Eur J Surg, 1998 Nov, 164(11), 825 - 9 Predictors of recurrence of fulminant bacterial peritonitis after discontinuation of antibiotics in open management of the abdomen; Visser MR et al.; OBJECTIVE: To assess a scoring system for predicting recurrence of fulminant bacterial peritonitis after discontinuation of antimicrobial treatment in patients being treated by open management of the abdomen for persistent bacterial peritonitis after perforation of the digestive tract, anastomotic disruption, or necrotising pancreatitis . DESIGN: Retrospective study . SETTING: University Hospital, The Netherlands . SUBJECTS: 58 consecutive patients . MAIN OUTCOME MEASUREMENTS: Recurrence of fulminant bacterial peritonitis and survival . RESULTS: 13 of the 58 patients (22%) died during the initial course of antimicrobial drugs . 14 of the remaining 45 patients had a recurrence of fulminant bacterial peritonitis after discontinuation of antimicrobial drugs, 4 of whom died . Predictive criteria included raised white cell count (WCC) (p = 0.02), duration of initial antibiotic treatment (p = 0.05), and deterioration in Simplified Acute Physiology Score (p = 0.05) . Using the WCC and the duration of initial antimicrobial treatment together with other variables that showed a predictive trend (body temperature, percentage band cells, underlying disease, and use of inotropic agents), in a new scoring system (0-12), fulminant bacterial peritonitis did not recur when the score was 0-3, but in 9 of 11 patients with a score of 6 or more it did (p < 0.001) . CONCLUSION: Patients at increased risk of recurrence of fulminant bacterial peritonitis during open management of the abdomen can be identified at the time of discontinuation of antimicrobial treatment by a new scoring system; antimicrobial treatment should not be discontinued in patients with a score of 6 or more. Int J Radiat Oncol Biol Phys, 1998 Nov 1, 42(4), 755 - 62 Bioreductive therapies: an overview of drugs and their mechanisms of action; Rauth AM et al.; PURPOSE: Bioreductively activated drugs have been used as antimicrobials, chemotherapeutic agents, and radiation sensitizers . The present paper is an overview of their mechanism of action and application in the treatment of cancer . MATERIALS AND METHODS: Drugs such as nitroimidazoles, mitomycins, and benzotriazine di-N-oxides were a focus of this research . Studies have ranged from the chemistry of the reductive process of activation to in vitro and in vivo studies in rodent and human cells, through to clinical testing . The variety of techniques and test systems brought to bear on these compounds is a strength of this field of research . RESULTS: A detailed chemical understanding of the mechanism of action of a variety of bioreductives is now available . The enzymatic processes by which these drugs are activated and the cofactors involved in this activation are becoming well understood . Recent advances have been made in the design and use of dual-function bioreductives, bioreductive triggers of drug activation, and DNA-targeted bioreductives . Significant success has been demonstrated clinically with bioreductive drugs, used in combination with radiation and front-line chemotherapeutic agents . The areas of antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT) are identified as new directions for bioreductive therapy . CONCLUSION: The use of bioreductively-activated drugs for the treatment of cancer has made steady progress . The success obtained clinically and the new molecular approaches currently being implemented promise significant advances in the future. Intensive Care Med, 1998 Oct, 24(10), 1106 - 9 Sweet's syndrome associated with systemic inflammatory response syndrome; Matthews PC et al.; Septic shock is characterised by infection causing a systemic inflammatory response, end-organ failure and acute circulatory collapse . Treatment consists of antimicrobial therapy and the supportive management of multi-organ failure . We report a case of what we believed to be septic shock due to pyelonephritis in a patient whose condition continued to deteriorate despite conventional treatment until the diagnosis of Sweet's syndrome was made . Once she was started on high dose steroids, her condition improved and she made a full recovery . We believe this to be the first case of a severe systemic inflammatory response syndrome associated with Sweet's syndrome. J Gastroenterol, 1998, 33 Suppl 10, 57 - 61 Eradication therapy of Helicobacter pylori . A review . Report from a workshop organized by the Swedish and Norwegian Medical Products Agencies, September 1995; Unge P; An expert meeting was organized by the Swedish and Norwegian Medical Products Agencies in September 1995 in order to review the current literature and opinions on detection and treatment of Helicobacter pylori . Ten people from these Agencies and 23 experts participated in the workshop and all were involved in the final manuscript, summarizing the background data and the conclusions (Info Lakemedelsverket 1:96) . This report is limited to the therapeutic issues . Therapeutic effect on H . pylori is shown for tetracyclines, nitroimidazoles, clarithromycin, and amoxicillin . Acid inhibitory drugs or bismuth salts increase the antibacterial activity . In vitro resistance to metronidazole is reported in cultures of 10%-40% of H . pylori-infected patients in Scandinavia . Primary resistance to clarithromycin and tetracyclines is rare and no resistance to amoxicillin is confirmed . The clinical significance of resistance is unclear when effective triple combinations are used in previously untreated patients, but should be considered in treatment failures . Recommended therapeutic regimens should achieve a more than 90% cure rate . Important factors when choosing therapy are efficacy, side-effects, ecological factors, duration of therapy, and cost-benefit . Four triple regimens are effective and relatively well documented: omeprazole/amoxicillin/metronidazole for 1 week, omeprazole/clarithromycin/metronidazole for 1 week, omeprazole/clarithromycin/amoxicillin for 1 week, or bismuth subnitrate or bismuth citrate/tetracycline/metronidazole for 10 days . Side-effects are less pronounced in the combinations without bismuth . Dual therapy is not recommended . Eradication therapy should be considered for patients with peptic ulcer disease, MALT-lymphoma and Menetriere's disease . Triple combinations, including two antimicrobials and a potent acid inhibitory drug or bismuth, are recommended. J Immunol Methods, 1998 Nov 1, 220(1-2), 123 - 8 A method to assess invasion and intracellular replication of Trypanosoma cruzi based on differential uracil incorporation; Yan W et al.; Screening of candidate trypanocidal compounds or factors affecting invasion of mammalian cells by the infective stages of Trypanosoma cruzi in tissue culture models has primarily involved labor-intensive microscopic counting of the parasites . A very efficient method for quantitating the inhibitory effect of antimicrobial agents or signaling pathways inhibitors on T . cruzi grown in L6E9 myoblasts was devised . This assay takes advantage of the selective incorporation of {3H}uracil into nucleic acids by replicating T . cruzi amastigotes . L6E9 rat myoblasts are submitted to gamma irradiation to inhibit their replication . Uracil uptake by uninfected cells is considerably decreased by this method . Nifurtimox, benznidazole, fexinidazole, MK-436, and megazol are drugs known to have activity against T . cruzi and were used in growth inhibition assays . The results demonstrated that {3H}uracil incorporation in the presence of different concentrations of nifurtimox and benznidazole closely correlated with the number of amastigotes per 100 myoblasts in Giemsa-stained monolayers under the conditions used . This method also has the advantage to differentiate between the effects of the compounds on the invasion and the replication steps of the infection with T . cruzi, as shown by the inhibitory effect of genistein when added in invasion assays. J Clin Periodontol, 1998 Nov, 25(11 Pt 2), 959 - 63; discussion 978-9 The use of locally delivered metronidazole in the treatment of periodontitis . Clinical results; Magnusson I; Local delivery of antimicrobials has been investigated as a possible method for controlling and treating periodontal disease . A number of antimicrobial agents have been studied both as adjunctive therapies with scaling and root planing and as stand-alone chemotherapies . More recent investigations have focussed on the delivery of antimicrobials in sustained-release formulations designed to maintain effective concentrations of drug within the periodontal pocket . This article provides an overview of the development of the use of locally-delivered metronidazole in periodontal therapy and the current state-of-the-art of the technique . It is concluded that treatment with local delivery of metronidazole seems to be as effective as scaling and root planing in untreated as well as in recall subjects . However, there are reasons to suggest that local delivery of metronidazole should not be used as a substitute for conventional treatment of periodontal disease, since side-effects of long-term use and repeated use are not known . The antibiotic regimen should preferably be used as an adjunct to surgical and non-surgical therapy. J Clin Periodontol, 1998 Nov, 25(11 Pt 2), 943 - 6; discussion 978-9 Local delivery of chemotherapeutic agents in periodontal therapy: has its time arrived? Finkelman RD, Williams RC. The concept of locally delivering chemotherapeutic agents to the periodontal pocket as a method to treat periodontal disease has been studied for over 20 years . A number of locally delivered chemotherapeutic agents in periodontal therapy are either currently available or under investigation . Clinical efficacy derives from sustained-release technology to maintain an effective concentration of drug within the periodontal pocket for a clinically relevant length of time . Studied drugs have mainly been antimicrobials, both antibiotics and antiseptics . Most agents have been tested as adjuncts to scaling and root planing; a few have been studied as stand-alone monotherapies . Collectively, the data indicate that the use of locally delivered antimicrobials as adjuncts results in a significant increase in the reduction of probing depth compared with scaling and root planing alone . In other trials, results in reducing probing depth following the use of stand-alone locally delivered antimicrobials have been equivalent to those of scaling and root planing over a specified time . This Symposium was organized to present the current state-of-the-art with regard to the use of locally delivered antimicrobials in the treatment of periodontal disease . 5 experts in the field who have had considerable experience in studying locally delivered antimicrobials presented data . These speakers reviewed the clinical findings regarding efficacy of 5 different antimicrobial agents . An ensuing panel discussion was to consider treatment recommendations for locally delivered antimicrobials. Int J Epidemiol, 1998 Oct, 27(5), 904 - 8 Topical antimicrobials applied to the umbilical cord stump: a new intervention against neonatal tetanus; Parashar UD et al.; BACKGROUND: Previous case-control studies of neonatal tetanus (NNT), a leading cause of infant mortality in developing countries, have suggested that antimicrobials applied after delivery to the umbilical cord stump may protect against this disease . However, assessment of their protective effect has been limited by the low prevalence of antimicrobial use in developing countries . METHODS: We conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh . We studied 359 cases (infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT), each matched to three living controls for gender, residence, and date of birth . RESULTS: In univariate analyses, the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants were protective against NNT . The application of antibiotics at delivery (odds ratio {OR} = 0.21, P = 0.019), hand washing by the delivery attendant (OR = 0.64, P = 0.005), and prior maternal immunization with tetanus toxoid (OR = 0.50, P < 0.001) remained protective in conditional logistic-regression analyses . Application of animal dung to the umbilical stump (OR = 2.31, P = 0.047) was hazardous . CONCLUSIONS: Effective and inexpensive topical antimicrobials provide a new prevention opportunity that could be used by traditional birth attendants and mothers to provide additional benefits to NNT control programmes based on maternal immunization with tetanus toxoid . Promotion of hygienic delivery and cord-care practices and increasing tetanus toxoid coverage remain cornerstones for the prevention of NNT deathsPIP: Neonatal tetanus (NNT) is a leading cause of infant mortality in developing countries . Findings from previous case-control studies of NNT have suggested that antimicrobials applied following delivery to the umbilical cord stump may protect against the disease . However, assessment of their protective effect has been hampered by the low prevalence of antimicrobial use in developing countries . The authors conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh . 359 cases were studied, infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT . Each case was matched to 3 living controls for gender, residence, and date of birth . Univariate analyses found the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants to protect against NNT . The application of antibiotics at delivery, hand washing by the delivery attendant, and prior maternal immunization with tetanus toxoid remained protective in conditional logistic-regression analyses . The application of animal dung to the umbilical stump was hazardous . Farmaco, 1998 Jul 30, 53(7), 462 - 7 Synthesis, structure elucidation and antimicrobial activity of some 3-hydroxy-2-naphthoic acid hydrazide derivatives; Dogan HN et al.; In this study, some 1,4-disubstituted thiosemicarbazide, 1,2,4-triazole and 1,3,4-thiadiazole type novel compounds derived from 3-hydroxy-2-naphthoic acid hydrazide were synthesized to screen for their antimicrobial activity . The structures of these substances were elucidated using elemental analysis and UV, 1H NMR, and mass spectral methods . All of these compounds were tested in vitro for their antibacterial and antifungal activity. Farmaco, 1998 Jul 30, 53(7), 455 - 61 Synthesis of substituted 2-ethoxycarbonyl- and 2-carboxyquinoxalin-3-ones for evaluation of antimicrobial and anticancer activity; Sanna P et al.; A series of variously substituted quinoxalin-3-ones bearing an ethoxycarbonyl or carboxy group in the C-2 position has been prepared and their structures proved by 1H NMR spectroscopy . The obtained compounds were investigated in vitro for antimicrobial and anticancer activities . Preliminary results showed a moderate activity against a few strains of bacteria but no significant anticancer and anti-HIV activity. Rev Port Cardiol, 1998 Oct, 17 Suppl 2, II41 - 6 Molecular mechanisms of arrhythmias; Janse MJ et al.; Most arrhythmias occur in patients with structural heart disease, where anatomical factors play an important role . Patients without structural heart disease may also suffer from arrhythmias, and recently the genetic basis for such so-called idiopathic arrhythmias has been elucidated . In the congenital long QT syndrome, characterized by a prolonged QT interval, torsade de pointes and sudden death, three aberrant ionic currents have been identified, resulting in a prolongation of the ventricular action potential, which in its turn may cause early afterdepolarization and torsade de pointes . In LQTS1, mutations in the KvLQT1 gene reduce the slow component of the delayed rectifier Iks; in LQTS, mutations in the Human Ether a-go-go Related Gene (HERG) reduce the rapid component of the delayed rectifier Iks . Both potassium currents are important determinants of repolarization: a reduction in outward currents carried by K+ ions prolongs the action potential . In LQTS3, there are mutation in the NA+ channel gene (SCN5A) which causes the channel to inactivate incompletely; the persistent inward current carried by Na+ ions also prolongs the action potential . In the Brugada syndrome, characterized by right bundle branch block, ST elevation in V1-V3 and sudden death, mutations have been observed in the Na+ channel gene, but it is as yet unclear which functional changes in the NA+ channel are responsible for the typical ECG changes and the arrhythmias . Various cardiac disorders may lead to changes in gene expression that modify channel function . In hypertrophy, the ventricular action potential is prolonged by a decrease in the inward rectifier and the transient outward current . After prolonged episodes of rapid electrical activity, the atrial action potential is shortened, because of a reduction in the Iks type calcium current . Finally, many carriers of mutated genes display no abnormalities on the ECG . It is conceivable that such individuals may show excessive QT prolongation when taking cardiac or noncardiac drugs (such as neuroleptics, antidepressants, antihistamines, antimicrobials, antimalarials) that block potassium currents. Antimicrob Agents Chemother, 1998 Dec, 42(12), 3245 - 50 Induction of resistance to azole drugs in Trypanosoma cruzi; Buckner FS et al.; Trypanosoma cruzi is the protozoan parasite that causes Chagas' disease, a frequently fatal illness affecting the heart and gastrointestinal systems . An estimated 16 million to 18 million people in Latin America and 50,000 to 100,000 people in the United States are infected with this pathogen . Treatment options for T . cruzi infections are suboptimal due to the toxicities and limited effectiveness of the available drugs . Azole antimicrobial agents have been discovered to have antitrypanosomal activity by inhibition of ergosterol synthesis . The triazole itraconazole was recently shown to produce a parasitologic cure rate of 53% in chronically infected patients (W . Apt et al., Am . J . Trop . Med . Hyg . 59:133-138, 1998), a result which may lead to more use of this family of drugs for the treatment of T . cruzi infections . In the experiments reported on here, resistance to azoles was induced in vitro by serial passage of mammalian-stage parasites in the presence of fluconazole for 4 months . These parasites were cross resistant to the other azoles, ketoconazole, miconazole, and itraconazole . They remained susceptible to benznidazole and amphotericin B . The azole-resistant phenotype was stable for more than 2 months of in vitro serial passage without fluconazole . In addition, the parasites resisted treatment in mice receiving ketoconazole . The rapid development of azole resistance in T . cruzi in vitro suggests that resistance to azole drugs has the potential to occur in patients and may pose an impediment to the progress being made in the treatment of T . cruzi infection. Boll Chim Farm, 1998 Sep, 137(8), 321 - 4 Synthesis and antimicrobial activity of N-Mannich bases of 3-{N'-sulphadoximino} isatin and its methyl derivative; Surendra et al.; Schiff's bases of isatin and 5-methyl isatin with sulphadoxine and then its N-Mannich bases were synthesised and evaluated for their anti-microbial activity . The piperidonemethyl group improved the activity and most of the compounds were more potent than the pure drugs. J Nat Prod, 1998 Nov, 61(11), 1337 - 9 New macrodiolide antibiotics, 11-O-monomethyl- and 11, 11'-O-dimethylelaiophylins, from Streptomyces sp . HKI-0113 and HKI-0114; Ritzau M et al.; Elaiophylin (1) and two new methyl derivatives, 11-O-monomethylelaiophylin (2) and 11,11'-O-dimethylelaiophylin (3), were isolated from the mycelium cake of Streptomyces strains HKI-0113 and HKI-0114 . The structures of 2 and 3 were determined by mass spectrometric and NMR investigations . Compounds 2 and 3 display antimicrobial and moderate cytotoxic activities. Ann Emerg Med, 1998 Dec, 32(6), 703 - 11 EMERGEncy ID NET: an emergency department-based emerging infections sentinel network . The EMERGEncy ID NET Study Group; Talan DA et al.; Acute infectious disease presentations among many at-risk patient groups (eg, uninsured, homeless, and recent immigrants) are frequently seen in emergency departments . Therefore EDs may be useful sentinel sites for infectious disease surveillance . This article describes the background, development, and implementation of EMERGE ncy ID NET, an interdisciplinary, multicenter, ED-based network for research of emerging infectious diseases . EMERGE ncy ID NET was established in cooperation with the National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) as part of the CDC's strategy to expand and complement existing disease detection and control activities . The network is based at 11 university-affiliated, urban hospital EDs with a combined annual patient visit census of more than 900,000 . Data are collected during ED evaluation of patients with specific clinical syndromes, and are electronically stored, transferred, and analyzed at a central receiving site . Current projects include investigation of bloody diarrhea and the prevalence of Shiga toxin-producing Escherichia coli, animal exposures and rabies postexposure prophylaxis practices, seizures and prevalence of neurocysticercosis, nosocomial ED Mycobacterium tuberculosis transmission, and hospital isolation bed use for adults admitted for pneumonia or suspected tuberculosis . EMERGE ncy ID NET also was developed to be a mechanism for rapidly responding to new diseases or epidemics . Future plans include study of antimicrobial use, meningitis, and encephalitis, and consideration of other public health concerns such as injury and national and international network expansion. Int J Antimicrob Agents, 1998 Aug, 10(3), 191 - 205 Ventilator-associated pneumonia; Visnegarwala F et al.; Mechanically ventilated patients are at a substantially higher risk for developing nosocomial pneumonia . Overall, there is a relatively constant 1&!TN!150;3% risk per day of developing pneumonia while receiving mechanical ventilation . The sensitivity and specificity of clinical criteria alone for diagnosis of ventilator-associated pneumonias (VAP) is low . Several techniques have been developed to sample and quantitate the lower respiratory tract to improve the diagnostic yield . Gram-negative bacillary pneumonias account for the majority of the VAP . Strategies for prevention of VAP such as use of sucralfate for stress ulcer prophylaxis and selective decontamination of the digestive tract have been the focus of many clinical studies . Cost-effective preventive measures are needed to combat the increasing antimicrobial resistance, growing population of immunocompromised patients and increasing number of mechanically ventilated patients. Eur J Clin Microbiol Infect Dis, 1998 Sep, 17(9), 615 - 21 Clinical and radiological features of pulmonary disease caused by rapidly growing mycobacteria in cancer patients; Jacobson K et al.; The role of rapidly growing mycobacteria in the pathogenesis of pulmonary disease is being increasingly recognized; however, the clinical significance of these mycobacteria in patients with underlying malignancy has not been well studied . Over a 6-year period, 37 cancer patients with rapidly growing mycobacteria isolated from respiratory specimens were identified at our center . Mycobacterium chelonae group was isolated in 24 cases and Mycobacterium fortuitum in 13 cases . Of the 24 cases with cultures yielding Mycobacterium chelonae group, eight met the study criteria for infection and were determined to be clinically significant, whereas only one of the Mycobacterium fortuitum isolates was determined to represent infection . An average of two antimicrobial agents were used for treatment, most commonly clarithromycin, ciprofloxacin, and trimethoprim/sulfamethoxazole . Although the isolation of rapidly growing mycobacteria represents colonization in most cases, these bacteria, especially the Mycobacterium chelonae group, may cause pulmonary disease in cancer patients . The clinical and radiological findings are usually non-specific in this population, and patients with respiratory cultures yielding rapidly growing mycobacteria should be assessed carefully to distinguish infection from colonization . Effective therapy can be provided with oral regimens that include at least two antibiotics to which the organism is susceptible. Gene, 1998 Nov 19, 222(2), 297 - 304 Sequence and expression of Drosophila Antigen 5-related 2, a new member of the CAP gene family; Megraw T et al.; A cDNA synthesized and cloned from Drosophila melanogaster mRNA was shown to encode a protein with significant identity to the protein encoded by the Drosophila Antigen 5-related (Agr) gene . Because of its similarity to Agr, this novel cDNA was termed Antigen 5-related 2 (Agr2) . The proteins encoded by Agr and Agr2 both belong to the CAP family of proteins, which include the mammalian Cysteine-rich secretory proteins, wasp venom Antigen 5 proteins, and plant group 1 Pathogenesis-related proteins . CAP family proteins share a common core sequence, and most appear to function extracellularly . Agr2 encodes a protein that is 254 amino acids in length . The cDNA contains a short 5' untranslated region (UTR) 36bp in length, and a 3' UTR of 46bp . The protein encoded by Agr2 has 48% identity and 61% similarity to that encoded by Agr . The Agr2 gene was localized to region 12F of the X chromosome and probably lies near the Agr gene . Agr2 RNA was approx . 950nt in length and was most abundant during the larval period, although transcripts could also be detected at other developmental stages . Transcription of Agr2 is initiated in the embryo within the midgut epithelium near the site where the third midgut constriction will form . As embryogenesis proceeds, Agr2 expression expands to form a domain located just posterior to the third midgut constriction . This domain corresponds to a single loop of the midgut in late-stage embryos . Based on its expression pattern and its similarity to other CAP family proteins, the Agr2 protein is hypothesized to function either as a novel type of protease inhibitor or as an antimicrobial protein. J Nephrol, 1998 Sep-Oct, 11(5), 261 - 5 Sepsis-induced acute renal failure: unusual clinical presentation; Feriozzi S et al.; We report 4 cases of sepsis-induced acute renal failure (ARF) with peculiar clinical presentation in which the renal biopsy was the only clue to a correct diagnosis . We observed 66 cases of ARF in a 4-year experience . Seven (11%) were associated with sepsis; in 3 of these (4.5%) a shock was present . Clinical picture of the remaining 4 cases (6%) was characterized by ARF with oligoanuria and proteinuria (> 2 g/L), fever, resistant to antimicrobial therapy, negative hemocultures and severe systemic symptoms . Such a presentation could suggest a non-infectious systemic disease; renal biopsies were carried out . Histological findings consisted of microabscesses of variable size in the interstitium and within the tubular lumina . A full-dose, broad-spectrum, i.v . antimicrobial therapy was started, with favourable outcome and recovery of renal function . Our clinical experience points out that the clinical picture of ARF in course of sepsis may be variable and that its relationship with septicaemia could not be readily discernible. Am J Med, 1998 Nov, 105(5), 424 - 30 Helicobacter pylori: rational management options; Peura D; In the treatment of Helicobacter pylori-associated peptic ulcer disease, the complexity (ie, frequency and duration) of drug administration, the presence or development of bacterial antibiotic resistance, and the occurrence of side effects influence patient compliance and eradication rates, which consequently affect the costs of treatment regimens . The National Institutes of Health Consensus Conference and 1997 Digestive Health Initiative Update Conference have recommended that all patients with gastric or duodenal ulcer and H . pylori infection, whether on first presentation or recurrence, be treated with antimicrobials . However, H . pylori resistance to antimicrobials, specifically to nitroimidazole compounds, has resulted in varied and decreasing success rates of treatment regimens . Comparing the efficacy, safety, and costs of current treatment strategies for the eradication of H . pylori, a combination triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is recommended as an effective alternative to standard bismuth-based triple therapy . When compared with other therapies, these offer more rapid symptomatic relief, improved tolerability, increased compliance and efficacy, and moderate costs. Liver, 1998 Oct, 18(5), 320 - 5 Fungal colonisation and fluconazole therapy in acute liver disease; Fisher NC et al.; BACKGROUND/AIMS: Fungal infection, particularly with Candida spp., has been identified as an important cause of morbidity and mortality in patients with acute liver failure . Fungal colonisation of superficial mucosal sites usually precedes invasive infection . We investigated colonisation patterns in patients with acute liver disease receiving fluconazole therapy in order to investigate the possibility of emergence of fluconazole-resistant C . albicans or other species . METHODS: During a 6-month study period, we studied all patients referred to our unit with acute liver disease by twice-weekly sampling and mycological analysis of specimens from superficial mucosal and other sites as appropriate . Patients were treated with prophylactic antimicrobials including 100 mg fluconazole daily in accordance with our usual protocol . RESULTS: Twenty-two patients with acute liver disease were studied, eight of whom underwent transplantation . Eighteen patients were colonised by fungi at presentation, and six developed secondary colonisation during fluconazole therapy . Four of these patients (all transplanted) became colonised by resistant species; one of these was Aspergillus fumigatus, which led to death . There were no other invasive fungal infections identified during the study period, and no fluconazole-resistant C . albicans were identified . CONCLUSIONS: Resistance to fluconazole is unlikely to develop in C . albicans during short-term fluconazole prophylaxis in acute liver disease, and in this study we did not find evidence of invasive disease from other Candida spp . during fluconazole therapy . However, in patients at particularly high risk, other strategies are required to prevent infection with Aspergillus spp. J Hosp Infect, 1998 Nov, 40(3), 193 - 201 Prevention of central venous catheter-related infection; Elliott TS et al.; Infections associated with central venous catheters continue to be a major source of sepsis, particularly in hospitalized patients . In developing a strategy for the prevention of these infections, the source and route of invasion of the causative micro-organisms need to be considered . The main source of micro-organisms is the patient's skin . They can gain access to a catheter at the time of insertion, as well as via the external or internal catheter surfaces . Attempts to reduce the incidence of infections range from the type of skin preparation selected, to care of the insertion site post-catheterization . Improvements in catheter design have also reduced the likelihood of infection and include the development of non-leachable smooth catheters with anti-adhesive coatings . More recently, catheters containing antimicrobial agents have become available and preliminary studies have demonstrated a reduction in microbial colonization and associated sepsis . Future preventative strategies may include the application of low voltage electric current in combination with antimicrobials. Aust Vet J, 1998 Oct, 76(10), 664 - 6 Surgical management of an abdominal abscess in a Malayan tapir; Lambeth RR et al.; A captive Malayan tapir was observed to have inappetence, weight loss, signs of depression, mild dehydration and diarrhoea . Haematological and serum biochemical tests showed anaemia, hypoproteinaemia, hyperfibrinogenaemia and neutrophilia with a left shift . Ultrasonic examination of the abdomen under anaesthesia revealed a well-encapsulated abscess . The abscess was marsupialised to the ventral body wall . Culture of the pus produced a mixed bacterial growth . Antimicrobial therapy was based on bacterial sensitivity results . Follow-up ultrasonic examinations showed resolution of the abscess . Ninety-one days after surgery the tapir began regurgitating food and water . An abscess originating from the stomach and occluding the lumen of the duodenum was identified at surgery . The abscess ruptured during surgical manipulations and the tapir was euthanased. Strahlenther Onkol, 1998 Nov, 174 Suppl 3, 90 - 2 Management of radiation injuries of vulva and vagina; Fraunholz IB et al.; BACKGROUND: Acute and late injuries of vulva and vagina are frequent and potentially serious complications in radiotherapy of gynecologic tumors . They still are reported poorly in literature . METHODS: Based on a literature search a survey will be given of the modalities, which are used or recommended for prophylaxis or treatment of these radiation injuries . The principles of the different measures will be discussed with available study results . RESULTS: Hygiene measures and the topical application of antimicrobial or granulation stimulating substances, which is mostly based on long standing clinical experience, are the principles of the treatment of acute reactions of vulva and vagina . The topical use of estrogen, which promotes proliferation of epithelium, is generally described in connection with treatment and prophylaxis of late radiation injuries . As a prophylaxis for the late reaction of vaginal stenosis, vaginal dilatation is recommended in literature . CONCLUSIONS: With the exception of a few reports on estrogen, there are no data about the effectiveness of the currently used medical substances . The local application of estrogen as prophylaxis of the acute reactions will therefore be examined in a prospective study. Strahlenther Onkol, 1998 Nov, 174 Suppl 3, 66 - 8 The treatment of late radiation effects with hyperbaric oxygenation (HBO); Plafki C et al.; BACKGROUND: Late radiation injuries may impose a negative influence on the quality of life in the affected patients . In several entities, standardized treatment protocols are lacking . Hyperbaric oxygenation (HBO) has been shown to have beneficial effects in the treatment of late radiation sequelae . MATERIAL AND METHODS: The basic principles of HBO are reviewed as well as clinical issues . Current study protocols are presented . RESULTS: During HBO-therapy the patient breathes pure oxygen at pressures above 100 kPa . The oxygen solubility within the fluid phase of the blood is largely increased . Biological effects include an increased oxygen diffusibility, improved collagen synthesis and neoangiogenesis as well as an enhancement of antimicrobial defenses . By decreasing the capillary filtration pressure a reduction of edema becomes possible . HBO has been shown to prevent complications following surgery in irradiated tissues . Its efficacy as an adjunct in the treatment of osteonecroses in radiation patients could be demonstrated . In addition, the loss of osseointegrated implants in the maxillofacial bones of these patients could be significantly reduced . Further indications include soft tissue necroses, hemorrhagic cystitis and proctitis in tumor patients that have been treated by radiotherapy as part of a multimodality approach . CONCLUSIONS: HBO in the treatment of late radiation effects is still subject of investigation, but remarkable results have been reported . Optimized treatment protocols need to be determined in various entities . The rate of side effects is acceptable low. J Indian Med Assoc, 1998 Jul, 96(7), 202 - 4 Comparative evaluation of antimicrobial activity of polyvinylpyrrolidone (PVP)-iodine versus topical antibiotics in cataract surgery; Chaudhary U et al.; Comparative evaluation of polyvinylpyrrolidone (PVP)-iodine versus topical broad-spectrum antibiotics for disinfecting the eye and surrounding area to prevent postoperative complications was carried out on 100 patients . PVP-iodine proved superior antiseptic for pre-operative preparation of eyes before cataract surgery . It was cheaper, caused minimal side-effects, reduced bacterial counts to a great extent and eliminated fungi completely. J Clin Pathol, 1998 Aug, 51(8), 568 - 75 A review of immunofluorescent patterns associated with antineutrophil cytoplasmic antibodies (ANCA) and their differentiation from other antibodies; Savige JA et al.; AIM: To describe the neutrophil fluorescent patterns produced by antineutrophil cytoplasmic antibodies (ANCA) with different antigen specificities, and by other auto- and alloantibodies . BACKGROUND: Most sera from patients with active generalised Wegener's granulomatosis result in diffusely granular cytoplasmic neutrophil fluorescence with internuclear accentuation (cANCA) and proteinase 3 (PR3) specificity . About 80% of the sera from patients with microscopic polyangiitis result in perinuclear neutrophil fluorescence with nuclear extension (pANCA) and myeloperoxidase (MPO) specificity, or a cANCA pattern with PR3 specificity . However, many different neutrophil fluorescence patterns are noted on testing for ANCA in routine immunodiagnostic laboratories . METHODS: Sera sent for ANCA testing, or containing a variety of auto- and alloantibodies, were studied . They were examined by indirect immunofluorescence according to the recommendations of the first international ANCA workshop, and for PR3 and MPO specificity in commercial and in-house enzyme linked immunosorbent assays (ELISA) . RESULTS: Sera with typical cANCA accounted for only half of all neutrophil cytoplasmic fluorescence . Other sera had "flatter" fluorescence without internuclear accentuation, and the corresponding antigens included MPO and bactericidal/permeability increasing protein (BPI), but were usually unknown . Peripheral nuclear fluorescence without nuclear extension occurred typically when the antigens were BPI, lactoferrin, lysozyme, elastase, or cathepsin G . Most types of ANA were evident on ethanol fixed neutrophil nuclei . AntidsDNA, antiRo, and antilamin antibodies resembled pANCA . Antimicrobial and antiribosomal antibodies produced cytoplasmic fluorescence, and antiGolgi antibodies, a pANCA . Sera from patients with anti-smooth muscle antibodies were associated with cytoplasmic fluorescence . There was no neutrophil fluorescence with anti-skeletal muscle and anti-heart muscle antibodies, anti-liver/kidney microsomal, antithyroid microsomal, or antiadrenal antibodies . Alloantibodies such as antiNB1 typically resulted in cytoplasmic fluorescence of only a subpopulation of the neutrophils . CONCLUSIONS: The ability to distinguish between different neutrophil fluorescence patterns, and the patterns seen with other auto- and alloantibodies is helpful diagnostically . However, the demonstration of MPO or PR3 specificity by ELISA will indicate that the neutrophil fluorescence is probably clinically significant, and that the diagnosis is likely to be Wegener's granulomatosis or microscopic polyangiitis. Br J Ophthalmol, 1998 Aug, 82(8), 919 - 25 Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh; Rahman MR et al.; AIM: The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries . The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis . METHODS: Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy . They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5% . The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals . The outcome measures were healing at 21 days and presence or absence of toxicity . If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial . RESULTS: 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin . One allocated to natamycin grew bacteria and therefore was excluded from the analysis . None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days . Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04) . If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers . Equal numbers of Aspergillus (22) and Fusarium (22) were grown . The Aspergillus were the most resistant to either primary treatment . CONCLUSIONS: Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available. Exp Cell Res, 1998 Nov 25, 245(1), 214 - 20 Induction of lactoferrin expression in murine ES cells by retinoic acid and estrogen; Geng K et al.; Lactoferrin is an iron-binding glycoprotein present in high concentrations in milk and exocrine fluids such as bile and tears . Many functions have been attributed to lactoferrin, including antimicrobial and antiviral activities, immunomodulation, and cell growth regulation . Lactoferrin expression is controlled by different regulators, including retinoic acid and estrogen . However, the expression pattern of lactoferrin in mammalian early development has not yet been reported . Murine embryonic stem cells are pluripotent cells that can contribute to all tissues and were used for this study . We show here that while no lactoferrin protein or mRNA was detected in untreated murine embryonic stem cells, retinoic acid and estrogen can induce high levels lactoferrin expression in these cells . Expression, demonstrated by reverse transcription-polymerase chain reaction, Western blot, immunofluorescence, and ELISA assay, was dose and time dependent . Our study provides an in vitro model for examining lactoferrin expression in early development and differentiation . Comp Biochem Physiol C Pharmacol Toxicol Endocrinol, 1998 Jul, 120(1), 121 - 6 Antimicrobial activity of the diterpenes flexibilide and sinulariolide derived from Sinularia flexibilis Quoy and Gaimard 1833 (Coelenterata: Alcyonacea, Octocorallia); Aceret TL et al.; The soft coral Sinularia flexibilis is rarely overgrown by bacteria and algae . Various studies have shown that it contains diterpenes that protect it from competitors and predators . However, of the many diterpenoids isolated from S . flexibilis, only sinulariolide has been studied for antibiotic properties . Samples of soft corals were collected from Orpheus Island and freeze-dried for chemical extraction and isolation of pure diterpenes . Antimicrobial activity of the diterpenes was determined using the disc assay method with antibiotics as controls and the minimum inhibitory concentrations of the diterpenes were determined using the Tube Dilution Technique . Two out of the five diterpenes tested (sinulariolide and flexibilide), showed marked antimicrobial activity and inhibited growth of Gram-positive bacteria . Flexibilide was effective even at concentrations as low as 5 ppm, whereas sinulariolide was effective at concentrations of 10 ppm . These compounds show potential as antibiotics. Proc Natl Acad Sci U S A, 1998 Nov 24, 95(24), 14337 - 42 Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes; Braun A et al.; We have analyzed the Drosophila immune response in domino mutant larvae, which are devoid of blood cells . The domino mutants have a good larval viability, but they die as prepupae . We show that, on immune challenge, induction of the genes encoding antimicrobial peptides in the fat body is not affected significantly in the mutant larvae, indicating that hemocytes are not essential in this process . The hemocoele of domino larvae contains numerous live microorganisms, the presence of which induces a weak antimicrobial response in the fat body . A full response is observed only after septic injury . We propose that the fat body cells are activated both by the presence of microorganisms and by injury and that injury potentiates the effect of microorganisms . Survival experiments after an immune challenge showed that domino mutants devoid of blood cells maintain a wild-type resistance to septic injury . This resistance was also observed in mutant larvae in which the synthesis of antibacterial peptides is impaired (immune deficiency larvae) and in mutants that are deficient for humoral melanization (Black cells larvae) . However, if domino was combined with either the immune deficiency or the Black cell mutation, the resistance to septic injury was reduced severely . These results establish the relevance of the three immune reactions: phagocytosis, synthesis of antibacterial peptides, and melanization . By working in synergy, they provide Drosophila a highly effective defense against injury and/or infection. Proc Natl Acad Sci U S A, 1998 Nov 24, 95(24), 14100 - 5 Nitrosative stress: metabolic pathway involving the flavohemoglobin; Hausladen A et al.; Nitric oxide (NO) biology has focused on the tightly regulated enzymatic mechanism that transforms L-arginine into a family of molecules, which serve both signaling and defense functions . However, very little is known of the pathways that metabolize these molecules or turn off the signals . The paradigm is well exemplified in bacteria where S-nitrosothiols (SNO)-compounds identified with antimicrobial activities of NO synthase-elicit responses that mediate bacterial resistance by unknown mechanisms . Here we show that Escherichia coli possess both constitutive and inducible elements for SNO metabolism . Constitutive enzyme(s) cleave SNO to NO whereas bacterial hemoglobin, a widely distributed flavohemoglobin of poorly understood function, is central to the inducible response . Remarkably, the protein has evolved a novel heme-detoxification mechanism for NO . Specifically, the heme serves a dioxygenase function that produces mainly nitrate . These studies thus provide new insights into SNO and NO metabolism and identify enzymes with reactions that were thought to occur only by chemical means . Our results also emphasize that the reactions of SNO and NO with hemoglobins are evolutionary conserved, but have been adapted for cell-specific function. Infect Immun, 1998 Dec, 66(12), 5948 - 54 Detection of anionic antimicrobial peptides in ovine bronchoalveolar lavage fluid and respiratory epithelium; Brogden KA et al.; Three small antimicrobial anionic peptides (AP) were originally isolated from an ovine pulmonary surfactant . However, their presence in bronchoalveolar lavage (BAL) fluid and tissues of the respiratory tract is unknown . In this study, we made affinity-purified rabbit polyclonal and mouse monoclonal antibodies to synthetic H-DDDDDDD-OH . Antibody specificity was assessed by a competitive enzyme-linked immunosorbent assay (ELISA), and the exact epitope binding sites were determined with analog peptides synthesized on derivatized cellulose . These antibodies were used to detect AP in BAL fluid by ELISA and in respiratory tissues by Western blot analysis and immunocytochemistry . BAL fluid from 25 sheep contained 0.83 +/- 0.33 mM AP (mean +/- standard deviation; range, 0.10 to 1.59 mM) and was antimicrobial . The presence of AP in BAL fluid was confirmed by reverse-phase high-pressure liquid chromatography fractionation followed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry on those fractions which were positive by competitive ELISA and demonstrated antimicrobial activity . In Western blots, polyclonal antibody PAB96-1 and monoclonal antibody 1G9-1C2 (5.0 micrograms/ml) detected four bands in solubilized turbinate and tracheal epithelial cells (53.7, 31.2, 28.0, and 25.7 kDa) and five bands in lung homogenates (53.5, 37.1, 31.2, 28.0, and 25.7 kDa) . Only a single band was seen in solubilized liver and small-intestine homogenates, and no bands were seen in blots containing BAL fluid, albumin, or kidney or spleen homogenates . In pulmonary-tissue sections, both antibodies PAB96-1 and 1G9-1C2 identified accumulated protein in the apical cytoplasm of the bronchial and bronchiolar epithelia, in the cytoplasm of pulmonary endothelial cells, and in an occasional alveolar macrophage . As a first step in identifying a candidate AP precursor gene(s), degenerate oligonucleotides representing all possible coding combinations for H-GADDDDD-OH and H-DDDDDDD-OH were synthesized and used to probe Southern blots of sheep genomic DNA . Following low-stringency washes and a 2-day exposure, strongly hybridizing bands could be identified . One degenerate oligonucleotide, SH87, was used as a hybridization probe to screen a sheep phage genomic library . Two independent phage contained the H-GADDDDD-OH coding sequence as part of a larger predicted protein . AP may originate as part of an intracellular precursor protein, with multistep processing leading to the release of the heptapeptide into mucosal secretions . There it may interact with other innate pulmonary defenses to prevent microbial infection. Infect Immun, 1998 Dec, 66(12), 5607 - 12 The lipopolysaccharide of Bordetella bronchiseptica acts as a protective shield against antimicrobial peptides; Banemann A et al.; Resistance profiles of the two Bordetella species B . bronchiseptica and B . pertussis against various antimicrobial peptides were determined in liquid survival and agar diffusion assays . B . bronchiseptica exhibited significantly higher resistance against all tested peptides than B . pertussis . The most powerful agents acting on B . bronchiseptica were, in the order of their killing efficiencies, cecropin P > cecropin B > magainin-II-amide > protamine > melittin . Interestingly, for B . bronchiseptica, the resistance level was significantly affected by phase variation, as a bvgS deletion derivative showed an increased sensitivity to these peptides . Tn5-induced protamine-sensitive B . bronchiseptica mutants, which were found to be very susceptible to most of the cationic peptides, were isolated . In two of these mutants, the genetic loci inactivated by transposon insertion were identified as containing genes highly homologous to the wlbA and wlbL genes of B . pertussis that are involved in the biosynthesis of lipopolysaccharide (LPS) . In agreement with this finding, the two peptide-sensitive mutants revealed structural changes in the LPS, resulting in the loss of the O-specific side chains and the prevalence of the LPS core structure . This demonstrates that LPS plays a major role in the resistance of B . bronchiseptica against the action of antimicrobial peptides and suggests that B . pertussis is much more susceptible to these peptides due to the lack of the highly charged O-specific sugar side chains. Khirurgiia (Mosk), 1998, (10), 54 - 7 {Treatment of pyogenic complications after reconstructive surgery on blood vessels with use of synthetic prosthesis}; Mikhailov IP et al.; Factors influencing result of surgical treatment of patients with festered postoperative wounds have been studied . Algorythm of determination of tactics for examination and treatment of this category of patients was established . The results obtained are based on the analysis of personal surgical treatment autcomes in 1526 patients with decompensated ischemia of extremities and 57 patients with clinical symptoms of deep suppuration . Division of purulent complications into primary and secondary is suggested . Effectiveness of various modes of prophylaxis was studied--systemic and indirect endolymphatic route for introduction antibiotics, intraoperative application of pellicle ESBA, usage of antimicrobial vascular prosthesis "SISAN" . The best results were obtained in the two latter methods . Various methods of surgical treatment in infected vascular prosthesis are reviewed. Crit Rev Oral Biol Med, 1998, 9(4), 399 - 414 Epithelial antimicrobial peptides: review and significance for oral applications; Weinberg A et al.; Epithelial tissues provide the first line of defense between an organism and the environment . Disruption of this barrier leads to bacterial invasion and subsequent inflammation . This is precisely the situation existing in the human oral cavity, where tissues are constantly exposed to a variety of microbial challenges that can lead to bacterially induced periodontal diseases, and to infections of the oral mucosa by bacteria, fungi, and viruses . With the recent discoveries of host-derived peptide antibiotics in mammalian mucosal epithelium, a new line of investigation is emerging to test the hypothesis that one class of these peptides, called "beta-defensins", functions to protect the host against microbial pathogenesis at these critical, confrontational sites . In that light, impairment of beta-defensin activity has recently been implicated in chronic bacterial infections in cystic fibrosis patients . The first direct evidence of expression of defensin peptides in the oral mucosa was the identification of a novel epithelial beta-defensin in mammalian tongue . It was shown to be upregulated in inflammation, suggesting that it participates in host defense . It is theorized that epithelial cell-derived antimicrobial peptides function to keep the natural flora of micro-organisms in a steady state in different niches such as the skin, the intestines, the airway, the endocervix, and the mouth . There is now evidence indicating that normal gingival epithelial cells and tissues express two beta-defensins, hBD-1 and the newly described hBD-2 . In addition, a cathelin-class antimicrobial peptide, designated LL-37 and found in human neutrophils, is also expressed in skin and gingiva . It is highly likely that these and/or other epithelial antimicrobial peptides play an important role in determining the outcome of the host-pathogen interaction at the oral mucosal barrier, and that they may have important future applications in antibiotic treatment. Clin Pediatr (Phila), 1998 Nov, 37(11), 665 - 71 Current attitudes regarding use of antimicrobial agents: results from physician's and parents' focus group discussions; Barden LS et al.; Antibiotics are widely prescribed for children with nonspecific upper respiratory tract infections, contributing to the recent emergence of resistant pneumococci . To understand the reasons for the overprescription of antibiotics, we conducted focus groups with parents and with pediatricians and family physicians to assess their attitudes regarding the use of antibiotics . Physicians asserted that their own antibiotic prescribing could be safely reduced . Parental expectation to receive antibiotics was a major factor influencing their overuse of antibiotics . Parents indicated that they would be satisfied with the medical visit even if antibiotics were not prescribed, provided the physician explained the reasons for the decision . This study highlights differences in physician and parent perceptions about antibiotic overuse and suggests that educational efforts to narrow this communication gap will be important for improving antibiotic use. Arzneimittelforschung, 1998 Oct, 48(10), 1019 - 23 Synthesis, antifungal activity and antibacterial evaluation of some 3-piperazinylmethyl-5-aryl-1H-1,2,4-triazoles; Papakonstantinou-Garoufalias SS et al.; Some new 3-piperazinylmethyl-5-aryl-1H-1,2,4-triazoles have been prepared and tested for their antifungal and antimicrobial activity . Among them, compounds 3g and 3h exhibited higher antifungal activity than ketoconazole against Cladosporium cladosporoides and Aspergillus niger respectively. Ann Pharmacother, 1998 Nov, 32(11), 1234 - 8 Information contents of drug advertisements: an Indian experience; Lal A; OBJECTIVE: To critically analyze the drug information contained in Indian pharmaceutical advertisements . DESIGN: Analysis of pharmaceutical advertisements supplied by drug representatives (DRs) to prescribers from July 1, 1995, to June 30, 1996 . SETTING: A university-affiliated urban teaching hospital in India . PARTICIPANTS: 585 pharmaceutical ad pamphlets . MAIN OUTCOME MEASURES: The ads supplied by DRs to physicians in different clinical departments of the hospital were collected . These were distributed to different systems/categories and a special reference to fixed-dose drug combinations was given . The drug information contained in these ads was evaluated by using a checklist, framed by incorporating the World Health Organization ethical guidelines for medicinal drug promotion and some relevant items from other studies . RESULTS: The most frequently occurring ads were for antimicrobial agents . The ads on fixed-dose drug combinations constituted 37.9% of the total . More than 85% of the ads mentioned the generic name, brand name, contents, and pharmaceutical dosage forms, as well as the name and address of the company . The information concerning adverse effects, precautions, contraindications, warnings, major interactions, ingredients known to cause problems, pharmacology, drug overdose, references, drug storage, and cost was present in less than 40% of these ads . CONCLUSIONS: There has been inadequate information in pharmaceutical ads supplied by DRs to the physicians in India . The current scenario could be improved by formulating some definite legislative guidelines for the minimum level of information to be included in pharmaceutical ads and adhering to that legislation. J Clin Pharmacol, 1998 Nov, 38(11), 1063 - 71 Pharmacodynamic interactions of ciprofloxacin, piperacillin, and piperacillin/tazobactam in healthy volunteers; Strenkoski-Nix LC et al.; Mathematical modeling methods were used to study pharmacokinetic and pharmacodynamic interactions of the antimicrobial combinations piperacillin plus ciprofloxacin and piperacillin plus tazobactam . Twelve healthy volunteers received the following treatments: piperacillin (4 g), ciprofloxacin (400 mg), piperacillin (4 g) plus ciprofloxacin (400 mg), and piperacillin (4 g) plus tazobactam (0.5 g), via intravenous infusion in a four-period crossover design . Serum drug concentrations were analyzed by means of high-performance liquid chromatography (HPLC), and inhibitory titers were performed against eight organisms . The pharmacodynamic response (growth or no growth) was modeled for each of the monotherapy courses using a Hill-type model where Emax was 1 (100% probability of no growth {P(NG)}), and EC50 was the concentration associated with a 50% P(NG) . For piperacillin plus ciprofloxacin, P(NG) was a function of 1) plasma concentrations for both drugs; 2) EC50 values from the monotherapy courses; and 3) theta, an interaction term that accommodates synergy, additivity, or antagonism . For piperacillin/tazobactam, the serum ultrafiltrate area under the inhibitory curve was compared with that of piperacillin alone to determine the benefit of tazobactam . The interaction between piperacillin and ciprofloxacin was additive . The addition of tazobactam to piperacillin was beneficial against certain organisms . The model developed can be used to evaluate the activity of combination regimens against representative pathogens. FEBS Lett, 1998 Oct 23, 437(3), 258 - 62 Parasin I, an antimicrobial peptide derived from histone H2A in the catfish, Parasilurus asotus; Park IY et al.; In response to epidermal injury, Parasilurus asotus, a catfish, secreted a strong antimicrobial peptide into the epithelial mucosal layer . The molecular mass of the antimicrobial peptide, named parasin I, was 2000.4 Da, as determined by matrix-associated laser desorption ionization mass spectrometry . The complete amino acid sequence of parasin I, which was determined by automated Edman degradation, was Lys-Gly-Arg-Gly-Lys-Gln-Gly-Gly-Lys-Val-Arg-Ala-Lys-Ala-Lys-Thr-Arg-Ser- Ser . Eighteen of the 19 residues in parasin I were identical to the N-terminal of buforin I, a 39-residue antimicrobial peptide derived from the N-terminal of toad histone H2A {Kim et al . (1996) Biochem . Biophys . Res . Commun . 229, 381-387}, which implies that parasin I was cleaved off from the N-terminal of catfish histone H2A . Parasin I showed strong antimicrobial activity, about 12-100 times more potent than magainin 2, against a wide spectrum of microorganisms, without any hemolytic activity . Circular dichroism spectra of parasin I indicated a structural content of 11% alpha-helix, 33% beta-sheet, and 56% random coils . The beta-sheet axial projection diagram of parasin I showed an amphipathic structure . Our results indicate that the catfish may produce parasin I from its histone H2A by a specific protease upon injury to protect against invasion by microorganisms. J Chromatogr B Biomed Sci Appl, 1998 Sep 25, 716(1-2), 325 - 34 Capillary electrophoresis with laser-induced fluorescence: a routine method to determine moxifloxacin in human body fluids in very small sample volumes; Moller JG et al.; The feasibility of capillary electrophoresis with HeCd laser-induced fluorescence detection as a validated routine method for bioanalytical analysis is reported . Method evaluation, validation and results of the determination of moxifloxacin (BAY 12-8039), a new antimicrobially active 8-methoxy-quinolone, in plasma and microdialysate are described . After a one step sample preparation the samples can be injected directly into the capillary . The volume of microdialysate and plasma, respectively, needed for more than 50 injections is only 10 microl and 20 microl . Total run time is less than 7 min using a 27 cm capillary on commercial instrumentation . An analysis time of less than 1 min was shown to be possible, however it could not be used routinely since appropriate instrumentation was not available . Evaluation is based on the relative corrected peak area (analyte/I.S.) . The method's dynamic range comprises three orders of magnitude (plasma: 2.5-5000 microg/l; microdialysate: 5-5000 microg/l) . Validation according to international guidelines yielded data on accuracy and precision of the method throughout the entire working range of inter-day precision: plasma <6%, microdialysate <5% and inter-day accuracy: plasma <2%, microdialysate <4% . The crossvalidation with an existing HPLC method utilizing clinical study samples shows linear correlation . In view of its adequate sensitivity and high selectivity capillary electrophoresis with laser-induced fluorescence is a very versatile tool in pharmacokinetic studies of quinolones, especially in situations with limited sample volumes: e . g . pediatrics, patients at risk, animal-, microdialysis- and tissue-kinetic studies . Validation parameters and other features, like high sample throughput and robustness, are comparable to or even better than HPLC . Further necessary improvements of the capillary electrophoresis with laser-induced fluorescence instrumentation (autosampler, vials, parallel capillaries) and its use in bioanalytical routine analysis are discussed. Chest, 1998 Nov, 114(5), 1264 - 8 Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction; O'Donnell WJ et al.; STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP . DESIGN: Prospective cohort evaluation . SETTING: University medical center . PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP . MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year . RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis . A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34) . Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse . CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP . Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis . A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk. J Leukoc Biol, 1998 Nov, 64(5), 595 - 9 Sulfite is released by human neutrophils in response to stimulation with lipopolysaccharide; Mitsuhashi H et al.; Exposure to sulfite, a well-known air pollutant, induces inflammatory reactions characterized by neutrophil infiltration into the airways . Using a simple and sensitive assay for sulfite concentration in biological fluids, we demonstrate herein that human neutrophils released significant amounts of sulfite (1.0 nmol/h/10(7) cells) in response to lipopolysaccharide (LPS), a major component of bacterial endotoxin . A large proportion of the sulfite release by neutrophils was dependent on inorganic sulfate contained in culture media, suggesting production via the sulfate reducing pathway in this response . We also show that glucocorticoids and FK506 completely inhibit LPS-mediated sulfite release by neutrophils . Given the well-known antimicrobial activities of sulfite, our results suggest that sulfite acts as a neutrophil mediator of host defense . A putative role of sulfite as an endogenous biological mediator is further underscored by the observation that in vivo administration of LPS is associated with a marked increase in the serum concentration of sulfite in Wistar rats . Inhibition of sulfite release by immunosuppressive agents may contribute to increased susceptibility to bacterial infection commonly associated with the administration of these drugs. Diagn Microbiol Infect Dis, 1998 Oct, 32(2), 131 - 5 Fluoroquinolone-resistant Moraxella catarrhalis in a patient with pneumonia: report from the SENTRY Antimicrobial Surveillance Program (1998); DiPersio JR et al.; Fluoroquinolone resistance in Moraxella catarrhalis isolates has been quite rare . This report presents a case history of a 22-year-old man with compromised immune status and severe pneumonia caused by M . catarrhalis . The organism was markedly resistant (MICs, 1.5- > 32 micrograms/mL) to several marketed fluoroquinolones including the agent (levofloxacin) used for concurrent and prior therapy . The emergence of this problematic strain seems related to chronic exposure of the patient to compounds in the class and poor patient compliance to prescribed medications . The strain was not clonally related to other M . catarrhalis strains isolated in the same hospital during early 1998 . This second documented case of a fluoroquinolone-resistant M . catarrhalis clinical isolate presents a warning that resistances can emerge in at-risk patients, and that surveillance systems (SENTRY) will be necessary to monitor for unusual organisms and spread of resistance phenotypes among commonly isolated respiratory tract pathogens. J Biol Chem, 1998 Nov 27, 273(48), 31985 - 91 Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plants; Koga J et al.; When plants interact with certain pathogens, they protect themselves by generating various chemical and physical barriers called the hypersensitive response . These barriers are induced by molecules called elicitors that are produced by pathogens . In the present study, the most active elicitors of the hypersensitive response in rice were isolated from the rice pathogenic fungus Magnaporthe grisea, and their structures were identified as cerebrosides A and C, sphingolipids that were previously isolated as inducers of cell differentiation in the fungus Schizophyllum commune . Treatment of rice leaves with cerebroside A induced the accumulation of antimicrobial compounds (phytoalexins), cell death, and increased resistance to subsequent infection by compatible pathogens . The degradation products of cerebroside A (fatty acid methyl ester, sphingoid base, and glucosyl sphingoid base) showed no elicitor activity . Hydrogenation of the 8E-double bond in the sphingoid base moiety or the 3E-double bond in the fatty acid moiety of cerebroside A did not alter the elicitor activity, whereas hydrogenation of the 4E-double bond in the sphingoid base moiety led to a 12-fold decrease in elicitor activity . Furthermore, glucocerebrosides from Gaucher's spleen consisting of (E)-4-sphingenine and cerebrosides from rice bran mainly consisting of (4E,8E)-4,8-sphingadienine and (4E,8Z)-4,8-sphingadienine showed no elicitor activity . These results indicate that the methyl group at C-9 and the 4E-double bond in the sphingoid base moiety of cerebrosides A and C are the key elements determining the elicitor activity of these compounds . This study is the first to show that sphingolipids have elicitor activity in plants. J Antibiot (Tokyo), 1998 Sep, 51(9), 857 - 71 Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems; Hershberger PM et al.; This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems . Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones . Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase . Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump. Clin Exp Immunol, 1998 Nov, 114(2), 258 - 63 Adhesion molecules in common variable immunodeficiency (CVID)--a decrease in L-selectin-positive T lymphocytes; Nordoy I et al.; CVID is immunologically characterized by defective antibody production . Various additional immunological abnormalities have been reported, but little is known of the role of adhesion molecules in CVID . In 31 CVID patients serum levels of L-selectin (CD62L), vascular cell adhesion molecule-1 (VCAM-1) (CD106) and intercellular adhesion molecule-1 (ICAM-1) (CD54) were significantly elevated compared with controls . In 15 CVID patients investigated, the number of L-selectin-positive cells was significantly reduced in both CD4+ and CD8+ lymphocytes compared with controls, and these changes were observed in both CD45RA+ and CD45RO+ subsets . In CD19+ lymphocytes the percentage of ICAM-1+ cells was significantly increased compared with controls . Fifty percent of the patients had splenomegaly . These patients demonstrated even higher serum levels of adhesion molecules, a lower percentage of L-selectin-positive and a higher percentage of CD38+ cells in many T lymphocyte subsets compared with both other CVID patients and controls . Finally, in this patient group the percentage of L-selectin-positive CD19+ lymphocytes was significantly reduced compared with both other patients and controls . These findings indicate a state of ongoing T lymphocyte activation in CVID, especially in the subgroup of patients with splenomegaly, which may contribute to the impaired antimicrobial defence observed in these patients. Toxicol Lett, 1998 Aug, 96-97, 47 - 51 Formation of nitric oxide by rat and hamster alveolar macrophages: an interstrain and interspecies comparison; Jesch NK et al.; Nitric oxide (NO) plays an important role in non-specific host defense, which can be recognized by its antimicrobial and cytotoxic activity against pathogens . However, there appear to exist interspecies differences in the ability of macrophages to generate NO . The object of this study was to determine whether there exist intraspecies differences in the production of NO . We compared NO formation by alveolar macrophages (AM) from five different rat strains (Sprague Dawley, Wistar, Lewis, Fisher, and Brown Norway), two different stocks of Syrian Golden hamsters, and one stock of Chinese hamsters . The AM were harvested by bronchoalveolar lavage and stimulated in vitro with various concentrations of LPS and/or IFN-gamma . The oxidation product of NO, nitrite, was measured in the AM supernatant by the Griess reaction . Upon stimulation with LPS and/or IFN-gamma, AM from all five rat strains were able to release NO, but the amount of NO produced differed significantly among the rat strains . However, none of the stimuli was able to induce AM from the two stocks of Syrian Golden hamsters as well as AM from the stock of Chinese hamsters to release measurable amounts of NO . These findings point to distinct regulatory mechanisms of the NO pathway in AM from different species and to variations of this mechanism in the AM from the investigated rat strains. J Immunol, 1998 Nov 15, 161(10), 5217 - 25 CD40 engagement triggers switching to IgA1 and IgA2 in human B cells through induction of endogenous TGF-beta: evidence for TGF-beta but not IL-10-dependent direct S mu-->S alpha and sequential S mu-->S gamma, S gamma-->S alpha DNA recombination; Zan H et al.; IgA are major effectors of antimicrobial defense in the respiratory and digestive tracts . We have analyzed the requirements for and the modalities of switching to IgA using our recently identified monoclonal model of human germinal center differentiation, CL-01 B cells . CL-01 cells bear surface IgM (sIgM) and sIgD and switch to all seven downstream isotypes in response to physiologic stimuli . In these cells, CD40 engagement by CD40 ligand induces production of endogenous TGF-beta and IL-10, expression of germline Ialpha1-Calpha1 and Ialpha2-Calpha2 transcripts, mature VHDJH-Calpha1 and VHDJH-Calpha2 transcripts, and IgA secretion . These events are associated with not only direct Smu-->Salpha, but also sequential Smu-->Sgamma, Sgamma-->Salpha DNA recombination, and are ablated by neutralizing anti-TGF-beta but not IL-10 Ab, and indicating that TGF-beta, not IL-10, is a crucial mediator of the transcriptional activation and recombination of human Calpha1 and Calpha2 genes . Our findings in CL-01 cells were reproduced in freshly isolated naive sIgM+ sIgD+ B lymphocytes . Thus, engagement of CD40, in the absence of other (known) stimuli, is sufficient to effectively induce switching to IgA in human B cells . This is effected by direct and sequential DNA recombination events, which are both dependent upon endogenous TGF-beta secreted by the CD40L-induced B cells. Lijec Vjesn, 1998 Jun, 120(6), 160 - 2 {Our initial experience with video-assisted thoracoscopic surgery (VATS)}; Ilic N et al.; Diagnostic and therapeutic potentials and our first two-year experience with video-assisted thoracic surgery (VATS) are reported . From May 1995 to April 1997, at the Department of Surgery, University Hospital Split, VATS approach was planned in 55 cases (recurrent pneumothorax in 23, tension pneumothorax in 1, traumatic effusion in 5, malignant metastatic lung tumor in 1, benignant lung tumor in 11, traumatic effusion in 5, suspected mediastinal lymph nodes in 4, long lasting unconfirmed pleural effusion in 9, foreign body in 1, mediastanal cyst in 1) . Of these, 48 procedures (87.2%) were performed using VATS (diagnostic thoracoscopy in 12, wedge resection with or without pleural abrasion in 21, partial pleurectomy in 1, decortications in 3, mediastinal lymph nodes biopsy in 4, lung biopsy in 7) . Seven patients (12.7%) underwent conventional posterolateral thoracotomy . Complications included persistent air leak in three patients, prolonged bleeding in one patient and supraventricular tachycardia in one patient . The mean duration of chest tube drainage after the procedure was 3.7 days (range 2 to 19 days), and mean hospital stay was 5.1 days (range 3 to 15 days) . All patients received routine antimicrobial chemoprophylaxis with single-dose ceftriaxone 2 g intravenously immediately prior to the surgery, and average postoperative patient-controlled analgesia with buprenorphine 0.15 mg . We conclude that VATS is a very useful alternative to conventional thoracotomy in managing cases of exploration, recurrent spontaneous pneumothorax, benign pulmonary lesions, solitary pulmonary nodes, early decortications and different intrathoracic biopsies. J Infect, 1998 Jul, 37 Suppl 1, 45 - 50 Cost issues in sequential therapy; Cooke J; Pharmacoeconomics is starting to be employed in strategic therapeutic decision making . Costs associated with antimicrobials included: (i) acquisition costs; (ii) preparation, administration and consumables costs; (iii) monitoring costs; (iv) costs of unwanted drug effects; (v) costs of resistance and therapeutic failures and (vi) costs of duration of stay . Most hospitals have a Drug and Therapeutics Committee but acquisition costs are still the most important economic criterion for acceptance for use, even though medicines only consume between 3 and 5% of total revenue costs, of which antibiotics account for around 15% . In any sequential programme acquisition costs and consumables are immediately realizable . Staff time and monitoring tests are less realizable but require changes in the way budgets are handled . Microbial resistance and risk management are difficult to quantify but are increasingly becoming important in strategic decision-making . The educational needs of health care decision makers in economic need addressing and mechanisms need to be put in place to enable the putative savings reported in the pharmacoeconomic literature to be realized. J Infect, 1998 Jul, 37 Suppl 1, 37 - 44 Sequential antibiotic therapy: the right patient, the right time and the right outcome; Davey P et al.; The aim of sequential therapy should be to provide better quality of care at lower cost . In comparison with i.v . therapy, oral administration is safer, more acceptable to the patient, facilitates early discharge from hospital and reduces the cost of consumables . However, if given to the wrong patient, oral antimicrobial therapy could both increase the cost and reduce the quality of care, either because of ineffective treatment, or unnecessary prolongation of treatment . Hospitals must develop policies for sequential therapy which define standards against which clinical care can be audited . The standards will need to be revised as new data become available from local audit and from research . Further research on sequential therapy is undoubtedly required, with particular emphasis on the reliability of absorption of oral drugs by hospitalized patients. J Infect, 1998 Jul, 37 Suppl 1, 30 - 6 Sequential antimicrobial therapy: pharmacokinetic and pharmacodynamic considerations in sequential therapy; MacGowan AP et al.; The pharmacodynamic factors important in sequential therapy are largely unknown . This is because most pharmacodynamic investigations concentrate on how bacterial populations respond to first antimicrobial exposures . However, it is likely that for B lactams T>MIC and for quinolones the antimicrobial AUC/MIC ratio will be important . Factors which reduce antimicrobial absorption will impact on these parameters and require further study. J Infect, 1998 Jul, 37 Suppl 1, 18 - 23 Sequential antimicrobial therapy: comparison of the views of microbiologists and pharmacists; Smyth ET et al.; Sequential antimicrobial therapy (SAT) is arousing keen interest in microbiologists and pharmacists . In an attempt to obtain information from these groups regarding the use of SAT in hospitals, an anonymized postal survey was carried out . A SAT questionnaire was circulated to consultant medical microbiologists, clinical microbiologists, and heads of pharmacy departments within the British Isles . Four hundred and forty-seven microbiologists and pharmacists returned completed questionnaires, giving a response rate of 29% . Just over half of medical microbiologists (MM) and pharmacists (PH) indicated that SAT was used in their institution in respiratory medicine, geriatrics, surgery and, significantly, to a lesser degree in paediatrics . The most common infections treated were pneumonia, bronchitis and wound infection . However, there were significant differences between MM and PH, with MM favouring greater use of SAT in peritonitis (P=0.03), septicaemia (P<0.01), bone infection (P<0.01), pyelonephritis (UTI) (P<0.01), and PH favouring use in bronchitis (P<0.01) . The ability to take oral fluids or a recognition of no potential absorption problems were key criteria in the decision process leading to the institution of SAT by MM and PH . Significantly more MM favoured employing criteria such as temperature <38 degrees C (P<0.01), no requirement for high tissue concentrations (P=0.02) and evidence of response to i.v . antimicrobial therapy (P<0.01) than PH . The most frequently "switched" antimicrobials were metronidazole, ciprofloxacin and co-amoxiclav . There were more than five times as many MM reporting the use of clindamycin than PH (P<0.01), whereas nearly twice as many PH cited use of cefuroxime (P<0.01) . Of those hospitals not employing SAT, most MM and PH concurred that the commonest reason to institute SAT was financial, followed by convenience to patients and staff . However, more PH than MM indicated that protocols (P<0.01) and a reduction in i.v . complications (P<0.01) were important to them . In promoting SAT, MM and PH felt they had the major role . Significantly, each profession felt that the other had a lesser role to play; MM as judged by the PH (P<0.01) and PH as judged by MM (P<0.01) . When promoting SAT, both MM and PH felt that "education for clinicians" followed by regular audit was the best way to ensure implementation . However, significant differences arose with PH regarding nurse education (P<0.01), SAT posters (P=0.02), regular review of patients (P=0.04) and patient's notes SAT stickers (P<0.01) as more important to them than MM . Significantly, less MM than PH (P<0.01) insisted that either the i.v . and PO antimicrobials were identical or were from the same group or class when "switching" . This survey highlights interesting comparisons between the approaches of MM and PH towards SAT and may indicate ways in which both groups may work together to bring about change. J Infect, 1998 Jul, 37 Suppl 1, 10 - 7 Strategies to rationalize sepsis management--a review of 4 years' experience in Dundee; Nathwani D et al.; Hospitals worldwide are facing an unprecedented crisis of rising cost of antibacterials due to the increasing rapid emergence and dissemination of antibiotic-resistant organisms, improper use of antibiotics and the use of broad spectrum parenteral agents . The last 25 years has seen the introduction of many measures to improve the quality of sepsis management, and specifically antimicrobial use . The present paper reviews the development, implementation and evaluation of some of the key strategies employed within the Dundee Teaching Hospitals NHS Trust (DTHT) to enhance recognition and assessment of sepsis and to rationalize the early and often empiric antibiotic treatment of patients in hospital with infection . Particular emphasis is given to optimizing the use of expensive parenteral agents in conjunction with promotion of oral switch therapy where appropriate. J Infect, 1998 Jul, 37 Suppl 1, 3 - 9 Programs promoting timely sequential antimicrobial therapy: an American perspective; Drew RH; Interventional programs promoting the timely conversion of intravenous to oral antimicrobial therapy have been reported from several hospitals in the U.S.A . and elsewhere . Factors influencing the initiation and conduct of these programs include technological advances, changes in health care delivery or reimbursement, publication of supportive clinical data and growth of clinical pharmacy services . Successful programs employ comprehensive, multidisciplinary strategies to contain antimicrobial-related expenditures using interventions based on structured criteria . Future emphasis on cost-effective drug therapy, advances in computer-based information technology and development of care maps can have favourable influences on the growth of these programs in the U.S.A. J Infect, 1998 Jul, 37(1), 68 - 70 Anaerobiospirillum succiniciproducens septicaemia: important aspects of diagnosis and management; Goddard WW et al.; Anaerobiospirillum succiniciproducens is a rare cause of septicaemia . A 63-year-old woman with liver cirrhosis and a history of melaena developed A . succiniciprodocens septicaemia . She owned two pet dogs and a cat . Despite supportive management and antibiotic treatment supported by in vivo testing, the patient died . The characteristics identification and antimicrobial susceptibility of A . succiniciproducens are discussed and previous reported underlying disease reviewed. J Infect, 1998 Jan, 36(1), 35 - 42 Prospective randomized study to compare imipenem 1.5 grams per day vs . 3.0 grams per day in infections of granulocytopenic patients; Bohme A et al.; The objective of this presented prospective randomized study was to compare the efficacy of empirical antimicrobial monotherapy with imipenem 3 x 0.5 g per day to 3 x 1.0 g per day for treatment of infections in neutropenic patients . A total of 192/220 febrile episodes were evaluable for clinical efficacy . The overall response rate was 53/93 (57%) vs . 57/99 (58%) . Of the different infection types, fever of unknown origin (FUO) showed the best response, with defervescence in 29/41 (71%) and 36/42 (86%) cases, respectively (not significant) . Unfavourable results were found in pneumonias {5/20 (25%) vs . 4/23 (17%)} . The median time until persistent defervescence was equal in both groups (2 days), likewise the median duration of imipenem therapy in responders (7 days) . The most frequent micro-organisms were Gram-negative, documented in 22% of the febrile episodes in the lower dosage group vs . 17% of all episodes in the patients with imipenem 3.0 g per day (Gram-positives 17% vs . 14%, fungal 5% vs . 8%) . In the lower dosage group, fever with abdominal symptoms occurred less frequently (8% vs . 15%), and significantly more patients tolerated imipenem without any side-effects (95.8% vs . 79.4%), especially regarding severe nausea/vomiting (2.1% vs . 11.8%) . Of the initial non-responders, 35/40 (88%) vs . 41/42 (98%) were cured after therapy modification . There was no significant difference in the use of further antibiotics such as aminoglycosides, glycopeptides, ceftazidime or amphotericin B, except a marginally higher use of metronidazole in patients with imipenem 3.0 g per day (3% vs . 10%) . Overall, we found no significant differences in efficacy between the two study groups, but more frequent side-effects with imipenem 3.0 g per day. Biochemistry, 1998 Nov 17, 37(46), 16033 - 40 Pore formation by nisin involves translocation of its C-terminal part across the membrane; van Kraaij C et al.; Nisin is an amphiphilic peptide with a strong antimicrobial activity against various Gram-positive bacteria . Its activity results from permeabilization of bacterial membranes, causing efflux of cytoplasmic compounds . To get information on the molecular mechanism of membrane permeabilization, a mutant of nisin Z containing the C-terminal extension Asp-(His)6 was produced . The biological and anionic lipid-dependent membrane activity of this peptide was very similar to that of nisin Z . Analysis of the pH dependence of model membrane interactions with the elongated peptide indicated the importance of electrostatic interactions of the C-terminus with the target membrane for membrane permeabilization . Most importantly, the membrane topology of the C-terminus of the molecule could be determined by trypsin digestion experiments, in which trypsin was encapsulated in the lumen of large unilamellar vesicles . The results show that the C-terminal part of the peptide translocates across model membranes . The pH and anionic lipid dependence of translocation closely paralleled the results of membrane permeabilization studies . Binding of nickel ions to the histidines blocked translocation of the C-terminus and concomitantly resulted in a 4-fold reduced capacity to induce K+ leakage . The results demonstrate for the first time that pore formation of nisin involves translocation of the C-terminal region of the molecule across the membrane. J Rheumatol, 1998 Nov, 25(11), 2249 - 53 Outcomes of children treated for Lyme disease; Wang TJ et al.; OBJECTIVE: To study the outcome of Lyme disease (LD) in children identified in a total population survey of an endemic island . METHODS: We conducted a population-based retrospective cohort study off the coast of Massachusetts . Twenty-five children who met the Centers for Disease Control case definition for prior LD were compared with 26 children without LD from the same community . All children with LD received antibiotics during the acute phase of their disease . All 51 children were invited for a clinical evaluation, including 12-lead electrocardiogram (EKG), and measurement of antibodies to Borrelia burgdorferi by antibody-capture ELISA and Western blot . RESULTS: At a mean of 3.2 years from the initial manifestation of LD, children with prior LD did not have a higher prevalence of musculoskeletal or neurological symptoms, examination abnormalities, abnormal EKG, or behavioral difficulties, compared to children with no history of LD . CONCLUSION: Children who receive appropriate antimicrobial therapy for LD appear to have no demonstrable longterm morbidity. Mayo Clin Proc, 1998 Nov, 73(11), 1114 - 22 Review of pharmacokinetics and pharmacodynamics of antimicrobial agents; Estes L; Pharmacokinetics is a science that has long been used in ascertaining the appropriate antimicrobial dose . It refers to the disposition of drugs in the body and includes absorption, bioavailability, distribution, protein binding, metabolism, and elimination . Pharmacodynamics is a newer science that relates to the interaction between the drug concentration at the site of action over time and the desired antimicrobial effect . This article reviews the principles of pharmacokinetics and pharmacodynamics as well as the clinical application of these two sciences to design antimicrobial dosing regimens for optimal results in individual patients. J Clin Microbiol, 1998 Dec, 36(12), 3713 - 7 Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation; Iwen PC et al.; The first case of disseminated aspergillosis caused by Aspergillus ustus in an allogeneic peripheral stem cell transplant patient is described . The patient, a 46-year-old female with a history of myelodysplastic syndrome, underwent high-dose chemotherapy and total body irradiation prior to transplantation . She was released from the hospital 49 days posttransplant (p.t.) in a stable condition with an absolute neutrophil count (ANC) of 2,700 cells per microl . Multiple antimicrobial agents, including itraconazole (ITR), were prescribed during hospitalization and at the time of discharge . Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present . The ANC at the time of readmission was 3,500 . Upon detection of a pulmonary nodule (day 67 p.t.), a bronchoalveolar lavage was performed; the lavage fluid was positive for both cytomegalovirus and parainfluenza virus and negative for fungus . The patient was placed on ganciclovir . A biopsy specimen from a leg lesion also noted on day 67 p.t . revealed septate hyphae consistent with Aspergillus species, and a culture subsequently yielded Aspergillus ustus . Confirmation detection of A . ustus was made by demonstration of characteristic reproductive structures with the presence of Hulle cells . On day 67 p.t., ITR was discontinued and liposomal amphotericin B (AMB) was initiated . The patient's condition worsened, and she died 79 days p.t . At the time of autopsy, septate hyphae were present in heart, thyroid, and lung tissues, with lung tissue culture positive for A . ustus . In vitro susceptibility testing indicated probable resistance to AMB but not to ITR . This case supports the need for the development of rapid methods to determine antifungal susceptibility. Rinsho Byori, 1998 Oct, 46(10), 978 - 86 {Consultation service for efficacious usage of laboratory tests based on logical reasoning and evidence}; Ishida H et al.; To effectively respond to the desire for consultation in clinical practice, we must prepare logical reasoning and evidence which rationally supports laboratory test selection, the interpretation of test results and recommendation of certain tests to physicians . Standard of medical decision making can be used for logic issues such as posttest probability, test characteristics and receiver operating characteristics (ROC) curves and establishing appropriate cut-off points . Although we usually obtain evidence by consulting authorities or the literature, good evidence can also be obtained from meta-analysis . In addition, we can demonstrate the relationship of laboratory tests among several frequently occurring diseases and epidemiological tendencies such as frequency of causative organisms at several infection sites and bacterial sensitivities to antimicrobial agents, because we have access to a large-scale laboratory database . To construct a well-organized knowledge base with explicit evidence, cooperation among many facilities is necessary to develop system, which allows the free exchange of data. J Travel Med, 1997 Dec 1, 4(4), 161 - 166 Prognostic Factors Related to Recovery from Diarrhea among U.S . Students with Diarrhea in Mexico; Mosavi A et al.; Background: Medical charts of subjects treated with placebo from five double-blinded placebo-controlled clinical trials were reviewed to determine pre-enrollment prognostic factors related to later recovery from diarrhea . Method: Recovery or time from initiation of a placebo until passage of the last unformed stool after being declared well was calculated for each subject . Results: A longer duration of diarrhea was associated with presence of fever (rate ratio = 0.34; 95% CI = 0.2-0.9), presence of an invasive pathogen in the stool (rate ratio = 0.35; 95% CI = 0.2-0.7) or a noninvasive pathogen in stool (rate ratio = 0.7; 95% CI = 0.6-1.0), severe abdominal pain or cramps (rate ratio = 0.5; 95% CI = 0.3-0.9), passage of more than five watery stools per 24 hours (rate ratio = 0.58; 95% CI = 0.4-0.8) . Severe vomiting predicted a shorter duration of post-enrollment diarrhea (rate ratio = 2.43; 95% CI = 1.1-5.6) . Conclusion: A number of clinical and microbiologic factors found in travelers with diarrhea in the present study predicted duration of untreated diarrhea . The authors suggest the use of antimicrobial therapy in travelers with predictors of a long duration of diarrhea . Data developed in the present study may be used to create a historical control for clinical trials of antidiarrheal compounds using the same study criteria. J Travel Med, 1997 Mar 1, 4(1), 3 - 7 Single Dose Ofloxacin plus Loperamide Compared with Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea; Ericsson CD et al.; Background: Although the use of the antimicrobial, trimethoprim-sulfamethoxazole, in combination with the antisecretory and antimotility agent, loperamide, has been shown to be efficacious in the treatment of traveler's diarrhea, the use of fluoroquinolone antimicrobials in combination with loperamide has less support in the literature . The present study was designed to compare the efficacy of ofloxacin versus ofloxacin plus loperamide in the treatment of acute traveler's diarrhea . Method: This prospective, randomized, evaluator-blinded treatment trial was conducted in Guadalajara, Mexico, during the summers of 1992-1994 . Adults newly arrived in Mexico from the United States who developed acute diarrhea of less than 2 weeks' duration were randomized to receive orally either: A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose stool, not to exceed 16 mg per day, for 3 days . The duration of illness was the number of hours elapsed from the beginning of therapy to the passage of the last unformed stool . Results: Ofloxacin and loperamide were well tolerated . Combination therapy with single dose ofloxacin plus loperamide was significantly more efficacious in reducing the duration of diarrhea than single dose ofloxacin or ofloxacin given for 3 days (p <.00001) . Furthermore, combination therapy was more efficacious when enterotoxigenic Escherichia coli (ETEC) was the pathogen (p <.01) or when no pathogen was isolated (p <.001) . Sixty-three percent of subjects passed no further unformed stools after the initial doses of combination therapy, and 91% were well by the end of the first 24 hours . Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone. Digestion, 1998 Nov-Dec, 59(6), 708 - 14 Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers' diarrhea; DuPont HL et al.; BACKGROUND/AIMS: Bacterial enteropathogens, the major cause of travelers' diarrhea, are customarily treated with antibacterial drugs . Rifaximin, a nonabsorbed antimicrobial was examined as treatment for travelers' diarrhea . METHODS: A randomized, prospective, double-blind clinical trial was carried out in 72 US adults in Mexico . Patients with acute diarrhea received one of three doses of rifaximin (200, 400 and 600 mg t.i.d.) or trimethoprim/sulfamethoxazole (TMP/SMX, 160 mg/800 mg b.i.d.) for 5 days . Results were compared with data from 2 placebo-treated historical control populations . RESULTS: The shortest duration of treated diarrhea was seen in the group receiving 200 mg rifaximin t . i.d (NS) . Clinical failure to respond to treatment occurred in 6 of 55 (11%) rifaximin-treated subjects versus 5 of 17 (29%) of TMP/SMX-treated subjects (NS) . Sixteen of twenty (80%) of the enteropathogens isolated from the rifaximin-treated subjects and 7 of 7 (100%) from the TMP/SMX group were eradicated by treatment (NS) . Sixteen of twenty-four (67%) enteropathogens identified were susceptible to TMP and all 24 were inhibited by</=50 microgram/ml of rifaximin . Rifaximin reduced the number of unformed stools passed during the first 24 h of treatment when compared with 2 control placebo groups (3.3 versus 5.1; p = 0.008 and 0.0001) and led to a reduced duration of post-enrollment diarrhea (mean values of 43.1 versus 68.1 and 81.9 h; p = 0.001) . CONCLUSIONS: Rifaximin shortened the duration of travelers' diarrhea compared with TMP/SMX and 2 earlier studied placebo-treated groups . A poorly absorbed drug if effective in treating bacterial diarrhea has pharmacologic and safety advantages over the existing drugs. Arq Gastroenterol, 1998 Apr-Jun, 35(2), 138 - 42 {Primary gastritis associated with Helicobacter pylori in children}; Kawakami E et al.; The aim of this paper was to investigate whether a correlation between dyspeptic symptoms and infection due to Helicobacter pylori could be established . We conducted a prospective study with 27 children who had Helicobacter pylori associated antral gastritis with endoscopic and histologic alterations, without any other peptic lesions . Helicobacter pylori was detected by rapid urease test and histology with hematoxylin and eosin and Giemsa stain . Endoscopy revealed antral nodularities in 20/27 (74%) and enantema in six cases (23%) . During histological examination active chronic superficial gastritis was confirmed in 26 cases (96%) . Twenty seven children were treated with antimicrobial therapy, eight of which presented infection eradication, six presented nodularities regression and symptoms remission in four . Of the 19 non-eradicated patients, eight (42%) became asymptomatic and 11 maintained symptoms . Statistical analysis to compare symptoms remission was not significant . Taking into account the results presented herewith, we concluded that antral nodularity was the most common endoscopic finding, and there was no sufficient evidence of a correlation between Helicobacter pylori infection and dyspeptic symptoms. Rev Prat, 1998 Sep 15, 48(14), 1541 - 6 {Control of multiple-resistant bacteria}; Lucet JC; The number of multiply-resistant bacteria, especially methicillin-resistant Staphyloccoccus aureus, has reached an alarming level in France . This number reflects the inadequacy of efforts against nosocomial infections, and non-respect of hygiene rules by hospital staff . Two mechanisms lead to multiple resistance: the selection of multiply-resistant bacteria by antimicrobials; and, once resistance is acquired, bacterial dissemination by hand-mediated cross transmission . Controlling the spread of multiple resistance thus requires both judicious use of antimicrobials, and compliance with basic rules of hygiene, particularly handwashing . Although the hospital setting favors the emergence and spread of bacterial resistance, this is also increasing, albeit to a lesser extent, in the non-hospital environment . The same measures of careful antimicrobial use and good hygiene should be applied. Pharmazie, 1998 Oct, 53(10), 686 - 90 Synthesis and antimicrobial activities of some new pyrrolylthieno{2,3-b}-quinoline derivatives; Geies AA et al.; 2-Acetyl-4-(p-chlorophenyl)-3-(1-pyrrolyl)-5,6,7,8- tetrahydrothieno{2,3-b}quinoline (4a) and its corresponding 2-carbohydrazide derivative 5 were prepared and used as key intermediates in the synthesis of the title compounds . Some of the synthesized compounds were screened for their antibacterial and antifungal activities. Pharmazie, 1998 Oct, 53(10), 680 - 4 Synthesis, spectral and antimicrobial properties of 5-chloroarylidene aromatic derivatives of imidazoline-4-one; Kiec-Kononowicz K et al.; The synthesis of new chloro-benzylidene substituted derivatives of hydantoin and their antimicrobial activity is reported . The structure-activity relationships showed that the antibacterial effect of investigated compounds depends on the distance of the phenyl ring from the amine residue and the kind of substitutes on the phenyl ring . In the investigated group of derivatives, 5-(2-chlorobenzylidene)-2-(4-fluorobenzylamine)-imidazoline-4-one and 5-(2-chlorobenzylidene)-2-(2-phenylethylamine)-imidazoline-4-one showed the best antibacterial activity against Moraxella catarrhalis. Infect Dis Obstet Gynecol, 1998, 6(4), 186 - 90 Chronic plasma cell endometritis in hysterectomy specimens of HIV-infected women: a retrospective analysis; Kerr-Layton JA et al.; OBJECTIVE: Abnormal uterine bleeding is a common and troublesome problem in human immunodeficiency virus (HIV)-infected women . We sought to evaluate endometrial pathology among HIV-infected women requiring hysterectomy to explore if endometritis may be common among these patients . METHODS: We performed a retrospective analysis of uterine pathology specimens obtained from HIV-infected and control patients requiring hysterectomy in two urban hospitals between 1988 and 1997 matched for age, surgical indication, and history of gonadotropin-releasing hormone (GnRH) use . Cases were evaluated for the presence of plasma cells and assigned a grade between 0 and 3 . RESULTS: Indications included cervical dysplasia (4), carcinoma in situ (2), abnormal uterine bleeding (3), and adnexal mass (3) . Some degree of abnormal uterine bleeding occurred in all cases . Plasma cell endometritis was twice as common in HIV-infected women compared to HIV-negative specimens (11/11 versus 11/22) (P < 0.05) . Plasma cell endometritis was also of a higher grade in specimens from HIV-infected women than in controls (P = 0.001) . CONCLUSION: Chronic endometritis was common and of a higher grade among HIV-infected women requiring hysterectomy in our series . Diagnosis and treatment of endometritis should be considered in HIV-infected women with uterine bleeding and/or tenderness . We speculate that antiretroviral and/or antimicrobial treatment for endometritis may effectively treat endometritis and eliminate the need for surgery in some HIV-infected women . We suggest that consideration and treatment of endometritis in HIV-1 infected women being evaluated for possible hysterectomy has the potential to reduce costs and morbidity for patients and providers who may be exposed during surgical procedures. Infect Dis Obstet Gynecol, 1998, 6(4), 155 - 9 The use of once-daily dosing of gentamicin in obstetrics and gynecology; Wiesenfeld HC et al.; Gentamicin is a widely-used antimicrobial agent for obstetric and gynecologic infections . Renewed excitement in this antibiotic has arisen from recent information supporting less frequent dosing . In this symposium, we will describe the pharmacokinetics of gentamicin and review new information advocating the use of once-daily administration of gentamicin. Coron Artery Dis, 1998, 9(6), 339 - 43 Chlamydia pneumoniae, antimicrobial therapy and coronary heart disease: a critical overview; Gupta S et al.; Traditional cardiovascular risk factors, such as smoking, hypercholesterolaemia and hypertension probably only explain about 50% of the prevalence and severity of coronary heart disease (CHD) . The recent interest in the association between Chlamydia pneumoniae and the pathogenesis and progression of atherosclerotic diseases is based on several lines of evidence-seroepidemiological studies, pathological specimen examinations, laboratory-based experiments, animal models and more recently, pilot intervention trials with anti-chlamydial antibiotics (Table 1) . Whether C . pneumoniae has a direct causal role in atherosclerosis (and its clinical sequelae), and whether antibiotics have a protective role in the secondary prevention of CHD remains unclear . The results from large scale, prospective antibiotic trials in CHD, currently in progress, should help to clarify these important issues. Zentralbl Bakteriol, 1995 Nov, 283(1), 49 - 60 In vitro antimicrobial susceptibility testing of Borrelia burgdorferi: influence of test conditions on minimal inhibitory concentration (MIC) values; Boerner J et al.; A broth microdilution assay was performed to determine the minimal inhibitory concentrations (MICs) of 25 antimicrobial agents for two strains of Borrelia (B.) burgdorferi sensu lato and one strain of B . hermsii . The method comprised BSK II medium lacking gelatin and an incubation period of 72 hours . To investigate the influence of reading mode and density of inoculum on MIC values, microscopical as well as macroscopical MIC reading was performed using standardized final inocula of 10(6) and 10(7) borreliae/ml . Data were processed by two-way analysis of variance . In the microdilution assay, MIC values were significantly influenced either by the inoculum density or reading mode . However, using clearly defined criteria for macroscopical endpoint determination, MICs from macroscopical and microscopical reading were found to be in close agreement . B . burgdorferi sensu lato strains tested were highly susceptible to azithromycin, erythromycin, mezlocillin, piperacillin as well as ceftriaxone, with MICs ranging from < or = 0.016 to 0.125 microgram/ml . B . hermsii was highly susceptible to azithromycin and erythromycin . In comparison to B . hermsii, the beta-lactam antibiotics revealed a significantly higher activity and gentamicin, ofloxacin, and rifampin revealed a significantly lower activity against B . burgdorferi sensu lato strains . To further investigate interactions between BSK II medium, incubation time, and antibiotic efficacy, an agar diffusion bioassay was performed . Out of seven antibiotics tested, the activities of mezlocillin, penicillin G, and piperacillin were significantly influenced by BSK II medium and incubation period and showed a marked decrease of on average 84.0% within 72 hours of incubation. Presse Med, 1998 Oct 10, 27(30), 1536 - 44 {Pharmacokinetics of anti-infective agents in continuous hemofiltration}; Jaumain H et al.; NEW ASSIST TECHNIQUES: Continuous hemofiltration and hemodiafiltration are two new renal replacement techniques offering continuous electrolyte regulation and hemodynamic stability in patients with multiple organ failure . These continuous techniques are being used more and more in intensive care, especially as renal replacement in case of septic shock, and probably have the additional benefit of removing toxins . EFFECT ON ANTIMICROBIALS: Little is known about the removal of drugs and in particular antimicrobials during continuous hemofiltration although both the specific pharmacokinetics of each drug and the patient's particular clinical situation plays an important role . DRUG DOSING: In the intensive care unit, knowledge of the effect of continuous hemofiltration on drug removal and pharmacokinetic profile is crucial for practical management due to the importance of avoiding infratherapeutic serum levels, or inversely toxic levels, in these seriously ill patients . Titration equations provided in most of the recent articles are hel