarding the treatment of community-acquired pneumonia (CAP), including the need for hospitalization, optimal timing of the switch from intravenous to oral antibiotic therapy and the discharge of patients . Validated treatment algorithms, such as the classification of community-acquired pneumonia, now enable decisions to be made on which patients with CAP require hospitalization, as well as identifying those who will benefit from early switch therapy . Generally, unstable CAP patients are suitable candidates for early switch therapy, which consists of rapid initiation of 1 - 2 days' intravenous therapy followed by 5 days' oral therapy, with early discharge from hospital after the receipt of one or two doses of oral antibiotic . Studies with intravenous cefuroxime and followed by oral cefuroxime axetil suggest this regimen is both effective and well tolerated as rapid switch therapy, and has the potential to reduce overall healthcare costs and improve patient satisfaction. Int J Clin Pract, 2000 Jul-Aug, 54(6), 353 - 5 Ceftriaxone-PMMA beads--a slow release preparation? Alonge TO, Fashina AN. The use of various drug delivery systems to achieve high levels of the desired antibiotic(s) at the site of infection has become commonplace in orthopaedic and trauma units the world over . One of these techniques uses the implantation of antibiotic-impregnated beads at operation sites . Commercial antibiotic beads such as the gentamicin bead are available but expensive, especially for patients in developing countries . We have shown that ceftriaxone-polymethylmethacrylate beads can be produced locally and at low cost in a resource-poor environment . We have also shown that such beads elute the antibiotic (ceftriaxone) effectively in vitro, achieving similar or better activity when measured by zones of inhibition against various bacteria species compared with standard antibiotic discs . This technique offers a cost-effective method of treating chronic bone infections in resource-poor settings. J Hematother Stem Cell Res, 2000 Oct, 9(5), 645 - 9 Clinical and laboratory features predicting a favorable outcome and allowing early discharge in cancer patients with low-risk febrile neutropenia: a literature review; Castagnola E et al.; To value feasibility of early discharge in febrile granulocytopenic patients, 27 original paper published in the last 11 years were analyzed concerning these clinical and therapeutic approaches . A Medline search of English language literature published in the last 11 years (1988-1999) used the key words neutropenia, fever, cancer, home-antibiotic therapy, short course of antibiotic therapy, and early discharge . Twenty-seven original papers fulfilling the study criteria were identified . In these studies, 5208 episodes were evaluated: there were 538 failures with 87 deaths . Features of low-risk patients who developed life-threatening infectious disease were related to general clinical condition, cancer control, bone marrow function, presence of clinical signs of infection, and social features . Careful risk assessment can allow safe recognition of low-risk patients with febrile neutropenia who can be discharged early and can be used to follow outpatient treatment programs to improve patients' quality of life as well as the use of economic resources. Artif Organs, 2000 Oct, 24(10), 829 - 33 Specific determination of endothelial cell viability in the whole cell fraction from cryopreserved canine femoral veins using flow cytometry; Park JC et al.; Abstract: An efficient method for specifically determining the viability of endothelial cells (EC) from cells dissociated from the human saphenous vein was investigated . Three different methods, trypan blue staining assay, {3H}-proline incorporation assay, and flow cytometry (FCM), combined with the fluorescein isothiocyanate conjugated with Griffonia simplicifolia agglutins (GS1-FITC)/propidium iodide (PI) double staining, were used . Both trypan blue staining and {3H} proline incorporation assays demonstrated less sensitivity to determine viability of EC differentially from the other cells . FITC-GS1 showed prominent binding to the vascular EC and could be counted by FCM including PI on dead cells . Following the cryopreservation process, the GS1-FITC/PI FCM analytical method was adopted to test simultaneously the viability of whole cells and EC from the same tissue, human saphenous veins, and mongrel dogs' femoral veins after harvesting, antibiotic solution treatment, and thawing . The viability of the whole cells from veins decreased with a significant difference (p < 0.05) from that of EC after thawing. Am J Cardiol, 2000 Dec 1, 86(11), 1279 - 81, A9 Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy; Ishii M et al.; This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals . A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs . The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity. Int J Immunopharmacol, 2000 Nov, 22(11), 935 - 42 Modification of tumor necrosis factor-induced acute toxicity D-galactosamine challenge by polymyxin B, an anti-endotoxin; Sakaguchi S et al.; Polymyxin B (PMB), an antibiotic with anti-endotoxin activity, was used to examine the participation of endogenously produced endotoxin in the enhancement of recombinant human tumor necrosis factor (rhTNF)-induced toxicity in D-galactosamine (GalN)-sensitized mice . GalN-sensitized mice (700 mg/kg, intraperitoneally (i.p.)) injected together with rhTNF (1x10(4) U/mouse, intravenously (i.v.)) exhibited severe symptoms, with 100% mortality at 18 h . However, mice pretreated with PMB (20 mg/kg, i.p.) showed protection against the rhTNF-induced lethality following GalN sensitization . Little or no effects were observed on alanine aminotransferase (ALT) activity or lactate dehydrogenase (LDH) isozyme leakage in serum in mice 7 h after administration of rhTNF alone . Administration of rhTNF to GalN-sensitized mice resulted in marked increases in ALT activity and LDH isozyme leakage relative to those in mice treated with rhTNF alone . In mice pretreated with PMB, the levels of ALT and LDH isozyme leakage 7 h after rhTNF/GalN injection were significant decreased as compared with those in mice treated with rhTNF/GalN . Similarly, injection of PMB markedly decreased lipid peroxide formation in the liver of the GalN-sensitized mice treated with rhTNF . The injection of a low endotoxin dose (0.1 mg/kg, i.p.) markedly increased the lethality in mice treated with rhTNF (5x10(3) U/mouse, i.v.) and GalN, and these animals showed 100% mortality at 8 h . These findings suggested that the extent of TNF-induced toxicity caused by GalN administration may be a result of synergism between TNF and gut-derived endotoxin . It is likely that endogenously produced endotoxin play a significant role in rhTNF/GalN-hypersensitized mice. Med Pregl, 2000 May-Jun, 53(5-6), 289 - 92 {Therapy of inflammatory changes in Bartholin's glands}; Bulatovic S et al.; INTRODUCTION: Bartholin's glands are bilateral structures whose function begins after puberty, so the diseases of these glands are most common during the reproductive period . Management of the inflammatory changes--abscess and cyst can be invasive and conservative, and quite often the changes become chronic, due to the failure of techniques . The aim of the study was to assess efficacy of various therapeutic approaches in the treatment of the inflammatory changes of Bartholin's glands . MATERIAL AND METHODS: The study was done at the Department of Obstetrics and Gynecology, Clinical Centre in Novi Sad, during the period 1993-1996, at the Dept . of Inflammatory Gynaecological Diseases . The total of 129 patients was treated . The first two years were analyzed retrospectively while during the years 1995 and 1996 a prospective study was done . The analysis of the therapeutic results was done according to the immediate efficacy of the therapeutic approach, incidence of recurrence, length of hospitalization and use of antibiotics . RESULTS: A total of 129 patients was treated, the mean age was 35.4 years . Cysts were treated in 14.7% and abscess in 85.3% of cases . Therapeutic approaches were different during different years . During 1993 and 1994 in majority of cases incision and complete extirpation of the glands were done, and rarely marsupialization, alone or in combination with silver nitrate (AgNO3) . In 1995 and 1996 in a majority of cases incision of the gland was performed, together with the AgNO3 application (94.3% in 1995, 64% in 1996) . In 1995 total gland extirpation was performed (5.7%) while in 1996 in 9 cases (36%) incision was done . The length of hospitalization was longer in earlier years, the shortest being when incision and AgNO3 application was performed (3.1/2.4 days) . The use of antibiotics was significantly lower in the years when incision and AgNO3 were used . DISCUSSION: Our results are in concordance with the results of similar studies except for the fact that in our group the changes were seen more often in the age group 30-39 years . The parity was of no significance . The recurrence of the disease when this method is applied is the same as in other studies--around 3%, whereas the complications were rare . The length of hospitalization and the cost of the antibiotic therapy is of great significance as well, and they can be brought to minimum by employment of this method . CONCLUSION: The therapeutic approach of incision and AgNO3 application in therapy of inflammatory changes of Bartholin's glands is an efficient, safe, simple and cheap method, which can easily be applied in ambulatory conditions. Arch Intern Med, 2000 Nov 27, 160(21), 3243 - 7 Clinical signs and symptoms predicting influenza infection; Monto AS et al.; BACKGROUND: New antiviral drugs are available for the treatment of influenza type A and type B infections . In clinical practice, antiviral use has rarely been guided by antecedent laboratory diagnosis . Defined clinical predictors of an influenza infection can help guide timely therapy and avoid unnecessary antibiotic use . OBJECTIVE: To examine which clinical signs and symptoms are most predictive of influenza infection in patients with influenza-like illness using a large data set derived from clinical trials of zanamivir . METHODS: This analysis is a retrospective, pooled analysis of baseline signs and symptoms from phase 2 and 3 clinical trial participants . It was conducted in mainly unvaccinated (mean age, 35 years) adults and adolescents who had influenza-like illness, defined as having fever or feverishness plus at least 2 of the following influenza-like symptoms: headache, myalgia, cough, or sore throat who underwent laboratory testing for influenza . Clinical signs and symptoms were evaluated in statistical models to identify those best predicting laboratory confirmation of influenza . RESULTS: Of 3744 subjects enrolled with baseline influenza-like symptoms, and included in this analysis, 2470 (66%) were confirmed to have influenza . Individuals with influenza were more likely to have cough (93% vs 80%), fever (68% vs 40%), cough and fever together (64% vs 33%), and/or nasal congestion (91% vs 81%) than those without influenza . The best multivariate predictors of influenza infections were cough and fever with a positive predictive value of 79% (P< . 001) . The positive predictive value rose with the increase in the temperature at the time of recruitment . CONCLUSION: When influenza is circulating within the community, patients with an influenza-like illness who have both cough and fever within 48 hours of symptom onset are likely to have influenza and the administration of influenza antiviral therapy may be appropriate to consider . Arch Intern Med . 2000;160:3243-3247. J Cell Biol, 2000 Nov 27, 151(5), 1025 - 34 Dissection of autophagosome biogenesis into distinct nucleation and expansion steps; Abeliovich H et al.; Rapamycin, an antifungal macrolide antibiotic, mimics starvation conditions in Saccharomyces cerevisiae through activation of a general G(0) program that includes widespread effects on translation and transcription . Macroautophagy, a catabolic membrane trafficking phenomenon, is a prominent part of this response . Two views of the induction of autophagy may be considered . In one, up-regulation of proteins involved in autophagy causes its induction, implying that autophagy is the result of a signal transduction mechanism leading from Tor to the transcriptional and translational machinery . An alternative hypothesis postulates the existence of a dedicated signal transduction mechanism that induces autophagy directly . We tested these possibilities by assaying the effects of cycloheximide and specific mutations on the induction of autophagy . We find that induction of autophagy takes place in the absence of de novo protein synthesis, including that of specific autophagy-related proteins that are up-regulated in response to rapamycin . We also find that dephosphorylation of Apg13p, a signal transduction event that correlates with the onset of autophagy, is also independent of new protein synthesis . Finally, our data indicate that autophagosomes that form in the absence of protein synthesis are significantly smaller than normal, indicating a role for de novo protein synthesis in the regulation of autophagosome expansion . Our results define the existence of a signal transduction-dependent nucleation step and a separate autophagosome expansion step that together coordinate autophagosome biogenesis. J Biol Chem, 2001 Mar 2, 276(9), 6529 - 36 Epub 2000 Nov 20. Activation of the endothelial nitric-oxide synthase by tumor necrosis factor-alpha . A novel feedback mechanism regulating cell death; Bulotta S et al.; Cell death via apoptosis induced by tumor necrosis factor-alpha (TNF-alpha) plays an important role in many physiological and pathological conditions . The signal transduction pathway activated by this cytokine is known to be regulated by several intracellular messengers . In particular, in many systems nitric oxide (NO) has been shown to protect cells from TNF-alpha-induced apoptosis . However, whether NO can be generated by the cytokine to down-regulate its own apoptotic program has never been studied . We have addressed this question in HeLa Tet-off cell clones stably transfected with the endothelial NO synthase under a tetracycline-responsive promoter . Endothelial NO synthase, induced about 100-fold in these cells by removal of the antibiotic, retained the characteristics of the native enzyme of endothelial cells, both in terms of intracellular localization and functional activity . Expression of the endothelial NO synthase was sufficient to protect from TNF-alpha-induced apoptosis . This protection was mediated by the generation of NO . TNF-alpha itself stimulated endothelial NO synthase activity to generate NO through a pathway involving its lipid messenger, ceramide . Our results identify a novel mechanism of regulation of a signal transduction pathway activated by death receptors and suggest that NO may constitute a built-in mechanism by which TNF-alpha controls its own apoptotic program. J Gynecol Obstet Biol Reprod (Paris), 2000 Oct, 29(6), 599 - 606 {Premature rupture of the membranes between 28 and 34 weeks of amenorrhea . Retrospective study apropos of 71 cases}; Mehdi A et al.; OBJECTIVE: The aim of our study is to compare the outcome of infants born after preterm premature rupture of the membranes (PPROM) between 28 and 34 weeks gestation . We compare two groups of infants: group A, infants born in hospitals without neonatal intensive care unit, after PPROM with long tocolysis, no maternal prophylactic antibiotic therapy and no systematic maternal steroid therapy . Group B with systematic maternal steroid therapy, maternal prophylactic antibiotic therapy, short tocolysis and born in an hospital with neonatal intensive care unit . The latency period (time from rupture of membranes to the onset of labor) authorized was 15 days in the group B and not limited in the group A . RESULTS: Death (13.8% vs 0%; p=0.022), neonatal infection (66.6% vs 28.6%; p=0.0013), and respiratory distress (63.8% vs 34.3%; p=0.0144) were less frequent in the group B . The group A infants passed more than ten days in intensive care unit (61.1% vs 37.1%; p=0.043) . Neonatal infection was not higher in the corticosteroid therapy group (41.2% vs 70.3%; p=0.0135) . There is more neonatal infection in the group A with long latency period (61.7% vs 24.3%; p=0.0014) and more chorioamnionitis (70.6% vs 24.3%; p<0.0001) . CONCLUSION: The association maternal steroid and antibiotic therapy, short latency period, and hospitalization of the pregnant woman close to a neonatal intensive care unit reduce significantly the neonatal morbidity after preterm premature rupture of the membranes. Injury, 2000 Nov, 31(9), 687 - 92 Total elbow arthroplasty as primary treatment for distal humeral fractures in elderly patients; Ray PS et al.; Distal humeral fractures are difficult to treat . In the elderly population, the problems are compounded by osteoporosis and gross comminution . Open reduction and internal fixation for such fractures is sometimes difficult and may be associated with poor results . Total elbow arthroplasty has been suggested as a last-ditch effort to salvage functional use for such difficult fractures in the elderly . We followed seven patients (seven elbows) with a mean age of 81.7 years at the time of injury . Open reduction and internal fixation was considered a difficult option for these fractures . They were treated with a total elbow arthroplasty using the semi-constrained Coonrad-Morrey elbow replacement prosthesis . The duration of follow up at present is between 2 and 4 years . At the latest follow up the mean arc of flexion is 20-130 degrees . Six patients have no pain while one complains of mild pain . All elbows are stable . The Mayo elbow performance score for five elbows is excellent and two scored good . All but one patient are satisfied with the result . One patient developed superficial wound infection which resolved after antibiotic therapy . One patient has developed post-operative triceps weakness . There have been no cases of deep infection, ulnar nerve neuritis or component failure . The rarity of this procedure suggests its very narrow spectrum of indication . We feel that the short-term results do suggest an important role for semi-constrained total elbow arthroplasty in managing carefully selected comminuted distal humeral fractures in the elderly, especially those that cannot be treated by conventional open reduction and internal fixation. Antimicrob Agents Chemother, 2000 Dec, 44(12), 3381 - 8 Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis; Roberts J et al.; The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis . Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls . Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge . Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis . Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues . The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either drug was seen after 6 days of treatment . Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B . Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection. Org Lett, 2000 Nov 2, 2(22), 3493 - 6 Synthesis of the functionalized tricyclic core of lactonamycin by oxidative dearomatization; Cox C et al.; {reaction: see text} We report in this Letter a synthesis of the densely oxygenated CDEF ring system (27) corresponding to that found in the recently discovered antibiotic lactonamycin . The key steps in the synthesis consist of an intramolecular Wessely oxidative lactonization of acid 18, followed by a hydroxyl-directed epoxidation of enol ether 21. Gac Med Mex, 2000 Sep-Oct, 136(5), 449 - 54 {Pneumonia complicated with empyema in children, to operate or not? Risk factors for surgery and review of the literature}; Furuya-Meguro ME et al.; The precise indication for surgery for pleural empyema is still a controversy . With the aim of identifying the risk factors associated with surgery in pediatric patients with empyema post-pneumonia, a retrospective case control study was performed . From 1992 to 1996, 18 children underwent surgery (cases) and 12 did not (controls) . The analyzed variables were those mentioned in the literature as risk factors . More than 25 days of evolution, more than three antibiotic schemes, fever, empyema organizing phase, two or more chest tubes lasting more than nine days, multiple loculations, trapped lung and paquipleura were associated with thoracostomy and decortication (p < 0.05) . We conclude that a pediatric patient with a late referral to the hospital, empyema organizing phase, and multiple loculations with large purulent collections no longer susceptible to drainage and complications that impair lung expansion will probably require major surgery. J Antibiot (Tokyo), 2000 Aug, 53(8), 828 - 36 Production of a new hybrid anthracycline 4-O-methylepelmycin by heterologous expression of dnrK in epelmycin-producing Streptomyces violaceus; Miyamoto Y et al.; A new hybrid anthracycline antibiotic was produced by heterologous expression of dnrK encoding carminomycin 4-O-metyltransferase in an epelmycin-producing Streptomyces violaceus . pMK100 was constructed by insertion of Steptomyces peucetius dnrK gene in Steptomyces-expression vector pIJ6021 and introduced to the epelmycin producer . The transformant produced a hybrid anthracycline antibiotic together with host epelmycins when cultured in antibiotic production medium in the presence of thiostrepton . The hybrid anthracycline was determined to be 7-O-L-rhodosaminyl-4-O-methyl-epsilon-rhodomycinone (4-O-methylepelmycin D) . However, the attempts on production of hybrid 4-O-methylaclarubicin and 4-O-methyl-1-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers with pMK 100 were unsuccessful. Yonsei Med J, 2000 Oct, 41(5), 556 - 62 Viability of cells in cryopreserved canine cardiovascular organs for transplantation; Park JC et al.; To determine applicability of the cryopreservation procedure for vessel grafts, the viability of endothelial cells (ECs) among the whole cells in three kinds of organs artery, vein, trachea in mongrel dogs was evaluated on the basis of histological analysis . The Griffonia simplicifolia agglutins-fluorescein isothiocyanate (GSA-FITC) and propidium iodide (PI) double staining methods were combined with flow cytometry (FCM), which was able to simultaneously determine the viability of whole cells and ECs from the same tissue, were performed after harvesting, after antibiotic solution treatment, and after cryopreservation and thawing . In most cases, the viability of ECs is lower than that of whole cells from veins and arteries . The viability of whole cells in veins was maintained until the antibiotic solution treatment and then decreased significantly after cryopreservation and thawing, while the ECs began to decrease significantly after the antibiotic solution treatment and more markedly decreased after thawing . The viability of ECs and whole cells from arteries was similar to that of the veins' conditions . The viability of whole cells from the trachea decreased with a similar pattern to that of the ECs from vessels . In consideration of maintaining cell viability among the three kinds of organs, the viability of arteries was better than that of the others . The cells in the trachea demonstrated a lower viability than the vessels . The effect of antibiotic solution treatment on the reduction of cell viability depends on the treatment time and temperature. J Dent Res, 2000 Oct, 79(10), 1808 - 14 Cytokine responses of oral epithelial cells to Porphyromonas gingivalis infection; Sandros J et al.; Accumulating evidence indicates that epithelia are not merely mechanical barriers but also important elements of the innate immune system . The present study was performed to examine cytokine responses of oral epithelial cells after infection with the periodontal pathogen Porphyromonas gingivalis . The KB-cell line and primary cultures of periodontal pocket epithelium were infected with P . gingivalis for assessment of bacterial invasion by an antibiotic protection assay, and examination of expression of interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha by in situ hybridization and immunohistochemistry . We observed that P . gingivalis induces a strong cytokine response, positively correlated with the adhesive/invasive potential of the infecting strain, in both KB cells and primary cultures . These findings indicate that the epithelial cells of the periodontal pocket are an integral part of the immune system, eliciting cytokine responses to a bacterial challenge . In this context, the adhesive/invasive phenotype of P . gingivalis appears to contribute to pathogenicity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000 Nov, 90(5), 564 - 6 Intracranial placement of a nasogastric tube after severe craniofacial trauma; Ferreras J et al.; Complications of intracranial placement of a nasogastric tube in patients with complex facial and skull base fractures are infrequent, though the associated morbidity and mortality are high . In such situations some authors advocate craniotomy to allow removal of the tube in several linear segments under direct visualization . Others advise tube removal nasally under antibiotic coverage . We present a case of complex craniofacial fracture in which a nasogastric tube was positioned intracranially 48 hours after admission . The tube was quickly removed through the nose, and the patient was discharged without neurologic problems. Acta Crystallogr C, 2000 Nov, 56 Pt 11, 1372 - 3 Norfloxacin dihydrate; Florence AJ et al.; The antibiotic norfloxacin recrystallizes from acetonitrile as a dihydrate with the norfloxacin molecule in a zwitterionic form, i.e . 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazin-4-io)-3-quinolinecarboxylate dihydrate, C(16)H(18)FN(3)O(3).2H(2)O. Acta Crystallogr C, 2000 Nov, 56 Pt 11, 1343 - 5 Tetracycline hydrochloride: a synchrotron microcrystal study; Clegg W et al.; The title compound, {(4S,4aS,5aS,6S,12aS)-2-aminohydroxymethylene-1, 2,3,4,4a,5,5a,6,11,12a-decahydro-6,10,12,12a-tetrahydroxy-6-methyl -1, 3,11-trioxonaphthacen-4-yl}dimethylammonium chloride, C(22)H(25)N(2)O(8)(+).Cl(-), a well known antibiotic, has been structurally characterized from an individual coarse powder grain by use of high-intensity synchrotron radiation, in conjunction with an exercise in ab initio powder diffraction structure solution . Free refinement of all H atoms establishes the major tautomeric form of the protonated tetracycline molecule without prejudice . The molecule has extensive intramolecular hydrogen bonding involving most of the potential donors and acceptors, and all intermolecular hydrogen bonding uses the chloride anion as acceptor. J Mol Microbiol Biotechnol, 2000 Oct, 2(4), 551 - 6 Application of redD, the transcriptional activator gene of the undecylprodigiosin biosynthetic pathway, as a reporter for transcriptional activity in Streptomyces coelicolor A3(2) and Streptomyces lividans; van Wezel GP et al.; redD encodes the transcriptional activator of the biosynthetic pathway for undecylprodigiosin, a red-pigmented, mycelium-bound antibiotic made by Streptomyces coelicolor A3(2) and Streptomyces lividans . A promoterless version of redD preceded by the efficiently used tuf1 ribosome binding site was inserted into two different plasmid vectors, providing a convenient reporter of transcriptional activity in both species . One plasmid, plJ2587, replicates autonomously in both Escherichia coli and streptomycetes, while the other, plJ2585, replicates in E . coli and can be transferred to streptomycetes by conjugation or transformation, whereupon it integrates stably at the chromosomal attachment site for the temperate phage phiC31 . The utility of the plasmids in detecting not only transcriptional activity, but also its regulation, was confirmed using the rrnAp, ermEp*, and glnRp promoters . The ability to screen visually and spectrophotometrically for red pigmentation should make the vectors particularly attractive for analysing the regulation of gene expression, and for the isolation of mutants, in both S . coelicolor and S . lividans. Pediatr Radiol, 2000 Oct, 30(10), 677 - 80 Ilio-psoas abscess in neonates: treatment by ultrasound-guided percutaneous drainage; Dib M et al.; Ilio-psoas abscess is rare in neonates and is usually treated by surgical drainage . We report two cases of ilio-psoas abscess in 15- and 21-day-old infants successfully treated by US-guided percutaneous drainage as a supplement to antibiotic therapy . Clinical improvement was observed within 24-48 h of drainage and subsequent imaging demonstrated resolution of the abscess cavity . The analysis of these cases and of those previously reported indicates that imaging is essential for diagnosis . In neonates, US-guided percutaneous drainage may represent the first-choice treatment of this disease in association with antibiotic therapy. J Biol Chem, 2001 Feb 2, 276(5), 3702 - 8 Epub 2000 Nov 08. Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90; Xu W et al.; ErbB receptors are a family of ligand-activated tyrosine kinases that play a central role in proliferation, differentiation, and oncogenesis . ErbB2 is overexpressed in >25% of breast and ovarian cancers and is correlated with poor prognosis . Although ErbB2 and ErbB1 are highly homologous, they respond quite differently to geldanamycin (GA), an antibiotic that is a specific inhibitor of the chaperone protein Hsp90 . Thus, although both mature and nascent ErbB2 proteins are down-regulated by GA, only nascent ErbB1 is sensitive to the drug . To reveal the underlying mechanism behind these divergent responses, we made a chimeric receptor (ErbB1/2) composed of the extracellular and transmembrane domains of ErbB1 and the intracellular domain of ErbB2 . The ErbB1/2 protein is functional since its kinase activity was stimulated by epidermal growth factor . The sensitivity of ErbB1/2 to GA was similar to that of ErbB2 and unlike that of ErbB1, indicating that the intracellular domain of the chimera confers GA sensitivity . This finding also suggests that the GA sensitivity of mature ErbB2 depends on cytosolic Hsp90, rather than Grp94, a homolog of Hsp90 that is restricted to the lumen of the endoplasmic reticulum, although both chaperones bind to and are inhibited by GA . Lack of Grp94 involvement in mediating ErbB2 sensitivity to GA is further suggested by the fact that a GA derivative with low affinity for Grp94 efficiently depleted ErbB2 protein in treated cells . To localize the specific region of ErbB2 that confers GA sensitivity, we made truncated receptors with progressive deletions of the cytoplasmic domain and tested the GA sensitivity of these molecules . We found that ErbB2 constructs containing an intact kinase domain retained GA sensitivity, whereas those lacking the kinase domain (ErbB2/DK) lost responsiveness to GA completely . Hsp90 co-immunoprecipitated with all ErbB2 constructs that were sensitive to GA, but not with ErbB2/DK or ErbB1 . Both tyrosine-phosphorylated and non-phosphorylated ErbB2 proteins were similarly sensitive to GA, as was a kinase-dead ErbB2 mutant . These data suggest that Hsp90 uniquely stabilizes ErbB2 via interaction with its kinase domain and that GA stimulates ErbB2 degradation secondary to disruption of ErbB2/Hsp90 association. Acta Paediatr, 2000 Sep, 89(9), 1068 - 71 Middle ear effusion IL-6 concentration in bacterial and non-bacterial acute otitis media; Barzilaia A et al.; BACKGROUND: The pathogenesis of acute otitis media is complex and multifactorial . It is characterized by inflammation of the middle ear with an infiltration of leukocytes, macrophages and mast cells . The resulting effusion contains a large amount of inflammatory mediators, among which are cytokines . OBJECTIVES: To test the role of IL-6 in the inflammatory process associated with acute otitis media . METHODS: We analyzed 20 middle ear fluid (MEF) sample pairs, obtained by aspiration before initiating antibiotic therapy (day 1) and during treatment (days 4-5), for the presence of IL-6 . IL-6 concentrations were assayed with an ELISA kit (detection limit 5 pg/ml) and were correlated with bacterial etiology and bacterial eradication from the middle ear . RESULTS: IL-6 was detected in all middle ear effusions analyzed . We found decreased IL-6 concentrations in culture negative MEF compared to culture positive MEF on both days I and 4-5 (day 1, 1752.20+/-1001.31 pg/ml vs 1216.20+/-1015.44 pg/ml, p = 0.19; days 4-5, 1049.36+/-472.40 pg/ml vs 800.33+/-676.00 pg/ml, p = 0.23); however, differences did not achieve statistical significance . Overall, a marked and significant decrease in IL-6 concentration occurred following 72-96 h of antibiotic therapy (1618.15+/-1004.88 pg/ml vs 936.85+/-581.05 pg/ml, p = 0.04) . While MEF IL-6 concentrations decreased in ears where bacteria persisted (1468.20+/-858.48 pg/ml vs 1044.80+/-514.16 pg/ml, p = 0.167) or were eradicated (2320.20+/-866.16 pg/ml vs 767.40+/-522.88 pg/ml, p = 0.029), a more prominent decline was demonstrated in the latter . CONCLUSIONS: These results strongly suggest the involvement of IL-6 in the ongoing inflammatory process in both bacterial and non-bacterial acute otitis media . Resolution of inflammation in the middle ear, especially where bacteria were eradicated, is reflected by low IL-6 levels. Mol Microbiol, 2000 Nov, 38(3), 482 - 92 The quarternary molecular architecture of TetA, a secondary tetracycline transporter from Escherichia coli; Yin CC et al.; TetA, a tetracycline cation/proton antiporter, was expressed in Escherichia coli with a C-terminal tag of six histidines, solubilized in dodecyl maltoside and purified in a single step using Ni2+ affinity chromatography . Two-dimensional crystals were obtained after reconstitution of purified protein with lipids . Electron microscopy of negatively stained crystals revealed a trigonal symmetry, from which we infer that this secondary transporter has a trimeric structure . An overall molecular envelope can be described by a triangle of side approximately 100 A enclosing a central stain-filled depression . These dimensions are consistent with those obtained from projection views of single, isolated TetA particles that also display a trimeric architecture, confirming that the threefold symmetry is not simply a consequence of crystal-packing interactions . These data represent the first direct view of the quarternary arrangement of any antibiotic efflux pump . They are fully consistent with biochemical data on TetA, which indicate that it functions as a multimer and that the monomer consists of two domains, one of which plays the major part in oligomerization interactions. Can J Microbiol, 2000 Oct, 46(10), 956 - 60 Isolation of a chitinase overproducing mutant of Streptomyces peucetius defective in daunorubicin biosynthesis; Vetrivel KS et al.; Streptomyces peucetius, producer of the antitumor anthracycline antibiotic daunorubicin, was mutagenized, and mutants defective in daunorubicin biosynthesis were screened . One mutant (SPVI), which failed to produce daunorubicin, was found to overproduce an extracellular chitinase . Time course analyses of chitinase production and of the extracellular protein profile showed that the increase in activity is due to increased synthesis of the enzyme protein . The production of chitinase in SPVI was repressed by glucose as in the case of wild-type S . peucetius . PFGE analysis of VspI restriction fragments of S . peucetius and SPVI showed that there was no major alteration in the mutant genome . The hybridization pattern of S . peucetius and SPVI genomic DNA digested with various restriction enzymes was identical when probed with dnrUVJI genes of the S . peucetius daunorubicin cluster and chiA of Streptomyces lividans 66 . The possible step affected in the daunorubicin biosynthetic pathway could be a polyketide synthase, since aklanonic acid, the earliest detectable intermediate in the daunorubicin pathway, was not synthesized in SPVI. JAMA, 2000 Nov 8, 284(18), 2361 - 7 Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients; Girou E et al.; CONTEXT: Invasive life-support techniques are a major risk factor for nosocomial infection . Noninvasive ventilation (NIV) can be used to avoid endotracheal intubation and may reduce morbidity among patients in intensive care units (ICUs) . OBJECTIVE: To determine whether the use of NIV is associated with decreased risk of nosocomial infections and improved survival in everyday clinical practice among patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) or hypercapnic cardiogenic pulmonary edema (CPE) . DESIGN AND SETTING: Matched case-control study conducted in the medical ICU of a French university hospital from January 1996 through March 1998 . PATIENTS: Fifty patients with acute exacerbation of COPD or severe CPE who were treated with NIV for at least 2 hours and 50 patients treated with mechanical ventilation between 1993 and 1998 (controls), matched on diagnosis, Simplified Acute Physiology Score II, Logistic Organ Dysfunction score, age, and no contraindication to NIV . MAIN OUTCOME MEASURES: Rates of nosocomial infections, antibiotic use, lengths of ventilatory support and of ICU stay, ICU mortality, compared between cases and controls . RESULTS: Rates of nosocomial infections and of nosocomial pneumonia were significantly lower in patients who received NIV than those treated with mechanical ventilation (18% vs 60% and 8% vs 22%; P<.001 and P =.04, respectively) . Similarly, the daily risk of acquiring an infection (19 vs 39 episodes per 1000 patient-days; P =.05), proportion of patients receiving antibiotics for nosocomial infection (8% vs 26%; P =.01), mean (SD) duration of ventilation (6 {6} vs 10 {12} days; P =.01), mean (SD) length of ICU stay (9 {7} vs 15 {14} days; P =.02), and crude mortality (4% vs 26%; P =.002) were all lower among patients who received NIV than those treated with mechanical ventilation . CONCLUSIONS: Use of NIV instead of mechanical ventilation is associated with a lower risk of nosocomial infections, less antibiotic use, shorter length of ICU stay, and lower mortality . JAMA . 2000;284:2361-2367. Clin Orthop, 2000 Nov, (380), 234 - 40 The anterior T-frame external fixator for high-energy proximal tibial fractures; Bal GK et al.; The authors' experience using anterior T-frame external fixation combined with percutaneous internal fixation for treatment of high-energy proximal tibial fractures is reported . Thirty-six patients (38 fractures) were reviewed who were treated during a consecutive 42-month period . Three patients died and one patient had an amputation for a Type IIIC open injury, leaving 20 males and 12 females with 21 closed and 13 open fractures (two Type II, seven Type IIIA, three Type IIIB, and one Type IIIC) . The average followup was 26 months . Fractures united at a mean of 20 weeks . Ten secondary surgical procedures were planned, including seven antibiotic bead removals with autogenous bone grafting and three soft tissue coverage procedures . Nine (26%) complications were found, including one deep infection (septic arthritis) and three pin tract infections, and one each malunion, nonunion, refracture, knee stiffness requiring manipulation under anesthesia, and deep venous thrombosis . The average Knee Society score was 85 for pain and 83 for function . All patients achieved full knee extension and mean flexion was 125 degrees . The anterior T-frame external fixator with percutaneous internal fixation is a reliable method to stabilize these injuries . It is simple, inexpensive, and effective. J Clin Pathol, 2000 Oct, 53(10), 770 - 3 Expression of human alpha-defensin 5 (HD5) mRNA in nasal and bronchial epithelial cells; Frye M et al.; BACKGROUND/AIMS: Human defensins are antibiotic peptides expressed in myeloid and epithelial cells . Human alpha-defensin 5 (HD5) has been detected in Paneth cell granules in the crypts of Lieberkuhn and has recently been identified in the female reproductive tract . The aim of this study was to investigate the presence of HD5 mRNA in nasal and bronchial epithelial cells . METHODS/RESULTS: Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis showed that HD5 mRNA was expressed infrequently and to varying degrees in bronchial and nasal epithelial cells . In situ hybridisation resulted in a positive signal in the epithelial layer of nasal polyps . HD5 mRNA was locally restricted to a specific area of epithelial cells and also occurred in submucosal glands . CONCLUSIONS: HD5 mRNA expression in nasal and bronchial epithelial cells is rare and seemed to be locally induced . The results indicate that HD5 might play a role in innate defence in nasal and bronchial epithelia. Pediatr Emerg Care, 2000 Oct, 16(5), 352 - 4 Pyomyositis of the leg with early neurologic compromise; Bibbo C et al.; Pyomyositis, although uncommon, is being reported with greater frequency in temperate climates . The presentation is similar to a number of infectious processes, and when associated with a traumatic event, the clinical picture may be confused with that of a musculoskeletal injury . This, coupled with an unfamiliarity of the disease, may result in a delay in diagnosis . Early antibiotic therapy may obviate surgery . Progression to the suppurative stage requires surgical drainage along with antibiotics . CT guided drainage may be accomplished in certain cases . In immunocompromised patients, progression to the septicemic stage is associated with high morbidity and mortality. Harefuah, 2000 Oct, 139(7-8), 278 - 9, 326 {Thrombocytopenic purpura as sole manifestation of brucellosis in children}; Marom R et al.; Thrombocytopenic purpura associated with brucellosis has rarely been described in children . The thrombocytopenic purpura is usually part of the array of manifestations of brucellosis, such as fever, malaise, arthralgia, arthritis, hepatosplenomegaly and lymphadenopathy . We describe a 4-year-old girl in whom severe thrombocytopenic purpura was the only manifestation of brucellosis and resolved after appropriate antibiotic therapy . We conclude that brucellosis should be included in the differential diagnosis of thrombocytopenic purpura in areas endemic for brucellosis, and when there is a history of exposure to infected food products. J Am Med Inform Assoc, 2000 Nov-Dec, 7(6), 593 - 604 Automatic detection of acute bacterial pneumonia from chest X-ray reports; Fiszman M et al.; OBJECTIVE: To evaluate the performance of a natural language processing system in extracting pneumonia-related concepts from chest x-ray reports . METHODS: DESIGN: Four physicians, three lay persons, a natural language processing system, and two keyword searches (designated AAKS and KS) detected the presence or absence of three pneumonia-related concepts and inferred the presence or absence of acute bacterial pneumonia from 292 chest x-ray reports . Gold standard: Majority vote of three independent physicians . Reliability of the gold standard was measured . Outcome measures: Recall, precision, specificity, and agreement (using Finn's R: statistic) with respect to the gold standard . Differences between the physicians and the other subjects were tested using the McNemar test for each pneumonia concept and for the disease inference of acute bacterial pneumonia . RESULTS: Reliability of the reference standard ranged from 0.86 to 0.96 . Recall, precision, specificity, and agreement (Finn R:) for the inference on acute bacterial pneumonia were, respectively, 0.94, 0.87, 0.91, and 0.84 for physicians; 0.95, 0.78, 0.85, and 0.75 for natural language processing system; 0.46, 0.89, 0.95, and 0.54 for lay persons; 0.79, 0.63, 0.71, and 0.49 for AAKS; and 0.87, 0.70, 0.77, and 0.62 for KS . The McNemar pairwise comparisons showed differences between one physician and the natural language processing system for the infiltrate concept and between another physician and the natural language processing system for the inference on acute bacterial pneumonia . The comparisons also showed that most physicians were significantly different from the other subjects in all pneumonia concepts and the disease inference . CONCLUSION: In extracting pneumonia related concepts from chest x-ray reports, the performance of the natural language processing system was similar to that of physicians and better than that of lay persons and keyword searches . The encoded pneumonia information has the potential to support several pneumonia-related applications used in our institution . The applications include a decision support system called the antibiotic assistant, a computerized clinical protocol for pneumonia, and a quality assurance application in the radiology department. J Antimicrob Chemother, 2000 Nov, 46(5), 831 - 4 Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits; Ghelardi E et al.; This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics . Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide . Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone . The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics. Adv Skin Wound Care, 2000 Jan-Feb, 13(1), 25 - 9 Osteomyelitis related to pressure ulcers: the cost of neglect; Hirshberg J et al.; Twelve patients with documented chronic osteomyelitis of the pelvis resulting from truncal pressure ulcers were examined retrospectively to identify the cost of treatment for this significant health care problem . The retrospective review of each case spanned an 18-month period--6 months prior to the initial positive bone biopsy to 1 year following bone biopsy . The financial charges associated with treatment of osteomyelitis were identified using the University of Michigan Health System's databases for hospital charges, professional charges, and pharmacy charges . Prior treatment of these patients included surgical debridement of the pressure ulcer, pelvic bone biopsy, and culture-specific antibiotic therapy . The total charges for this group of 12 patients was $715,204, or an average charge of $59,600 per patient . Each patient was hospitalized, with hospitalization charges of $587,212, or an average of $48,934 per patient . Pharmacy charges for culture-specific antibiotics totaled $85,217 for the 12 patients . Six of 8 flap repairs achieved successful surgical closure of the pressure ulcer (75%) postantibiotic therapy . Surgery charges are not included in the totals. Expert Opin Investig Drugs, 2000 Nov, 9(11), 2505 - 17 The association of infection and coronary artery disease: an update; Davydov L et al.; Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections . This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (cytomegalovirus, Chlamydia pneumoniae and Helicobacter pylori) in atherogenesis and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease . The interactions of cytomegalovirus and the arterial wall have been extensively studied . However, despite the successful preliminary therapeutic trials with the use of macrolides in augmenting possible C . pneumoniae-induced cardiovascular events, the exact mechanisms of how C . pneumoniae enters the arterial wall remains unknown at this point . For H . pylori, regardless of the large number of studies performed to assess the association between H . pylori and coronary artery disease, no definitive conclusion could be made at this time, due to contradictory results . Before one can widely adopt the use of antibiotics or antiviral agents as treatment for atherosclerosis, further studies must be designed to address some important issues . In vivo animal models need to be established to further examine the various hypotheses regarding the interaction of infectious agents and atherosclerosis and restenosis . Large-scale prospective cohort studies should be designed to relate evidence of infection to future risk of cardiovascular diseases . Confounding variables, such as other cardiovascular risk factors and socio-economic status, should be controlled in order to strengthen the association . Further interventional studies are also required to establish the best antibiotic or antiviral regimen to maximise efficacy and minimise side effects. Expert Opin Investig Drugs, 2000 Feb, 9(2), 273 - 99 Antifungal peptides: potential candidates for the treatment of fungal infections; De Lucca AJ; Many diversely produced natural peptides, as well as those produced semisynthetically and synthetically, have been found to inhibit the growth or even be lethal to a wide range of fungi . Some of these have the potential to aid mankind in combating mycoses caused by emerging pathogens or as a result of the increasing number of antibiotic-resistant fungi . Antifungal peptides may also assist in non-medical fields such as agriculture . For example, introduction by transgenic research of antifungal peptides could improve crop production yields by increasing host resistance to fungal invasion . The aim of this review is to provide information on research on these important peptides. Surg To