Ned Tijdschr Tandheelkd, 1996 Jan, 103(1), 3 - 5 {Discoloration of teeth by drugs}; de Wit ME et al.; Since 1979 the Dutch Centre for Monitoring of Adverse Reactions to Drugs received 37 reports of tooth discoloration, attributed to the use of drugs . It concerned sixteen males and 21 females with an average age of respectively twelve and 26 years . Most cases were attributed to the use of amoxicillin (n = 16) and doxycycline or minocycline (n = 7) . Pseudo-discolorations are chiefly caused by antimicrobial agents, possibly by chromogenic precipitates in the pellicle or by overgrowth with chromogenic micro-organisms. Thorax, 2002 Apr, 57(4), 366 - 71 The pulmonary physician in critical care * 4: Nosocomial pneumonia; Ewig S et al.; Much progress has been made in the understanding of nosocomial pneumonia but important issues in diagnosis and treatment remain unresolved . The controversy over diagnostic tools should be closed . Instead, every effort should be made to increase our ability to make valid clinical predictions about the presence of ventilator associated pneumonia and to establish criteria to guide restricting empirical antimicrobial treatment without causing patient harm . More emphasis must be put on local infection control measures such as routine surveillance of pathogens, definition of controlled policies of antimicrobial treatment, and effective implementation of strategies of prevention. J Clin Microbiol, 2002 Apr, 40(4), 1346 - 51 Identification of medically relevant Nocardia species with an abbreviated battery of tests; Kiska DL et al.; Identification of Nocardia to the species level is useful for predicting antimicrobial susceptibility patterns and defining the pathogenicity and geographic distribution of these organisms . We sought to develop an identification method which was accurate, timely, and employed tests which would be readily available in most clinical laboratories . We evaluated the API 20C AUX yeast identification system as well as several biochemical tests and Kirby-Bauer susceptibility patterns for the identification of 75 isolates encompassing the 8 medically relevant Nocardia species . There were few biochemical reactions that were sufficiently unique for species identification; of note, N . nova were positive for arylsulfatase, N . farcinica were positive for opacification of Middlebrook 7H11 agar, and N . brasiliensis and N . pseudobrasiliensis were the only species capable of liquefying gelatin . API 20C sugar assimilation patterns were unique for N . transvalensis, N . asteroides IV, and N . brevicatena . There was overlap among the assimilation patterns for the other species . Species-specific patterns of susceptibility to gentamicin, tobramycin, amikacin, and erythromycin were obtained for N . nova, N . farcinica, and N . brevicatena, while there was overlap among the susceptibility patterns for the other isolates . No single method could identify all Nocardia isolates to the species level; therefore, a combination of methods was necessary . An algorithm utilizing antibiotic susceptibility patterns, citrate utilization, acetamide utilization, and assimilation of inositol and adonitol accurately identified all isolates . The algorithm was expanded to include infrequent drug susceptibility patterns which have been reported in the literature but which were not seen in this study. Med Pregl, 2001 Nov-Dec, 54(11-12), 547 - 51 {Use of aminopenicillins in hospitals and outpatient facilities}; Mikic SS et al.; INTRODUCTION: Ampicillins are thought to be the most widely used antibiotics . Although ampicillin is included in the WHO list of essential drugs, its per-oral administration is not recommended, whereas amoxicillin is recommended due to its identical antimicrobial spectrum and better pharmacokinetic characteristics . Instead, per oral form of amoxicillin is recommended because of its identical antimicrobial spectrum and better pharmacokinetic characteristics . MATERIAL AND METHODS: Drug utilization evaluation of aminopenicillins (ampicillin and amoxcillin) was performed at the Clinic for Infectious Diseases . Clinical Center of Novi Sad and in the Outpatient Health Care Center, Novi Sad "Liman" (Department of General Practice Children's Health Care Department and Ear, Nose and Throat Department) during one calendar month in the year 2000 . RESULTS: The use of aminopenicillin was 5.1 Defined Daily Doses per 100 bed-days (5.1 DDD/100 BD) at the Clinic for Infectious Diseases . Ampicillin was used in 37.64% of patients and amoxicillin in 13.13% . In Outpatient Health Care Center (OHCC), Department of General Practice, aminopenicillins were prescribed in 1.02 Defined Daily Doses per 1000 inhabitants per day (DDD/1000 inh/day); ampicillin being prescribed in 24.51% and amoxicillin in 75.49%, and it is an optimal ratio . In Children's Health Care Department, OHCC, in children older than 14 years, aminopenicillins were prescribed in 0.37 pediatric DDD/1000 inh/day (ampicillin 40.5%, amoxicillin 59.5%) . In the same department, in the age group between 3 and 14 years it was 0.31 pediatric DDD/1000 inh/day (ampicillin 22.5%, amoxicillin 77.5%), while in the age group from 1 to 3 years there were 0.006 pediatric DDD/1000 inh/day prescribed (amoxicillin 100%) . At the Ear, Nose and Throat Department, OHCC aminopenicillins were prescribed in 0.02 DDD/1000 inh/day (amoxicillin 100%) . CONCLUSIONS: Our research showed a change in habits in regard to prescriptions towards the recommended protocol . Oral administration of ampicillin has decreased, especially in comparison to the earlier period in which it had dominated in our primary health care. East Afr Med J, 2001 Oct, 78(10), 518 - 22 Antimicrobial susceptibility and plasmids from Escherichia coli isolated from rats; Gakuya FM et al.; OBJECTIVES: To determine if antimicrobial resistance occurs in E . coli isolated from rats and if this resistance is transferable via plasmids . METHODS: Sixty Escherichia coli isolates obtained from 215 rats trapped in and around Nairobi, Kenya, were analysed for antimicrobial susceptibility to eleven commonly used antimicrobials . Plasmid DNA analysis and in-vitro conjugation tests were conducted on twenty two resistant isolates . RESULTS: A total of 12 (20%) E . coli were resistant to at least one of the commonly used drugs including ampicillin, sulphamethoxazole and streptomycin . Eight (13.3%) isolates were multidrug resistant . The drug resistant E . coli fell into five plasmid profile groups with plasmids ranging between two and 98 megadaltons (Mda) . Resistance to ampicillin was transferable . CONCLUSION: The results of this study show that rats from the study area may form an important reservoir for drug-resistant E . coli that could pose a public health hazard. Microsc Res Tech, 2002 Apr 1, 57(1), 23 - 7 Identification, characterization, and physiological actions of factor H as an adrenomedullin binding protein present in human plasma; Pio R et al.; A recently discovered adrenomedullin binding protein has been characterized as complement factor H, an important regulator of the complement cascade . This review will describe the evidence that led to the identification of factor H as an adrenomedullin binding protein and will address the implications that such binding has in the radioimmunoassay of AM in plasma . We will also describe the possible physiological implications of AM binding: namely, factor H suppresses the antimicrobial activity of AM, enhances AM-mediated induction of cyclic-AMP in rat fibroblasts, and augments the AM-mediated growth of a human cancer cell line . These initial studies suggest that factor H may be an important factor in the regulation of AM physiology . The elucidation of the mechanisms that modulate AM activity will be necessary for the understanding of the role of AM in normal and pathological conditions . J Infect Dis, 2002 Mar 15, 185(6), 797 - 804 Epub 2002 Feb 20. Borrelia burgdorferi are susceptible to killing by a variety of human polymorphonuclear leukocyte components; Lusitani D et al.; The killing of Borrelia burgdorferi by intact human polymorphonuclear leukocytes (PMNL) and by individual PMNL components was compared . Intact PMNL killed B . burgdorferi 6.5-fold more efficiently and 5-fold more completely when spirochetes were opsonized with specific antibodies . U-cytoplasts, which have activatable oxidase, killed opsonized B . burgdorferi with an efficiency similar to that of intact PMNL in killing unopsonized B . burgdorferi . Although B . burgdorferi were susceptible to H(2)O(2) and nitric oxide, PMNL lysates killed B . burgdorferi nearly as well as intact PMNL killed opsonized B . burgdorferi, suggesting a critical role for granule contents . B . burgdorferi were killed by the PMNL antimicrobial components elastase, LL-37, bactericidal/permeability-increasing protein, and human neutrophil peptide-1 . B . burgdorferi had limited susceptibility to killing by lysozyme and were not killed by azurocidin, proteinase 3, or lactoferrin . The efficient killing of B . burgdorferi by a variety of PMNL mechanisms highlights the paradoxical persistence of spirochetes in vivo. Arq Gastroenterol, 2001 Jul-Sep, 38(3), 203 - 6 Triple therapy with clarithromycin, amoxicillin and omeprazole for Helicobacter pylori eradication in children and adolescents; Kawakami E et al.; BACKGROUND: Helicobacter pylori infection presents high prevalence in developing countries, but there are few pediatric assays evaluating antimicrobial treatment . OBJECTIVE: The aim of this study was to investigate Helicobacter pylori eradication rate using a short regimen (7 and 10 days) of triple therapy with clarithromycin, amoxicillin and omeprazole . PATIENTS AND METHODS: Twenty-five Hp positive patients who presented severe epigastralgia, were submitted to antimicrobial treatment with amoxicillin (50 mg/kg/day--maximum dose 1 g bid), clarithromycin (30 mg/kg/day--maximum dose 500 mg bid) and omeprazole (0.6 mg/kg/day--maximum dose 20 mg bid) during 7 or 10 days . After 2 months, clinical symptoms were evaluated and gastric biopsies were taken to test Hp eradication . RESULTS: Overall eradication rate was achieved in 16/25 patients (64%--IC(95% = 45-83%), in 11/15 (73%--IC(95%) = 51-95%) patients who used 10 days therapy course and in 5/10 (50%--IC(95%) = 19-81%) who used 7 days therapy course . Eradication drugs were well accepted and adverse effects were reported in two patients (8%) . CONCLUSIONS: This triple therapy regimen had moderate efficacy (64%) . The data suggests that 10 days therapy course achieves better eradication rate (73%) than 7 days course (50%) to treat Hp infection in our population. Compend Contin Educ Dent Suppl, 2001, (32), 4 - 6;quiz 22 Recurrent oral ulcers--an overview; Gaffar A; Recurrent oral ulcers (ROUs) are the most common oral mucosal disease . The etiology of ROUs is complex . The factors include mechanical trauma, genetics, stress, smoking, and viral and bacterial infections . Treatment modalities depend on the differential diagnosis of ROUs and could consist of antimicrobial agents, anti-inflammatory agents, immunomodulators, or over-the-counter medications . New therapy available in the form of a coating polymer, Colgate ORABASE Soothe.N.Seal, is clinically proven to provide rapid relief and healing of ROUs. Arch Pediatr, 2002 Feb, 9(2), 130 - 5 {Acquisition of secondary resistance after failure of a first treatment of Helicobacter pylori infection in children}; Kalach N et al.; AIMS: To assess the frequency of acquisition of secondary Helicobacter pylori resistant-strains after a first course of antimicrobial treatment . PATIENTS AND METHODS: A retrospective study was performed during the 1994-2000 period, in 15 girls and eight boys, mean age 10.9 +/- 4.8 years (1.4-17 years), with Helicobacter pylori gastritis (culture and antimicrobial susceptibility) presenting a failure of first course treatment, with during one week a proton pump inhibitor and amoxicillin together with either clarithromycin (n = 14) or metronidazole (n = 9) . Two endoscopies were performed, the first at the time of diagnosis and the second after the failure of bacterial eradication demonstrated by a positive 13C urea breath test six weeks after the end of treatment . Antimicrobial susceptibility of all Helicobacter pylori strains was tested after each endoscopy and before starting a second course of the treatment . RESULTS: Comparison of antimicrobial susceptibility before and after the first course of treatment showed that Helicobacter pylori strains were all sensitive to amoxicillin, clarithromycin-resistant in eight children (34.7%) before treatment vs 12 (52.1%) after treatment, p = 0.42, ns, metronidazole-resistant in 13 (56.5%) vs 12 (52.1%), p = 0.80, ns, and both clarithromycin and metronidazole-resistant in four (17.3%) vs seven (30.4%), p = 0.63, ns . Among the 14 children treated by a triple therapy including clarithromycin, three (21.4%) developed a secondary resistance to clarithromycin and in one metronidazole resistance was no more detected . Among the nine children treated with a triple therapy including metronidazole, none developed a secondary resistance to metronidazole and one developed a secondary resistance to clarithromycin . CONCLUSION: This study shows the absence of amoxicillin-resistant strains, a high initial clarithromycin-resistant strains level (primary resistance), increasing after a first course of treatment, and for metronidazole a high initial level of resistance not influenced by treatment . Secondary clarithromycin-resistance of Helicobacter pylori strains following the first course of treatment could account for failure of bacterial eradication and suggests the importance of antimicrobial susceptibility. Planta Med, 2002 Mar, 68(3), 277 - 81 Antimicrobial activity of 9-O-acyl- and 9-O-alkylberberrubine derivatives; Kim SH et al.; For the structure-activity relationship study on berberrubine derivatives, a series of compounds bearing 9-O-acyl- and 9-O-alkyl-substituents were synthesized and tested for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi . Octanoyl, decanoyl, lauroyl derivatives among the acyl analogs and hexyl, heptyl, octyl, nonyl, decyl, undecyl derivatives among the alkyl analogs showed strong antimicrobial activity against Gram-positive bacteria and fungi . As a whole, alkyl analogs were more active than acyl analogs for antimicrobial activity . Synthesized derivatives had no activity on Gram-negative bacteria . Too short or too long substituents decreased activity . These results suggest that the presence of lipophilic substituents with moderate sizes might be crucial for the optimal antimicrobial activity. Eur J Vasc Endovasc Surg, 2002 Mar, 23(3), 241 - 3 Bacterial colonisation of Doppler probes on vascular surgical wards; Kibria SM et al.; AIM: hospital acquired infections cost the NHS 1 pound sterling billion each year and medical equipment may act both as source and vector of nosocomial infection . This study examined bacterial contamination of Doppler ultrasound probes (USP) in routine use on vascular surgical wards in six hospitals and the knowledge of staff about the potential for cross infection from contaminated probes . METHODS: probe head impressions and swab cultures of probe holders were plated on mannitol salt agar before and after cleaning with a paper towel . Putative S . aureus isolates were identified to species level and susceptibility to selected antimicrobials tested . Concurrently, junior medical staff were surveyed about probe cleaning protocols . RESULTS: methicillin susceptible S . aureus was isolated from 2/21 (10%) with near confluent bacterial growth from six others (28%) . The latter may have obscured low numbers of S . aureus . Further since swabs were plated without prior enrichment culture, it is likely that contamination with S . aureus might have been underestimated . No positive cultures were obtained after wiping the USP with a paper towel . 22/23 (95%) junior doctors failed to clean the USP prior to use . CONCLUSION: USP contamination with pathogenic bacteria occurs under "in-use" conditions and junior medical staff are unaware of simple measures to prevent this . Strict guidelines for USP cleaning between patient use should, therefore, be adopted particularly when monitoring postoperative graft patency . Eur J Clin Microbiol Infect Dis, 2002 Jan, 21(1), 53 - 5 Xylitol concentrations in the saliva of children after chewing xylitol gum or consuming a xylitol mixture; Tapiainen T et al.; Xylitol prevents otitis media when given to children regularly five times per day . To find a more convenient dosing schedule, an enzymatic assay was used to measure xylitol concentrations in the saliva of 65 children after giving them xylitol chewing gum or syrup in doses equal to those used in clinical trials . Although concentrations high enough to have an antimicrobial effect were attained, the xylitol disappeared from the saliva within 15 min . This finding indicates that high peak concentrations are more important for efficacy than the amount of time the xylitol concentration exceeds that needed to produce an antimicrobial effect . A schedule with the same single doses given less frequently could be clinically effective in preventing otitis media. Nature, 2002 Apr 11, 416(6881), 640 - 4 Epub 2002 Mar 24. The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein; Gottar M et al.; The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body . The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway . Loss-of-function mutations in either pathway reduce the resistance to corresponding infections . The link between microbial infections and activation of these two pathways has remained elusive . The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA) . PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members . Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections . By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene . The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila. Mol Hum Reprod, 2002 Apr, 8(4), 341 - 9 Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells; King AE et al.; The natural antibiotic molecules, beta-defensins 1 and 2 (HBD1/2) and secretory leukocyte protease inhibitor (SLPI), have an important role in mucosal defence and are present in the uterus . This study details their regulation in primary endometrial epithelial cells and in two endometrial cell lines (MFE/HES) . Cells were treated with proinflammatory molecules and mimics of infection {lipopolysaccharide (LPS) and lipoteichoic acid (LTA)} . mRNA for HBD1, HBD2 and SLPI was detected in primary endometrial epithelial cells using real-time quantitative PCR . HBD1 mRNA was present at very low levels preventing conclusive study of its regulation . However, HBD2 mRNA expression was increased by interferon-gamma, interleukin (IL)-1beta alone and IL-1beta+tumour necrosis factor (TNF)-alpha . SLPI mRNA was not affected by proinflammatory mediators, although protein levels fell in the presence of IL-1beta+TNFalpha . LPS had little effect on antimicrobial expression . However, there was a trend towards increased expression with LTA treatment for 4-8 h . Antimicrobial expression in endometrial cell lines was similar to that in primary cells, although SLPI was increased by IL-1beta+TNFalpha treatment . These results suggest that in endometrium some natural antibiotics (e.g . SLPI) may be constitutively expressed providing a basal level of protection, while others (e.g . HBD2) are inducible allowing maximal antimicrobial activity during infection . Natural antimicrobials will have an important role in endometrium in protecting against infection. Brain, 2002 Apr, 125(Pt 4), 722 - 31 Minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease; Tikka TM et al.; CSF from patients with motor neurone disease (MND) has been reported to be toxic to cultured primary neurones . We found that CSF from MND patients homozygous for the D90A CuZn-superoxide dismutase (CuZn-SOD) mutation, patients with sporadic MND and patients with familial MND without CuZn-SOD mutations significantly increased apoptosis and reduced phosphorylation of neurofilaments in cultured spinal cord neurones when compared with the effects of CSF from patients with other neurological diseases . Exposure of spinal cord cultures to MND CSF also triggered microglial activation . The toxicity of MND CSF was independent of the presence of the CuZn-SOD mutation, and it did not correlate with gelatinase activity or the presence of immunoglobulin G autoantibodies in the CSF . The concentrations of glutamate, aspartate and glycine in MND CSF were not elevated . Antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptors prevented the toxic CSF-induced neuronal death but not microglial activation, whereas minocycline, a tetracycline derivative with anti-inflammatory potential independent of antimicrobial activity, reduced both the apoptotic neuronal death and microglial activation . We conclude that the cytotoxic action of CSF is prevalent in all MND cases and that microglia may mediate the toxicity of CSF by releasing excitotoxicity-enhancing factors. Salud Publica Mex, 2002 Jan-Feb, 44(1), 26 - 32 Carriage of antibiotic-resistant pneumococci in a cohort of a daycare center; Gomez-Barreto D et al.; OBJECTIVE: To define epidemiologic relationships to determine the prevalence and potential risk factors for nasopharyngeal colonization by antibiotic-resistant pneumococci, their serotypes and their antibiotic susceptibility patterns in children attending a daycare center (DCC) . MATERIAL AND METHODS: A prospective cohort study was conducted among children (n = 53) attending the DCC at Hospital Infantil de Mexico Federico Gomez, which is staffed by 20 employees . Patients were enrolled in the study during a two-year period from September 1997 to September 1999 . All the participants were followed prospectively, swabbing them every four months . The strains recovered were typed and screened for susceptibility to several antibiotics . The daycare records were reviewed also . Odds ratios and fisher's exact test: or chi square test of significance were computed from contingency tables as appropriate . Exact 95% confidence intervals were computed for odds ratios . Data analysis was performed using Epi statistics program version 6.04 a . RESULTS: Pneumococci were recovered from 45/53 of the infants at one or more visits . A total of 178 isolates were carried . The carriage rate was 47% . Only 7 adults acquired pneumococci during the study . Types 6, 14, 19 and 23 were prevalent and represented 77% of the total . Antibiotic-resistant strains were higher to penicillin and erythromycin . CONCLUSIONS: Children were frequent carriers of pneumococci, the rate of carriage was high in infancy and tended to decrease with age . The types commonly carried by children were the same as those causing invasive disease . There is a high proportion of carriers with antibiotic-resistant S . pneumoniae strains . Children who have had frequent antimicrobial courses are at particular risk. J Biol Chem, 2002 Jun 21, 277(25), 22656 - 61 Epub 2002 Mar 21. The major conformational IgE-binding epitopes of hevein (Hev b6.02) are identified by a novel chimera-based allergen epitope mapping strategy; Karisola P et al.; A novel approach to localize and reconstruct conformational IgE-binding epitope regions of hevein (Hev b6.02), a major natural rubber latex allergen, is described . An antimicrobial protein (AMP) from the amaranth Amaranthus caudatus was used as an immunologically non-IgE-binding adaptor molecule to which terminal or central parts of hevein were fused . Hevein and AMP share a structurally identical core region but have different N-terminal and C-terminal regions . Only 1 of 16 hevein-allergic patients showed weak IgE binding to purified native or recombinant AMP . Chimeric AMP with the hevein N terminus was recognized by IgE from 14 (88%) patients, and chimeric AMP with the hevein C terminus was recognized by IgE from 6 (38%) patients . In contrast, chimeric AMP containing the hevein core region was recognized by IgE from only two patients . When both the N-terminal and C-terminal regions of hevein were fused with the AMP core, IgE from all 16 patients bound to the chimera . This chimera was also able to significantly inhibit (>70%) IgE binding to the native hevein . On the contrary, linear synthetic peptides corresponding to hevein regions in the AMP chimeras showed no significant IgE binding capacity in either enzyme-linked immunosorbent assay or inhibition enzyme-linked immunosorbent assay . These results suggest that the IgE binding ability of hevein is essentially determined by its N-terminal and C-terminal regions and that major IgE-binding epitopes of hevein are conformational . The chimera-based epitope mapping strategy described here provides a valuable tool for defining structural epitopes and creating specific reagents for allergen immunotherapy. Microbes Infect, 2002 Mar, 4(3), 361 - 72 Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity; Ramanathan B et al.; Antimicrobial peptides are important host-defense molecules of innate immunity . Cathelicidins are a diverse family of potent, rapidly acting and broadly effective antimicrobial peptides, which are produced by a variety of cells . This review examines the classification, antimicrobial spectrum, mechanism of action, and regulation of cathelicidins. Microbes Infect, 2002 Mar, 4(3), 325 - 31 Outer membrane proteins: key players for bacterial adaptation in host niches; Lin J et al.; Outer membrane proteins (OMPs) of Gram-negative bacteria have diverse functions and are directly involved in the interaction with various environments encountered by pathogenic organisms . Thus, OMPs represent important virulence factors and play essential roles in bacterial adaptation to host niches, which are usually hostile to invading pathogens . Understanding the structure and functions of bacterial OMPs will facilitate the design of antimicrobial drugs and vaccines . In this paper, we will present a brief review on OMPs that contribute to bacterial adaptive responses including iron uptake, antimicrobial peptide resistance, serum resistance, and drug/bile resistance. J Nat Prod, 2002 Mar, 65(3), 364 - 7 Bioactive metabolites from a marine-derived strain of the fungus Emericella variecolor; Malmstrom J et al.; From a marine-derived strain of the fungus Emericella variecolor, varitriol (1), varioxirane (2), dihydroterrein (3), and varixanthone (4), besides the known mold metabolites ergosterol, terrein, shamixanthone, and tajixanthone hydrate, were identified . The chemical structures of 1-4 were established by means of spectroscopic techniques and some chemical transformations . In the NCI's 60-cell panel, varitriol (1) displayed increased potency toward selected renal, CNS, and breast cancer cell lines . Varixanthone (4) showed antimicrobial activity. Biochem Cell Biol, 2002, 80(1), 65 - 74 Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity; Strom MB et al.; This review focuses on important structural features affecting the antimicrobial activity of 15-residue derivatives of lactoferricins . Our investigations are based on an alanine-scan of a 15-residue bovine lactoferricin derivative that revealed the absolute necessity of two tryptophan residues for antimicrobial activity . This "tryptophan-effect" was further explored in homologous derivatives of human, caprine, and porcine lactoferricins by the incorporation of one additional tryptophan residue, and by increasing the content of tryptophan in the bovine derivative to five residues . Most of the resulting peptides display a substantial increase in antimicrobial activity . To identify which molecular properties make tryptophan so effective, a series of bovine lactoferricin derivatives were prepared containing non-encoded unnatural aromatic amino acids, which represented various aspects of the physicochemical nature of tryptophan . The results clearly demonstrate that tryptophan is not unique since most of the modified peptides were of higher antimicrobial potency than the native peptide . The size and three-dimensional shape of the inserted "super-tryptophans" are the most important determinants for the high antimicrobial activity of the modified peptides . This review also describes the use of a "soft-modeling" approach in order to identify important structural parameters affecting the antimicrobial activity of modified 15-residue murine lactoferricin derivatives . This QSAR-study revealed that the net charge, charge asymmetry, and micelle affinity of the peptides were the most important structural parameters affecting their antimicrobial activity. Biochem Cell Biol, 2002, 80(1), 49 - 63 Towards a structure-function analysis of bovine lactoferricin and related tryptophan- and arginine-containing peptides; Vogel HJ et al.; The iron-binding protein lactoferrin is a multifunctional protein that has antibacterial, antifungal, antiviral, antitumour, anti-inflammatory, and immunoregulatory properties . All of these additional properties appear to be related to its highly basic N-terminal region . This part of the protein can be released in the stomach by pepsin cleavage at acid pH . The 25-residue antimicrobial peptide that is released is called lactoferricin . In this work, we review our knowledge about the structure of the peptide and attempt to relate this to its many functions . Microcalorimetry and fluorescence spectroscopy data regarding the interaction of the peptide with model membranes show that binding to net negatively charged bacterial and cancer cell membranes is preferred over neutral eukaryotic membranes . Binding of the peptide destabilizes the regular membrane bilayer structure . Residues that are of particular importance for the activity of lactoferricin are tryptophan and arginine . These two amino acids are also prevalent in "penetratins", which are regions of proteins or synthetic peptides that can spontaneously cross membranes and in short hexapeptide antimicrobial peptides derived through combinatorial chemistry . While the antimicrobial, antifungal, antitumour, and antiviral properties of lactoferricin can be related to the Trp/Arg-rich portion of the peptide, we suggest that the anti-inflammatory and immunomodulating properties are more related to a positively charged region of the molecule, which, like the alpha- and beta-defensins, may act as a chemokine . Few small peptides are involved in as wide a range of host defense functions as bovine and human lactoferricin. Biochem Cell Biol, 2002, 80(1), 109 - 12 Bovine lactoferrin and lactoferricin derived from milk: production and applications; Tomita M et al.; Bovine lactoferrin is produced on an industrial scale from cheese whey or skim milk . The safety of purified lactoferrin has been confirmed from the results of a reverse mutation test using bacteria, a 13-week oral repeated-dose toxicity study in rats, and clinical studies . In order to apply active lactoferrin to various products, a process for its pasteurization was developed . Subsequently, lactoferrin has been used in a wide variety of products since it was first added to infant formula in 1986 . A pepsin hydrolysate of lactoferrin is also used in infant formula . This hydrolysate contains a potent antimicrobial peptide named lactoferricin that is derived from the lactoferrin molecule by pepsin digestion . Semilarge-scale purification of lactoferricin can be performed by hydrophobic interaction chromatography . Lactoferricin also exhibits several biological actions and appears to be the functional domain of lactoferrin . Recent studies have demonstrated that oral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans . The results of these studies strongly suggest that the effects of oral lactoferrin are mediated by modulation of the immune system . Further elucidation of the clinical efficacy and mechanism of action of lactoferrin will increase the value of lactoferrin-containing products. Compend Contin Educ Dent, 1999, 20(4 Suppl), 4 - 12; quiz 34 The supplemental use of antibiotics in periodontal therapy; Walker C; Many antibiotics and other chemotherapeutic agents have been used as adjuncts to mechanical periodontal therapy with mixed results . This article reviews the clinical and microbial results obtained after the systemic administration of tetracyclines, penicillins, clindamycin, and metronidazole, as well as the combination of metronidazole and Augmentin as adjuncts to conventional periodontal treatment . The major adverse effects associated with each of these antibiotics are given, as well as the potential for the emergence of antibiotic resistance in the periodontal flora . Recently, the introduction of a new generation of controlled-release, locally applied antimicrobial agents provides the clinician with the opportunity to treat individual periodontal sites with high concentrations of medication . The clinical effects obtained from multicenter clinical trials with PerioChip, which contains chlorhexidine, and with Atridox, which contains doxycycline, are summarized . Finally, suggestions are given both for the selection of an antimicrobial agent and for minimizing the development of antibiotic resistance in the periodontal flora. Compend Contin Educ Dent, 1999, 20(4 Suppl), 13 - 8; quiz 34-5 Local delivery of antimicrobials: a new era in the treatment of adult periodontitis; Killoy WJ; This article discusses the principles, products, and techniques currently available for local delivery of antimicrobials in the treatment of adult periodontitis . Four principles provide the scientific basis for the treatment of periodontitis: it is caused by bacteria; it cannot be cured, but it can be controlled; clinicians cannot remove all the plaque and calculus; and periodontitis reinfects . This article stresses how the local delivery of antimicrobials can help the clinician achieve the goals of arresting the disease and maintaining the disease in the arrested or controlled state . Rationales for reevaluating the treated patient and treatment options are presented . Local-delivery systems are reviewed, stressing those available in the United States . Pharmacokinetics, multicenter randomized trials, and techniques are presented. Dev Comp Immunol, 2002 Jun, 26(5), 471 - 9 Activity of antimicrobial skin peptides from ranid frogs against Batrachochytrium dendrobatidis, the chytrid fungus associated with global amphibian declines; Rollins-Smith LA et al.; Accumulating evidence suggests that a chytrid fungus, Batrachochytrium dendrobatidis, is responsible for recent declines in amphibian populations in Australia, Central America, Europe, and North America . Because the chytrid infects the keratinized epithelium of the skin, we investigated the possible role of antimicrobial peptides produced in the skin as inhibitors of infection and growth . We show here that 10 peptides representing eight families of peptides derived from North American ranid frogs can effectively inhibit growth of this chytrid . The peptides are members of the ranatuerin-1, ranatuerin-2, esculentin-1, esculentin-2, brevinin-2, temporin, palustrin-3, and ranalexin families . All the tested peptides inhibit growth of mature fungal cells at concentrations above 25 microM, and some of them inhibit at concentrations as low as 2 microM . A comparison of the sensitivity of infectious zoospores with that of mature cells showed that the zoospores are inhibited at significantly lower concentrations of peptides . To determine whether cold temperature interferes with the inhibitory effects of these peptides, we tested their effectiveness at both 22 and 10 degrees C . Although the peptides inhibit at both temperatures, they appear to be more effective against zoospores at the lower temperature . These results suggest that the ranid frogs have, within their repertoire of antimicrobial substances, a number of skin peptides that should be a deterrent to chytrid infection . This may provide some natural resistance to infection, but if environmental factors inhibit the synthesis and release of the skin peptides, the pathogen could gain the advantage. Dev Comp Immunol, 2002 Jun, 26(5), 445 - 59 Induction of nitric oxide and respiratory burst response in activated goldfish macrophages requires potassium channel activity; Stafford JL et al.; Potassium channel activity is important for modulating mammalian macrophage antimicrobial functions . The involvement of potassium channels in mediation of immune cell function in lower vertebrates, such as teleost, has not been explored . Since relatively little is known about the types of potassium channels present in fish macrophages, pharmacological blockers with broad ranges of activity were tested: 4-aminopyridine (4-AP), quinine, and tetraethylammonium chloride (TEA) . The potassium channel blockers inhibited reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) production by goldfish macrophages activated with bacterial lipopolysaccharide (LPS) and/or macrophage activating factor (MAF)-containing supernatants . Quinine was the most potent inhibitor with an IC(50) of 50 microM, while the other blockers, 4-AP and TEA, had IC(50) of 1.2 and 0.6mM, respectively . A reversible depolarization of the goldfish macrophage plasma membrane potential (Vm) was observed following treatments with potassium channel blockers, and was related to transcriptional changes in the inducible nitric oxide synthase gene (iNOS) . Down-regulation of antimicrobial activities and depolarization of the goldfish macrophage plasma membrane were not a consequence of reduced cell number or viability, suggesting that potassium channels are required for generation of appropriate goldfish macrophage antimicrobial functions. Cell Microbiol, 2002 Mar, 4(3), 167 - 76 Association of a macrophage galactoside-binding protein with Mycobacterium-containing phagosomes; Beatty WL et al.; Mycobacteria reside intracellularly in a vacuole that allows it to circumvent the antimicrobial environment of the host macrophage . Although the mycobacterial phagosome exhibits selective fusion with vesicles of the endosomal system, identification of host and bacterial factors associated with phagosome bio-genesis is limited . To identify these potential factors, mAbs were generated to a membrane preparation of mycobacterial phagosomes isolated from M . tuberculosis-infected macrophages . A mAb recognizing a 32-35 kDa macrophage protein associated with the phagosomal membrane of Mycobacterium was identified . N-terminal sequence analysis identified this protein as Mac-2 or galectin-3, a galactoside-binding protein of macrophages . Galectin-3 (gal-3) was shown to accumulate in Mycobacterium-containing phagosomes during the course of infection . This accumulation was specific for phagosomes containing live mycobacteria and occurred primarily at the cytosolic face of the phagosome membrane . In addition, bind-ing of gal-3 to mycobacterial phosphatidylinositol mannosides (PIMs) demonstrated a novel interaction between host carbohydrate-binding proteins and released mycobacterial glycolipids . Infection of macrophages from gal-3-deficient mice indicated that the protein did not play a role in infection in vitro . In contrast, infection of gal-3-deficient mice revealed a reduced capacity to clear late but not early infection. Biochem Biophys Res Commun, 2002 Mar 29, 292(2), 441 - 8 Production of antiviral and antitumor proteins MAP30 and GAP31 in cucurbits using the plant virus vector ZYMV-AGII; Arazi T et al.; ZYMV-AGII (zucchini yellow mosaic virus-AGII) is a recombinant nonpathogenic potyvirus-based vector system for the expression of foreign genes in cucurbit plants and their edible fruits, including squash, cucumber, melon, watermelon, and pumpkin . MAP30 (Momordica anti-HIV protein, 30 kDa) and GAP31 (Gelonium anti-HIV protein 31 kDa) are multifunctional plant proteins with activity against HIV-1 virus . These proteins are also effective against other viruses, tumor cells, and microbes . We report here the production and characterization of biologically active MAP30 and GAP31 in squash plant by expression of their genes using the ZYMV-AGII vector . Recombinant expressed MAP30 and GAP31 exhibit comparable antiviral, antitumor, and antimicrobial activities as their counterparts from their original plant sources, with EC(50)s in the ranges of 0.2-0.3 nM for HIV-1 . These results demonstrate for the first time the amplification and production of therapeutic proteins, MAP30 and GAP31, in common vegetables . This provides valuable alternative food sources of these antiviral, antitumor, and antimicrobial agents for therapeutic applications . (c)2002 Elsevier Science (USA). Nat Rev Immunol, 2001 Nov, 1(2), 135 - 45 Toll-like receptors and innate immunity; Medzhitov R; Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects . In mammals, these receptors have evolved to recognize conserved products unique to microbial metabolism . This specificity allows the Toll proteins to detect the presence of infection and to induce activation of inflammatory and antimicrobial innate immune responses . Recognition of microbial products by Toll-like receptors expressed on dendritic cells triggers functional maturation of dendritic cells and leads to initiation of antigen-specific adaptive immune responses. Kekkaku, 2002 Feb, 77(2), 79 - 86 {CT diagnosis of pulmonary infectious diseases}; Murayama S; Generally, the patient's inflammatory reaction is obvious, and the characteristic infiltrative shadow as pneumonia in the chest radiograph is recognized, no more imaging study is needed . However, when (1) radiographic finding is uncommon as a pneumonia; (2) antimicrobial drug treatment is ineffective; or (3) stenosis of central bronchi causing pneumonia by lung cancer and so on is suspicious, more precise imaging information of computed tomography (CT) is necessary . Recently, high resolution CT of lung disease as a new diagnostic method has been introduced, and diagnostic efficacy of CT has markedly advanced . Although the high resolution CT diagnosis based on the minute anatomy of the lung is also applied for the pulmonary infectious disease, their analysis and arrangement is not yet established since a large number of pathogens and various images exist . In reading CT films, it is necessary to consider patient's immune status . Infectiosity and size of the pathogen must be also considered . In this manuscript, CT imaging characteristics of lung infectious diseases are clarified by taking these points into account. Kekkaku, 2002 Feb, 77(2), 61 - 6 {Interpretive compatibility of antimycobacterial susceptibility for Mycobacterium tuberculosis determined by proportion test method on egg-based Ogawa media and broth microdilution test, BrothMIC MTB}; Higa M et al.; The antimycobacterial susceptibility test method newly proposed by the Japanese Society for Tuberculosis, a proportion method on egg-based Ogawa media, was evaluated in comparison with microdilution test for Mycobacterium tuberculosis complex, BrothMIC MTB-1 (Kyokuto Pharmaceutical Inc., Tokyo) . In the evaluation, five antimicrobial agents, streptomycin, ethambutol, kanamycin, isoniazid and rifampicin were included . Through repeated testings of the three reference strains against five antimicrobial agents, both test methods were found to be highly precise . All the minimum inhibitory concentrations (MICs) determined by BrothMIC MTB fell within 3 log2 dilutions, however a total of 11 MICs resulted in indeterminate(I) interpretations . Whereas, all the test results by a proportion method on Ogawa media were comparable to the expected interpretations . However, three of 48 testings resulted in undeterminable interpretations due to insufficient growth on the growth control media . A total of 127 clinical isolates of M . tuberculosis complex were tested by both methods, and 89 to 90% of the test results were comparable with each other in category interpretations . However, 7.1 to 9.4% of MICs determined by BrothMIC MTB resulted in indeterminate(I), and 0.8 to 3.1% of discrepant interpretations were observed . In conclusion, both test methods were highly precise and comparable in determining antimycobacterial susceptibility for M . tuberculosis complex . Several advantages and disadvantages in each test method were discussed. J Vet Pharmacol Ther, 2001 Dec, 24(6), 433 - 8 Comparative studies on Polyferm and Fermosorb, two oral (ferment + sorbent) - type preparations designed for therapy/prophylaxis of intestinal infections in animal neonates; Biziulevicius GA et al.; Polyferm and Fermosorb are oral acid resistant antimicrobial enzyme preparations designed specifically for therapy/prophylaxis of intestinal infections in animal neonates . Both are authorized for use throughout the former Soviet Union, but until now only Fermosorb is being applied on a large scale . The comparative studies on these two preparations, described in this paper, were carried out in order to find differences between the preparations . Characteristics that were compared included stability of the preparations in acidic environment as well as in storage (in vitro studies), and their efficacy for the treatment and prophylaxis of colibacillosis in newborn calves (in vivo studies) . Results of in vitro studies revealed that proteolytic enzymes of Polyferm (as well as lytic enzymes of Fermosorb) were suitably (and in a very similar magnitude) protected from the influence of the acidic environment . The complete enzyme activity retention period in storage at room temperature of Polyferm and Fermosorb was equally high (5 years) . In vivo studies performed on 2000 calves revealed that both preparations were highly effective and, although the efficacy of Polyferm was a bit lower than that of Fermosorb (93.6% vs . 95.0%, 94.6% vs . 95.8% for therapy and prophylaxis of colibacillosis, respectively), no statistically significant differences in the number of Polyferm vs . Fermosorb cured/protected animals were found . It is concluded that there were no reasons, other than the lack of supportive advertising materials, that might impede the utility of Polyferm. J Vet Pharmacol Ther, 2001 Dec, 24(6), 423 - 31 Effects of altered plasma alpha-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysis; Kuroha M et al.; Effects of altered plasma alpha-1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis . Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions . Binding parameters were obtained from an in vitro study using ultrafiltration . Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs . Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased . Plasma concentration-time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated . All of the total plasma concentration-time profiles were different from those at normal AGP level . The differences were characterized by a higher initial concentration with faster or similar elimination . Unbound plasma concentration-time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level . These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required. J Vet Pharmacol Ther, 2001 Dec, 24(6), 385 - 90 An assessment of antimicrobial consumption in food producing animals in Kenya; Mitema ES et al.; Antimicrobial agents are useful for control of bacterial infections in food animals and man . Their prudent use in these animals is important to control any possible development and transfer of resistance between animals and man . The objective of this study was to generate quantitative information to evaluate antimicrobial usage patterns by animal species, route of administration, antimicrobial class and type of use from 1995 to 1999 in Kenya . Theses data are essential for risk analysis and planning and can be helpful in interpreting resistance surveillance data, and evaluating the effectiveness of prudent use efforts and antimicrobial resistance mitigation strategies . Data on quantities of active substance classes were collected from the official records of the Pharmacy and Poisons Board of the Ministry of Health and analysed in MS Excel 2000 program . The mean antimicrobial consumption for the 5-year period was 14 594 +/- 1457 kg per year . This was distributed in the various antimicrobial classes as follows: 7975 kg (54.65%) of tetracyclines, 3103.96 kg (21.27%) of sulfonamides and 954.5 kg (6.56%) of aminoglycosides, 905 kg (6.20%) of beta-lactams, 94 kg (0.64%) of quinolones, 35 kg (0.24%) of macrolides and 24 kg (0.16%) of others (tiamulin) . Mean consumption per year among the various food animals was: 10 989 +/- 357 kg in large animals (cattle, sheep, pigs and goats), 2906 +/- 127 kg in poultry alone and 699 +/- 427 kg in both large animals and poultry . These quantities represented 56.56% (8255 kg) consumption per year for parenteral use, 41.79% (6098 kg) for oral use and 1.65% (241 kg) for topical use (intramammary and eye ointments) in cattle . With respect to intended use in food producing animals, the mean consumption per year was: 13 178 kg (90.30%) for therapeutic use (ST), 4 kg (0.03%) for prophylactic treatment (PT) and 1411 +/- 246 kg (9.67%) was used both for therapeutic and prophylactic purposes (GPT) . The study confirmed that antimicrobials are not used for growth promotion in Kenya . There was no specific trend in the quantities of active antimicrobial classes . This study has revealed that the tetracyclines, sulfonamides and trimethoprim, nitrofurans aminoglycosides, beta-lactams and the quinolones are the most commonly used drugs in food-producing animals in Kenya . Tetracyclines contributed approximately 55% of the total consumption, and there was an increasing trend in the consumption of quinolones from 1998. J Am Chem Soc, 2002 Mar 27, 124(12), 2951 - 6 Total synthesis of (-)-tetrazomine . Determination of the stereochemistry of tetrazomine and the synthesis and biological activity of tetrazomine analogues; Scott JD et al.; The first total synthesis of the potent antitumor antibiotic (-)-tetrazomine has been accomplished . A new method for the formation of the allylic amine precursor to an azomethine ylide has been developed and exploited in an efficient {1,3}-dipolar cycloaddition to afford the key tetracyclic intermediate used in the synthesis of (-)-tetrazomine . Several analogues of tetrazomine have been synthesized and tested for antimicrobial and biochemical activity. Farmaco, 2002 Jan, 57(1), 79 - 87 Synthesis and antimycobacterial activity of 3-aryl-, 3-cyclohexyl- and 3-heteroaryl- substituted-2-(1H(2H)-benzotriazol-1(2)-yl)prop-2-enenitriles, prop-2-enamides and propenoic acids . II; Sanna P et al.; A series of 32 3-aryl-, 3-cyclohexyl-, and 3-heteroaryl-substituted-2-(1H(2H)-benzotriazol-1(2)-yl)-prop-2-enenitriles, prop-2-enamides and propenoic acids, was synthesized as a part of our research in the antitubercular field, according to an international program with the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) . This work reports the preparation and analytical and spectroscopic characterization (MS, UV, IR, 1H NMR) of all compounds synthesized . Among these only a few compounds (E-4b,c, E-5a, E-7e and E-8d) were found to be endowed with modest growth inhibition of Mycobacterium tuberculosis . However, the obtained results allowed to acquire interesting structure-activity relationships. Farmaco, 2002 Jan, 57(1), 39 - 44 Antimicrobial activity of 5-arylidene aromatic derivatives of hydantoin . Part 2; Szymanska E et al.; Various 5-chloroarylidene-2-amino substituted derivatives of imidazoline-4-one were synthesized and evaluated for their activity in vitro against Mycobacterium tuberculosis and other type strains of bacteria and fungi . 2-Chloro- and 2,4-dichlorobenzylidene substituted hydantoins exhibited antimycobacterial effect . The most potent compounds 3i, 3j, 3o, 3q and 3s were classified for further tests . The antimitotic effect of the investigated hydantoins was also examined. Expert Rev Mol Diagn, 2001 May, 1(1), 30 - 8 DNA array technology and diagnostic microbiology; Anthony RM et al.; Near instantaneous detection of pathogens from clinical material, combined with simultaneous prediction of their antimicrobial resistance profiles, would revolutionize the impact of microbiology on the management of infection . Array-based assays allow a range of characteristics to be rapidly and simultaneously determined . At present these systems have found their primary role as research tools for the monitoring of mRNA expression in the form of DNA microarrays or 'chips' . As fabrication costs reduce and validated targeted arrays are developed, it is inevitable they will be used for more routine applications . Microfluidics offers the exciting possibility of combining purification, amplification and detection in a single disposable device; microarrays are particularly suitable for use within these systems . Arrays will become an important tool for clinical diagnostics. J Wound Care, 2002 Feb, 11(2), 53 - 5 Why do some cavity wounds treated with honey or sugar paste heal without scarring? Topham J. As well as having antimicrobial properties, honey and sugar paste are associated with scarless healing in some cavity wounds . This article uses evidence to suggest why these products can modify excessive collagen production to prevent scarring. J Trauma, 2002 Mar, 52(3), 463 - 8 Blood culturing practices in a trauma intensive care unit: does concurrent antibiotic use make a difference? Schermer CR, Sanchez DP, Qualls CR, Demarest GB, Albrecht RM, Fry DE. BACKGROUND: Febrile trauma patients have repeated blood cultures drawn during a prolonged hospitalization . We examined the diagnostic yield of blood cultures in severely injured patients to determine whether concurrent antimicrobial therapy or prophylactic administration of antibiotics affects blood culture growth . We also determined how rapidly growth changed to determine whether total numbers of blood cultures could be decreased . The hypotheses of the study were that concurrent antimicrobial administration affects blood culture yield, prophylactic administration alters the culture result, and repetitive culturing is unnecessary . METHODS: A retrospective chart review of trauma patients with minimum Injury Severity Score of 15 and minimum 5-day intensive care unit length of stay was performed . The dates and results of blood cultures and antibiotic type and administration dates were recorded . "Prophylactic" antibiotics were defined as antibiotics administered on admission to the unit . Computer software was used to match the blood culture date to the period of antimicrobial administration . Categorical data were compared using Fisher's exact test . RESULTS: Two hundred fifty-eight patients met entry criteria, and 208 charts were complete for review . One hundred twenty-nine patients had 347 sets of blood cultures drawn . The positive blood culture rate was 10.8% in patients off antibiotics, and 13.9% in patients on antibiotics (p = 0.68) . All prophylactic antibiotics included a beta-lactam . Only 18% of positive blood cultures in patients receiving prophylactic antibiotics were sensitive to beta-lactams as opposed to 59% sensitivity in those who did not receive prophylaxis (p = 0.03) . One hundred seventy-six sets of blood cultures were performed after an initial positive culture . Only three patients with an initial positive culture had a second positive culture with a different organism . The mean time to culturing a new organism after initial growth was 19 days . CONCLUSION: Concurrent antimicrobial administration does not alter blood culture yield . Prophylactic administration alters the type of organism cultured . Little new information is gained from repetitive culturing. Eur J Med Chem, 2002 Mar, 37(3), 197 - 206 Synthesis, characterisation and biological activity of novel 4-thiazolidinones, 1,3,4-oxadiazoles and some related compounds; Kucukguzel SG et al.; Two novel series of 4-thiazolidinone derivatives, namely 2-substituted-3-({4-(4-methoxybenzoylamino)benzoyl}amino)-4-thiazolidinones (7a-e) and 2-{4-(4-methoxybenzoylamino)benzoylhydrazono}-3-alkyl-4-thiazolidinones (5a-c) together with 2-{4-(4-methoxybenzoylamino)phenyl}-5-(substituted phenyl)amino-1,3,4-oxadiazoles (6a-c) have been synthesised as title compounds . N(1)-{4-(4-methoxybenzoylamino)benzoyl}-N(2)-substituted methylene hydrazines (3a-e) and 1-{4-(4-methoxybenzoylamino)benzoyl}-4-substituted phenyl thiosemicarbazides (4a-f) were also prepared and used as intermediate to give the title compounds . All synthesised compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv and antimicrobial activities against various bacteria and fungi . Compounds 7a and 7b were found as the most active derivatives demonstrating 90 and 98% inhibition of mycobacterial growth of M . tuberculosis H37Rv in the primary screen at 6.25 microg mL(-1), respectively . However, level II assay revealed that the MIC values were not less than 6.25 microg mL(-1) . None of the compounds showed significant antimicrobial activity against the microorganisms used whereas 3a and 7a inhibited the growth of several bacteria and fungi. Biochemistry, 2002 Mar 26, 41(12), 4096 - 106 Role of the oxyanion binding site and subsites S1 and S2 in the catalysis of oligopeptidase B, a novel target for antimicrobial chemotherapy; Juhasz T et al.; Oligopeptidase B is a member of a novel serine peptidase family, found in Gram-negative bacteria and trypanosomes . The enzyme is involved in host cell invasion, and thus, it is an important target for drug design . Oligopeptidase B is specific for substrates with a pair of basic residues at positions P1 and P2 . The sensitivity of substrates to high ionic strength suggests that the arginines interact with the carboxylate ions of the enzyme . On the basis of a three-dimensional model, two carboxyl dyads (Asp460 and Asp462 and Glu576 and Glu578) can be assigned as binding sites for arginines P1 and P2, respectively . The dyads are involved in several events: (i) substrate binding, (ii) substrate inhibition at high substrate concentrations (different inhibitory mechanisms were demonstrated with substrates bearing one and two arginine residues), (iii) enzyme activation at millimolar CaCl2 concentrations with substrates having one arginine, and (iv) interaction of Ca2+ with the dyads which simplified the complex pH dependence curves . Titration with a product-like inhibitor revealed the pK(a) of the carboxyl group that perturbed the pH-kcat/Km profiles . The OH group of Tyr452 is part of the oxyanion binding site, which stabilizes the transition state of the reaction . Its role studied with the Tyr452Phe variant indicates that (i) the catalytic contribution of the OH group depends on the substrate and (ii) the catalysis is, unusually, an entropy-driven process at physiological temperature . The NH group of the scissile peptide bond accounts for the deviation of the reaction from the Eyring plot above 25 degrees C, and for abolishing potential nonproductive binding. Pol Merkuriusz Lek, 2001 Dec, 11(66), 491 - 4 {The relation between Chlamydia pneumoniae infection and abdominal aortic aneurysm}; Wolski A et al.; The aim of our study was to evaluate the frequency of C . pneumoniae infection in abdominal aortic aneurysm (AAA) patients by measuring C . pneumoniae specific serum IgG, IgM and IgA levels and the activation of their immune system by measuring the concentrations of IL-10, IL-12, IFN-gamma and TNF-alpha in patients' serum . Microimmunofluorescence method was applied to evaluate the level of anti-C . pneumoniae IgG, IgA and IgM . The concentrations of cytokines were evaluated using ELISA method . Serologic markers of persistent C . pneumoniae infection have been detected in 25/28 (89.3%) patients and in 6/20 (30%) healthy controls . In 40% (10/25) of patients with serologic markers of persistent C . pneumoniae infection high titers of specific IgG and IgA indicated active infection--reinfection or exacerbation of chronic infection . Mean concentrations of IL-10, IL-12, IFN-gamma and TNF-alpha indicated lack of protection against intracellular pathogens . Since all patients in this group were diagnosed as having symptomatic AAA, we suggest that active infection can exacerbate inflammation in the AAA wall and accelerate progression of the disease . In our opinion patients with active C . pneumoniae infection may be candidates to the antimicrobial treatment. Curr Mol Med, 2001 Mar, 1(1), 137 - 51 Natural T cell immunity to intracellular pathogens and nonpeptidic immunoregulatory drugs; Poccia F et al.; Natural T (NT) lymphocytes recognize infected cells or microbial compounds without the classical genetic restriction of polymorphic major histocompatibility complex (MHC) molecules . This innate recognition pathway results in a broad and rapid antimicrobial response that may be critical for controlling the spread of intracellular pathogens, requiring the elimination of the infecting agent from both extracellular spaces and host cells . NT cells are mainly composed of alphabeta and gammadelta T lymphocytes that express natural killer (NK) receptors and recognize preferentially various nonpeptidic antigens . Similar to NK cells, NT lymphocytes can 'see' and kill target cells deficient in the expression of one or more MHC class I molecules . NT cells expressing the alphabeta TCR can recognize lipid and lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules, whereas phosphocarbohydrates and akilamines induce constitutive responses in most Vgamma9Vdelta2 NT lymphocytes . The remaining fraction of gammadelta NT cells express the Vdelta1 chain associated with different Vgamma-chains and may directly recognize self-antigens such as MICA, MICB or CD1 molecules . It is possible that NT lymphocytes may play two opposite roles during intracellular infections . First, in the acute phase, they may be critical for the initiation of pathogen elimination . Second, in the chronic phase, NT cells may be dangerous, if their potential autoreactivity is not well controlled . It is conceivable that novel strategies of immune intervention against emerging and re-emerging intracellular pathogens, such as human immundeficiency virus (HIV), hepatitis-C virus (HCV) and Mycobacterium tuberculosis (MTB) may involve the control of NT cell activation/anergy by (nonpeptidic) immunoregulatory drugs. Pharmacotherapy, 2002 Mar, 22(3 Pt 2), 71S - 79S The rationale for aerosolized antibiotics; Flume P et al.; In order for an antimicrobial agent to be effective, it must fulfill two requirements . First, the agent must reach the site of infection and remain in the vicinity for an adequate length of time . Second, it must bind to a target site and remain bound for a length of time sufficient to disrupt the life cycle of the cell . Once these requirements are met, the drug is able to exert its antimicrobial activity against the cell . In an effort to better understand and predict the killing activity of antibiotics, we have attempted to develop parameters that describe the accumulation and diffusion of drug to and from body sites (pharmacokinetics) and quantify how much of a compound is needed at the site of infection to yield the desired effect (minimum inhibitory concentration) . Furthermore, integration of these parameters allows us to evaluate host, drug, and microbial factors and formulate criteria to assess and predict drug activity in patients (pharmacodynamics) . Knowledge and application of pharmacodynamic principles can assist clinicians in optimizing antimicrobial therapy by allowing them to maximize the antimicrobial activity of an agent while minimizing patient exposure and thus reducing the likelihood of toxicity. Antimicrob Agents Chemother, 2002 Apr, 46(4), 1141 - 3 In vitro activities of a new des-fluoroquinolone, BMS 284756, and seven other antimicrobial agents against 151 isolates of Eikenella corrodens; Goldstein EJ et al.; The des-fluoroquinolone BMS 284756 was active in vitro against all 151 clinical strains of Eikenella corrodens at a MIC of < or = 0.25 microg/ml and was comparable in activity to moxifloxacin and levofloxacin . The MIC at which 90% of the isolates were inhibited by penicillin G was 2 microg/ml; MICs for 8.6% of the strains (13 of 151) were > or = 4 microg/ml, including for two beta-lactamase-producing isolates . Amoxicillin-clavulanate and ampicillin-sulbactam inhibited all strains at a MIC of < or = 1 microg/ml. Antimicrob Agents Chemother, 2002 Apr, 46(4), 1114 - 6 Susceptibilities of Mycobacterium marinum to gatifloxacin, gemifloxacin, levofloxacin, linezolid, moxifloxacin, telithromycin, and quinupristin-dalfopristin (Synercid) compared to its susceptibilities to reference macrolides and quinolones; Braback M et al.; The susceptibility pattern of Mycobacterium marinum was determined . Quinupristin-dalfopristin and telithromycin were less active than clarithromycin . Linezolid showed good antimicrobial activity at clinically achievable concentrations . Gatifloxacin, levofloxacin, and moxifloxacin displayed activities similar to those of ciprofloxacin . Gemifloxacin was less active . The Etest method showed variable agreement with the reference method. Antimicrob Agents Chemother, 2002 Apr, 46(4), 1032 - 7 Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp . and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000; Pfaller MA et al.; Posaconazole, ravuconazole, and voriconazole are new triazole derivatives that possess potent, broad-spectrum antifungal activity . We evaluated the in vitro activity of these investigational triazoles compared with that of itraconazole and amphotericin B against 239 clinical isolates of filamentous fungi from the SENTRY Program, including Aspergillus spp . (198 isolates), Fusarium spp . (7 isolates), Penicillium spp . (19 isolates), Rhizopus spp . (4 isolates), Mucor spp . (2 isolates), and miscellaneous species (9 isolates) . The isolates were obtained from 16 different medical centers in the United States and Canada between January and December 2000 . In vitro susceptibility testing was performed using the microdilution broth method outlined in the National Committee for Clinical Laboratory Standards M38-P document . Overall, posaconazole was the most active compound, inhibiting 94% of isolates at a MIC of < or = 1 microg/ml, followed by voriconazole (91%), amphotericin B (89%), ravuconazole (88%), and itraconazole (70%) . All three new triazoles demonstrated excellent activity (MIC, < or = 1 microg/ml) against Aspergillus spp . (114 Aspergillus fumigatus, 22 Aspergillus niger, 13 Aspergillus flavus, 9 Aspergillus versicolor, 8 Aspergillus terreus, and 32 Aspergillus spp.): posaconazole (98%), voriconazole (98%), ravuconazole (92%), amphotericin B (89%), and itraconazole (72%) . None of the triazoles were active against Fusarium spp . (MIC at which 50% of the isolates tested were inhibited {MIC(50)}, >8 microg/ml) or Mucor spp . (MIC(50), >8 microg/ml) . Posaconazole and ravuconazole were more active than voriconazole against Rhizopus spp . (MIC(50), 1 to 2 microg/ml versus >8 microg/ml, respectively) . Based on these results, all three new triazoles exhibited promising activity against Aspergillus spp . and other less commonly encountered isolates of filamentous fungi . The clinical value of these in vitro data remains to be seen, and in vitro-in vivo correlation is needed for both new and established antifungal agents . Surveillance efforts should be expanded in order to monitor the spectrum of filamentous fungal pathogens and their in vitro susceptibility as these new antifungal agents are introduced into clinical use. Antimicrob Agents Chemother, 2002 Apr, 46(4), 943 - 6 Development of a whole-cell assay for peptidoglycan biosynthesis inhibitors; Barbosa MD et al.; Osmotically stabilized Escherichia coli cells subjected to freezing and thawing were utilized as the source of enzymes for a peptidoglycan pathway assay that can be used to simultaneously test all targets of the committed steps of cell wall biosynthesis . The use of (14)C-labeled UDP-N-acetylglucosamine (UDP-GlcNAc) as a substrate allows the direct detection of cross-linked peptidoglycan formed . The assay was validated with known antibiotics . Fosfomycin was the strongest inhibitor of the pathway assay, with a 50% inhibitory concentration of 1 microM . Flavomycin, bacitracin, vancomycin, D-cycloserine, penicillin G, and ampicillin also inhibited formation of radiolabeled peptidoglycan by the E . coli cells . Screening of compounds identified two inhibitors of the pathway, Cpd1 and Cpd2 . Subsequent tests with a biochemical assay utilizing purified enzyme implicated UDP-GlcNAc enolpyruvyl transferase (MurA) as the target of Cpd1 . This compound inhibits the first enzyme of the pathway in a time-dependent manner . Moreover, enzyme inactivation is dependent on preincubation in the presence of UDP-GlcNAc, which forms a complex with MurA, exposing its active site . Cpd1 also displayed antimicrobial activity against a panel of microorganisms . The pathway assay used in conjunction with assays for individual enzymes provides an efficient means of detecting and characterizing novel antimicrobial agents. J Heart Lung Transplant, 2002 Mar, 21(3), 354 - 9 Nocardia infection in lung transplant recipients; Husain S et al.; BACKGROUND: Nocardia is responsible for infection in both normal and immunocompromised hosts . Organ transplant recipients are increasingly recognized as a sub-group of immunocompromised patients in whom nocardia is an important pathogen . The frequency of nocardia in organ transplant recipients varies between 0.7% and 3% . Nocardia infection has largely been reported in heart, kidney and liver transplant recipients . Presentations of nocardia in lung transplant recipients have been restricted primarily to case reports . The present study reviews the clinical and epidemiologic characteristics of nocardia infection in lung transplant recipients at our institution . METHODS: A retrospective cohort study of 473 lung transplant recipients from January 1991 to November 2000 was done at a university hospital . Patient demographics, immunosuppressive regimen at the time of isolation of nocardia species, use of trimethoprim-sulfamethoxazole for Pneumocystis carinii prophylaxis, rejection episodes in the preceding 6 months, concurrent pathogens, site of infection, radiologic findings and treatment and outcome were recorded . RESULTS: Nocardia infection was found in 2.1% (10 of 473) of our lung transplant recipients . Median time of onset was 34.1 months after transplantation . Nocardia species included N farcinica in 30% (3 of 10), N nova in 30% (3 of 10), N asteroides complex in 30% (3 of 10) and N brasiliensis in 10% (1 of 10) of patients . Post-transplant diabetes was present in 50% (5 of 10) of patients . The primary indication for lung transplantation was emphysema in 40% (4 of 10) . Native lung involvement was noted in 75% (3 of 4) of patients with single lung transplant . Breakthrough nocardia infection were noted in 6 patients who were receiving trimethoprim-sulfamethoxazole prophylaxis for P carinii pneumonia; all breakthrough isolates remained susceptible to trimethoprim-sulfamethoxazole . Overall mortality was 40% (4 of 10) . All patients (3 of 3) with infection due to N farcinica, except 1 (1 of 7) with infection due to other nocardia species, died . Seventy-five percent (3 of 4) of deaths were attributable to nocardia infection . CONCLUSIONS: Nocardia infection tended to involve the native lung in single lung transplant recipients . Trimethoprim-sulfamethoxazole for P carinii prophylaxis at the doses given was not protective against nocardiosis in these patients . Infection with N farcinica was associated with poor outcome . Thus, species identification and extended courses of antibiotics based on antimicrobial susceptibility testing are important in management of these patients. Infect Immun, 2002 Apr, 70(4), 1860 - 6 Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binding ability of interleukin-8 in human endothelial cells; Elass E et al.; Interleukin-8 (IL-8), a C-X-C chemokine bound to endothelium proteoglycans, initiates the activation and selective recruitment of leukocytes at inflammatory foci . We demonstrate that human lactoferrin, an antimicrobial lipopolysaccharide (LPS)-binding protein, decreases both IL-8 mRNA and protein expression induced by the complex Escherichia coli 055:B5 LPS/sCD14 in human umbilical vein endothelial cells . The use of recombinant lactoferrins mutated in the LPS-binding sites indicates that this inhibitory effect is mediated by an interaction of lactoferrin with LPS and CD14s that suppresses the endotoxin biological activity . Furthermore, since dimeric IL-8 and lactoferrin are both proteoglycan-binding molecules, the competition between these proteins for heparin binding was investigated . Lactoferrin strongly inhibited the interaction of radiolabeled IL-8 to immobilized heparin, whereas a lactoferrin variant lacking the amino acid residues essential for heparin binding was not inhibitory . Moreover, this process is specific, since serum transferrin, a glycoprotein whose structure is close to that of lactoferrin, did not prevent the interaction of IL-8 with heparin . These results suggest that the anti-inflammatory properties of lactoferrin during septicemia are related, at least in part, to the regulation of IL-8 production and also to the ability of lactoferrin to compete with chemokines for their binding to proteoglycans. Curr Allergy Asthma Rep, 2002 Jan, 2(1), 16 - 25 Allergic adverse reactions to sulfonamides; Choquet-Kastylevsky G et al.; Antimicrobial sulfonamides were the first antimicrobial agents used effectively to treat infectious diseases . However, because they may cause severe adverse drug reactions (ADRs) and because more effective agents have since been developed, sulfonamides now are used for only a few indications in specific groups, such as AIDS patients . Skin reactions, from benign rash to potentially lethal toxidermias, are the most frequent ADRs to sulfonamides . Other major ADRs include acute liver injury, pulmonary reactions, and blood dyscrasias . Although the mechanisms involved have not been fully elucidated, reactive metabolites appear to play a pivotal role . The hydroxylamine and nitroso metabolites of sulfamethoxazole, the most frequently used sulfonamide today, can bind covalently to proteins because of their chemical reactivity, resulting in the induction of specific adverse immune responses . Therefore, changes in the activity of metabolic and detoxification pathways are associated with a greater risk for developing allergic reactions to sulfonamides . Allergies to sulfonamides, particularly sulfamethoxazole (often used in combination with trimethoprim as co-trimoxazole), are more frequent in AIDS patients, but the reason for this increased risk is not fully understood . No valid tools are available to predict which patients have a greater risk for developing allergies to sulfonamides . Diagnosis is essential to avoid a possible evolution toward severe reactions and readministration of the offending drug . In patients who absolutely require further treatment, successful desensitization may be achieved. J Clin Periodontol, 2002 Feb, 29(2), 87 - 91 The effects of subgingival calculus on the clinical outcomes of locally-delivered controlled-release doxycycline compared to scaling and root planing; Johnson LR et al.; BACKGROUND, AIM: The effect of subgingival calculus on the clinical outcomes of the local delivery of antimicrobials is unknown . This study examines the clinical outcomes of treatment with locally delivered controlled-release doxycycline (DH) or scaling and root planing (SRP) in subsets of adult periodontitis patients with known baseline levels of subgingival calculus . METHODS: The data examined were obtained from 393 patients who participated in 2 multi-center trials . All patients had baseline subgingival calculus levels assessed and were then treated at baseline and month 4 with either DH or SRP . Clinical attachment levels (CAL), pocket depth (PD) and bleeding on probing (BOP) were assessed at baseline and months 1, 2, 4, 5, 6, 8 and 9 . RESULTS: Treatment with either DH or SRP resulted in significant statistical and clinical improvements in CAL, PD and BOP . These clinical outcomes were equivalent regardless of the extent of subgingival calculus present at baseline . CONCLUSIONS: The results indicate that the primary clinical effects of these therapies are the result of a disruption and reduction of the subgingival plaque and not the effect of the removal of subgingival calculus and contaminated cementum. Int J Dermatol, 2002 Jan, 41(1), 28 - 31 Scrofuloderma and Sweet's syndrome; Mahaisavariya P et al.; BACKGROUND: In recent years, the rare association of Sweet's syndrome with nontuberculous mycobacterial lymphadenitis has been reported . OBJECTIVE: To report the clinical, demographic, and bacteriologic data and association with Sweet's syndrome of 18 patients with scrofuloderma and scrofuloderma-like condition caused by nontuberculous mycobacterial infections seen during the past 7 years (1994-2000) . METHODS: In all patients, a biopsy specimen was obtained for histopathologic and microbiologic studies . Patients from whom Mycobacterium tuberculosis and nontuberculous mycobacteria were isolated from the culture of skin biopsy specimens were included . Deep fungal infection was excluded by the lack of a fungal element in histologic section and cultural methods . The patients were treated with antimicrobials or antituberculous drugs according to the causative species . RESULTS: Eighteen cases of scrofuloderma (nine male, nine female; mean age, 36.9 years) were found among 104 patients with cutaneous tuberculosis and nontuberculous mycobacterial cutaneous infections . Sixteen of the 18 cases had lymphadenitis as the underlying focus of scrofuloderma: 15 cases occurred in the cervical group and one case in the inguinal area . One case drained from the soft tissue and one from the paranasal air sinus . Five cases had multiple episodes of Sweet' s syndrome during the course of treatment . Most cases in this group (four of the five) were middle-aged women with cervical lymphadenitis, and the most common species were rapid growers . CONCLUSIONS: Age, sex, and the site of infection may have some influence on the association with Sweet's syndrome in nontuberculous mycobacterial infections. Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi, 2002, 12(2), 105 - 19 {Study on the detection methods of Helicobacter pylori from clinical specimens}; Murata Y et al.; We have attempted the detection of Helicobacter pylori using biopsy specimen (tunica mucosa vestibulum ventriculi, tunica mucosa corpus ventriculi) and of Helicobacter pylori Specific Antigen (HpSA) from feces of patients with stomach-duodenum disease . During 1991-2000, 753 patients had biopsy test for Gram-stained smear, culture, rapid urease test (RUT), and HpSA by ELISA . As a result, Gram stained smear positive were 609 (44.6%) in 1,357 specimens, culture positive were 984 (72.5%) in 1,357 specimens, and RUT positive were 445 (59.4%) in 749 specimens in method with stomach specimens . 85 (94.4%) in 90 specimens with method of HpSA were positive, and we defined that indirect detection method using feces was most significance compared with other invasive direct method using endoscopy . In addition, antimicrobial susceptibility tests were examined with 5 agents for 349 strains of H . pylori, the MICs of amoxicillin were <0.01-0.19 microgram/ml (MIC80: 0.02 microgram/ml), and clarithromicin were <0.01-50 microgram/ml (MIC80: 0.04 microgram/ml) . Amoxicillin resistant strain was not observed. J Periodontol, 2002 Feb, 73(2), 167 - 72 Comparison of conventional periodontal maintenance versus scaling and root planing with subgingival minocycline; Meinberg TA et al.; BACKGROUND: Alternative regimens using subgingival antimicrobials compared to conventional periodontal maintenance (PM) may lead to more efficient protocols . The purpose of this study was to evaluate treatment time and clinical and radiographic outcomes in 2 periodontitis cohorts, one receiving conventional PM and the other receiving scaling and root planing (SRP) and multiple doses of subgingival minocycline . METHODS: Moderate to advanced chronic periodontitis patients were concurrently treated with either: 1) scaling and root planing and 4 subgingival doses of minocycline microspheres in all > or = 5 mm pockets over a 6-month period (RP/M; n = 24 patients); or 2) conventional 3-month periodontal maintenance (PM; n = 24 patients) . Clinical and radiographic measurements, including probing depth (PD), clinical attachment level (CAL), and interproximal bone height (BH), were analyzed in 2 premolar/molar interproximal > or = 5 mm pockets at baseline and 1 year using paired t tests, analysis of variance, chi-square analysis, and correlation coefficients . RESULTS: Baseline clinical and radiographic data were similar between RP/M and PM patients . Probing depths showed greater mean improvement in RP/M (0.9 +/- 0.1 versus 0.4 +/- 0.1 mm, P = 0.02), with 25% of subjects in RP/M gaining > or = 2 mm compared to 4.2% in PM (differences were statistically significant) . The mean loss in bone height and percent subjects losing bone height were less in RP/M (0.05 +/- 0.05 mm; 12.5%) than PM (0.09 +/- 0.08 mm; 16.7%), but bone height differences were not statistically significant . A subset of RP/M molar furcation sites responded with similar PD reduction and no BH loss over 1 year . While cross-sectional RP/M data between CAL and BH, or PD and CAL were highly correlated, changes over 1 year were not correlated among any of these parameters . CONCLUSIONS: Scaling and root planing and subgingival minocycline in experimental sites took little time (<5 minutes/appointment), but resulted in more probing depth reduction and less frequent bone height loss than conventional periodontal maintenance. Epidemiol Infect, 2002 Feb, 128(1), 21 - 7 Non-invasive pneumococcal disease and antimicrobial resistance: vaccine implications; Kyaw MH et al.; We reviewed laboratory data on non-invasive pneumococcal isolates reported from all diagnostic laboratories in Scotland during the period 1988-99 . Of 4491 isolates from hospitalized patients, 654 (64.7%) were from sputum, 79 (7.8%) from the nasopharynx and 278 (27.5%) from other superficial sites . The serogroups included in the 23-valent polysaccharide vaccine caused 96.9% of all non-invasive disease in all age groups . The 7-, 9-, and 11-valent conjugated vaccine serogroups were responsible for 87-94%, 85-93%, 74-81% and 75-84% of non-invasive disease respectively in age groups < 2 years, < or = 5 years, > or = 65 years and all ages . The coverage of non-susceptible penicillin and erythromycin non-invasive isolates was > 99% and > 95% with the 23-valent polysaccharide and 7-11-valent conjugate vaccines respectively . The eight most common serogroups were 23, 9, 6, 19, 14, 3, 15 and 11 (in descending order) . The serogroups associated with antimicrobial resistance in non-invasive disease were similar to those found in invasive disease . The finding of a similar serogroup distribution in both invasive and non-invasive disease (regardless of the site of clinical isolate), is consistent with serogroups colonizing non-sterile sites and having the potential to invade . The availability of conjugated vaccines reinforces the importance of systematic surveillance to determine accurately and regularly the coverage of pneumococcal serogroups and types causing both invasive and non-invasive disease. Ann Pharmacother, 2002 Mar, 36(3), 530 - 2 Pharmacodynamics in the evaluation of drug regimens; Bhavnani SM et al.; We believe, especially in an era of increasing antimicrobial resistance, that the integration of PK/PD models and stochastic techniques provides a powerful new tool to clinicians, researchers, and regulatory agencies alike . By using techniques such as these, we can begin to level the playing field so that PK/PD measures for therapeutic agents can be more accurately compared with greater certainty, and not be limited to discussions of susceptibility method variation or comparisons of MIC results. Am J Med, 2002 Feb 15, 112(3), 204 - 11 Antimicrobial therapy of gram-negative bacteremia at two university-affiliated medical centers; Graff LR et al.; PURPOSE: To describe antimicrobial prescribing practices and patient outcomes associated with the treatment of aerobic gram-negative rod bacteremia at two university-affiliated medical centers . SUBJECTS AND METHODS: All adult patients with gram-negative bacteremia (N = 326) who were at Stanford and University of California, San Francisco (UCSF) Hospitals from September 1, 1996 through August 31, 1997 were evaluated via retrospective review of medical records . RESULTS: Most patient characteristics were similar between institutions; however, patients at Stanford were more likely to have had a diagnosis of bone marrow transplantation, liver failure, or poor nutritional status, while more patients at UCSF had solid organ transplant, diabetes, pulmonary disease, or hypotension . The bacteriology was similar at both sites, with Escherichia coli the predominant pathogen (139 {43%} of 326) . The majority of episodes were community acquired (67% {218/326}) . Patients at Stanford were more likely to have been treated empirically with aminoglycosides (28% vs . 7%, P <0.001) and noncephalosporin beta-lactams (31% vs . 11%, P <0.001), while patients at UCSF were more likely to have received cephalosporins (62% vs . 29%, P <0.001) and fluoroquinolones (21% vs . 11%, P = 0.02) . These patterns continued for definitive therapy . Overall mortality was 60 (19%) of 326 . Several risk factors were associated with 14-day mortality, including severity of illness, neutropenia, diabetes mellitus, use of vasopressors, and empiric use of a noncephalosporin beta-lactam . CONCLUSION: Prescribing practices for the treatment of gram-negative bacteremia differed significantly in the two institutions despite similar patients and pathogens. Curr Opin Investig Drugs, 2001 Dec, 2(12), 1681 - 90 Combinatorial biosynthesis in microorganisms as a route to new antimicrobial, antitumor and neuroregenerative drugs; Hutchinson CR et al.; Combinatorial biosynthesis utilizes the genes of biosynthetic pathways that produce microbial products to create novel chemical structures . The engineering of mondular polyketide synthase (PKS) genes has been the major focus of this effort and has led to the production of analogs of macrolide antibiotics like the erythromycins and their derived ketolides, and of the immunosuppressive macrolide FK-520 (Fujisawa Pharmaceutical Co Ltd) . Approaches to making analogs of the promising antitumor compounds known as epothilones are also being explored . Lead compounds for further study have resulted and routes to analogs of other pharmacologically important compounds have been established . To facilitate this work, many new tools for manipulating and studying the multifunctional PKSs have been developed including the development of Escherichia coli as a PKS expression last . These developments have resulted in faster ways of engineering PKS to produce new compounds for the development of chemotherapeutic agents from natural products. J Chemother, 2002 Feb, 14(1), 47 - 53 Experimental studies on synergism between aminoglycosides and the antimicrobial antiinflammatory agent diclofenac sodium; Annadurai S et al.; The antiinflammatory agent diclofenac sodium (Dc) exhibited remarkable antibacterial effects both in vitro and in vivo . Fifteen different bacteria sensitive to Dc as well as to a number of common antibiotics were tested for synergistic effects in vitro . Disc diffusion test with Dc and aminoglycosides assessed by stringent computation showed clear-cut synergism . Synergism between Dc and streptomycin (Sm) was found to be statistically significant (p < or = 0.01) when compared with their individual effects . By the checkerboard assessment procedure, the fractional inhibitory concentration (FIC) index of this combination was found to be 0.49, confirming synergism . The mouse protective capacity of this combination was then evaluated in vivo against S . typhimurium as the virulent infecting bacterium, and the size of bacterial load determined from infected autopsied animals . Statistical analysis by Student's 't' test suggested this drug combination is highly synergistic; synergism was also noted between Dc and other aminoglycosides. J Pept Res, 2001 Nov, 58(5), 433 - 41 Structure-function studies on the amphibian peptide brevinin 1E: translocating the cationic segment from the C-terminal end to a central position favors selective antibacterial activity; Kumari VK et al.; Brevinin 1E, which has the sequence FLPLLAGLAANFLPKIFCKITRKC, is an antimicrobial peptide isolated from the skin secretions of the European frog Rana esculenta . Both the linear and the disulfide-bridged forms have relatively broad-spectrum antibacterial as well as hemolytic activities . The antibacterial and hemolytic activities and biophysical properties of synthetic peptides corresponding to brevinin 1E and its analog in which the segment CKITRKC has been transposed to a central location resulting in the sequence FLPLLAGLCKITRKCAANFLPKIF have been investigated . Our studies indicate that the analog peptide has antibacterial activity comparable with brevinin 1E, but with considerably reduced hemolytic activity . The linear variant of the analog has no hemolytic activity, unlike the linear form of brevinin 1E . The biological activities can be explained on the basis of relative affinities for anionic and zwitterionic lipids . A cluster of cationic amino acids flanked on one side by a hydrophobic stretch of amino acids and another side composed of apolar amino acids appears to favor preferential antibacterial activity. Curr Allergy Asthma Rep, 2001 Jul, 1(4), 364 - 72 Antibiotic theory in otitis media; Gungor A et al.; Otitis media is currently the most common diagnosis made by clinicians, which has a major impact on managed care . The emergence of resistant bacterial pathogens has caused controversy over the use of antibiotics when acute otitis media (AOM) is diagnosed . All infants with AOM and all older children with severe AOM should be treated with antibiotics, despite concerns about rising rates of resistant bacterial pathogens . Some older children with nonsevere AOM may be candidates for initial observation, although this is not confirmed by clinical trials . Antimicrobial agents are not required for otitis media with effusion of recent onset but may be considered if this effusion becomes chronic; in these cases, tympanostomy tube placement may be indicated . Antimicrobial prophylaxis for prevention of recurrent AOM should be reserved for selected patients because of the possible emergence of resistant organisms . Tympanostomy tube placement is a more reasonable option today. Semin Respir Infect, 2002 Mar, 17(1), 65 - 71 Emergency department management of acute respiratory infections; Ward MA; Respiratory tract infections are one of the most common problems prompting visits to the emergency department . Although many are the result of self-limited viral illnesses, these infections may result in substantial morbidity and, rarely, mortality . Prompt recognition and appropriate treatment can reduce morbidity and largely prevent mortality . Careful selection of antimicrobial agents is essential to maximize benefit and prevent overuse, which contributes to the emergence of antibiotic resistance. Am J Pathol, 2002 Mar, 160(3), 841 - 8 CAP37, a novel inflammatory mediator: its expression in endothelial cells and localization to atherosclerotic lesions; Lee TD et al.; Cationic antimicrobial protein of 37 kd (CAP37), originally isolated from human neutrophils, is an important multifunctional inflammatory mediator . Here we describe its localization within the vascular endothelium associated with atherosclerotic plaques . Evidence from in vitro immunocytochemical, Northern blot, and reverse transcriptase-polymerase chain reaction analysis indicates that CAP37 is induced in endothelial cells in response to inflammatory mediators . Endothelial-derived CAP37 shows sequence identity with an extensive region of neutrophil-derived CAP37 . This is the first demonstration of endogenous endothelial CAP37, confirmed by sequence analysis . We suggest that, because of its induction and location in the endothelium and its known monocyte- and endothelial-activating capabilities, CAP37 has potential to modulate monocyte/endothelial dynamics at the vessel wall in inflammation. J Ethnopharmacol, 2002 Apr, 80(1), 25 - 35 Screening of African medicinal plants for antimicrobial and enzyme inhibitory activity; Tshibangu JN et al.; Seven plant species, belonging to different families, were collected in the eastern part of the Republic of Congo (Kivu) based on ethnopharmacological information . Their dichloromethane and methanolic extracts were tested for biological activity . Five of the seven collected plants exhibited antiplasmodial activity with IC(50) values ranging from 1.1 to 9.8 microg/ml . The methanolic extract of Cissampelos mucronata was the most active one showing activity against chloroquine sensitive (D6) and chloroquine resistant (W2) Plasmodium falciparum strains with IC(50) values of 1.5 and 1.1 microg/ml, respectively . Additionally, this extract significantly inhibited the enzyme tyrosine kinase p56(lck) (TK) . The dichloromethane extract of Amorphophallus bequaertii inhibited the growth of Mycobacterium tuberculosis with a MIC of 100 microg/ml and the methanolic extract of Rubus rigidus inhibited the activity of both enzymes HIV1-reverse transcriptase (HIV1-RT) and TK p56(lck). J Altern Complement Med, 2002 Feb, 8(1), 77 - 83 Comparison of propolis skin cream to silver sulfadiazine: a naturopathic alternative to antibiotics in treatment of minor burns; Gregory SR et al.; BACKGROUND: Propolis, a naturopathic substance derived from bees wax extract, has recently been praised for its antimicrobial, anti-inflammatory, and cicatrization-enhancing properties . OBJECTIVE: In our study, we compare these properties in a high-grade Brazilian propolis skin cream directly with silver sulfadiazene (SSD) in the treatment of minor burns (superficial second degree) in the ambulatory care setting (less than 20% total body surface area burned) . SETTINGS/LOCATION: The study was conducted at the burn clinic in Pronto Socorro para Queimaduras, Gioania, Brazil . SUBJECT: Patients were admitted to the study only if their initial presentation for burn care was within 48 hours postinjury and if bilateral wounds of similar depth and quality were present . INTERVENTIONS: Patients had propolis skin cream applied to one wound and SSD applied to the other selected wound on initial presentation and underwent debridement and dressings change the following morning . Patients subsequently returned to the clinic every 3 days to have the wounds checked and dressings changed . At these check-ups, wounds were cultured for microbial growth and photographed to document inflammation and cicatrization . Patients were instructed not to disturb their wounds or change their dressings at home, thus propolis skin cream and SSD were applied to the wounds only at the specified 3-day intervals . RESULTS: Our preliminary results do not show any significant difference in microbial colonization between wounds treated with SSD and propolis skin cream, however, wounds treated with propolis skin cream consistently showed less inflammation and more rapid cicatrization then those treated with SSD . CONCLUSION: Propolis skin cream appears to have a beneficial effects on the healing of partial thickness burn wounds . If dressings had been changed more frequent the antimicrobial and wound healing effects would have been enhanced. Int Surg, 2001 Jan-Mar, 86(1), 62 - 6 Descending necrotizing mediastinitis: a case report and review of the literature; Balkan ME et al.; Descending necrotizing mediastinitis (DNM) is a highly fatal disease and as infection spreads along deep cervical planes into the mediastinum, widespread cellulitis, necrosis, abscess formation, and sepsis may occur . Early diagnosis is crucial for starting aggressive treatment without delay . Cervicothoracic computed tomography (CT) scanning may be useful for early diagnosis and preoperative evaluation of the surgical approach . Optimal treatment includes broad-spectrum antimicrobial therapy and extensive cervicomediastinal and transthoracic drainage . Clamshell incision provides an excellent exposure of both thoracic cavities and all mediastinal structures with minimal morbidity . We report here a fatal case of DNM with bilateral empyema and purulent pericarditis due to an odontogenic abscess with a brief review of the literature. Ostomy Wound Manage, 2001 Jun, 47(6), 36 - 42, 44-9 Management and prevention of venous leg ulcers: a literature-guided approach; Kunimoto BT; Managing venous leg ulcers involves management techniques that are indicated both in the treatment of all chronic leg ulcers and those that are specific to venous leg ulcers . The first step in managing venous leg ulcers is performing a holistic assessment of the patient . Once this is complete, any systemic or local factors that may affect wound healing should be addressed . This approach to managing the whole patient is critically important because if significant general wound healing factors are not treated, other specific attempts at healing the venous ulcer will be fruitless . This paper reviews nutritional supplementation, wound bed preparation, antimicrobial therapy, venous insufficiency, compression therapy, different bandage systems, therapeutic adjuncts to compression therapy, and recent advances in vascular surgery . Recurrence prevention also is discussed. Compend Contin Educ Dent, 2001 Dec, 22(12), 1086 - 8 Surface disinfectants: read the labels; Molinari JA; There are a few basic long-standing guidelines, which can assist in the selection and safe use of chemical disinfectants (Table 2) . Even though these were developed before the current availability of many of the premixed antimicrobial sprays and wipes, they remain applicable and most important, appropriate. Acta Vet Scand, 2001, 42(3), 365 - 75 Diagnoses and treatments in health-classified fattening herds rearing pigs all in-all out; Heinonen M et al.; This study describes diseases encountered, medications used and veterinary involvement in all in--all out finishing herds belonging to one pork production system . The finishing herds had a particular management and housing regime . The pigs originated from health classified farrowing units . Information on 207,442 pigs was collected from 595 log books . Altogether 91% of the pigs received no treatments . Four percent of the batches of pigs were given antimicrobial mass medications . The local veterinarian visited the herds on average 2.6 times during the finishing period and made the diagnoses in more than half of the cases . At least one pig was affected with arthritis or tail biting in more than half of the batches, whereas locomotory diseases were recorded in one third of the batches . All other diagnoses were encountered in 1%-13% of the batches . Only a few pigs were treated individually in the affected groups . Antimicrobial drugs were given to 8% and other medicines to 0.7% of the pigs . The diagnosis was missing at least for one pig in 29% of the batches and the information about the medicine use in 8% of the treatments was missing . The study shows that it is possible to rear finishing pigs with only a small proportion of the animals needing treatments . The need of mass medications was low, because infectious diseases affecting the whole herd were uncommon . The recommendations for antimicrobial use given by the authorities had been followed quite well . The farmers and the veterinarians should be educated in order to realise the importance of proper record keeping. Insect Biochem Mol Biol, 2002 Apr, 32(4), 369 - 75 Immunopeptides in the defense reactions of Glossina morsitans to bacterial and Trypanosoma brucei brucei infections; Boulanger N et al.; Several dipteran insects are vectors of parasites causing major human infectious diseases . Among these, the tsetse fly, Glossina spp., is responsible for the transmission of trypanosomes, the pathogens responsible for sleeping sickness in Africa . A better understanding of insect-parasite interactions will help establish new strategies to fight this important often fatal disease . Antimicrobial peptides (AMPs) are part of the humoral immune response in insects during bacterial, fungal and parasitic infections . Here, we studied the immune response of Glossina morsitans to bacteria and to Trypanosoma brucei brucei by analyzing the synthesis of AMPs as markers of the humoral immune response . By reversed-phase chromatography, mass spectrometry analysis, Edman degradation and in vitro antimicrobial assays of the hemolymph of immune-challenged adults of G . morsitans, we identified three AMPs: a cecropin, an attacin and a defensin . These three AMPs were found to be induced upon systemic bacterial infection and also after per os infections by bacteria and parasites. FEMS Microbiol Lett, 2002 Jan 22, 207(1), 91 - 5 Increased expression of the multidrug efflux genes acrAB occurs during slow growth of Escherichia coli; Rand JD et al.; Intrinsic antimicrobial resistance of Escherichia coli is elicited by the gene products of the multidrug efflux acrAB-tolC operon . In this paper, we have shown that acrAB is regulated as a function of the growth rate of E . coli during growth in batch and chemostat culture . In chemostat culture, expression of acrAB is inversely related to growth rate irrespective of the limiting nutrient . The level of expression of acrAB is greater under glucose limitation compared with either iron or nitrogen limitation . Increase in expression of acrAB confers a greater resistance to ciprofloxacin, and the implications for a clinical situation are discussed . Slow growth rate regulation of acrAB transcription does not require the presence of the stationary-phase sigma factor . A putative gearbox consensus sequence was identified at the -10 region of the acrAB promoter. Br J Haematol, 2002 Mar, 116(4), 920 - 2 Adoptive therapy with monocyte-derived macrophages in the setting of high-dose chemotherapy and peripheral blood stem cell transplantation; Krause SW et al.; In an attempt to ameliorate chemotherapy-induced side-effects after transplantation of autologous peripheral blood stem cells (PBSCT), we tested the reinfusion of autologous macrophages (MAC) that are known to be potent antimicrobial effector cells and cytokine producers . Ten patients were treated with two sequential cycles of high-dose chemotherapy followed by PBSCT . Before the second cycle of PBSCT, mononuclear cells were harvested, cultured for 8 d in order to induce MAC maturation and reinfused 3 d after PBSCT without clinical problems . However, MAC infusions did not substantially alleviate the toxicity of autologous PBSCT. J Hosp Infect, 2002 Mar, 50(3), 165 - 9 Quality indicators for antibiotic control programmes; Nathwani D et al.; Antimicrobial control measures are commonly perceived to lead to an improvement in quality of prescribing, cost-effectiveness and reduction in resistance . All three outcomes have been subject to scrutiny . As proper use of resources needs to be balanced with provision of high-quality health care, the effectiveness of control measures (antibiotic policies or formularies) must be monitored.Measurement of quality by using specific indicators has been suggested as an effective measure of performance . We describe a model for evaluating core aspects of antimicrobial control programmes, aimed at improving the quality of glycopeptide prescribing by 'appropriate use guidelines' . Prioritizing indicator settings within antimicrobial control programmes is essential if limited resources are to be used most effectively . Indicator development, evaluation and feedback ought to be multi-disciplinary to ensure ownership and long-term benefit . Arch Pharm Res, 2002 Feb, 25(1), 28 - 38 Synthesis, antimicrobial and molluscicidal activities of new benzimidazole derivatives; Nofal ZM et al.; A series of benzimidazole Schiff's bases, thiosemicarbazides were synthesized, azole ring systems as 1,3,4-triazole, 1,3,4-oxadiazole were prepared . 1-Methylbenzimidazole incorporated to substituted dithio-carbamate, thiophenol, diethylamine via acetamido group were synthesized . A series of pyrimidinobenzimidazoles, triazinobenz-imidazoles, and 2-(acetonylamino)-1-methylbenzimidazole were prepared . The antimicrobial and molluscicidal activities of some newly prepared compounds were carried out. Ned Tijdschr Tandheelkd, 1992 Jul, 99(7), 245 - 6 {Microbiological diagnostics in periodontal treatment}; de Graaff J et al.; Periodontal diseases are bacterial infections . The rationale for the use of microbiological diagnostics in periodontal treatment of severe periodontitis patients is discussed as well as the use of adjunct antimicrobial therapy for the elimination of specific bacterial species. Am J Health Syst Pharm, 2002 Feb 15, 59 Suppl 1, S9 - 13 Current strategies for managing the patient with sepsis; Kuhl DA; Key elements of the current approach to treating sepsis are reviewed, and examples are given to illustrate the difficulty of designing and evaluating trials in sepsis . A patient with sepsis is likely to have symptoms characteristic of the systemic inflammatory response syndrome . Initially, ruling out noninfective causes, locating the site of infection, and obtaining cultures before beginning antimicrobial therapy are critical . Aggressive fluid resuscitation and hemodynamic support are used to restore tissue perfusion and normalize cellular metabolism . Vasopressor therapy with dopamine or norepinephrine is needed in patients unresponsive to fluid resuscitation . Dobutamine should be administered in patients whose cardiac output is inadequate despite optimization of fluids and pressors . Supportive care includes deep vein thrombosis prophylaxis, nutrition support, stress ulcer prophylaxis, and management of acute lung injury . Attempts to modify the sepsis response and improve the outcome in these patients have yielded limited benefits . Recent small studies have shown benefits with low-dose hydrocortisone in patients with refractory sepsis . One challenge in study design is that a therapy may target a subset of patients that cannot be identified at the outset . Management of patients with suspected or documented sepsis focuses on hemodynamic support, appropriate antimicrobial therapy, and other supportive care. Am J Health Syst Pharm, 2002 Feb 15, 59(4), 349 - 54 Use of patients' own medications in small hospitals; Norstrom PE et al.; The prevalence, management, and adverse events associated with the use of a patient's personal medications in hospitals were studied . A questionnaire comprised of 17 questions was mailed in November 1999 to the pharmacy directors of a random sample of 300 small (< or = 200-bed capacity) hospitals selected from the American Hospital Association 1999 membership directory . A follow-up mailing was sent to nonrespondents in early December 1999 . The total usable response rate was 54.6% . The mean bed capacity was 76.6, and 70.8% of facilities had < or = 100 beds . Most facilities provided acute care, were nonprofit organizations, and were located in rural areas . A majority (90%) of the pharmacy directors surveyed allowed patients to use their own medications in the hospital . Elderly patients were most likely to bring their personal medications to use in the hospital, and pharmacists were the health professionals most likely to identify patients' personal medications . Circumstances in which patients were allowed to use their own medication, provided there was a physician's order, included prepackaged courses of therapy or antimicrobial courses and nonformulary medications, excluding controlled substances . Loss of personal medication and medication errors were the most frequently identified problems with allowing patients to use personal medications . Most small hospitals allowed the use of pati