Gut, 2002 Sep, 51(3), 356 - 61 Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis; Bajaj-Elliott M et al.; BACKGROUND: beta-Defensins are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces where their production is augmented by infection or inflammation . Helicobacter pylori colonises the gastric epithelium causing persistent gastric inflammation leading to antral and corpus gastritis, and peptic ulcer disease . AIMS: To evaluate the role of beta-defensins in the innate immune response of the gastric epithelium to infection and inflammation, we have assessed mRNA expression and regulation of human beta-defensins 1 and 2 (hBD1, hBD2) by H pylori and proinflammatory stimuli . We have also compared gene and peptide expression of these bactericidal agents in H pylori induced gastritis with that in normal gastric mucosa . METHODS: Modulation of expression of hBD1 and hBD2 by various stimuli was studied in three (AGS, MKN7, MKN45) gastric epithelial cell lines by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) . Defensin mRNA expression was measured by semiquantitative RT-PCR in gastritis tissue and compared with controls . Peptide localisation was assessed by immunohistochemistry . RESULTS: Cytotoxic H pylori and interleukin 1 beta (IL-1 beta) markedly upregulated expression of hBD2 in a dose and time dependent manner in both AGS and MKN7 cell lines . A modest increase in hBD1 expression was also noted during infection . Interestingly, induction of hBD1 gene expression by IL-1 beta was only observed in MKN7 cells . The magnitude of this response was delayed and reduced compared with hBD2 expression . In gastric biopsies, hBD2 was undetectable in normal gastric antrum but a marked increase was observed in H pylori positive gastritis compared with control tissue (p<0.001) . Constitutive expression of hBD1 was observed in normal gastric mucosa and there was a significant increase in gastritis (p<0.05) . Immunohistochemistry revealed a parallel increase in hBD1 and hBD2 peptide expression in gastritis tissue with positive staining confined to the surface epithelium of the gastric glands . CONCLUSIONS: Modulation of beta-defensin expression by pathogenic and/or inflammatory stimuli and their cellular localisation places these antimicrobial peptides in the front line of innate host defence in the human stomach. Am J Vet Res, 2002 Aug, 63(8), 1111 - 7 Relationship of vitamin E supplementation and antimicrobial treatment with acute-phase protein responses in cattle affected by naturally acquired respiratory tract disease; Carter JN et al.; OBJECTIVE: To correlate serum concentrations of fibrinogen (Fib), haptoglobin (Hap), serum amyloid-A (SAA), and alpha-1 acid glycoprotein (AGP) with clinical respiratory tract disease and response to treatment in transport-stressed feedlot cattle fed vitamin E-supplemented diets . ANIMALS: 387 heifer calves (mean initial weight, 197 kg) . PROCEDURE: Calves purchased from an order buyer were delivered to a feedlot to study the effects of dietary supplementation with 2,000 IU of vitamin E for 0, 7, 14, or 28 days after arrival . Serum or plasma Fib, Hap, SAA, and AGP concentrations were measured on days 0, 7, and 28 after arrival as well as at the time of treatment for respiratory tract disease with antimicrobial drugs and after completion of treatment . RESULTS: Vitamin E supplementation was associated with decreased treatment costs . In cattle that were not recognized as sick or responded positively to 1 antimicrobial treatment, serum Hap concentrations were significantly lower on days 0 and 7 than concentrations for cattle that required > 1 treatment . Serum Hap concentrations and ratios of Hap to SAA on day 0 significantly correlated with the number of antimicrobial treatments required . Serum Hap concentrations at the time of initial treatment were significantly lower for cattle that required only 1 treatment, compared with those that required > 1 treatment . CONCLUSIONS AND CLINICAL RELEVANCE: Serum Hap concentrations are of potential value for use in assessing feedlot cattle that may become ill as a result of respiratory tract disease and for use in monitoring treatment efficacy. J Reprod Med, 2002 Jul, 47(7), 591 - 6 Fatal disseminated herpes simplex virus infection in a previously healthy pregnant woman . A case report; Frederick DM et al.; BACKGROUND: In contrast to the frequent occurrence of localized herpes simplex virus (HSV) infections during pregnancy, disseminated disease has rarely been reported . CASE: A 21-year-old woman in the 27th week of gestation developed a catastrophic illness characterized by fever, progressive pneumonia, respiratory failure, leukopenia, disseminated intravascular coagulation (DIC), anicteric hepatitis, septic shock and acute renal failure . Initial studies for an infectious etiology were negative . In spite of empiric broad-spectrum antimicrobial therapy, her condition continued to deteriorate . Sparse vesicular skin lesions suggestive of HSV infection subsequently appeared . Despite initiation of acyclovir therapy, the patient died . HSV type 2 was cultured from a skin vesicle, and at autopsy there was extensive necrosis of the liver and lung with immunohistochemical stains positive for HSV antigen . CONCLUSION: In the third trimester of pregnancy, HSV can occasionally disseminate in immunocompetent women . A clinical syndrome of unexplained fever, pneumonia, anicteric hepatitis, leukopenia and DIC without mucocutaneous lesions should prompt investigation and possible treatment for disseminated HSV infection. Eur J Gastroenterol Hepatol, 2002 Jul, 14(7), 745 - 52 Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease; Wehkamp J et al.; OBJECTIVE : Various antimicrobial peptides such as defensins are part of innate immunity and contribute to the intestinal barrier that may be defective in inflammatory bowel disease (IBD) . This study investigated beta-defensin mRNA and peptide expression in the colon from controls and patients with Crohn's disease, ulcerative colitis or unspecific colitis as inflammatory controls . METHODS : Mucosal mRNA expression was measured by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for human beta-defensin 1 (HBD-1) and human beta-defensin 2 (HBD-2) in CaCo-2 cells and in biopsies from 103 patients (33 controls, 24 Crohn's disease patients, 36 ulcerative colitis patients, 10 unspecific colitis patients) . Paraffin-embedded tissue from colonic resections was tested for HBD-1 and HBD-2 peptides by immunohistochemistry . RESULTS : HBD-1 mRNA was expressed constitutively whereas HBD-2 was induced by pro-inflammatory cytokines in CaCo-2 cells . HBD-1 mRNA was detectable in 61% of control and Crohn's disease biopsies and 53% of ulcerative colitis biopsies . HBD-2 transcript was expressed differentially, with 18% of control biopsies positive as opposed to 34% in Crohn's disease and 53% in ulcerative colitis . HBD-2 mRNA but not HBD-1 mRNA was expressed preferentially in inflamed areas . Immunohistochemical investigation demonstrated the presence of defensin peptides in colonic epithelium as well as the differential induction in IBD . CONCLUSIONS : HBD-1 is expressed constitutively in colonic tissue irrespective of inflammation . HBD-2 is barely present in uninflamed colon but it is induced in inflammation . The lower expression of HBD-2 in Crohn's disease compared with ulcerative colitis indicates different responses of the mucosal innate defence . Defensins may play a crucial role in controlling pathogen invasion in IBD, although the functional significance remains to be established. J Trauma, 2002 Aug, 53(2), 245 - 50; discussion 250-1 Persistent systemic inflammatory response syndrome is predictive of nosocomial infection in trauma; Bochicchio GV et al.; BACKGROUND: Admission systemic inflammatory response syndrome (SIRS) score has been previously reported to be an accurate predictor of infection and outcome in trauma . However, these data were limited to only one SIRS score at admission . A prior study in surgical intensive care unit (ICU) patients reported that the SIRS score on ICU day 2 declined after completion of resuscitation, and was a more accurate predictor of outcome . Our objective in this follow-up study was to prospectively evaluate the utility of daily SIRS scores in prediction of nosocomial infection and outcome in high-risk trauma patients . METHODS: Prospective data were collected on 702 consecutive trauma patients admitted over a 12-month period to the ICU . SIRS scores were calculated daily . Centers for Disease Control and Prevention guidelines were used for the diagnosis of infection . Multivariate linear regression was used for statistical analysis . RESULTS: Five hundred seventy-three (82%) patients sustained blunt injuries and 129 (18%) sustained penetrating injuries . The mean age was 43 +/- 21 years, with an overall mortality of 11.4% . Two hundred ninety (41.3%) of the study patients acquired a nosocomial infection (respiratory site most common), with an associated mortality rate of 12.4% . SIRS (defined as SIRS score >/= 2) on hospital days 3 through 7 was a significant predictor of nosocomial infection and hospital length of stay . Persistent SIRS to hospital day 7 was associated with a significant risk for increased mortality (relative risk, 4.7; 95% confidence interval, 1.41-12.87; p = 0.047) . CONCLUSION: Persistent SIRS is predictive of nosocomial infection in trauma . Daily monitoring of SIRS scores is easily accomplished and should be considered in all high-risk trauma patients . Persistent SIRS in trauma should initiate early diagnostic interventions for determination of source of infection, and consideration of early empiric antimicrobial therapy. Biol Neonate, 2002 Aug, 82(2), 96 - 102 Effects of exogenous surfactant and recombinant human copper-zinc superoxide dismutase on oxygen-dependent antimicrobial defenses; Walti H et al.; The use of human recombinant CuZn superoxide dismutase (rhSOD) in addition to exogenous surfactant has been studied as a therapeutic strategy to prevent acute and chronic lung injury in premature infants with blood monocytes (MO) . However, scavenging of superoxide by rhSOD may compromise bacterial killing by phagocytes . In the present study, we investigated the interaction of exogenous surfactant and rhSOD with the antibacterial activity of human blood MO . MO were preincubated in the presence or absence of: (1) modified natural surfactant (Curosurf); 1 mg/ml); (2) rhSOD (2,500 U/ml) and (3) bovine catalase (25,000 U/ml) . Bacteria (Legionella pneumophila or Escherichia coli) were then added and incubated for 6 h . Viable bacteria were determined by counting colony-forming units . The ability of the MO to generate superoxide anions (O2-) in response to bacterial infection was also investigated . The antibacterial capacity of MO was not impaired by the presence of rhSOD either alone or combined with Curosurf . In some instances, bactericidal activity was even potentiated by the addition of rhSOD . Exposure of MO to catalase interfered with the increased bacterial killing of MO and rhSOD, suggesting that hydrogen peroxide (H2O2) production was critically important in the process of bacterial killing . Both bacterial species were also found to induce the generation of intra- and extracellular O2- by MO . Data indicate that rhSOD potentiates the killing of bacteria by human MO . The mechanism of action appears to be related to the ability of bacteria to induce the generation of O2-, which in turn is converted to H2O2 in the presence of rhSOD . This has important implications in the development of therapeutic intervention strategies using antioxidant therapy in premature infants with respiratory distress syndrome . Phytochemistry, 2002 Sep, 61(2), 181 - 7 Globulixanthones C, D and E: three prenylated xanthones with antimicrobial properties from the root bark of Symphonia globulifera; Nkengfack AE et al.; Two prenylated xanthone derivatives, named globulixanthones C and D and one bis-xanthone, designated globulixanthone E, have been isolated from the root bark of Symphonia globulifera . The structures of these compounds were elucidated by a detailed spectroscopic analysis . They have been shown to exhibit in vitro significant antimicrobial activity against a range of micro-organisms. J Contemp Dent Pract, 1999 Nov 15, 1(1), 9 - 15 Use of a whitening dentifrice for control of chlorhexidine stain; Tilliss TS; A major drawback to clinicians prescribing and patients using chlorhexidine rinse is the development of extrinsic staining . In order to assess the effectiveness of a whitening dentifrice in controlling chlorhexidine stain, fifty-seven subjects rinsed with chlorhexidine twice daily while brushing twice daily with either fluoridated whitening or a fluoridated regular dentifrice . Stain was assessed at 1, 2, and 3 month intervals using a stain index with two components; one with parameters for color intensity and one for tooth percentage covered with stain . Facial surfaces accumulated less stain than lingual surfaces . For many, although not all surfaces, and at many, although not all time periods, the group utilizing the whitening dentifrice exhibited less staining . It is advantageous to recommend a whitening dentifrice that has demonstrated stain suppression when prescribing a chlorhexidine rinse . Improved patient satisfaction leading to increased compliance with the antimicrobial regimen is a desired outcome. J Photochem Photobiol B, 2002 Jul, 67(3), 149 - 56 Photoinactivation of vesicular stomatitis virus by a photodynamic agent, chlorophyll derivatives from silkworm excreta; Lim DS et al.; The efficacy of chlorophyll derivatives from silkworm excreta (CpD) in photodynamic antimicrobial chemotherapy (PACT) was studied . An enveloped animal virus, vesicular stomatitis virus (VSV), was used as a target organism . For CpD mediated PACT, the viruses in suspensions were treated with various doses of CpD (15-60 microg/ml) and visible red light was fixed at 120 mJ/cm(2) . The antiviral effect of the CpD-PACT was measured 1 h after light irradiation by the extent of suppression of plaque forming units (pfu) . In cultures inoculated with PACT-treated VSV, suppression of pfu was prominent and the results were demonstrated in a dose-dependent manner . In assays of RT-PCR, a single dose of 30 microg/ml CpD and light caused complete inhibition of viral RNA synthesis in the host cells, which agreed with the complete loss of plaque forming activity observed in pfu assays . An in vitro transcription assay for viral RNA using {3H}UTP and gel electrophoresis for the level of M protein was conducted . A gradual decrease in viral RNA transcription and an immediate decrease in M protein levels were observed in cells inoculated with the CpD-PACT-treated virus . These results demonstrated that CpD is a potential photodynamic antiviral agent, which causes inactivation of the matrix protein as well as transcription mechanisms involved in VSV replication. J Agric Food Chem, 2002 Aug 14, 50(17), 4812 - 5 Detection of traces of tetracyclines from fish with a bioluminescent sensor strain incorporating bacterial luciferase reporter genes; Pellinen T et al.; Bioluminescent Escherichia coli K-12 strain for the specific detection of the tetracycline family of antimicrobial agents was optimized to work with fish samples . The biosensing strain contains a plasmid incorporating the bacterial luciferase operon of Photorhabdus luminescens under the control of the tetracycline responsive element from transposon Tn10 (Korpela et al . Anal . Chem . 1998, 70, 4457-4462) . The extraction procedure of oxytetracycline from rainbow trout (Oncorhynchus mykiss) tissue was optimized . There was neither need for centrifugation of homogenized tissue nor use of organic solvents . The lowest levels of detection of tetracycline and oxytetracycline from spiked fish tissue were 20 and 50 microg/kg, respectively, in a 2-h assay . The optimized assay protocol was tested with fish that were given a single oral dose of high and low concentrations of oxytetracycline . The assay was able to detect oxytetracycline residues below the European Union maximum residue limits, and the results correlated well with those obtained by conventional HPLC (R = 0.81). Spectrochim Acta A Mol Biomol Spectrosc, 2002 Jun, 58(8), 1713 - 9 The stereochemical diversity of a new SNONS binucleating ligand towards 3d metal ions; Naik AD et al.; A new binucleating ligand containing phenoxide as an endogenous bridging group, 2,6-diformyl-p-cresol bis(2-furanthiocarboxyhydrazone) and its binuclear Co(II), Ni(II), Cu(II) and Zn(II) complexes with chloride ion as an exogenous bridge, have been obtained . The complexes were characterized by elemental analysis, molar conductivities, magnetic moment measurements at room temperature, electronic, IR, 1H-NMR, EPR, FAB spectral studies and thermal data . The copper complex assumes a tetranuclear structure composed of two binuclear units related by a center of symmetry . The dimeric nature of copper(II) complex is supported by FAB . This complex is EPR silent . Room temperature magnetic moment reveals the operation of a significant antiferromagnetic spin exchange between the metal centers . Ligand and its copper and zinc complexes exhibit fluorescence at room temperature in DMF . All the compounds show an appreciable antimicrobial activity. Fitoterapia, 2002 Aug, 73(5), 424 - 7 Antimicrobial activity of some Sri Lankan Rubiaceae and Meliaceae; Jayasinghe UL et al.; Ninety solvent extracts (n-hexane, dichloromethane and methanol) obtained from the leaves, bark and stem of 13 Sri Lankan Rubiaceae and two Sri Lankan Meliaceae plants have been screened for antibacterial and antifungal activities . Morinda tinctoria, Mussaenda frondosa, Psychotria gardneri and Psychotria stenophylla displayed the widest spectrum of antibacterial activity. J Altern Complement Med, 2002 Jun, 8(3), 333 - 40 The effectiveness of processed grapefruit-seed extract as an antibacterial agent: II . Mechanism of action and in vitro toxicity; Heggers JP et al.; OBJECTIVES: Recent testimonials report grapefruit-seed extract, or GSE (Citricidal) to be effective against more than 800 bacterial and viral strains, 100 strains of fungus, and a large number of single and multicelled parasites . This study investigated GSE for antibacterial activity at varying time intervals and concentration levels and tissue toxicity at varying concentrations in an effort to determine if a concentration existed that was both microbicidal and nontoxic and in what period of time . DESIGN: Gram-negative and gram-positive isolates were introduced into graduated dilutions of GSE (twofold concentrations ranging from 1:1, through 1:512) for determination of bacterial activity . In vitro assays with human skin fibroblast cells were also performed at the same dilutions to determine toxicity . RESULTS: These tests indicated that from the 1:1 through the 1:128 concentrations, GSE remained toxic as well as bactericidal . However, test results indicated that at the 1:512 dilution, GSE remained bactericidal, but completely nontoxic . CONCLUSIONS: The initial data shows GSE to have antimicrobial properties against a wide range of gram-negative and gram-positive organisms at dilutions found to be safe . With the aid of scanning transmission electron microscopy (STEM), the mechanism of GSE's antibacterial activity was revealed . It was evident that GSE disrupts the bacterial membrane and liberates the cytoplasmic contents within 15 minutes after contact even at more dilute concentrations. J Am Geriatr Soc, 2002 Aug, 50(8), 1416 - 20 The effect of culture-positive influenza type A on resource use and adverse events in nursing home residents; Drinka PJ et al.; OBJECTIVES: To determine adverse clinical events and resource utilization associated with culture-positive influenza A in nursing home residents . DESIGN: A retrospective cohort study with cases and controls . SETTING: Seven hundred twenty-one-bed skilled nursing facility . PARTICIPANTS: One hundred fifty-four residents (21% of all residents) from whom influenza A was isolated during the 1997/98 season and matched controls . MEASUREMENTS: Baseline parameters, staff interventions, diagnostic tests, and adverse events were recorded from 60 days before to 60 days after specimen collection . The difference between each individual's before and after measurements determined excess utilization secondary to influenza . Controls were studied to determine time series effects . RESULTS: Baseline Minimum Data Set and nutritional parameters demonstrated significantly greater (P <.05) feeding dependency and lower serum albumin in the control group . Time series effects in the control group were negligible . Among cases, there were nine deaths within 30 days; among controls, there were four (chi2 P =.26) . Within 30 days of onset, an average excess of 18 notations by nursing staff, one phone call to the physician, and one to family was noted per case . In half of cases, a nonscheduled physician visit was required . There was a 20% excess in physician orders for oxygen and bronchodilators . Chest x-rays were performed in half of the cases, and antibiotics were prescribed to half . Sixteen percent of cases had radiographic pneumonia, and 2% had congestive heart failure . The average cost for excess chest x-rays, laboratory services, antimicrobials, ambulance calls, hospital days, and emergency room and physician visits was $943.44 . This does not include efforts by nursing home staff who accommodate functional decline on-site . CONCLUSION: An unexpected finding was that there were more impaired individuals who were less likely to have influenza detected or less likely to acquire influenza in the control group than in the influenza group . The morbidity, mortality, excess staff effort, and measured expenditure justify efforts to prevent influenza. Kidney Int, 2002 Sep, 62(3), 1026 - 33 Multicenter clinical trial results with the LifeSite hemodialysis access system; Schwab SJ et al.; BACKGROUND: The LifeSite Hemodialysis Access System is a subcutaneous access device designed to maximize blood flow while minimizing access-related complications . The purpose of this study was to compare the efficacy and safety of the LifeSite System to a similar but transcutaneous access device, the Tesio-Cath Hemodialysis Catheter . METHODS: The study was conducted in two phases . A multi-center randomized prospective design was utilized for the first phase (Phase 1) where thirty-four patients were enrolled in the Tesio-Cath group and 36 patients into the LifeSite group where 0.2% sodium oxychlorosene was used as an antimicrobial solution for the LifeSite . A nonrandomized, but otherwise identical, second phase of the study followed where a 70% isopropyl alcohol solution was utilized as the antimicrobial solution for 34 additional LifeSite patients (Phase 2) . RESULTS: Device function was evaluated in Phase 1 of the trial . Actual blood flow (determined by ultrasound dilution) was greater in the LifeSite versus the Tesio-Cath group (358.7 vs . 331.8 mL/min, P < 0.001 for machine-indicated blood flow of 400 mL/min) . Infection comparisons were performed for all three groups encompassing Phase 1 and 2 of the trial; Tesio-Catheter, LifeSite System with oxychlorosene, and LifeSite System with 70% isopropyl alcohol . Device-related infections were defined as systemic bacteremia without another obvious site of origin and exit site infections requiring systemic antibiotics or device removal . This revealed infection rates per 1000 device use days of 1.3 for the LifeSite alcohol group, 3.3 for the Tesio-Cath group, and 3.4 per for the LifeSite oxychlorosene group . There was no statistically significant difference in device related infection rates between the Tesio-Cath and the LifeSite oxychlorosene groups . There were significant differences in infection rate between LifeSite alcohol group and the other two groups (P < 0.05) . Device thrombosis was defined by the need for instillation of thrombolytic agents to maintain blood flow>300 mL/min . There was no difference in the need for thrombolytic infusions between the LifeSite oxychlorosene group and the Tesio-Cath group (P = 0.1496); however, the LifeSite alcohol group required significantly fewer thrombolytic infusions than the Tesio-Cath group (P = 0.0295) to maintain adequate blood flow . Device survival at 6 months after stratification by diabetic status and adjusting for age was significantly better in the LifeSite alcohol group (89.9%) than in the LifeSite oxychlorosene group (64.8%, P = 0.0286) and in the Tesio-Cath (69.1%, P = 0.0292) group . CONCLUSIONS: The LifeSite Hemodialysis Access System, when used with 70% isopropyl alcohol as an antimicrobial solution, provides superior performance with a lower infection rate and better device survival than a standard cuffed tunneled hemodialysis catheter. Arch Dermatol, 2002 Aug, 138(8), 1082 - 6 Use of antimicrobial agents in consumer products; Tan L et al.; OBJECTIVES: To summarize available data on the effectiveness of antimicrobial ingredients in consumer products such as hand lotions and soaps and to discuss the implications of such use on antimicrobial resistance . DATA SOURCES: We searched the MEDLINE database, 1966 to 2001, using the search term resistance qualified with the terms consumer product(s), OR soap, OR lotion, OR triclosan, and LexisNexis and the World Wide Web using the search strategy antimicrobial resistance AND consumer product . DATA EXTRACTION: English-language articles were selected that provided information on the use of antimicrobial ingredients in consumer products and the effect of this use on antimicrobial resistance . DATA SYNTHESIS: Despite the recent substantial increase in the use of antimicrobial ingredients in consumer products, the effects of this practice have not been studied extensively . No data support the efficacy or necessity of antimicrobial agents in such products, and a growing number of studies suggest increasing acquired bacterial resistance to them . Studies also suggest that acquired resistance to the antimicrobial agents used in consumer products may predispose bacteria to resistance against therapeutic antibiotics, but further research is needed . Considering available data and the critical nature of the antibiotic-resistance problem, it is prudent to avoid the use of antimicrobial agents in consumer products . CONCLUSIONS: The use of common antimicrobials for which acquired bacterial resistance has been demonstrated should be discontinued in consumer products unless data emerge to conclusively show that such resistance has no effect on public health and that such products are effective at preventing infection . Ultimately, antibiotic resistance must be controlled through judicious use of antibiotics by health care professionals and the public. Curr Pharm Biotechnol, 2002 Sep, 3(3), 197 - 225 Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis; Schroeder EK et al.; Tuberculosis resurged in the late 1980s and now kills more than 2 million people a year . The reemergence of tuberculosis as a potential public health threat, the high susceptibility of human immunodeficiency virus-infected persons to the disease, and the proliferation of multi-drug-resistant (MDR) strains have created much scientific interest in developing new antimycobacterial agents to both treat Mycobacterium tuberculosis strains resistant to existing drugs, and shorten the duration of short-course treatment to improve patient compliance . Bacterial cell-wall biosynthesis is a proven target for new antibacterial drugs . Mycolic acids, which are key components of the mycobacterial cell wall, are alpha-alkyl, beta-hydroxy fatty acids, with a species-dependent saturated "short" arm of 20-26 carbon atoms and a "long" meromycolic acid arm of 50-60 carbon atoms . The latter arm is functionalized at regular intervals by cyclopropyl, alpha-methyl ketone, or alpha-methyl methylethers groups . The mycolic acid biosynthetic pathway has been proposed to involve five distinct stages: (i) synthesis of C20 to C26 straight-chain saturated fatty acids to provide the alpha-alkyl branch; (ii) synthesis of the meromycolic acid chain to provide the main carbon backbone, (iii) modification of this backbone to introduce other functional groups; (iv) the final Claisen-type condensation step followed by reduction; and (v) various mycolyltransferase processes to cellular lipids . The drugs shown to inhibit mycolic acid biosynthesis are isoniazid, ethionamide, isoxyl, thiolactomycin, and triclosan . In addition, pyrazinamide was shown to inhibit fatty acid synthase type I which, in turn, provides precursors for fatty acid elongation to long-chain mycolic acids by fatty acid synthase II . Here we review the biosynthesis of mycolic acids and the mechanism of action of antimicrobial agents that act upon this pathway . In addition, we describe molecular modeling studies on InhA, the bona-fide target for isoniazid, which should improve our understanding of the amino acid residues involved in the enzyme's mechanism of action and, accordingly, provide a rational approach to the design of new drugs. Phytother Res, 2002 May, 16(3), 264 - 6 Analgesic and antiinflammatory properties of Sideritis lotsyi var . Mascaensis; Hernandez-Perez M et al.; The antiinflammatory, analgesic and antimicrobial activities of crude ethanol extracts of Sideritis lotsyi var . mascaensis (Lamiaceae), and chloroform and aqueous fractions were evaluated in mice using paw and ear oedema induced by carrageenan and 12-o-tetradecanoyl-phorbol-acetate (TPA), respectively, as inflammation models, the writhing test induced by acetic acid for evaluating analgesic activity and the disk-diffusion method for testing antimicrobial actions . The results obtained demonstrated significant topical antiinflammatory and analgesic activities for the ethanol extract and chloroform fraction, but no relevant antimicrobial activity against the microorganisms tested. Phytother Res, 2002 May, 16(3), 199 - 209 Cellular pharmacology studies of shikonin derivatives; Chen X et al.; The naphthoquinone pigment, shikonin, isolated from Lithospermum erythrorhizon Sieb . et Zucc.(Boraginaceae) and its derivatives are the active components isolated from the Chinese herbal therapeutic, Zicao . Historically, Zicao root extracts have been used to treat macular eruption, measles, sore-throat, carbuncles and burns . Multiple pharmacological actions have been attributed to shikonin, e.g . antiinflammatory, antigonadotropic and anti-HIV-1 activity . In this review, several therapeutic applications of shikonin will be summarized including its pleiotropic, antiinflammatory and antitumour effects . Widely diverse and sometimes conflicting activities have been attributed to shikonin, e.g . wound healing, enhanced granuloma formation, suppression of local acute inflammatory reactions, inhibition of angiogenesis, inhibition of select chemokine ligands, inhibition of DNA topoisomerase activity, inhibition of platelet activation and antimicrobial activity . Comparison of the various reported mechanisms of action for shikonin lead us to hypothesize that shikonin is an effective inhibitor of protein-protein interaction with multiple targets in both the intracellular and extracellular compartments . This general inhibitory effect can account for the broad spectrum of shikonin biological and pharmacological activities. Farmaco, 2002 Jul, 57(7), 569 - 72 Synthesis and antimicrobial activity of some pyridinyliminothiazoline derivatives; Turan-Zitouni G et al.; The synthesis of some pyridinyliminothiazoline derivatives starting from N-pyridine-N'-phenyl thiourea and alpha-halogenoacetophenones is described . The chemical structures of the compounds were elucidated . The prepared compounds were tested for antimicrobial activity. Am J Infect Control, 2002 Aug, 30(5), 288 - 95 New national surveillance system for hemodialysis-associated infections: initial results; Tokars JI et al.; BACKGROUND: Hemodialysis patients have frequent infections, especially of the vascular access site, and often harbor antimicrobial-resistant pathogens . Therefore a voluntary national system was created to monitor and prevent infections in these patients . METHODS: From October 1999 to May 2001, participating centers recorded the number of chronic hemodialysis outpatients that were treated (denominator) . Several outcome events, including infections of the vascular access site, were monitored . Data were reported on paper forms or via an Internet-based data entry and analysis system . RESULTS: Among 109 participating centers, the vascular access infection rate per 100 patient-months was 3.2 overall and varied markedly by type of vascular access: 0.56 for native arteriovenous fistulas, 1.36 for synthetic arteriovenous grafts, 8.42 for cuffed catheters, and 11.98 for noncuffed catheters . Among 76 dialysis centers reporting at least 200 patient-months of data, 11 had a significantly low and 14 a significantly high rate of vascular access infection . CONCLUSION: Initial results from the first national project to monitor infections in patients undergoing hemodialysis indicate that vascular access infections were common and that risk varied substantially among different vascular access types and different dialysis centers . These results can be used for quality improvement at individual centers and to help evaluate the efficacy of specific infection control measures. Vaccine, 2002 Aug 19, 20(25-26), 3055 - 67 Overview: cause and prevention in biowarfare and bioterrorism; Hilleman MR; Bioweaponry is rooted in the ancient past . It became a science in the early 20th century following the breakthrough discoveries in microbiology and immunology of the late 1800s . The 20th century, with its major and minor wars, saw the research and development of biological weapons capable of immense destruction of life, which were used both by nations in preparation for military warfare and by individuals who engage in asymmetric warfare . Treaties, international agreements, and political pursuits have not been able either to control or to rid the world of bioweapons . The tools for specific defense against bioweapons consist of vaccines against both viruses and bacteria, and of antibiotics and drugs against bacteria . Vaccines and antimicrobials are of limited usefulness because of the large number of possible microbes that can be used for weapons, because of antimicrobial resistance to drugs and antibiotics, and because of limitations in technical feasibility for developing vaccines and antibacterials against certain of the agents . Induction of non-specific innate immunity by immunostimulatory vaccines (at one time licensed) needs to be explored for possible immunoprophylactic-therapeutic activity when administered immediately following exposure to bioweapon pathogens . The ideal solution to the bioweapons problem lies in measures to end their development and application throughout the world . Emphasis was made at the recent World Economic Forum of the need to end poverty and hunger in the world as a means to reduce the incentive to engage in warfare . Added to this is betterment of health, focused mainly on preventable diseases . A further solution to the problem may lie in the development of modern robotic systems for rapid forensic detection of development and production of bioweapons by "rogue" nations and even by individuals . This review deals with the specifics of the development of bioweapons and their control by vaccines, by therapy with antibacterials, by non-specific immunostimulants, by advanced systems for detection of development and deployment of biological agents of destruction, and by political and health-giving initiatives . Clin Rev Allergy Immunol, 2002 Aug, 23(1), 105 - 22 Inflammation in lung transplantation for CF . Immunosuppression and modulation of inflammation; Mallory GB Jr; Lung transplantation is an accepted therapy for selected individuals with end-stage lung disease due to cystic fibrosis (CF) . Recent data show that CF recipients of lung transplantation have survival as good as those of any other diagnostic group . After transplantation, CF patients confront the major threats to life and health of graft infection and rejection . Inflammation is the common mediator of injury to the lung in both these instances . Graft infection after lung transplantation involves the same micro-organisms as are typical with CF as well as opportunistic agents . Prophylactic strategies and aggressive diagnosis via bronchoscopy are both critical in the effective treatment of post-transplant lung infections . Graft rejection involves the detection and recognition of foreign antigen and the subsequent activation of specific T-lymphocyte clones leading to inflammatory injury to the donor organ . Immunosuppression is used to prevent and/or modulate host response to the donor organ and titrated to serum therapeutic drug monitoring and transbronchial biopsy findings . Precise clinical monitoring and aggressive diagnostic approaches are crucial to minimizing graft injury and enhancing life after transplantation . Although most CF lung transplant recipients experience both graft infection and rejection and the 5-yr survival rate remains at approx 50%, improvement in diagnosis and therapy continue over time . With the introduction of new approaches to antimicrobial therapy, new immunosuppressant agents and promising strategies to promote immune tolerance, survival after lung transplantation is likely to improve in the coming decades. Dtsch Tierarztl Wochenschr, 2002 Jul, 109(7), 300 - 5 {Do lactoferrin, lysozyme and the lactoperoxidase-thiocyanate-hydrogen peroxide-system cause negative microbiological results in mastitis secretions?}; Schmedt Auf Der Gunne H et al.; Lactoferrin, lysozyme and the lactoperoxidase-thiocyanate-peroxide-system are naturally occurring antimicrobial components of milk . The objective of this study was to examine, whether these components were responsible for negative results, when mastitis milk is cultured microbiologically . Quarter milk samples from 75 cows with clinical mastitis on a dairy farm in Brandenburg were submitted for microbiological culture and analysed for the content and the activities of the three components . Animals from all stages of lactation with clinical mastitis were included in the study . Animals were examined clinically and milk samples were collected prior to first treatment . Secretions from quarters with clinical mastitis were compared to those of neighbouring quarters without clinical mastitis . Secretions with positive cultural results were compared to those with negative results . The concentrations or activities of the three factors were significantly higher in the diseased quarters than in the quarters without clinical signs of mastitis . The concentration of lysozyme increased with severity of the clinical signs (local swelling and changes in secretion) . The concentration of lactoferrin was significantly higher in quarters with slight alterations of glandular tissue than in quarters with medium or severe alterations (P < 0.05) . LPS-activities did not correlate with the severity of clinical signs . No differences in the concentration of lactoferrin or LPS-activities were seen between mastitis with positive and negative culture results . The concentration of lysozyme was even higher in culturally positive samples than in negative samples (P < 0.05) . Results from this study indicate that the three factors examined did not impair the results of microbiological culture of milk samples from quarters with clinical mastitis. Otolaryngol Head Neck Surg, 2002 Jul, 127(1), 7 - 12 Maxillary sinus puncture and culture in the diagnosis of acute rhinosinusitis: the case for pursuing alternative culture methods; Benninger MS et al.; OBJECTIVE: Traditional assessments of the microbial flora associated with acute bacterial rhinosinusitis have relied on maxillary sinus punctures (taps) and culture . These taps are now considered the gold standard for obtaining cultures and are used as the method of identifying bacterial pathogens in antimicrobial trials . Maxillary sinus taps are limited by discomfort to the patients and technical concerns . Because of these factors, the standard of performing taps has limited antibiotic trials and microbial surveillance . Alternatives to maxillary sinus taps have been explored . STUDY DESIGN: We conducted a retrospective, systematic review of the literature from 1950 to 2000 of articles comparing culture techniques in the nose and paranasal sinuses for acute bacterial rhinosinusitis . RESULTS: Nasal cultures have poor correlation to maxillary sinus cultures, whereas there is 60% to 85% concordance between endoscopically guided middle meatal cultures and maxillary sinus cultures . These studies, however, are all limited by small sample sizes and therefore are inadequate to make any concrete recommendations regarding the relative role of endoscopically guided middle meatal cultures as a formal method of pathogen identification in acute bacterial rhinosinusitis . CONCLUSION: A formal prospective study with sufficient sample size to assess the concordance between the microbial flora of the maxillary sinus punctures and middle meatal cultures in acute rhinosinusitis is recommended. Scand J Infect Dis, 2002, 34(6), 456 - 9 Linezolid for the treatment of central nervous system infections in neurosurgical patients; Viale P et al.; We report our experience with linezolid in the treatment of 5 patients with central nervous system infections subsequent to neurosurgical interventions . In all cases, initial antimicrobial treatment regimens, including a glycopeptide, either failed or were associated with significant adverse events . The good clinical outcome and the absence of significant side-effects associated with linezolid suggest that it may be an attractive alternative for the treatment of central nervous system infections, particularly in settings characterized by a high incidence of multiresistant Gram-positive pathogens. Immunology, 2002 Aug, 106(4), 517 - 25 Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells; Duits LA et al.; Human beta-defensins are broad-spectrum antimicrobial peptides known to be produced by epithelial cells . It was recently shown that beta-defensins also display chemotactic activity for dendritic cells (DC) and T cells, and thus may serve to link innate and adaptive immunity . The aim of the present study was to explore expression of mRNA for these peptides in mononuclear phagocytes and DC . The results revealed that monocytes, monocyte-derived-macrophages (MDM), and monocyte-derived-dendritic cells (DC) all express human-beta-defensin-1 (hBD-1) mRNA . hBD-1 mRNA expression by monocytes and MDM was increased after activation with interferon-gamma (IFN-gamma) and/or lipopolysaccharide (LPS) in a dose- and time-dependent fashion . Alveolar macrophages showed an intense hBD-1 expression, which could not be further increased . Expression of hBD-1 mRNA by immature DC was low, and increased considerably after maturation . Monocytes, MDM, alveolar macrophages and DC showed a limited expression of human beta-defensin-2 (hBD-2) mRNA, which could only be increased in monocytes and alveolar macrophages by IFN-gamma and/or LPS in a dose- and time-dependent fashion . Immunocytochemical stainings demonstrated the expression of hBD-2 peptide by freshly isolated blood monocytes and alveolar macrophages in cytospin preparations. AACN Clin Issues, 2002 Aug, 13(3), 410 - 20 Antimicrobial resistance in the intensive care unit: understanding the problem; Houghton D; Antimicrobial resistance is a problem that affects healthcare delivery around the globe . Factors associated with antimicrobial resistance include overuse or misuse of antimicrobial agents, immunosuppressed patients, and increased technology . Cellular mechanisms of antimicrobial resistance include the decreased uptake of a drug, efflux of the drug, enzymatic inactivation, and alterations in the antimicrobial target site . New treatment options are currently available for resistant organisms . Therapeutic strategies such as antibiotic control policies and antibiotic "cycling" have been proposed as methods for minimizing the emergence of more resistant organisms . Little evidence is available to indicate that these strategies are effective in limiting the emergence of resistance . Clinicians are urged to be judicious in their use and choice of antimicrobials. Vet Microbiol, 2002 Sep 2, 88(3), 259 - 73 Characterisation of Escherichia coli O157 isolates from Danish cattle and human patients by genotyping and presence and variants of virulence genes; Nielsen EM et al.; Escherichia coli O157 isolates obtained from 17 Danish cattle herds and from a national surveillance programme of cattle at slaughter were genotyped by pulsed-field gel electrophoresis (PFGE) and characterised with respect to presence of and variation in virulence factors . The characteristics of the cattle strains were compared to human clinical isolates from the same time period . All verocytotoxin (VT)-producing E . coli O157 (VTEC O157) from cattle possessed all typical VTEC O157:H7 virulence factors and had either the VT2c-variant alone or together with VT1 . Among human isolates the dominant toxin profile was VT2 + VT2c . Only one PFGE group was represented on each farm, indicating that introduction and establishment of new E . coli O157 strains to these cattle farms is probably not common . Among E . coli O157 isolates from cattle, 22.8% were not VT-producing . The majority of these possessed the eae gene and all other genotypic and phenotypic traits typical for E . coli O157:H7 . On the basis of the virulence characteristics, it is concluded that the VTEC O157 strains isolated from Danish cattle are potential human pathogens . However, the observed differences between cattle and human isolates with regard to VT-profile, genotype and antimicrobial resistance could be important, i.e . either Danish cattle might not be the most important reservoir for human infections or Danish cattle mostly harbour VTEC O157 isolates that are less likely to cause human disease. J Pharm Biomed Anal, 2002 Aug 22, 30(1), 141 - 50 The in vitro metabolism of thalicarpine, an aporphine-benzyltetrahydroisoquinoline alkaloid, in the rat . API-MS/MS identification of thalicarpine and metabolites; Wu WN et al.; The in vitro metabolism of an antitumor, hypotensive, and antimicrobial aporphine-benzyltetrahydroisoquinoline alkaloid, thalicarpine was studied after incubation with rat hepatic S9 fraction in the presence of an NADPH-generating system . Unchanged thalicarpine (46% of the sample) plus eight metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS/MS data . The proposed metabolic pathways for thalicarpine are proposed, and the three metabolic pathways are: (1) N-demethylation; (2) aporphine ring oxidation; and (3) benzylic oxidation/reduction . Pathway 1 formed N-desmethyl thalicarpine (M1, 6%) . Pathway 2 produced three minor keto/hydroxy metabolites (M2-M4, each 2-7%) . Pathway 3 formed a major (M6, 28%) and three minor (M5, M7 and M8, each 2-3%) benzylic-cleavage metabolites . Thalicarpine is substantially metabolized by this rat hepatic system. Expert Opin Investig Drugs, 2002 Aug, 11(8), 1161 - 70 Iseganan HCl: a novel antimicrobial agent; Giles FJ et al.; Iseganan HCl is an antimicrobial peptide under development for the prevention of oral mucositis, a severe consequence of some chemotherapy and radiation therapy regimens . Several attributes of iseganan make it an optimal candidate for study in this clinical situation where both local and systemic host defenses may be impaired . These include broad spectrum and rapid bactericidal activity, a lack of observed resistance and cross-resistance and stability in biological fluids . Clinical trials of patients receiving stomatotoxic chemotherapy followed by a haematopoietic stem cell transplant show iseganan reduces the occurrence of oral mucositis and ameliorates sequelae such as mouth pain, throat pain and difficulty swallowing . Iseganan is well-tolerated, which is partly attributable to a lack of systemic absorption following topical oral administration . Other promising areas of investigation include topical oral application for the prevention of ventilator-associated pneumonia and nebulisation for treatment of chronic lung infection in patients with cystic fibrosis . Future studies will expand on the role of iseganan as a novel antimicrobial. Expert Opin Investig Drugs, 2002 Aug, 11(8), 1149 - 59 Virulence as a target for antimicrobial chemotherapy; Alksne LE; Bacterial resistance to present day antibiotics has become a dangerous threat to public health . Consequently, the pharmaceutical industry must provide new agents and novel classes to combat bacterial disease and to stay a step ahead of the rapid evolution of bacterial resistance mechanisms . The need for novel antibacterials has resulted in a search for previously unexplored targets for chemotherapy, utilising the new techniques of genomics to identify them . Several targets currently under investigation are involved in the process of bacterial virulence . These targets are unique in that their inhibition, by definition, should interfere with the process of infection rather than with bacterial viability . If successful, virulence inhibition may represent a 'kinder, gentler' approach to chemotherapy in which the pathogen is disarmed rather than killed outright. Expert Opin Pharmacother, 2002 Aug, 3(8), 1131 - 51 The evolution and role of macrolides in infectious diseases; Blondeau JM; Two of the most significant changes in the field of infectious disease management during the last few decades are the emergence of atypical and/or new pathogens that may have devastating consequences and the re-emergence of well-recognised organisms that have acquired antimicrobial resistance through a variety of mechanisms . Erythromycin, the prototype macrolide, was originally marketed approximately five decades ago as a useful alternative agent in the treatment of patients allergic to beta-lactam antibiotics . While clinically useful, its pharmacokinetic and adverse-event profile limited the use of erythromycin to these individuals . Enhancements of the macrolide structure circumvented many of the limitations of erythromycin and resulted in the development of azithromycin and clarithromycin . The clinical uses of clarithromycin and azithromycin are substantially wider than erythromycin due to the wide spectra of activity against the atypical and newer pathogens . In addition, these agents are well-tolerated and have a pharmacokinetic profile that allows once- or twice-daily administration . Studies also indicate that the more common of the two mechanisms of macrolide resistance in the US and Canada imparts only low-level resistance . The multitude of studies substantiating clinical as well as bacteriological success with these two agents indicates that, when used appropriately, they will stand the test of time and continue to be useful antimicrobial agents. Curr Gastroenterol Rep, 2002 Aug, 4(4), 308 - 18 Foodborne illness: new developments concerning an old problem; Kasowski EJ et al.; Foodborne illnesses continue to cause substantial morbidity and mortality in the United States, primarily as gastroenteritis but occasionally as other syndromes as well . Most of these illnesses are caused by a variety of widely known infectious agents, principally viruses, and are probably the result of common mistakes in food handling in the home or in restaurants . The epidemiology of foodborne illness is evolving . Major changes in food production, distribution, and consumption have created opportunities for new pathogens to emerge and for old ones to reemerge, and the potential for widespread outbreaks is increasing . Antibiotic resistance in bacterial pathogens resulting from the widespread use of antimicrobial agents in animal husbandry is also an important concern . Clinicians must be aware of the changing epidemiology of foodborne illness to recognize and manage these conditions in the clinical setting . In addition, clinicians are critical in the reporting of recognized or suspected foodborne illness, so that public health authorities are able to investigate, understand, and ultimately better control them . A number of new techniques have been employed, and others under development will improve our ability to recognize and cope with foodborne diseases. J Clin Pathol, 2002 Aug, 55(8), 577 - 80 Survey of infection in patients receiving antibody replacement treatment for immune deficiency; Pettit SJ et al.; BACKGROUND: Primary antibody deficiency disorders are a heterogeneous group of disorders, which are treated by regular infusions of immunoglobulin . Despite replacement treatment, patients remain susceptible to infection . Effective management of infections is necessary to prevent the complications of chronic infection . AIMS: This retrospective survey of clinical practice examined the management of infections in patients who receive immunoglobulin replacement for immune deficiency . METHODS: Patients who received immunoglobulin replacement treatment in Newcastle during the year 2000 were identified . Medical records were reviewed . Basic clinical information and details of immunoglobulin replacement treatment were recorded . Episodes of infection were defined by documented symptoms, signs, or investigation results, and by the prescription of an antibiotic course . Details of episodes of infection and antimicrobial treatment were recorded . RESULTS: Thirty seven patients received immunoglobulin replacement during 2000 . There were 101 episodes of infection . There was no correlation between the frequency of infection and the IgG trough value . Respiratory tract infections were most common (71 of 101) . Where documented, 80% of infections were associated with clinical signs, 21% with pyrexia, and 64% with a raised C reactive protein value . Microbiological culture was performed in 30% of infections . Antimicrobial treatment was instituted along "best guess" lines in 99 of 101 episodes of infection . CONCLUSIONS: Management of respiratory tract infections represents the largest problem in antibody deficient patients . Greater use of microbiological culture might allow more effective prescription of antimicrobial treatment . The generation of treatment guidelines and improved communication with general practitioners could improve the management of all episodes of infection. Biochem Biophys Res Commun, 2002 Aug 9, 296(1), 167 - 71 A novel antimicrobial function for a ribosomal peptide from rainbow trout skin; Fernandes JM et al.; An antimicrobial peptide was purified from skin secretions and epithelial cells of rainbow trout by cation exchange and reversed phase chromatography . Partial N-terminal amino acid sequence of the purified peptide revealed 100% identity with the first 11 residues of a 40S ribosomal peptide from medaka fish . Its molecular mass, determined by matrix-associated laser desorption/ionisation mass spectrometry, was found to be 6676.6Da . These results indicate that this antimicrobial peptide is likely to be the 40S ribosomal protein S30 . It is active at submicromolar concentrations, with an effective 50% reduction concentration of 0.02-0.04 microM against Planococcus citreus . Thus, in addition to its conventional function in the cell as part of the small ribosomal subunit, this peptide may play a role in protection against intracellular or extracellular pathogens. Biochemistry, 2002 Aug 6, 41(31), 10070 - 6 Two states of cyclic antimicrobial peptide RTD-1 in lipid bilayers; Weiss TM et al.; RTD-1 is a recently discovered cyclic peptide that, like other well-studied antimicrobial peptides, appears to bind to the lipid matrix of cell membrane in the initial stage of activity . We studied the states of RTD-1 bound to lipid bilayers by two methods: oriented circular dichroism and X-ray diffraction . RTD-1 shows two physically distinct bound states in lipid bilayers like magainins, protegrins, alamethicin, and melittin that were previously studied . However, the nature of transition between the two states is different for RTD-1 as compared with the aforementioned peptides . In one of the two states, RTD-1 is oriented with its backbone ring parallel to the plane of the bilayer . Only in this state RTD-1 induces membrane thinning . But the effect of membrane thinning is much weaker than all other peptides, suggesting that the mechanism of RTD-1 may be different from the other peptides. Biochemistry, 2002 Aug 6, 41(31), 9852 - 62 Solid-state NMR investigations of peptide-lipid interaction and orientation of a beta-sheet antimicrobial peptide, protegrin; Yamaguchi S et al.; Protegrin-1 (PG-1) is a broad-spectrum beta-sheet antimicrobial peptide found in porcine leukocytes . The mechanism of action and the orientation of PG-1 in lipid bilayers are here investigated using (2)H, (31)P, (13)C, and (15)N solid-state NMR spectroscopy . (2)H spectra of mechanically aligned and chain-perdeuterated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) bilayers indicate that PG-1 at high concentrations destroys the orientational order of the aligned lamellar bilayer . The conformation of the lipid headgroups in the unoriented region is significantly altered, as seen from the (31)P spectra of POPC and the (2)H spectra of headgroup-deuterated 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine . These observations indicate that PG-1 disrupts microbial membranes by breaking the extended bilayer into smaller disks, where a significant fraction of lipids is located in the edges of the disks with a distribution of orientations . These edges allow the lipid bilayer to bend back on itself as in toroidal pores . Interestingly, this loss of bilayer orientation occurs only in long-chain lipids such as POPC and not in shorter chain lipids such as 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine (DLPC) . To understand the mode of binding of PG-1 to the lipid bilayer, we determined the orientation of PG-1 in DLPC bilayers . The (13)CO and (15)N chemical shifts of Val-16 labeled PG-1 indicate that the beta-strand axis is tilted by 55 degrees +/- 5 degrees from the bilayer normal while the normal of the beta-sheet plane is 48 degrees +/- 5 degrees from the bilayer normal . This orientation favors interaction of the hydrophobic backbone of the peptide with the hydrophobic core of the bilayer and positions the cationic Arg side chains to interact with the anionic phosphate groups . This is the first time that the orientation of a disulfide-stabilized beta-sheet membrane peptide has been determined by solid-state NMR. J Periodontol, 2002 Jul, 73(7), 726 - 34 Inhibition of matrix metalloproteinase-mediated periodontal bone loss in rats: a comparison of 6 chemically modified tetracyclines; Ramamurthy NS et al.; BACKGROUND: Chemically modified tetracyclines (CMTs), devoid of antimicrobial activity, inhibit pathologically elevated collagenase activity both in vivo and in vitro . In the current study, doxycycline and 5 different CMTs were tested to prevent matrix metalloproteinase (MMP)-dependent periodontal tissue breakdown in an animal model of periodontitis . METHODS: Adult male rats received intragingival injections with either 10 microl of physiologic saline or Escherichia coli endotoxin (1 mg/ml) every other day for 6 days and were distributed into 8 treatment groups (12 rats/group): saline (S), endotoxin alone (E), E + CMT-1, E + CMT-3, E + CMT-4, E + CMT-7, E + CMT-8, and doxycycline . All animals were treated daily with 1 ml of 2% carboxymethyl cellulose (CMC) alone or containing one of the above-mentioned CMTs (2 mg/day) orally . The gingival tissues were removed, extracted, and assayed for gelatinase (GLSE) . Some rat maxillary jaws from each treatment group were fixed in buffered formalin and processed for histology and immunohistochemistry for the cytokines tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, and MMP-2 and MMP-9 . RESULTS: Endotoxin injection induced elevated GLSE activity (functional assay and osteoclast-mediated bone resorption), the former identified as predominantly MMP-9 (92 kDa GLSE) by gelatin zymography . All 6 tetracyclines (2 mg/day) inhibited periodontal breakdown in the following order of efficacy: CMT-8 > CMT- 1 > CMT-3 > doxycycline > CMT-4 > CMT-7 . Immunohistochemistry was positive for TNF, IL-1, and IL-6 in the inflammatory cells from untreated endotoxin rat tissues, whereas treatment with CMTs decreased the number of immuno-positive stained cells for cytokines and MMPs . The in vivo efficacy of these drugs varied with CMT structure and was significantly correlated with bone resorption: r2 = -0.77, P<0.01; gelatinase inhibitory activity: r2 = -0.84, P <0.01; and serum drug concentrations . CONCLUSION: Since both conventional (antimicrobial) and non-antimicrobial tetracyclines inhibited periodontal bone resorption induced by endotoxin injection, MMP-mediated bone loss in this model can be prevented by inhibition of MMPs. Clin Infect Dis, 2002 Aug 15, 35(4), 395 - 402 Epub 2002 Jul 23. Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal; Fry AM et al.; Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance . During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin . No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001) . There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio {OR}, 0.41; 95% confidence interval {CI}, 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment . The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given. J Hosp Infect, 2002 Jul, 51(3), 160 - 7 Hospital-acquired pneumonia: challenges and options for diagnosis and treatment; Harmanci A et al.; The management of hospital-acquired pneumonia (HAP) presents a major challenge for the clinician . The insensitivity of current diagnostic methods and the increasing prevalence of nosocomial pathogens with multiple antibiotic resistance complicate the issue . Use of mechanical ventilation and broad-spectrum antimicrobials in the intensive care setting predipose patients to acquire HAP more frequently with antimicrobial-resistant pathogens . Controversy exists regarding the patients in which invasive diagnostic testing is indicated; the timing of these procedures is another subject of debate . Proper empirical therapy is fundamental to a favourable outcome, and the selection of inappropriate agents to which pathogens are resistant contributes significantly to morbidity and mortality . In general, there is agreement on the requirement for a thorough knowledge of the local causative organisms and the pathogens' resistance profiles . A wide variety of antimicrobials can be used either as monotherapy or in combinations. Aliment Pharmacol Ther, 2002 Jul, 16(7), 1203 - 8 Review article: Helicobacter pylori infection and gastric outlet obstruction - prevalence of the infection and role of antimicrobial treatment; Gisbert JP et al.; The prevalence of Helicobacter pylori infection in peptic ulcer disease complicated by gastric outlet obstruction seems to be, overall, lower than that reported in non-complicated ulcer disease, with a mean value of 69% . However, H . pylori infection rates in various studies range from 33% to 91%, suggesting that differences in variables, such as the number and type of diagnostic methods used or the frequency of non-steroidal anti-inflammatory drug intake, may be responsible for the low prevalence reported in some studies . The resolution of gastric outlet obstruction after the eradication of H . pylori has been demonstrated by several studies . It seems that the beneficial effect of H . pylori eradication on gastric outlet obstruction is observed early, just a few weeks after the administration of antimicrobial treatment . Furthermore, this favourable effect seems to remain during long-term follow-up . Nevertheless, gastric outlet obstruction does not always resolve after H . pylori eradication treatment and an explanation for the failures is not completely clear, non-steroidal anti-inflammatory drug intake perhaps playing a major role in these cases . Treatment should start pharmacologically with the eradication of H . pylori even when stenosis is considered to be fibrotic, or when there is some gastric stasis . In summary, H . pylori eradication therapy should be considered as the first step in the treatment of duodenal or pyloric H . pylori-positive stenosis, whereas dilation or surgery should be reserved for patients who do not respond to such medical therapy. Planta Med, 2002 Jul, 68(7), 640 - 2 Erythrinaline alkaloids and antimicrobial flavonoids from Erythrina latissima; Wanjala CC et al.; The seed pods of Erythrina latissima yielded erysotrine, erysodine, syringaresinol, vanillic acid, a new erythrina alkaloid, (+)-10,11-dioxoerysotrine, which was lethal to brine shrimp and 2-(5'-hydroxy-3'-methoxy phenyl)-6-hydroxy-5-methoxybenzofuran, which showed strong antimicrobial activity against the yeast spores, Gram-positive and Gram-negative bacteria . The root bark gave four known pterocarpans which showed moderate to strong antifungal activity against the yeast spores and three known flavonoids showed antimicrobial activity against all test microorganisms. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2002 Jun, 93(6), 660 - 70 An update on the controversies in bacterial endocarditis of oral origin; Carmona IT et al.; OBJECTIVES: The aim of this review was to evaluate the evidence implicating dental procedures in bacterial endocarditis (BE) development and the basis for antimicrobial prophylaxis (AP) . STUDY DESIGN: In this article, the literature is reviewed and meaningful findings about epidemiology, pathogenesis, and AP guidelines for BE of oral origin are highlighted . Available results are used to formulate clinical recommendations for the dental practitioner . RESULTS: The nature of dental procedures that cause bacteremia, patients at risk for BE, and the effectiveness of AP guidelines, continue to be points of controversy . There appears to be further evidence to support the important role of oral health status in the prevention of BE of dental origin . CONCLUSIONS: One objective of the dental practitioner in caring for patients at risk for BE should be to promote oral health care . There are no hard data on which to scientifically base the need for AP in patients at risk for BE . However, it would appear prudent, at least from the medicolegal perspective, to provide AP, at least to persons with previous BE or prosthetic heart valves and to those undergoing oral surgery, periodontal treatment, or implant placement. J Bacteriol, 2002 Aug, 184(16), 4555 - 72 From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways; Gerdes SY et al.; Novel drug targets are required in order to design new defenses against antibiotic-resistant pathogens . Comparative genomics provides new opportunities for finding optimal targets among previously unexplored cellular functions, based on an understanding of related biological processes in bacterial pathogens and their hosts . We describe an integrated approach to identification and prioritization of broad-spectrum drug targets . Our strategy is based on genetic footprinting in Escherichia coli followed by metabolic context analysis of essential gene orthologs in various species . Genes required for viability of E . coli in rich medium were identified on a whole-genome scale using the genetic footprinting technique . Potential target pathways were deduced from these data and compared with a panel of representative bacterial pathogens by using metabolic reconstructions from genomic data . Conserved and indispensable functions revealed by this analysis potentially represent broad-spectrum antibacterial targets . Further target prioritization involves comparison of the corresponding pathways and individual functions between pathogens and the human host . The most promising targets are validated by direct knockouts in model pathogens . The efficacy of this approach is illustrated using examples from metabolism of adenylate cofactors NAD(P), coenzyme A, and flavin adenine dinucleotide . Several drug targets within these pathways, including three distantly related adenylyltransferases (orthologs of the E . coli genes nadD, coaD, and ribF), are discussed in detail. Protein Pept Lett, 2002 Feb, 9(1), 53 - 7 Synthetic antibiotic peptides database; Wade D et al.; A computerized database for synthetic antibiotic peptides, the SAPD, has been created and is available on the Internet at web address, The SAPD is modelled on two pre-existing computer databases for naturally occurring peptide antibiotics, the Antimicrobial Sequences Database and the Peptaibol Database, and it will contain both chemical and biological information on all published synthetic antibiotic peptides. Protein Pept Lett, 2002 Feb, 9(1), 31 - 7 Cloning and expression of human beta-defensin-2 gene in Escherichia coli; Fang X et al.; Human beta-defensin-2 (hBD-2), a small cationic peptide, exhibits a broad range of antimicrobial activity . It has been found to play important roles in innate and adaptive immune responses against microbial invasion . For the purposes of this study, hBD-2 gene was cloned from the lesions of human condyloma acuminatum . An expression vector was constructed and transformed into E . coli . hBD-2 was expressed as a fusion protein in both the soluble and insoluble forms, which was further confirmed by western blotting analysis. J Nat Prod, 2002 Jul, 65(7), 960 - 4 Isolation of S-n-butylcysteine sulfoxide and six n-butyl-containing thiosulfinates from Allium siculum; Kubec R et al.; Isolation and identification of (S(S)R(C))-S-n-butylcysteine sulfoxide (1) from the bulbs of Allium siculum is reported . This compound was found in all parts of the plant (bulbs, stem, leaves, and flowers) along with known compounds (S(S)R(C))-S-methyl- and (R(S)R(C))-(E)-S-(1-propenyl)cysteine sulfoxides (2 and 3, respectively) . In addition, six n-butyl-containing thiosulfinates (4-9) have been found in a CH2Cl2 extract of the bulbs . Structures were determined by a combination of spectral methods (primarily NMR and MS) and by comparison with authentic compounds obtained by synthesis . Antimicrobial activities of 4-7 and 9 are reported. Int J Med Microbiol, 2002 Jun, 291 Suppl 33, 125 - 37 Standardised in vitro susceptibility testing of Borrelia burgdorferi against well-known and newly developed antimicrobial agents--possible implications for new therapeutic approaches to Lyme disease; Hunfeld KP et al.; Lyme disease represents a disorder of potentially chronic proportions, and relatively little is known about the in vivo pharmacodynamic interactions of antimicrobial agents with borreliae . So far, evidence-based drug regimens for the effective treatment of Lyme disease have not been definitively established . Moreover, therapeutic failures have been reported for almost every suitable antimicrobial agent currently available . Resistance to treatment and a protracted course of the disease, therefore, continue to pose problems for clinicians in the management of patients suffering from chronic Lyme disease . Further characterisation of the antibiotic susceptibility pattern and a better understanding of the interactions of B . burgdorferi with antimicrobial agents are urgently needed and continue to be crucial owing to considerable differences in the experimental conditions and test methods applied . The development of easily performed, new techniques for the sensitivity testing of B . burgdorferi provides the opportunity to study factors affecting the bacteriostatic and bactericidal action of recently introduced chemotherapeutic agents under more standardised conditions . For the first time, these studies provide direct evidence that, in addition to beta-lactams, macrolides, and tetracyclines which are recommended for stage-dependent treatment of Lyme borreliosis, other recently introduced substances, such as fluoroquinolones, everninomycins, and the ketolide family of antimicrobial agents, also show enhanced in vitro activity against borreliae . Some of these compounds, if effective in vivo as well, may prove to be useful agents in the treatment of certain manifestations of Lyme disease . As such, their potential role should be evaluated further by in vivo experiments and clinical trials . Finally, these antimicrobial agents may turn out to be very effective therapeutic alternatives on account of their oral availability, favourable pharmacodynamic profiles, and high tissue levels in cases where beta-lactames or tetracyclines cannot be administered without detrimental side-effects. Crit Care Clin, 2002 Jul, 18(3), 529 - 52 Infection in the chronically critically ill: unique risk profile in a newly defined population; Kalb TH et al.; Although CCI is defined as prolonged ventilatory failure with tracheotomy stemming from preceding critical illness, the contention that multisystem debilities impact on most CCI patients' care and recovery is a central thesis of this volume . Perhaps reflecting the combined debilities inherent in CCI, infectious complications take their toll in morbidity, mortality, and persistent ventilatory insufficiency . Enhanced susceptibility to infection results from a potent admixture of barrier breakdown, exposure to virulent and resistant nosocomial pathogens, and postulated "immune exhaustion" that stems from the combined impact of comorbidities and the sequellae of critical illness . Strategies to improve outcome in CCI-related infection include standard measures of support especially nutrition, reducing environmental inoculum through pulmonary hygiene measures, skin care, and limiting barrier breaches, and appropriate antimicrobials directed at likely pathogens . Future stratification of patient risk on the basis of immune phenotype or genotype and potential immunomodulatory prophylaxis may be around the corner, as new prospects in the pharmaceutical armamentarium are presently undergoing testing. J Craniofac Surg, 2002 Jul, 13(4), 497 - 500 Complete osseous regeneration of a large skull defect in a patient with cutis aplasia: a conservative approach; Rhee ST et al.; Cutis aplasia (or aplasia cutis congenita) is a congenital absence of all skin layers, often extending through bone . This defect usually occurs in the scalp and can be extensive, exposing the dura mater, and deeper meninges . Treatment regimens for cutis aplasia have included early operative intervention, including skin and bone grafts, local scalp flaps, or free flaps to close the defect . In addition to the significant perioperative risks, these invasive procedures may inhibit the osteogenic potential of the dura to initiate and sustain bony closure of the defect . We report a case of an infant with Adams-Oliver syndrome and cutis aplasia involving a large portion of the skull that was treated conservatively with topical Silvadene dressings . No surgical treatment of bone or soft tissue reconstruction was necessary . This case report is the first to our knowledge to document complete bony restoration of the cranial vault through serial three-dimensional CT scans . The intensive therapeutic intervention in this case report allowed early discharge from the hospital, a gradual amelioration of the patient's alopecia as the hair-bearing scalp slowly covered the defect, and precluded the need for any subsequent bony reconstruction of the cranial vault . We hypothesize that conservative treatment of cutis aplasia maintains dural induction of osseous regeneration, and any treatment plan for bony defects of cutis aplasia should consider maintenance of dural integrity . Although further investigation is warranted, an initial trial of antimicrobial dressing care might optimally promote secondary closure of the cranial vault without the need for surgical intervention. Lupus, 2002, 11(6), 340 - 7 Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE; Lander SA et al.; The primary objectives of this study were to evaluate the safety and efficacy of the cyclooxygenase-2 inhibitor celecoxib in systemic lupus erythematosus (SLE) patients both with and without a self-reported sulfa drug allergy and to review the literature on the use of nonsteroidal agents in SLE subjects . A retrospective review of medical records was performed for 50 SLE patients seen by a community-based rheumatologist and treated with open label celecoxib in doses of 200-400 mg/day for a period of 1-9 months . A MEDLINE search of all articles pertaining to the use of NSAIDs in patients with SLE since 1966 was undertaken . We noted that, in this cohort of celecoxib-treated SLE patients from an office rheumatology practice, the majority demonstrated some improvement, and little toxicity was observed . SLE patients with self-reported sulfa allergies were not more likely to have adverse reactions to celecoxib than non-sulfa allergic patients . The literature review performed herein reveals that, although NSAID toxicity should be a continuing concern in an SLE population, structural dissimilarities between celecoxib and the sulfonamide antimicrobials may make true cross-allergenicity less likely to be a clinical problem . These results suggest that patients with SLE can be safely and effectively treated with celecoxib; however, further studies are needed to assess the effectiveness and safety of all NSAIDs in SLE. Curr Opin Mol Ther, 2002 Jun, 4(3), 236 - 41 Peptidomic approaches in proteomic research; Jurgens M et al.; Peptides play a central role in many physiological processes . In order to comprehensively analyze all peptides and small proteins of a whole organism or a subsystem (peptidome), technologies other than 2-D gel electrophoresis are required . Although systematic efforts directed at peptides and peptidomes, comparable to the numerous proteomics projects, are largely lacking to date, a number that employ liquid chromatography or affinity purification and mass spectrometric identification have now been developed and applied successfully to the analysis of a variety of different peptide sources . Furthermore, distinct peptide classes, such as antimicrobial peptides or peptides related to metabolic diseases such as diabetes/obesity, are once again receiving attention . Here we discuss peptides in terms of their applicability to serve as diagnostic markers (or more generally as biomarkers), as well as therapeutic targets or lead compounds . There are also a number of technological challenges that need to be overcome in the study of potent animal venoms and plant toxins, both of which are generally peptides and which are discussed as potential lead compounds for therapeutic intervention in diseases such as cancer. Plant Mol Biol, 2002 Sep, 50(1), 59 - 69 Characterization of a stamen-specific cDNA encoding a novel plant defensin in Chinese cabbage; Park HC et al.; We isolated a stamen-specific cDNA, BSD1 (Brassica stamen specific plant defensin 1) that encodes a novel plant defensin peptide in Chinese cabbage (Brassica campestris L . ssp . pekinensis) . Plant defensins are antimicrobial peptides containing eight highly conserved cysteine residues linked by disulfide bridges . In BSD1, the eight cysteine residues and a glutamate residue at position 29 are conserved whereas other amino acid residues of the plant defensins consensus sequence are substituted . BSD1 transcripts accumulate specifically in the stamen of developing flowers and its level drops as the flowers mature . The recombinant BSD1 produced in Escherichia coli showed antifungal activity against several phytopathogenic fungi . Furthermore, constitutive over-expression of the BSD1 gene under the control of the cauliflower mosaic virus (CaMV) 35S promoter conferred enhanced tolerance against the Phytophthora parasitica in the transgenic tobacco plants. Infect Control Hosp Epidemiol, 2002 Jul, 23(7), 382 - 7 Prevalence of surgical-site infections and patterns of antimicrobial use in a large tertiary-care hospital in Ho Chi Minh City, Vietnam; Sohn AH et al.; BACKGROUND: Few studies have been conducted in Vietnam on the epidemiology of healthcare-associated infections or antimicrobial use . Thus, we sought to determine the prevalence of and risk factors for surgical-site infections (SSIs) and to document antimicrobial use in surgical patients in a large healthcare facility in Vietnam . METHODS: We conducted a point-prevalence survey of SSIs and antimicrobial use at Cho Ray Hospital, Ho Chi Minh City, a 1,250-bed inpatient facility . All patients on the 11 surgical wards and 2 intensive care units who had surgery within 30 days before the survey date were included . RESULTS: Of 391 surgical patients, 56 (14.3%) had an SSI . When we compared patients with and without SSIs, factors associated with infection included trauma (relative risk {RR}, 2.65; 95% confidence interval {CI95}, 1.60 to 4.37; P < .001), emergency surgery (RR, 2.74; CI95, 1.65 to 4.55; P < .001), and dirty wounds (RR, 3.77; CI95, 2.39 to 5.96; P < .001) . Overall, 198 (51%) of the patients received antimicrobials more than 8 hours before surgery and 390 (99.7%) received them after surgery . Commonly used antimicrobials included third-generation cephalosporins and aminoglycosides . Thirty isolates were identified from 26 SSI patient cultures; of the 25 isolates undergoing antimicrobial susceptibility testing, 22 (88%) were resistant to ceftriaxone and 24 (92%) to gentamicin . CONCLUSIONS: Our data show that (1) SSIs are prevalent at Cho Ray Hospital; (2) antimicrobial use among surgical patients is widespread and inconsistent with published guidelines; and (3) pathogens often are resistant to commonly used antimicrobials . SSI prevention interventions, including appropriate use of antimicrobials, are needed in this population. Mikrobiologiia, 2002 May-Jun, 71(3), 345 - 8 {Photoquenching of the bioluminescence of the genetically engineered Escherichia coli TG1 (pXen7) strain in the presence of photodithazine}; Strakhovskaia MG et al.; The photoquenching of the bioluminescence of the genetically engineered Escherichia coli TG1 (pXen7) strain was studied in the presence of the photosensitizer photodithazine, a glucosamine salt of chlorin e6 . The photosensitized quenching of the bioluminescence was found to correlate with the colony-forming ability of the strain . The data obtained are discussed from the standpoint of using biosensor luminescent bacterial systems for the assessment of the efficiency of photosensitizers in antimicrobial photochemotherapy. J Biol Chem, 2002 Oct 4, 277(40), 37597 - 603 Epub 2002 Jul 22. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis; Hunter HN et al.; The antibacterial and antifungal peptide hepcidin (LEAP-1) is expressed in the liver . This circulating peptide has recently been found to also act as a signaling molecule in iron metabolism . As such, it plays an important role in hereditary hemochromatosis, a serious iron overload disease . In this study, we report the solution structures of the hepcidin-20 and -25 amino acid peptides determined by standard two-dimensional (1)H NMR spectroscopy . These small cysteine-rich peptides form a distorted beta-sheet with an unusual vicinal disulfide bridge found at the turn of the hairpin, which is probably of functional significance . Both peptides exhibit an overall amphipathic structure with six of the eight Cys involved in maintaining interstrand connectivity . Hepcidin-25 assumes major and minor conformations centered about the Pro residue near the N-terminal end . Further NMR diffusion studies indicate that hepcidin-20 exists as a monomer in solution, whereas hepcidin-25 readily aggregates, a property that may contribute to the different activities of the two peptides . The nuclear Overhauser enhancement spectroscopy spectra of the hepcidin-25 aggregates indicate an interface for peptide interactions that again involves the first five residues from the N-terminal end. Cochrane Database Syst Rev . 2002;(3):CD003254. Antibiotic regimens for management of intraamniotic infection; Hopkins L et al.; BACKGROUND: Intraamniotic infection is associated with maternal morbidity and neonatal sepsis, pneumonia and death . Although antibiotic treatment is accepted as the standard of care, few studies have been conducted to examine the effectiveness of different antibiotic regimens for this infection and whether to administer antibiotics intrapartum or postpartum . OBJECTIVES: To study the effects of different maternal antibiotic regimens for intraamniotic infection on maternal and perinatal morbidity and mortality . SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2002) and the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2002) . SELECTION CRITERIA: Trials where there was a randomized comparison of different antibiotic regimens to treat women with a diagnosis of intraamniotic infection were included . The primary outcome was perinatal morbidity . DATA COLLECTION AND ANALYSIS: Data were extracted from each publication independently by the authors . MAIN RESULTS: Two eligible trials (181 women) were included in this review . No trials were identified that compared antibiotic treatment with no treatment . Intrapartum treatment with antibiotics for intraamniotic infection was associated with a reduction in neonatal sepsis (relative risk (RR) 0.08; 95% confidence interval (CI) 0.00, 1.44) and pneumonia (RR 0.15; CI 0.01, 2.92) compared with treatment given immediately postpartum, but these results did not reach statistical significance (number of women studied = 45) . There was no difference in the incidence of maternal bacteremia (RR 2.19; CI 0.25, 19.48) . There was no difference in the outcomes of neonatal sepsis (RR 2.16; CI 0.20, 23.21) or neonatal death (RR 0.72; CI 0.12, 4.16) between a regimen with and without anaerobic activity (number of women studied = 133) . There was a trend towards a decrease in the incidence of post-partum endometritis in women who received treatment with ampicillin, gentamicin and clindamycin compared with ampicillin and gentamicin alone, but this did not reach statistical significance (RR 0.54; CI 0.19, 1.49) . REVIEWER'S CONCLUSIONS: The conclusions that can be drawn from this meta-analysis are limited due to the small number of studies . For none of the outcomes was a statistically significant difference seen between the different interventions . Current consensus is for the intrapartum administration of antibiotics when the diagnosis of intraamniotic infection is made; however, the results of this review neither support nor refute this although there was a trend towards improved neonatal outcomes when antibiotics were administered intrapartum . No recommendations can be made on the most appropriate antimicrobial regimen to choose to treat intraamniotic infection. Pharm World Sci, 2002 Jun, 24(3), 95 - 9 Non-observance of guidelines for surgical antimicrobial prophylaxis and surgical-site infections; Lallemand S et al.; OBJECTIVE: A prospective multicentre study was conducted to assess major aspects of surgical prophylaxis and to determine whether inappropriate antimicrobial prophylaxis was a factor associated (risk or protective factor) with surgical site infection (SSI) . METHOD: Surgical prophylaxis practices were assessed by analysing four variables: indication, antimicrobial agent, timing and duration . Univariate and multivariate analyses were carried out to identify predictors of SSI among patient-specific, operation-specific and antimicrobial prophylaxis-specific factors . RESULTS: The frequency of SSI was 2.7% (13 SSI in 474 observations) . Total compliance of the prescription with guidelines was observed in 41.1% of cases (195 prescriptions) . Of the 139 patients who received an inappropriate drug, 126 (90.6%) received a drug with a broader spectrum than the recommended drug . Prophylaxis was prolonged in 71 (87.7%) of the 81 patients who received prophylaxis for inappropriate lengths of time and 43 (61.4%) of the 70 patients who did not receive prophylaxis at the optimal moment were treated too late . Multivariate analysis clearly demonstrated that SSI was associated with multiple procedures (relative risk 8.5), short duration of prophylaxis (relative risk 12.7) and long-term therapy with antimicrobial agents during the previous year (relative risk 8.8) . CONCLUSIONS: The ecological risk of the emergence of resistance associated with the frequent use of broad-spectrum antibiotics and prophylaxis for longer periods was not offset by individual benefit to the patients who received inappropriate prophylaxis. Anat Embryol (Berl), 2002 Jul, 205(4), 315 - 23 Epub 2002 Jun 14. The human false vocal folds -- an analysis of antimicrobial defense mechanisms; Kutta H et al.; Inflammatory processes often lead to pathologic changes in the area of the larynx . A moistening function of the false vocal folds has been described frequently . Up to now we have little knowledge of the role of the false vocal folds in protection against pathogenic agents . The present study analyzes the structures of the false vocal folds in their relations to antimicrobial defense mechanisms . Investigations were performed on false vocal folds of larynges from 34 cadavers using histologic, histochemical and immunohistochemical methods . Seromucous glands, together with epithelial and goblet cells of the folds, synthesize a complex mucus layer . In all of the investigated samples this layer contains carbohydrates including N-acetyl-glucosamine, N-acetyl-galactosamine, galactose, mannose, fucose, and sialic acids . Furthermore, antimicrobial peptides like lactoferrin, lysozyme, alpha and beta defensins are also found in these structures . IgA, produced by plasma cells in the false vocal folds, is frequently integrated in the secretory product . Synthesized mucins, antimicrobial peptides and immunoglobulins form a specialized protective substance that is secreted mainly at the true vocal folds . Here the layer functions to lubricate the true vocal folds, resulting in positive functional consequences during vocal production . Moreover, together with immunocompetent cells, the protective layer seems to play a major role in antigen defense and prevents invasion of pathogenic agents. Int J Antimicrob Agents, 2002 Jun, 19(6), 576 - 82 Antibacterial effect of intraprostatic zinc injection in a rat model of chronic bacterial prostatitis; Cho YH et al.; High levels of prostatic zinc are associated with prostatic antimicrobial activities and are depressed in patients with chronic prostatitis . We investigated the inhibition of bacterial growth in the rat prostate with chronic prostatitis after intraprostatic injection of zinc and compared two different types of zinc delivery . Ninety male Wistar rats were used in the study . Experimental chronic bacterial prostatitis was induced by instillation of bacterial suspension (Escherichia coli 10(8) per ml) into the prostatic urethra . Animals were followed for 4 weeks and then injected intraprostatically with either 0.2 ml of zinc liposome (ZL) or zinc solution (ZS) (0.04 M zinc sulphate) or 0.2 ml of phosphate-buffered saline (PBS) for the controls . Ten rats in each group were sacrificed 4, 6 and 8 weeks after injection . The inhibition of inflammation and its consequences were analyzed microbiologically and histologically . Prostatic zinc concentrations were measured by inductively coupled plasma atomic emission spectrometry . Microbiological culture of the prostates demonstrated bacterial growth inhibition by the intraprostatic injection of zinc . The average infection rates and mean log(10) cfu/g of the zinc-treated groups were significantly lower than those of the controls . The histopathology showed resolving prostatitis in zinc-treated groups compared with the controls . Prostatic zinc levels were higher in the zinc-treated groups than in the controls 4 and 6 weeks after zinc injection (P<0.05) . However, the ZL and ZS groups were found to be effectively identical in terms of prostatic zinc levels, bacterial cfu, and histological findings throughout the experiment period . The intraprostatic injection of zinc inhibited bacterial growth by increasing zinc levels in the rat prostatitis model . Our results suggest that the local application of zinc to the prostate may be a new treatment for chronic bacterial prostatitis at the point of its pathogenesis. Arch Pharm Res, 2002 Jun, 25(3), 250 - 7 Synthesis and antimicrobial activity of new substituted anilinobenzimidazoles; Nofal ZM et al.; A series of benzimidazole derivatives carrying different heterocycles such as 1,2,3-thiadiazole, 1,3,4-thiadiazole, thiazolidine, 2,3-dihydro-thiazole, 1,3,4-oxadiazole, semicarbazone and substituted thiosemi-carbazones were synthesized . Also a series of 1-methylbenzimidazole carrying hydroxy ethyl-amide, substituted sulfonyl hydrazide and benzoyl hydrazide from aminobenzoyl group at position 2 of 1-methylbenzimidazole were synthesized . The antimicrobial evaluation of some of the new compounds was carried out. J Infect Dis, 2002 Jul 15, 186(2), 240 - 5 Epub 2002 Jul 03. Cytokine release by lipopolysaccharide-stimulated whole blood from patients with typhoid fever; House D et al.; The ex vivo cytokine response to lipopolysaccharide (LPS) of whole blood from patients with typhoid fever was investigated . Tumor necrosis factor (TNF)-alpha release by LPS-stimulated blood was found to be lower during acute typhoid fever than after a course of antimicrobial therapy (P<or=.001) . Ex vivo interleukin (IL)-1beta, but not IL-1 receptor antagonist, release was also depressed during the acute stage of typhoid fever . Low ex vivo production of TNF-alpha was associated with delayed recovery . No association was found between the TNFA-308 promoter polymorphism and LPS-induced TNF-alpha release, either during an active infection or after treatment . In acute typhoid fever, the ability of peripheral blood leukocytes to release proinflammatory cytokines in response to an inflammatory stimulus is depressed, and this may contribute to delayed recovery following antibiotic treatment. Biol Pharm Bull, 2002 Jul, 25(7), 923 - 7 Optimal dose of omeprazole for CYP2C19 extensive metabolizers in anti-Helicobacter pylori therapy: pharmacokinetic considerations; Kita T et al.; In anti-Helicobacter pylori therapy using omeprazole and antimicrobials, the efficacy can be related to the CYP2C19 genotype groups; the eradication rates were 83% in extensive metabolizers and 100% in poor metabolizers . The present study was undertaken to help predict the optimal dosage of omeprazole for extensive metabolizers in this therapy . Seven healthy Japanese subjects, classified based on the CYP2C19 genotype into extensive metabolizers (n=4) and poor metabolizers (n=3), participated in this study . Each subject received a single oral dose of omeprazole 20, 40, and 80 mg, with at least a 1-week washout period between each dose . Plasma concentrations of omeprazole and its two metabolites were monitored for 12 h after each dose of medication . After each dose was administered, the pharmacokinetic profiles of omeprazole and its two metabolites were significantly different between extensive metabolizers and poor metabolizers . The area under the plasma concentration-time curve (AUC) of omeprazole in extensive metabolizers was disproportionally increased 3.2- or 19.2-fold with dose escalation from 20 to 40 or 80 mg omeprazole, respectively . In contrast, the AUC of omeprazole was proportionally increased with the higher dose in poor metabolizers . The AUC of omeprazole after 20 mg administration to poor metabolizers was almost equal to the AUC in extensive metabolizers after 80 mg administration . In anti-H . pylori therapy, the recommended dose of omeprazole for extensive metabolizers is suggested to be a maximum of 80 mg x 2/d based on pharmacokinetic considerations. Am J Health Syst Pharm, 2002 Jul 15, 59(14), 1357 - 65 Cost-effectiveness of gemifloxacin: results from the GLOBE study; Halpern MT et al.; The cost-effectiveness of treatment with oral gemifloxacin versus oral clarithromycin for acute exacerbations of chronic bronchitis (AECB) was evaluated . Economic outcomes were assessed for the Gemifloxacin Long-term Outcomes in Bronchitis Exacerbations study . This prospective double-blind, controlled, health outcomes study compared health, economic, and clinical outcomes after randomized treatment with either oral gemifloxacin or oral clarithromycin for AECB . Base case analysis was performed from the third-party payer's perspective and considered the costs of respiratory tract infection-related medical care . Analysis from the societal perspective also included costs of lost productivity . Treatment effectiveness was measured as the proportion of patients without recurrence requiring antimicrobial treatment following resolution of the initial AECB . Data sources included the outcomes study itself and standard U.S . cost sources . Compared with clarithromycin, gemifloxacin treatment resulted in significantly more patients without AECB recurrence requiring antimicrobial treatment after 26 weeks (73.8% versus 63.8%, p = 0.024) . Fewer patients receiving gemifloxacin were hospitalized (5 of 214 patients versus 14 of 224 patients, p = 0.059), and they had less time off from usual activities (8.3 days versus 10.1 days) . The mean direct cost per patient receiving gemifloxacin was $127 less than with clarithromycin ($247 versus $374, respectively); mean total costs (direct plus indirect) per patient were $329 less for patients receiving gemifloxacin ($1413 versus $1742) . Gemifloxacin dominated clarithromycin in cost-effectiveness analysis . Bootstrap analysis indicated that the probability of gemifloxacin being both cost saving and more effective than clarithromycin is 88% from a payer's perspective and 84% from the societal perspective . Gemifloxacin was more cost-effective, improving AECB outcomes and producing substantial cost offsets compared with clarithromycin. J Infus Nurs, 2002 Jul-Aug, 25(4), 244 - 9 A clinical study comparing the skin antisepsis and safety of ChloraPrep, 70% isopropyl alcohol, and 2% aqueous chlorhexidine; Hibbard JS et al.; ChloraPrep (2% chlorhexidine gluconate + 70% isopropyl alcohol {CHG + IPA} in a 3.0-mL applicator) is a recently approved antiseptic for preoperative skin preparation . This controlled open-label trial assessed the immediate and persistent antimicrobial efficacy and safety of CHG + IPA compared with 70% IPA or a 2% CHG aqueous solution alone . Each antiseptic significantly reduced abdominal and inguinal microbial counts from baseline at 10 minutes, 6 hours, and 24 hours (P =.0001) . CHG + IPA provided significantly more persistent antimicrobial activity on abdominal sites than IPA (P =.003) or CHG (P =.028) at 24 hours . No skin irritations were reported for any of the three antiseptics. J Pediatr Orthop, 2002 Jul-Aug, 22(4), 506 - 10 Outpatient parenteral antimicrobial therapy in osteoarticular infections in children; Maraqa NF et al.; There are few data on the use of outpatient parenteral antimicrobial therapy (OPAT) in the management of osteoarticular infections (OAIs) in childhood . The objective of this study was to determine if OPAT is safe and effective in the management of OAIs . Using their OPAT database, the authors evaluated the use of OPAT in children younger than 18 years old treated for OAIs between January 1, 1995, and December 31, 1999 . One hundred eighty-four OAIs were treated in 179 patients over 5 years . OPAT involved central venous lines (CVLs) in 110 (59.8%), peripherally inserted central catheters (PICCs) in 71 (38.6%), and peripheral cannulas in 3 (1.6%) . One hundred eighteen (64%) OPAT courses were completed without interruption . Rehospitalization occurred in 48 (26.1%) courses and occurred earlier with PICC . OPAT complications were catheter-related in 58 (30%) courses, not catheter-related in 60 (32%), and unknown in 10 (5.3%) . The mechanical complication rate was 6.3 per 1,000 catheter-days (CVL 4.2, PICC 10.6), and the rate of infectious complications was 2.7 per 1,000 catheter-days (CVL 2.8, PICC 2.4) . One hundred sixty-eight (98%) of 172 evaluable OAIs were cured . Four (2.2%) patients failed treatment: one had recurrence and three had persistent infection . The authors conclude that OPAT can be safely used to manage OAIs in children without compromising outcome . Mechanical complications are more common with PICCs. J Urol, 2002 Aug, 168(2), 593 - 8 Demographic and clinical characteristics of men with chronic prostatitis: the national institutes of health chronic prostatitis cohort study; Schaeffer AJ et al.; PURPOSE: We describe the study design of the National Institutes of Health Chronic Prostatitis Cohort (CPC) study characterizing men with chronic prostatitis/the chronic pelvic pain syndrome . MATERIALS AND METHODS: All 488 men screened into the CPC study before close of recruitment on August 22, 2001 were selected for analysis . The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, was used to measure symptoms . A comprehensive history, physical examination and demographic profile were obtained from each participant . Generalized Mantel-Haenszel procedures were used to investigate baseline associations between selected factors and symptoms . RESULTS: Chronic prostatitis/chronic pelvic pain syndrome is a chronic syndrome affecting men over a wide age range . The majority of CPC study participants are white, well educated and affluent . However, lower education, lower income and unemployment were associated with more severe symptoms . Patients most frequently reported pain in the perineum and tenderness in the prostate . The highest self-reported diseases were genitourinary (55%), allergies (53%), neurological (40%) and hematopoietic, lymphatic or infectious (40%) . This disease has a significant negative impact on mental and physical domains of quality of life . Almost all patients (95%) reported antimicrobial drug use . Of these 488 participants 280 (57%) reported the previous or current use of 5 or more categories of prostatitis related treatments . CONCLUSIONS: Chronic prostatitis/chronic pelvic pain syndrome is a multifactorial problem affecting men of all ages and demographics . Patients with the chronic pelvic pain syndrome have dismal quality of life and many have benefited only minimally from empirical, goal directed therapy . Long-term followup of this cohort may answer important questions on the natural treated history of this syndrome. Crit Care Med, 2002 Jul, 30(7), 1644 - 7 Lemierre's syndrome: an unusual cause of sepsis and abdominal pain; Hoehn S et al.; OBJECTIVE: To describe a patient with Lemierre's syndrome who presented with acute abdominal findings and to describe the evaluation and treatment of this syndrome . DESIGN: Case report . SETTING: A 38-bed, pediatric intensive care unit at a tertiary care children's hospital . PATIENT: One patient presenting with signs of severe sepsis and acute abdominal pain . INTERVENTIONS: Intravenous hydration, inotropic support, thoracostomy tube drainage of a pleural effusion, and prolonged antimicrobial therapy . MEASUREMENT AND MAIN RESULTS: The patient presented with severe sepsis and abdominal pain . After Fusobacterium necrophorum grew in blood cultures, anaerobic antimicrobial therapy was initiated . Doppler duplex ultrasonography and magnetic resonance venography demonstrated thrombus formation in the left internal jugular vein . Computed tomography of the chest demonstrated bibasilar lung nodules consistent with septic emboli . The patient was treated with ampicillin-sulbactam and metronidazole intravenously for 3 wks, followed by a 3-wk course of oral amoxicillin/clavulanate . He had a good recovery, and his thrombus had resolved at the time of discharge . CONCLUSION: Lemierre's syndrome occurs in young, otherwise healthy patients, and it thus needs to remain high on the differential diagnosis for this group of patients presenting with severe sepsis . The diagnosis can be confounded by a lack of symptoms of pharyngitis at the time of presentation and end-organ dysfunction associated with severe sepsis, suggesting alternative sources of infection. Crit Care Med, 2002 Jul, 30(7), 1478 - 82 Plasma and tissue pharmacokinetics of cefpirome in patients with sepsis; Joukhadar C et al.; OBJECTIVE: Broad initial antibiotic treatment is crucial for patients experiencing septic shock or severe sepsis . Fourth-generation beta-lactam antibiotics, such as cefpirome, are frequently favored in these conditions because of their low toxicity and wide antimicrobial coverage . From recent data, however, there is circumstantial evidence that one reason for the high mortality rate of patients with sepsis might be an impaired penetration of antimicrobial agents from the central compartment to the infectious focus . Thus, the present study aimed at describing penetration properties of cefpirome to the target site of many bacterial infections, which is the extracellular space fluid of soft tissues . DESIGN: Prospective comparative study of two groups . SETTING: An intensive care unit and research ward in a university hospital . SUBJECTS: The study population included 12 patients with septic shock or severe sepsis and a control group of six overall age-matched healthy volunteers . INTERVENTIONS: To measure cefpirome penetration into the interstitial space fluid of skeletal muscle, we employed microdialysis after single intravenous administration of 2.0 g of cefpirome to patients and healthy volunteers . MEASUREMENTS AND MAIN RESULTS: Maximum concentration and area under the concentration vs . time values in interstitium were significantly lower in patients compared with the control group (p <.004) . Cefpirome area under the concentration time values for plasma were 16.0 +/- 1.1 mg.min/mL (mean +/- sem) and 18.8 +/- 1.1 mg.min/mL in patients and healthy volunteers, respectively (p =.075, not significant) . In both study groups, mean cefpirome concentrations in interstitium and plasma exceeded 28 microg/mL throughout the observation period of 240 mins and covered completely minimal inhibitory concentration values for a range of clinically relevant pathogens . CONCLUSION: Cefpirome concentrations reached in tissue interstitium and plasma exceeded minimal inhibitory concentrations of most clinically relevant pathogens in patients with sepsis . Thus, cefpirome exhibits a tissue pharmacokinetic profile, which seems to be particularly valuable for the empirical therapy of patients with sepsis. Int J Antimicrob Agents, 2002 Jul, 20(1), 65 - 8 Comparative antimicrobial activity of lysosubtilin and its acid-resistant derivative, Fermosorb; Biziulevieius GA et al.; Comparative data are given on the in vitro activity of lysosubtilin against micro-organisms and its acid-resistant derivative, Fermosorb . The lytic activity Fermosorb against all micro-organisms tested was higher (in the range of 0.9-7.7 and 4.1-13.5% for bacteria and filamentous fungi/yeasts, respectively) than that achieved by the action of lytic enzymes present in lysosubtilin solution . All six lysosubtilin-resistant strains tested were Fermosorb-susceptible . Considering the increase in the incidence of antibiotic resistance antimicrobial enzymotherapy or enzymoprophylaxis by means of Fermosorb might be considered for the treatment of intestinal infections in animals. Bioorg Med Chem Lett, 2002 Aug 19, 12(16), 2121 - 3 The synthesis and biological evaluation of a novel series of antimicrobials of the oxazolidinone class; Sciotti RJ et al.; A novel series of antimicrobials of the oxazolidinone class is disclosed . These compounds are characterized relative to previously described analogues by a 'halostilbene-derived' pharmacophore and demonstrate enhanced antimicrobial activity against key Gram-positive pathogens when compared to Linezolid. J Ethnopharmacol, 2002 Aug, 81(3), 357 - 64 Cancer prevention and therapy with kiwifruit in Chinese folklore medicine: a study of kiwifruit extracts; Motohashi N et al.; Kiwi gold fruits were extracted successively with hexane, acetone, methanol and 70% methanol, and further fractionated by silica gel and ODS column chromatographies for the assays of various biological activities . Five fractions H1, H2 (hexane extract), Al, A2 (acetone extract) and M2 (methanol extract) showed selective cytotoxic activity against human oral tumor cell lines, which was more sensitive than human gingival fibroblasts . More hydrophilic fractions {70M3, 70M4, 70M5} of 70% methanol extract displayed higher anti-HIV activity, radical generation and O2- scavenging activity . The antibacterial activity of 70% methanol extracts {70M0, 70M1, 70M2, 70M3, 70M4} was generally lower than that of more lipophilic fractions (hexane, acetone, methanol extracts), although each fraction did not show any specific antimicrobial action . All fractions were inactive against Helicobacter pylori . These results demonstrate that gold kiwifruit extracts contain valuable, various bioactive materials, which can be separated wit