Clin Microbiol Rev, 1997 Oct, 10(4), 611 - 36 Interleukin-12 in infectious diseases; Romani L et al.; Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that is crucially involved in a wide range of infectious diseases . In several experimental models of bacterial, parasitic, viral, and fungal infection, endogenous IL-12 is required for early control of infection and for generation and perhaps maintenance of acquired protective immunity, directed by T helper type 1 (Th1) cells and mediated by phagocytes . Although the relative roles of IL-12 and gamma interferon in Th1-cell priming may be to a significant extent pathogen dependent, common to most infections is that IL-12 regulates the magnitude of the gamma interferon response at the initiation of infection, thus potentiating natural resistance, favoring Th1-cell development; and inhibiting Th2 responses . Treatment of animals with IL-12, either alone or as a vaccine adjuvant, has been shown to prevent disease by many of the same infectious agents, by stimulating innate resistance or promoting specific reactivity . Although IL-12 may enhance protective memory responses in vaccination or in combination with antimicrobial chemotherapy, it is yet unclear whether exogenous IL-12 can alter established responses in humans . Continued investigation into the possible application of IL-12 therapy to human infections is warranted by the role of the cytokine in inflammation, immunopathology, and autoimmunity. Vestn Otorinolaringol, 1997, (4), 40 - 1 {Efficacy of polymer suture material "kapromed" in otorhinolaryngological practice}; Klochikhin AL et al.; When used in suturing, polymer material capromed containing antimicrobial substances proved its efficacy in laryngectomy, plastic reconstruction of pharyngo- and tracheostoma, management of operative wounds on the neck, especially in patients with laryngeal cancer preexposed to radiation treatment and other surgical interventions on ENT . Compared to conventional suture materials (silk, lavsan, catgut, capron), capromed improved the outcomes of surgical treatment, reduced the number of pyoinflammatory complications. Langenbecks Arch Chir, 1997, 382(4 Suppl 1), S42 - 6 {Surgical therapy of pleural empyema with tauroline}; Bieselt R; Empyema continues to be a significant problem in spite of improved surgical techniques and the use of new, more potent antimicrobial agents . This report describes our experience in the treatment of empyema at the Clemens Hospital in Munster, Germany, from 1990 to 1996 . Basic to conservative treatment are closed drainage with intensive irrigation and instillation of Taurolin, a chemotherapeutic agent against bacterias, yeasts and mycetes . This treatment has been employed since 1990 and given 86 patients with just empyema or in combination with decortication . The superiority of this method to other methods of treatment is discussed on the basis of our results. J Am Vet Med Assoc, 1997 Oct 1, 211(7), 875 - 7 Management of a congenitally shortened soft palate in a dog; Sylvestre AM et al.; An 8-week-old puppy that was examined because of a nasal discharge was found to have a congenitally shortened soft palate . The palate was partially rebuilt with pharyngeal flaps constructed from the tonsillar crypts . The reconstructed soft palate extended approximately 40% of the distance between the caudal aspect of the hard palate and rostral tip of the epiglottis . During the first 18 months after surgery, the dog had 3 episodes of halitosis, sneezing, and mucopurulent nasal discharge but responded to antimicrobial treatment . The dog was fed dry dog food and drank water from an elevated bowl . Water would flow from the dog's nose if it drank water with its head lowered . Compensatory mechanisms likely play an important role in the outcome of animals with this condition. Antimicrob Agents Chemother, 1997 Oct, 41(10), 2297 - 9 In vitro activities of 10 antimicrobial agents against bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women; Puapermpoonsiri S et al.; The in vitro activities of 10 antimicrobial agents against 159 bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women were determined . Clindamycin, imipenem, cefmetazole, amoxicillin, amoxicillin-clavulanate, and metronidazole were highly active against all anaerobic isolates except Prevotella bivia and Mobiluncus species, which were resistant to amoxicillin and metronidazole, respectively . Cefotiam, ceftazidime, and ofloxacin were variably effective, while cefaclor was the least effective agent. Proc R Soc Lond B Biol Sci, 1997 Sep 22, 264(1386), 1287 - 91 Adaptation to the fitness costs of antibiotic resistance in Escherichia coli; Schrag SJ et al.; Policies aimed at alleviating the growing problem of drug-resistant pathogens by restricting antimicrobial usage implicitly assume that resistance reduces the Darwinian fitness of pathogens in the absence of drugs . While fitness costs have been demonstrated for bacteria and viruses resistant to some chemotherapeutic agents, these costs are anticipated to decline during subsequent evolution . This has recently been observed in pathogens as diverse as HIV and Escherichia coli . Here we present evidence that these gentic adaptations to the costs of resistance can virtually preclude resistant lineages from reverting to sensitivity . We show that second site mutations which compensate for the substantial (14 and 18% per generation) fitness costs of streptomycin resistant (rpsL) mutations in E . coli create a genetic background in which streptomycin sensitive, rpsL+ alleles have a 4-30% per generation selective disadvantage relative to adapted, resistant strains . We also present evidence that similar compensatory mutations have been fixed in long-term streptomycin-resistant laboratory strains of E . coli and may account for the persistence of rpsL streptomycin resistance in populations maintained for more than 10,000 generations in the absence of the antibiotic . We discuss the public health implications of these and other experimental results that question whether the more prudent use of antimicrobial chemotherapy will lead to declines in the incidence of drug-resistant pathogenic microbes. Curr Eye Res, 1997 Oct, 16(10), 1056 - 60 The antimicrobial susceptibility of Mycobacterium chelonae isolated from corneal ulcer; Hu FR et al.; PURPOSE: To determine the in vitro susceptibility of Mycobacterium chelonae isolates from corneal ulcers to various traditional and newly-developed antimicrobial agents, alone or in combination . METHODS: Fifteen strains of M . chelonae isolated from corneal ulcers were collected at the National Taiwan University Hospital from 1989 to 1993 . Susceptibility to antimicrobial agents was tested by the broth microdilution method to determine the minimum inhibitory concentration (MIC) . The antimicrobial effects of combinations of antimicrobial agents were assessed by the checkerboard titration method to determine the fractional inhibitory concentration (FIC) index . RESULTS: The MIC results showed that traditional antituberculous drugs had poor activity against M . chelonae . In the aminoglycoside group, tobramycin and amikacin had better activity than gentamicin . Among macrolides, clarithromycin was especially effective, with an MIC ranging from 0.125 to 1 microgram/ml . Among various beta-lactam antibiotics, imipenem was the only one to demonstrate good anti-mycobacterial activity . Of the quinolone group, ciprofloxacin was the most effective, with an MIC ranging from 0.5 to 16 micrograms/ml . Combination of an aminoglycoside with imipenem, ciprofloxacin or clarithromycin all showed antagonistic effect . CONCLUSIONS: The results suggested that amikacin, clarithromyicn, imipenem and ciprofloxacin had good in vitro antimicrobial activity against M . chelonae . However, no synergistic effect could be demonstrated for combinations of an aminoglycoside with other effective drugs. Crit Care Clin, 1997 Oct, 13(4), 741 - 62 Antibiotic-induced convulsions; Wallace KL; Convulsive episodes are associated with the use of a number of antimicrobial agents . Although seizures may be a feature of the disease being treated, antibiotics should be considered possible causes of seizures, particularly if suggested by temporal relationships between seizure activity and drug administration . The astute clinician should be aware of the clinical settings in which antibiotic-induced seizures occur, be familiar with likely agents and their mechanisms of toxicity, and be prepared to institute appropriate management directed at this adverse effect of antimicrobial therapy. J Heart Valve Dis, 1997 Sep, 6(5), 553 - 61 Biocompatibility of silver-modified polyester for antimicrobial protection of prosthetic valves; Tweden KS et al.; BACKGROUND AND AIMS OF THE STUDY: The biocompatibility of a silver-coated polyethylene terephthlate (PET, polyester) fabric for the inhibition of prosthetic valve endocarditis (PVE) associated with mechanical heart valves (MHVs) was assessed . The infrequency of PVE is outweighed by mortality rates commonly exceeding 50% . These high mortality rates have been attributed to the poor effect of antibiotic therapy on colonized valves and infected myocardial tissue . Silver has been used as an antimicrobial for centuries due to its general effectiveness and relative lack of toxicity . Our previous work has shown PET polyester fabric coated with metallic silver by an ion beam-assisted deposition (IBAD) process to: (i) be effective in vitro in the inhibition of microbial attachment and colonization; (ii) be tightly adherent and low leaching; and (iii) promote tissue ingrowth and the organization of tissue pannus in a short-duration (five weeks) sheep mitral mechanical heart valve model . METHODS: This paper addresses additional biocompatibility assessment consisting of a cell compatibility assay in which serum extracts of silver-coated fabric were exposed to fibroblasts for 48 hours, after which cell viability and function were measured . The amount of silver in the extract was measured using elemental analysis techniques . RESULTS: No signs of toxicity were seen in the cells until the extract concentration reached 1200 p.p.m . Ten-week duration mechanical valve replacement studies in sheep with uncoated or coated polyester sewing cuffs showed comparable tissue ingrowth and mature pannus with a suggestion of a thinner pannus on the silver-coated fabric . Additional antimicrobial testing confirmed the effectiveness of this coating in inhibiting colonization of polyester fabric . CONCLUSIONS: These current results, together with the earlier data, suggest that IBAD silver coating on polyester facilitates healing and may provide protection against PVE. Proc Natl Acad Sci U S A, 1997 Oct 14, 94(21), 11508 - 13 Molecular immune responses of the mosquito Anopheles gambiae to bacteria and malaria parasites; Dimopoulos G et al.; Immune responses of the malaria vector mosquito Anopheles gambiae were monitored systematically by the induced expression of five RNA markers after infection challenge . One newly isolated marker encodes a homologue of the moth Gram-negative bacteria-binding protein (GNBP), and another corresponds to a serine protease-like molecule . Additional previously described markers that respond to immune challenge encode the antimicrobial peptide defensin, a putative galactose lectin, and a putative serine protease . Specificity of the immune responses was indicated by differing temporal patterns of induction of specific markers in bacteria-challenged larvae and adults, and by variations in the effectiveness of different microorganisms and their components for marker induction in an immune-responsive cell line . The markers exhibit spatially distinct patterns of expression in the adult female mosquito . Two of them are highly expressed in different regions of the midgut, one in the anterior and the other in the posterior midgut . Marker induction indicates a significant role of the midgut in insect innate immunity . Immune responses to the penetration of the midgut epithelium by a malaria parasite occur both within the midgut itself and elsewhere in the body, suggesting an immune-related signaling process. Aust N Z J Surg, 1997 Oct, 67(10), 742 - 4 Sclerosing encapsulating peritonitis after intraperitoneal use of povidone iodine; Keating JP et al.; BACKGROUND: The use of intraperitoneal povidone iodine as an agent for peritoneal lavage in colorectal surgery is controversial . Although it possesses a wide range of antimicrobial activity and is rapidly lethal to dissociated colorectal cancer cells in vitro, concern about its potential toxicity remains . METHODS: Two cases of sclerosing encapsulating peritonitis (SEP) following elective colorectal surgery are presented . In each case the peritoneal cavity was lavaged with an aqueous povidone iodine solution . The surgical literature on the intraperitoneal use of povidone iodine is reviewed . RESULTS: Significant morbidity resulted from the postoperative development of SEP in both of our patients . In one patient an ileo-anal pouch could not be fashioned following an initial colectomy, and in the second patient a small-bowel obstruction required a laparotomy and a period of intravenous nutrition before an oral diet could be tolerated . CONCLUSION: The use of povidone iodine for peritoneal lavage in colorectal surgery is to be cautioned against in concentrations of > 1%. Gastroenterology, 1997 Oct, 113(4), 1118 - 28 Gastritis in urease-immunized mice after Helicobacter felis challenge may be due to residual bacteria; Ermak TH et al.; BACKGROUND & AIMS: Oral immunization with recombinant Helicobacter pylori urease (rUre) coadministered with a mucosal adjuvant protects mice against challenge with Helicobacter felis . In this study, the duration of protection and gastritis after challenge were characterized at sequential time intervals up to 1 year . METHODS: Outbred Swiss-Webster mice were orally immunized with rUre plus adjuvant and examined for the presence of H . felis infection and leukocyte infiltration into the gastric mucosa . RESULTS: When defined by gastric urease activity, 70%-95% of rUre-immunized mice were protected for between 2 and 57 weeks . Challenge with H . felis increased the inflammatory response in the gastric mucosa of rUre-immunized mice, which also had elevated CD4+ and CD8+ T cells . The CD8+ cells represented a population of gastric intraepithelial cells, which expressed the mucosal alpha E-integrin . Epithelial changes consisting of parietal cell loss and hyperplasia of the epithelium occurred in approximately 20% of the mice . Antimicrobial triple therapy significantly decreased the degree of gastritis and epithelial alteration in the stomach . CONCLUSIONS: These results indicate that oral immunization of mice with rUre produces a long-lasting inhibition of H . felis infection but that residual bacteria may produce a persistent lymphocytic infiltration under these experimental conditions. Transgenic Res, 1997 Sep, 6(5), 337 - 47 Interleukin 2 promoter/enhancer controlled expression of a synthetic cecropin-class lytic peptide in transgenic mice and subsequent resistance to Brucella abortus; Reed WA et al.; The addition of an antimicrobial that can be synthesized by the mammalian immune system at the point of challenge may enhance disease resistance . A possible group of agents are cecropins, broad-spectrum antimicrobial peptides, which have been described and characterized . They are relatively non-toxic to normal cells from multicellular organisms but are toxic to a wide range of bacteria, protozoa and fungi, as well as infected and abnormal cells . Twenty-six lines of transgenic mice were produced by pronuclear injection of DNA consisting of the 5'-flanking region from -593 to +110 of the mouse interleukin 2 (IL-2) gene, Shiva 1a (a synthetic cecropinclass lytic peptide), and the SV40 polyadenylation/splice signal . A reverse-transcription PCR assay determined that two lines of transgenic mice were produced whose spleen-derived lymphocytes could be induced to transcribe and mature mRNA for Shiva 1a by exposure to 3.25 mg ml-1 of Con A . Two lines were challenged with an inoculation of 5 x 10(4) Brucella abortus strain 2308 . After four weeks, there were significantly fewer B . abortus organisms in the spleens of transgenic mice than in non-transgenic control mice of the same strain (p < 0.05) . Since the controlling regions of the IL-2 enhancer and the amino acid sequence of the signal peptide are highly conserved among several species, it is likely that this recombinant gene will function in other mammals. FEMS Immunol Med Microbiol, 1997 Sep, 19(1), 57 - 64 Effect of antimicrobial agents, especially fosfomycin, on the production and release of Vero toxin by enterohaemorrhagic Escherichia coli O157:H7; Yoh M et al.; In 1996, Japan had several large outbreaks of enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection . We surveyed physicians who examined and treated these patients, and found that most of the patients (95.9%) received antimicrobial agents as treatments, in particular, fosfomycin comprised 84.0% of the prescribed treatment . Since the administration of antimicrobial agents for EHEC infection is under discussion, we also analyzed the effects of 7 antimicrobial agents including fosfomycin on the production and release of Vero toxins (VTs) by EHEC . The addition of fosfomycin into EHEC culture in CAYE broth at 5 h after the start of incubation caused a marked increase of VT1 release and production, as revealed by an immunological toxin assay (RPLA) . However, a cytotoxicity assay of Vero cells showed a small increase of biological activity in the specimens treated with fosfomycin because the Vero cell assay reflects total cytotoxicity of VT1 and VT2 . These results indicate that further study is necessary before concluding whether antimicrobial agents actually worsen an EHEC infection. EMBO J, 1997 Oct 15, 16(20), 6120 - 30 The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense; Williams MJ et al.; Mammals and insects employ similar Rel/NF-kappaB signaling cascades in their humoral immune responses . The mammalian interleukin-1 type I receptor (IL-1R) is one way of activating this cascade . The Drosophila Toll protein, whose cytoplasmic domain shows striking similarity to that of the IL-1R, acts in the humoral antimicrobial response . Here we demonstrate that a second IL-1R-related Drosophila protein, 18-Wheeler (18W), is a critical component of the humoral immune response . 18-wheeler is expressed in the larval fat body, the primary organ of antimicrobial peptide synthesis . In the absence of the 18W receptor, larvae are more susceptible to bacterial infection . Nuclear translocation of the Rel protein Dorsal-like immunity factor (Dif) is inhibited, though nuclear translocation of another Rel protein, Dorsal, is unaffected . Induction of several antibacterial genes is reduced following infection, relative to wild-type: attacin is reduced by 95%, cecropin by 65% and diptericin by 12% . Finally, 18-wheeler (18w) expression is induced in response to infection and, in addition to the receptor form, four immune-specific transcripts and proteins are produced. Infect Immun, 1997 Oct, 65(10), 4173 - 8 Redundant contribution of myeloperoxidase-dependent systems to neutrophil-mediated killing of Escherichia coli; Rosen H et al.; Neutrophil microbicidal activity is a consequence of overlapping antimicrobial systems that vary in prominence according to the conditions of the neutrophil-microbe interaction, the nature of the microbe, and its metabolic state . In this study, normal, myeloperoxidase-deficient, and respiratory burst-deficient (chronic granulomatous disease {CGD}) neutrophils killed Escherichia coli with equivalent, high efficiencies . Killing by CGD and myeloperoxidase-deficient neutrophils was not augmented by supplements, such as exogenous H2O2 and myeloperoxidase, directed at ameliorating their metabolic defects, suggesting that nonoxidative microbicidal systems were sufficient for a full microbicidal effect . Neutrophils with an intact myeloperoxidase antimicrobial system (normal or appropriately supplemented deficient cells) were capable of rapidly suppressing E . coli DNA synthesis, while unsupplemented CGD or myeloperoxidase-deficient cells were far less effective, indicating that the myeloperoxidase system was active in normal neutrophils . The degree of DNA synthesis inhibition by myeloperoxidase-sufficient neutrophils could account, in a cell-free system, for most of the observed microbicidal activity . While the myeloperoxidase system was active and probably bactericidal, it was not rate limiting for microbicidal activity and appears to have been redundant with other microbicidal systems in the cell . Rapid and extensive inhibition of bacterial DNA synthesis appears to be an indicator of myeloperoxidase activity in neutrophils. Clin Infect Dis, 1997 Sep, 25(3), 584 - 99 Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals; Shlaes DM et al.; Antimicrobial resistance results in increased morbidity, mortality, and costs of health care . Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs . Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms . A comprehensively applied infection control program will interdict the dissemination of resistant strains. J Mol Recognit, 1997 Mar-Apr, 10(2), 73 - 87 Simulated dipeptide recognition by vancomycin; Li D et al.; The antimicrobial activity of vancomycin and related glycopeptide antibiotics is due to stereospecific recognition of polypeptide components in bacterial cell walls . To better understand how these antibiotics recognize polypeptide determinants, we have developed dynamic models of the complexes formed by the vancomycin aglycon and two different dipeptide ligands, Ac-D-ala-D-ala and Ac-D-ala-gly . Molecular dynamics simulations of the two complexes, initially conditioned with distance constraints derived from two-dimensional nuclear magnetic resonance (NMR) studies, are conformationally stable and propagate in a manner consistent with the NMR-derived constraints after the constraints are removed . Free energy calculations accurately predict the relative binding affinity of these two complexes and help validate the simulation models for detailed structural analysis . Although the two ligands adopt similar conformations when bound to the antibiotic, there are clear differences in the configuration of intermolecular hydrogen bonds, the overall shape of the antibiotic, and other structural features of the two complexes . This analysis illustrates how complex structural and dynamic factors interrelate and contribute to differences in binding affinity. J Clin Periodontol, 1997 Sep, 24(9 Pt 1), 603 - 9 The comparative effect of acidified sodium chlorite and chlorhexidine mouthrinses on plaque regrowth and salivary bacterial counts; Yates R et al.; Acidified sodium chlorite (ASC) is recognised as a highly potent, broad spectrum antimicrobial system that has been successfully developed for uses in veterinary, food processing and medical device fields . The current studies aimed to investigate the persistence of antimicrobial action and plaque inhibitory properties of 3 ASC mouthrinses by comparison with positive control, chlorhexidine 0.12%, and placebo control, water, rinses . Both studies were randomised, double-blind, cross-over 5-cell designs balanced for carryover . The 1st study involved 15 healthy subjects who immediately before and at 30, 60, 180, 300 and 420 min after rinsing provided 2 ml saliva samples . The samples were immediately processed for total anaerobic bacterial counts recorded after 96 h incubation . Washout periods were a minimum of 3 days . The second study involved 20 healthy subjects who on day 1 of each study were rendered plaque free, suspended normal oral hygiene methods and commenced rinsing twice daily with the allocated rinse . On day 5, plaque was scored by index and area after disclosing with erythrosin . Washout periods were 2 1/2 days . The 3 ASC and chlorhexidine rinses produced similar reductions in salivary bacterial counts which remained significantly below the placebo control to 7 h . There were no significant differences between ASC and chlorhexidine rinses except at 30 and 60 min when significantly greater reductions were produced by 2 ASC rinses compared to the chlorhexidine rinse . Plaque indices and areas were considerably and significantly lower with the ASC and chlorhexidine rinses compared to the placebo rinse . There were no significant differences between plaque scores for the 3 ASC rinses and the chlorhexidine rinse, although for 2 ASC rinses plaque scores were lower than for the chlorhexidine rinse . The results indicate that the 3 ASC rinses have equivalent plaque inhibitory action to chlorhexidine as a rinse . Similar to chlorhexidine, the plaque inhibitory action of the rinses appears to be derived from a persistence of antimicrobial action in the mouth. Clin Infect Dis, 1997 Sep, 25(3), 551 - 73 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever . Infectious Diseases Society of America; Hughes WT et al.; This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee . The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline . The targeted providers are internists, pediatricians, and family practitioners . The targeted patients and setting for the fever and neutropenia guideline are hospitalized individuals with neutropenia secondary to cancer chemotherapy . Panel members represented experts in adult and pediatric infectious diseases and oncology . The guidelines are evidence-based . A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed . The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council . An executive summary, algorithms, and tables highlight the major recommendations . The guideline will be listed on the IDSA home page at http://www.idsociety.org. Transplantation, 1997 Sep 15, 64(5), 748 - 52 Use of aerosolized colistin sodium in cystic fibrosis patients awaiting lung transplantation; Bauldoff GS et al.; BACKGROUND: In patients with cystic fibrosis (CF) who are awaiting lung transplant, prolonged exposure to systemic antibiotics has frequently led to airway colonization with resistant isolates of Pseudomonas . This resistance limits the arsenal of effective antimicrobials available for infections after the initiation of immunosuppression and has been considered a theoretical deterrent to lung transplantation . METHODS: Twenty CF transplant candidates with "pan-resistant" Pseudomonas received maintenance antibiotic therapy with aerosolized colistin sodium (75 mg b.i.d.), and intravenous antibiotics were eliminated . Ten other CF candidates did not use colistin sodium . Sputum cultures and antibiotic sensitivities were followed every 3-6 weeks . RESULTS: All 20 candidates (100%) who used aerosolized colistin sodium became colonized with sensitive isolates of Pseudomonas in an average of 45.1+/-20.2 days . In contrast, only 3 of 10 CF transplant candidates (30%) who did not use colistin sodium later became colonized with sensitive isolates . The mean time to spontaneous emergence of sensitive organisms was 144.6+/-48.0 days in candidates who did not use colistin sodium and was significantly longer than in the candidates who used colistin sodium (P=0.007) . The occurrence of redeveloping sensitive isolates of Pseudomonas was significantly greater in the candidates who used colistin sodium (P<0.05) . Of the candidates who used colistin sodium, six have been transplanted at our institution . In five of these six recipients (83.3%) bacterial cultures taken from the explanted lungs continued to demonstrate sensitive organisms . CONCLUSION: Aerosolized colistin sodium may be a useful therapy to promote emergence of sensitive microbes in CF candidates with pan-resistant isolates of Pseudomonas. Rinsho Byori, 1997 Sep, 45(9), 859 - 64 {Present status and advances in detecting Shiga toxin-producing Escherichia coli O157}; Miki K et al.; Currently, detection of Shiga toxin-producing Escherichia coli(STEC) in stool samples is based on the isolation method in most clinical laboratories . The procedures are as follows: i) isolation with selective agar plates, ii) biological test with differential media, iii) serological test of anti-O antisera, iv) detection of toxin or toxin gene . These procedures take 4 days, therefore more rapid method is required . In the near future, a rapid detection method that detects STEC directly from stool samples will be introduced . Polymerase-chain reaction (PCR), enzyme-linked immuno-sorbent assay (ELISA), detection of serum anti-O157 antibodies are now available in clinical laboratories . Result of PCR for detection Shiga toxin gene and serum anti-O157 antibodies are described . Fifteen stool and serum samples from patients suspected of STEC infection were examined . With the culture and PCR method, 2 patients were positive by both methods and the results were confirmed in both cases . Six patients were positive by the antibodies detection method . From these results, the PCR method using stool samples was useful as a rapid detection method in clinical laboratories . Detection of serum antibodies has been simplified and is not an expensive method . Therefore, the method is useful for clinical diagnosis of STEC infection, especially, for diagnosing HUS or after antimicrobial agents have been administered to patients. Intensive Care Med, 1997 Aug, 23(8), 873 - 7 Pharmacokinetics of piperacillin and tazobactam in critically ill patients with renal failure, treated with continuous veno-venous hemofiltration (CVVH); van der Werf TS et al.; OBJECTIVE: Kinetics of piperacillin (pip), in combination with the beta-lactamase inhibitor tazobactam (taz) have been studied in volunteers and patients in relatively stable conditions . The fixed drug preparation appeared to have ideal pharmacokinetic properties if renal function was normal or slightly impaired, but no data are available for critically ill patients in anuric renal failure . This study should provide such data . PATIENTS, DESIGN: We studied the pharmacokinetics in nine patients with multiple organ failure, including anuric renal failure, treated with continuous veno-venous hemofiltration (CVVH) . Patients received a standard schedule of 4 g pip and 0.5 g taz administered over 0.5 h intravenously, 8 hourly . During 2 consecutive days, the serum levels of both compounds were determined, and total clearance (CIT) was calculated from serum concentrations . RESULTS: All nine patients completed day 1, and 8 completed day 2 of the protocol . On day 1, single-dose kinetics showed considerable spread, but pip/taz serum levels followed the pattern as expected, with a pip/taz concentration ratio of 20:1 . On day 2, however, taz serum concentrations showed a relative increase as compared to pip, resulting in a change in the serum pip/taz concentration ratio to 10:1 on day 2 . The CIT of pip was 2.52 +/- 1.38 l/h (t 1/2: 5.9 +/- 2.9 h), and CIT of taz 4.44 +/- 2.28 l/h (t 1/2: 8.1 +/- 3.7 h) . The CIT and t 1/2 of pip and taz correlated highly significantly with clearance by CVVH . Despite a higher CIT, taz has a longer half-life, because of a higher volume of distribution . CONCLUSION: In CVVH dependent patients, pip/taz fixed drug preparations can be used initially, but the pip dosage should be increased relative to that of taz (or interval-adjusted) to prevent cumulation of taz, as compared to the active antimicrobial agent pip. Clin Infect Dis, 1997 Sep, 25 Suppl 2, S258 - 61 Antimicrobial culture and susceptibility testing has little value for routine management of secondary bacterial peritonitis; Dougherty SH; The traditional surgical practice of routinely culturing specimens from patients with community-acquired intraabdominal infections, such as appendicitis, contributes little to the management of the individual patient, either initially or later when infectious complications have developed . Instead of performing routine cultures for peritonitis, a modified approach that still facilitates hospital surveillance for microbial resistance patterns should be used. Clin Infect Dis, 1997 Sep, 25 Suppl 2, S254 - 7 In defense of routine antimicrobial susceptibility testing of operative site flora in patients with peritonitis; Wilson SE et al.; The species and number of bacteria present at a surgical site correlate with postoperative wound infection . When organisms cultured from intraabdominal infections are resistant to the presumptive antimicrobial therapy, the incidence of postoperative wound and intraabdominal infections is significantly increased . Knowledge of operative site culture data allows identification of resistant organisms, leads to an early change in therapy, and guides selection of antimicrobials for treatment of postoperative complications . Anaerobic susceptibility data vary geographically, even differing within hospitals in the same city . Surveillance of resistance patterns of bacteria causing intraabdominal infections facilitates accurate initial therapy . Failure of treatment in the absence of bacteriologic results confirming appropriate antimicrobial therapy may be difficult to rationalize on a medicolegal basis . In summary, it is advisable for surgeons to perform cultures and susceptibility tests for both aerobic and anaerobic organisms present in intraabdominal infections. Conn Med, 1997 Aug, 61(8), 451 - 8 Hyperkalemia and trimethoprim-sulfamethoxazole: a new problem emerges 25 years later; Perazella MA; Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity . A previously unreported and potentially lethal adverse reaction associated with "high dose" trimethoprim-sulfamethoxazole therapy, hyperkalemia, was described . Subsequent to the descriptions of hyperkalemia with "high dose" trimethoprim-sulfamethoxazole, a handful of cases noted the development of hyperkalemia with "standard dose" trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis . A surveillance study of patients treated with "standard dose" trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium associated with trimethoprim-sulfamethoxazole therapy . Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole-induced hyperkalemia . Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion . Hence, trimethoprim-sulfamethoxazole therapy was found to be associated with a new adverse reaction, hyperkalemia, nearly 25 years after its introduction into clinical practice as an antimicrobial agent. J Biomater Appl, 1995 Apr, 9(4), 363 - 71 Water and antimicrobial agent permation of PU and PHEMA membranes in relation to their surface and bulk properties; Pulat M et al.; Four types of polyurethane (PU) and two types of 2-polyhydroxyethylmethacrylate (PHEMA) membranes were prepared by convenient methods . Surface properties, water and antibacterial agent permeabilities of PU membranes were investigated . Water permeability values were determined in the region of 2000 g/m2.24 h . The membranes were found to have sufficient permeability toward antibacterial agents of 1% Silver Sulfadiazine and Bacitracin 10,000 UI-Neomycin sulphate 100 mg ointment. Transfusion, 1997 Sep, 37(9), 953 - 9 Effects of resuscitation fluids on nonadaptive immune responses; Sillett HK et al.; BACKGROUND: Colloidal plasma-expander fluids are commonly used as an alternative to blood components in the resuscitation of patients suffering from hemorrhagic shock and trauma . Of these, hydroxyethyl starch is also used as a cryopreservative, and these dual properties have been utilized in the development of a blood storage system that allows the direct transfusion of red cells . The prolonged intravascular persistence of hydroxyethyl starch suggests that phagocytic clearance may be impaired and that the presence of hydroxyethyl starch could exacerbate transfusion-induced immunomodulation . STUDY DESIGN AND METHODS: The effects of colloidal resuscitation fluids on the activation response and phagocytic function of polymorphonuclear cells (PMNs) and monocytes in normal peripheral blood were examined . To mimic the hemolysis associated with cryopreservation, the effects of 1- and 5- percent red cell lysate were studied . Flow cytometric assays were used in all cases . RESULTS: The percentage of phagocytic monocytes and PMNs was not altered; nor were the rates of phagocytosis impaired after incubation with resuscitation fluids . Upregulation of cell surface integrin during activation was similarly unmodified by the fluids . CONCLUSION: Hydroxyethyl starch and other resuscitation fluids do not affect some important antimicrobial functions of the nonadaptive arm of the immune response . This suggests that posttrauma or transfusion-induced immunomodulation is not exacerbated by inhibition at this level. J Am Acad Dermatol, 1997 Sep, 37(3 Pt 1), 365 - 81; quiz 382-4 Antimicrobial agents for the dermatologist . II . Macrolides, fluoroquinolones, rifamycins, tetracyclines, trimethoprim-sulfamethoxazole, and clindamycin; Epstein ME et al.; This article is the second of a two-part series reviewing antimicrobial agents that are used by the dermatologist . In part I we reviewed beta-lactam antibiotics and related compounds . In this section we again emphasize some newer agents (macrolides, fluoroquinolones) as well as some of the more commonly employed older agents (rifamycins, tetracyclines, trimethoprim-sulfamethoxazole, and clindamycin. AJR Am J Roentgenol, 1997 Oct, 169(4), 1039 - 43 Imaging of puerperal septic thrombophlebitis: prospective comparison of MR imaging, CT, and sonography; Twickler DM et al.; OBJECTIVE: Our objective was to compare prospectively the abilities of MR imaging, CT, and sonography to reveal puerperal septic thrombophlebitis in the pelvis . SUBJECTS AND METHODS: Seventy-six women with puerperal fever for 5 days refractory to antimicrobial therapy underwent MR imaging, CT, and sonography . We obtained unenhanced axial CT images followed by enhanced images after the administration of an oral contrast agent for which we followed a specific protocol . Axial T1- and T2-weighted spin-echo MR images with phase reconstruction and sagittal T1-weighted MR images were obtained . Real-time sonography was performed using Doppler color flow mapping and spectral waveform analysis . RESULTS: Of the 76 women, 64 completed studies with all three techniques . Ovarian vein thrombosis was diagnosed in 12 women . True-positive results were indicated when at least two of the three studies showed the presence of a clot; true-negative results were indicated when at least two of the three studies showed a lack of thrombosis . MR imaging and CT revealed both ovarian veins in all cases (64/64) . Sonography revealed 33 (52%) of 64 right ovarian veins and 15 (23%) of 64 left ovarian veins . MR imaging (sensitivity, 92%; specificity, 100%) and CT (sensitivity, 100%; specificity 99%) were comparable in all but two cases . In one such case, MR imaging showed patency, CT revealed findings interpreted as thrombosis, and sonography showed flow in the partially occluded vein . In the second such case, bilateral thrombosis was seen on CT, but interpretations based on sonography and MR imaging were left-sided thrombosis only . Sonography correctly revealed six of the 12 cases of ovarian vein thrombosis . CONCLUSION: CT and MR imaging proved to be the studies of choice in the evaluation of ovarian vein thrombosis. Semin Liver Dis, 1997, 17(3), 203 - 17 Spontaneous bacterial peritonitis; Guarner C et al.; Spontaneous bacterial peritonitis (SBP) is considered a bacterial infection of ascitic fluid without any intraabdominal, surgically treatable source of infection . Multiple variants of this infection with a different clinical setting and outcome have been described during the past decade . Bacterial translocation from the gut to mesenteric lymph nodes, depressed activity of the reticuloendothelial phagocytic system and decreased antimicrobial capacity of ascitic fluid seem to be the main steps in the pathogenesis of ascitic fluid infection . Diagnosis of ascitic fluid infection is based on clinical suspicion and analysis of ascitic fluid, especially white cell count and culture in blood culture bottles . A low threshold for performing an abdominal paracentesis is the key for an early diagnosis and treatment . A third-generation cephalosporin is the treatment of choice, achieving a cure rate higher than 80% . Nonazotemic patients with nonadvanced, uncomplicated SBP may be treated with oral ofloxacin . Prophylactic selective intestinal decontamination with oral norfloxacin is extremely useful in preventing SBP in patients that are at high risk for developing SBP, such as hospitalized cirrhotic patients with gastrointestinal hemorrhage or low ascitic fluid total protein . Primary or secondary long-term prophylaxis of SBP also decreases the incidence of SBP, but these patients should be carefully observed for detecting possible infections caused by quinolone-resistant organisms . Since long-term prognosis of SBP patients is poor, survivors should be considered for liver transplantation. J Biol Chem, 1997 Sep 26, 272(39), 24480 - 7 A novel family of small cysteine-rich antimicrobial peptides from seed of Impatiens balsamina is derived from a single precursor protein; Tailor RH et al.; Four closely related peptides were isolated from seed of Impatiens balsamina and were shown to be inhibitory to the growth of a range of fungi and bacteria, while not being cytotoxic to cultured human cells . The peptides, designated Ib-AMP1, Ib-AMP2, Ib-AMP3, and Ib-AMP4, are 20 amino acids long and are the smallest plant-derived antimicrobial peptides isolated to date . The Ib-AMPs (I . balsamina antimicrobial peptides) are highly basic and contain four cysteine residues which form two intramolecular disulfide bonds . Searches of protein data bases have failed to identify any proteins with significant homology to the peptides described here . Characterization of isolated cDNAs reveals that all four peptides are encoded within a single transcript . The predicted Ib-AMP precursor protein consists of a prepeptide followed by 6 mature peptide domains, each flanked by propeptide domains ranging from 16 to 35 amino acids in length . Such a primary structure with repeated alternating basic mature peptide domains and acidic propeptide domains has, to date, not been reported in plants. J Biol Chem, 1997 Sep 26, 272(39), 24224 - 33 Critical role of lipid composition in membrane permeabilization by rabbit neutrophil defensins; Hristova K et al.; We have examined the interactions of the six known rabbit neutrophil defensin antimicrobial peptides with large unilamellar vesicles (LUV) made from various lipid mixtures based on the lipid composition of Escherichia coli membranes . We find that the permeabilization of LUV made from E . coli whole lipid extracts differs dramatically from that of single-component LUV made from palmitoyl-oleoyl-phosphatidylglycerol (POPG) . Specifically, defensins NP-1, NP-2, NP-3A, NP-3B, and a natural mixture of the six defensins cause fast nonpreferential leakage of high molecular weight dextrans as well as the low molecular weight fluorophore/quencher pair 8-aminonapthalene-1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide (DPX) from E . coli whole lipid LUV through large, transient membrane lesions . In contrast, release of ANTS/DPX from POPG LUV induced by the defensins is slow and graded with preference for DPX (Hristova, K., Selsted, M . E., and White, S . H . (1996) Biochemistry 35, 11888-11894) . Interestingly, defensins NP-4 and NP-5 alone do not induce leakage from E . coli whole lipid LUV, whereas only NP-4 is ineffective with POPG LUV . Examination of the sequences of the six defensins suggests that the inactivity of NP-4 and NP-5 may be due to their lower net positive charge and/or the substitution of a Thr for the Arg or Lys that follows the fourth Cys residue . We found the presence of three major lipid components of E . coli whole lipid to be essential for creation of the large lesions observed in LUV: phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin . Cardiolipin appears to play a key role because no leakage can be induced when only phosphatidylglycerol and phosphatidylethanolamine are present . These results indicate the importance of membrane lipid composition in the permeabilization of cell membranes by rabbit defensins. FEBS Lett, 1997 Sep 1, 414(1), 27 - 32 Structure of genes for dermaseptins B, antimicrobial peptides from frog skin . Exon 1-encoded prepropeptide is conserved in genes for peptides of highly different structures and activities; Vouille V et al.; We cloned the genes of two members of the dermaseptin family, broad-spectrum antimicrobial peptides isolated from the skin of the arboreal frog Phyllomedusa bicolor . The dermaseptin gene Drg2 has a 2-exon coding structure interrupted by a small 137-bp intron, wherein exon 1 encoded a 22-residue hydrophobic signal peptide and the first three amino acids of the acidic propiece; exon 2 contained the 18 additional acidic residues of the propiece plus a typical prohormone processing signal Lys-Arg and a 32-residue dermaseptin progenitor sequence . The dermaseptin genes Drg2 and Drg1g2 have conserved sequences at both untranslated ends and in the first and second coding exons . In contrast, Drg1g2 comprises a third coding exon for a short version of the acidic propiece and a second dermaseptin progenitor sequence . Structural conservation between the two genes suggests that Drg1g2 arose recently from an ancestral Drg2-like gene through amplification of part of the second coding exon and 3'-untranslated region . Analysis of the cDNAs coding precursors for several frog skin peptides of highly different structures and activities demonstrates that the signal peptides and part of the acidic propieces are encoded by conserved nucleotides encompassed by the first coding exon of the dermaseptin genes . The organization of the genes that belong to this family, with the signal peptide and the progenitor sequence on separate exons, permits strikingly different peptides to be directed into the secretory pathway . The recruitment of such a homologous 'secretory' exon by otherwise non-homologous genes may have been an early event in the evolution of amphibian. Aliment Pharmacol Ther, 1997 Aug, 11(4), 811 - 9 The vascular and glandular organoprotective properties of metronidazole in the rodent stomach; Ko JK et al.; BACKGROUND: The gastroprotective action of metronidazole, an antimicrobial used in the therapy against Helicobacter pylori infection, is unclear . Thus, the aim of the present investigation was to study the organoprotective action and antiulcer mechanisms of this drug in rodents . METHODS AND RESULTS: Metronidazole (10 mg/kg), given either per os or intraperitoneally, 30 min beforehand, reduced ethanol (40%, 10 mL/kg, p.o.)-induced gastric mucosal damage in male rats . Likewise, oral administration of metronidazole dose-dependently attenuated the indomethacin (30 mg/kg, p.o.)-induced gastric lesion formation and the concurrent depletion of mucosal mucus . However, metronidazole did not affect the basal mucosal prostaglandin E2 content . In an ex vivo gastric chamber preparation, 40% ethanol incubation markedly lowered transmucosal potential difference and increased mucosal vascular permeability in rat stomachs . Incubation with all doses of metronidazole did not modulate gastric mucosal blood flow nor transmucosal potential difference, either before or after ethanol treatment . Nevertheless, the increase in vascular permeability by 40% ethanol was significantly alleviated by either p.o . or i.p . metronidazole pretreatment . In addition, exposure of the isolated rabbit gastric gland preparation to metronidazole (10(-5) and 10(-4) M) significantly attenuated the damaging action of 10% ethanol . CONCLUSION: It is concluded that metronidazole possesses a direct vascular and glandular organoprotective property in the rodent stomach . However, the anti-ulcer action does not appear to involve prostaglandins nor act through the improvement of gastric mucosal blood flow . Preservation of intramucosal mucus may partly contribute to the prevention of indomethacin-induced ulceration in rats. J Gastroenterol Hepatol, 1997 Aug, 12(8), 590 - 8 Review: eradication of Helicobacter pylori . Problems and recommendations; Huang JQ et al.; The successful isolation of Helicobacter pylori from stomachs of patients with gastritis and peptic ulcer has revolutionized our concepts of the pathogenesis of gastritis, peptic ulcer, gastric cancer and gastric B cell lymphoma . Eradication of H . pylori heals gastritis and H . pylori-related peptic ulcer . After a successful cure of H . pylori infection, virtually no recurrence of duodenal ulcer is seen . However, treatment to cure the infection has proved difficult . Numerous clinical trials have been attempted, but as yet no ideal regimen has been identified . Monotherapies have many drawbacks and should be avoided . Dual therapies combining a proton pump inhibitor (PPI) and an antimicrobial agent provide higher eradication rates than those involving two antimicrobial agents . Bismuth-based triple therapies are more effective than dual therapies in eradicating H . pylori infections . However, poor compliance and frequent adverse effects have made these combinations less favourable in clinical practice . Proton pump inhibitor-based triple therapies have shown more consistent and higher eradication rates with a short duration of treatment, good patient compliance, fewer side effects, prompt symptom relief and fast ulcer healing . Results from PPI-based quadruple therapies are promising; however, large multicentre clinical trials are needed to confirm the effect and the complex regimen again may compromise compliance outside of the clinical trial setting . Eradication of H . pylori infection is cost-effective in the long-term management of peptic ulcer disease compared with maintenance therapy with antisecretory drugs. Gen Pharmacol, 1996 Dec, 27(8), 1311 - 6 Gliotoxin and related epipolythiodioxopiperazines; Waring P et al.; 1 . Gliotoxin belongs to the epipolythiodioxopiperazine class of secondary metabolites . These compounds show a diverse range of biological activity including antimicrobial, antifungal and antiviral properties . They also display potent in vitro and in vivo immunomodulating activity . 2 . Their properties resulted in a number of early studies designed to exploit their possible chemotherapeutic value, although the general toxicity of most members of this class has precluded clinical use . 3 . Most recently, their selective immunosuppressive properties have led to the possibility of ex vivo treatment of tissue to selectively remove immune cells responsible for tissue rejection . The mode of action of gliotoxin appears to be via covalent interaction to proteins through mixed disulphide formation and gliotoxin has been shown to inhibit a number of thiol requiring enzymes . 4 . Gliotoxin is also a potent inducer of apoptotic cell death in a number of cells . Gliotoxin and other members of this class of toxins may be produced in vivo during the course of fungal infections and contribute to the aetiology of the disease. Antimicrob Agents Chemother, 1997 Sep, 41(9), 2064 - 6 In vitro susceptibilities to amphotericin B, itraconazole, and miconazole of filamentous fungi isolated from patients with cystic fibrosis; Hennequin C et al.; The antimicrobial activities of amphotericin B, itraconazole, and miconazole against 101 filamentous fungi from patients with cystic fibrosis were tested by a reproducible microdilution method . Itraconazole was very active against Aspergillus species and Scedosporium species (MIC at which 90% of the isolates were inhibited {MIC90}, 0.06 to 0.5 mg/liter), whereas amphotericin B was less effective (MIC90, 0.5 to 8 mg/liter). Antimicrob Agents Chemother, 1997 Sep, 41(9), 2037 - 40 Comparative susceptibilities of various animal-pathogenic mycoplasmas to fluoroquinolones; Hannan PC et al.; The in vitro activities of six antimicrobial agents were tested against 162 mycoplasma strains of eight species isolated from poultry and livestock at different geographic sites . Tiamulin was most active (MICs at which 90% of the isolates were inhibited {MIC90s}, 0.025 to 0.25 microg/ml); enrofloxacin and danofloxacin had near equivalent activities (MIC90s, 0.05 to 1.0 microg/ml), but were much more active than flumequine (MIC90s, 1 to 50 microg/ml) . The MIC90s of tylosin and oxytetracycline were 0.25 to > 100 microg/ml and 0.25 to 100 microg/ml, respectively. Antimicrob Agents Chemother, 1997 Sep, 41(9), 2029 - 32 Pharmacokinetic interaction between itraconazole and ceftriaxone in Yucatan miniature pigs; Cavalier A et al.; Since ceftriaxone and itraconazole are highly protein bound, are excreted via a biliary pathway, and are in vitro modulators of the efflux pump P glycoprotein, a pharmacokinetic interaction between these antimicrobial agents can be hypothesized . Therefore, we evaluated the pharmacokinetics of itraconazole and ceftriaxone alone and in combination in a chronic model of catheterized miniature pigs . Itraconazole does not influence ceftriaxone kinetic behavior . The mean areas under the concentration-time curve (AUC) were 152.2 microg x h/ml (standard deviation {SD}, 22.5) and 129.2 microg x h/ml (SD, 41.2) and the terminal half-lives were 1.1 h (SD, 0.3) and 0.9 h (SD, 0.2) when ceftriaxone was given alone and combined with itraconazole, respectively . Regarding itraconazole kinetics, ceftriaxone was shown to alter the disposition of the triazole . Contrary to what was expected, the AUC (from 0 to 8 h) decreased from 139.3 ng h/ml with itraconazole alone to 122.7 ng h/ml with itraconazole and ceftriaxone combined in pig 1, from 398.5 to 315.7 ng x h/ml in pig 2, and from 979.6 to 716.6 ng x h/ml in pig 3 (P of <0.01 by analysis of variance). Antimicrob Agents Chemother, 1997 Sep, 41(9), 1859 - 66 Characterization of anti-Toxoplasma activity of SDZ 215-918, a cyclosporin derivative lacking immunosuppressive and peptidyl-prolyl-isomerase-inhibiting activity: possible role of a P glycoprotein in Toxoplasma physiology; Silverman JA et al.; The immunosuppressive agent cyclosporin A (CsA) also possesses broad-spectrum antimicrobial activity . Previous investigators have reported that the obligate intracellular protozoan Toxoplasma gondii is sensitive to CsA . We have measured the sensitivity of Toxoplasma to 26 CsA derivatives that maintain only a subset of the parent compound's activity . We identified one compound, SDZ 215-918, that is a particularly potent inhibitor of parasite invasion and replication, with a 50% inhibitory concentration of 0.45 microg/ml, which is 10-fold lower than that of CsA . Kinetic studies demonstrate that activity has a rapid onset (half-life, < or = 20 min) and is initially reversible, although long-term exposure (> 24 h) to 5 microg/ml is lethal; in contrast, this concentration had no effect on host cell protein synthesis or cell division . SDZ 215-918 acts directly on the parasite, as demonstrated by inhibition of macromolecular synthesis in host-free extracellular parasites . Inhibition of invasion is due to a reduction in parasite motility . SDZ 215-918 does not bind to cyclophilins, the ubiquitous cyclosporin-binding proteins, but is a potent inhibitor of the mammalian P glycoprotein, a member of the ATP binding cassette transporter superfamily and the pump responsible for multidrug resistance in cancer and parasite cell lines . SDZ 215-918 blocks the efflux of rhodamine 123 from extracellular parasites, consistent with inhibition of a P glycoprotein-like pump . We suggest that a P glycoprotein or a related transporter plays a crucial role in the biology of Toxoplasma and may be a novel target for antiparasitic compounds . Preliminary studies with animals indicate that SDZ 215-918 inhibits parasite growth in vivo; its relationship to CsA may make it suitable for clinical development. Behring Inst Mitt, 1997 Mar, (99), 58 - 72 Of microbes, macrophages and nitric oxide; Bogdan C; One of the most prominent functions of nitric oxide (NO) is its participation in antimicrobial and antiviral defense . This paper summarizes the evidence for this function and compiles the infectious agents which are currently thought to be controlled via high out-put generation of NO as it occurs in activated macrophages and other cells expressing the inducible isoform of NO-synthase (iNOS, NOS-2) . Several less appreciated forms of interaction between NO and microbes will also be reviewed, including the role of NO as an immunosuppressive or tissue-destructive molecule during the course of infections, the regulation of microbial antioxidant systems by host cell-derived NO, the contribution of NO to parasite stage conversion, the induction or suppression of macrophage iNOS by microbial products, and the existence of endogenous NO synthase pathways in certain bacteria and parasites. J Antimicrob Chemother, 1997 Aug, 40(2), 235 - 40 Antibiotic MICs and short time-killing against Helicobacter pylori: therapeutic potential of kanamycin; Irie Y et al.; We compared the susceptibility of Helicobacter pylori to several antibiotics, expressed as MICs and as bactericidal effectiveness in short (3 h) time-killing studies . Of the antimicrobial agent tests, clarithromycin and amoxycillin had the lowest MIC50, 0.063 and 0.125 mg/L respectively, for 24 strains of H . pylori . Minocycline, levofloxacin and lansoprazole followed, with MIC50s of 0.5, 1, and 2 mg/L, respectively . Three-hour time-killing studies using a standard strain demonstrated a different pattern . At 4 x MIC, kanamycin, metronidazole and clarithromycin produced 4.4, 2.6 and 2.1 log decreases in viability, whereas the remaining seven antibiotics (including amoxycillin) were less bactericidal . Amoxycillin's lack of bactericidal activity during brief incubations was confirmed by examining several different clinically isolated H . pylori strains . Clarithromycin's effect, on the other hand, was strain- and concentration-dependent . Kanamycin was the most potent antibiotic in short time-killing studies, with concentrations of 1 x MIC and 4 x MIC producing a reduction of more than 2 and 4 log respectively in all ten strains . Our data suggest that the MIC of antimicrobial agents against H . pylori does not necessarily predict their activity in short time-killing studies . Furthermore, our short time-kill data suggest kanamycin as a potential therapeutic choice for H . pylori infection, even though this agent's MIC would suggest limited activity. J Antimicrob Chemother, 1997 Aug, 40(2), 221 - 6 Evaluation of bactericidal activity and lag of regrowth (postantibiotic effect) of five antiseptics on nine bacterial pathogens; Fuursted K et al.; Lag of regrowth or postantibiotic effect (PAE) relates to suppression of bacterial regrowth following short exposure to an antimicrobial agent . A delay in regrowth has not yet been studied for antiseptics to any great extent . We therefore examined and compared the lag of regrowth and the bactericidal activity of five antiseptics (chloramine T, chlorhexidine, povidone-iodine, phenoxyethanol and mandelic-lactic acid) against nine bacterial pathogens . Delay in regrowth was determined by application of two concentration-time schedules: a test concentration at the MBC with a contact time of 1 h or using fixed suboptimum concentration of each antiseptic for 2 min (optimum concentrations sterilized the culture, impeding assessment of regrowth) followed by a neutralization-dilution step and subsequent viable counting to follow bacterial regrowth . Each antiseptic displayed a different spectrum of activity in terms of MIC or MBC, bactericidal effect and lag of regrowth . The delay in regrowth varied from 0 to 5.7 h with only a few discrepancies between the two treatment schedules . Mandelic-lactic acid and chloramine T induced a significantly longer lag as compared with the other agents, whereas phenoxyethanol produced the shortest lag values . No significant correlation between the killing rate and the lag of regrowth could be demonstrated . Information on bactericidal activity, as well as lag of regrowth, could be a useful screening method for the efficacy of antiseptics . Moreover, data on lag of regrowth could contribute to the choice of antiseptic and guide in determining the optimum interval between repeated applications of antiseptics. J Antimicrob Chemother, 1997 Aug, 40(2), 189 - 94 A rapid drug susceptibility test for Mycobacterium tuberculosis using the hybridization protection assay; Koga H et al.; The conventional drug susceptibility tests for Mycobacterium tuberculosis are time-consuming and the results are available only after 2-4 weeks . We have recently reported a new, simple and fast M . tuberculosis drug susceptibility test, using the hybridization protection assay (HPA), that allows the detection of isoniazid- or rifampicin-resistant strains of M . tuberculosis within 24 h of incubation . In the present study, the scope of application of our new test was extended to another two first-line antimycobacterial agents, namely ethambutol and streptomycin, and a quinolone antimicrobial agent, ciprofloxacin . The ethambutol-, streptomycin- and ciprofloxacin-resistance characteristics of M . tuberculosis were also delineated within 72 h of incubation with or without the drug . The results of our novel and rapid drug susceptibility test for M . tuberculosis were not only comparable to those determined by the conventional method, but became available within a few days of incubation . Our results also suggest that the drug susceptibility test using HPA might also be useful for detecting organisms resistant to antimicrobial agents other than antimycobacterials. Br J Nutr, 1997 Aug, 78(2), 237 - 49 Influence of foliage from African multipurpose trees on activity of rumen protozoa and bacteria; Newbold CJ et al.; Samples and extracts of foliage from African multipurpose trees were screened for their effects on rumen protozoa and bacteria with a view to predicting their safety as feed supplements and for identifying species with potential antiprotozoal activity . The species tested were Acacia aneura, Chamaecytisus palmensis, Brachychiton populneum, Flindersia maculosa, Sesbania sesban, Leucaena leucocephala and Vernonia amyedalina . Antimicrobial effects were mild except for S . sesban, which was highly toxic to rumen protozoa in vitro, and A . aneura, which was toxic to rumen bacteria . The antiprotozoal factor in S . sesban was apparently associated with the fraction of the plant containing saponins . When S . sesban was fed to sheep, protozoal numbers fell by 60% after 4 d, but the population recovered after a further 10 d . In vitro experiments demonstrated that washed protozoa from later times were no more resistant to S . sesban than on initial exposure, suggesting that other micro-organisms, probably the bacteria, adapted to detoxify the antiprotozoal agent . Thus S . sesban may be useful in suppressing protozoa and thereby improving protein flow from the rumen, but only if the bacterial metabolism of the antiprotozoal factor can be avoided. World Health Organ Tech Rep Ser, 1997, 867, 1 - 74 The use of essential drugs . Seventh report of the WHO Expert Committee; The concentration-dependent membrane activity of cecropin A; Department of Pharmacology, Infectious Diseases Section, and Johnson Foundation for Molecular Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6084, USACecropin A is a naturally occurring, linear, cationic, 37-residue antimicrobial peptide . The precise mechanism by which it kills bacteria is not known, but its site of action is believed to be the cell membrane . To investigate the nature of its membrane activity, we examined the ability of cecropin A to alter membrane permeability in synthetic lipid vesicles and in Gram-negative bacteria . Cecropin A exerted distinctly different types of membrane activity depending on its concentration . In synthetic lipid vesicles, cecropin A dissipated transmembrane electrochemical ion gradients at relatively low concentrations, but much higher concentrations were required to release an encapsulated fluorescent probe . Cecropin A dissipated ion gradients whether or not the vesicle membranes contained anionic lipid, although the presence of anionic lipid dramatically increased peptide binding, and modestly increased the release of an encapsulated probe . Cholesterol did not prevent the dissipation of ion gradients by low concentrations of peptide, but it did inhibit release of the encapsulated probe by high concentrations of peptide . At the highest concentrations examined, cecropin A remained monomeric in solution, and did not aggregate, lyse, or otherwise alter vesicle size . In Gram-negative bacteria, cecropin A was potently bactericidal at concentrations which dissipated ion gradients in lipid vesicles, but much higher concentrations were required to cause the release of cytoplasmic contents . These findings point to the conclusion that cecropin A kills bacteria by dissipating transmembrane electrochemical ion gradients . They weigh against theories comparing the antimicrobial activity of cecropin A to the release of encapsulated probes from lipid vesicles, and against roles for cholesterol or anionic lipid headgroups in the selectivity of peptide action against bacteria. Clin Otolaryngol, 1997 Aug, 22(4), 358 - 61 Chronic suppurative otitis media and cholesteatoma . Vanishing diseases among Western populations? Alho OP, Jokinen K, Laitakari K, Palokangas J. A population-based survey of patients who had undergone surgery for chronic ear disease over the past 30 years in northern Finland revealed that the number of new surgical cases of both chronic suppurative otitis media and cholesteatoma has declined sharply after a peak in 1971-1974 and is now almost non-existent in contrast to the number of patients being operated on for chronic dry perforations, which has remained more or less the same . Most of the patients with chronic suppurative otitis media and cholesteatoma had had chronic ear trouble as early as the 1940s or 1950s . Moreover, if an active chronic otitis media developed in these cases, it started at a younger age than in cases with an onset after the 1950s . These facts may indicate that the decrease seen in this population is in close connection with the introduction of antimicrobials in the treatment of acute otitis media in the mid-1950s in the area. Inflamm Res, 1997 Aug, 46(8), 310 - 9 A matrix metalloproteinase inhibitor reduces bone-type collagen degradation fragments and specific collagenases in gingival crevicular fluid during adult periodontitis; Golub LM et al.; OBJECTIVE AND DESIGN: To determine whether an inhibitor of matrix metalloproteinases (MMPs), administered to human subjects in a dental school research clinic, can reduce bone-type collagen degradation fragments in oral inflammatory exudates containing excessive levels of collagenase . MATERIALS AND SUBJECTS: Gingival crevicular fluid (GCF) was collected from 18 subjects with adult periodontitis whose clinical findings (gingival inflammation, pocket depth, and bone loss on radiographs) predicted excessive MMP activity in their periodontal pockets . TREATMENT: One month before the baseline appointment, plaque and calculus were removed from the teeth by supra- and subgingival scaling . After collection of GCF from 8-12 pocket sites per subject and recording of clinical indices, 12 of the 18 subjects were treated with doxycycline at a low dosage (20 mg b.i.d.) known via an extensive literature to suppress mammalian MMP activity by a non-antimicrobial mechanism . The remaining 6 subjects were followed without drug treatment . METHODS: At the baseline, 1 and 2-month appointments, GCF samples were analyzed for ICTP . (carboxyterminal peptide, a pyridinoline-containing fragment of Type I collagen) and osteocalcin by radioimmunoassay, as well as collagenolytic enzyme activity and MMP species (Western blot) . Statistical analyses were determined by ANOVA . RESULTS: GCF ICTP and functional collagenase activity (but not osteocalcin levels) were significantly reduced (p < 0.05) in the doxycycline-treated subjects at both 1 and 2 month evaluations: there was no such change in the non-treated subjects . Western blots revealed that neutrophil-type collagenase (MMP-8) was the predominant MMP; MMP-13, which has been associated with pathologic collagenolysis including bone resorption, was detected in human GCF for the first time and was more substantially reduced than MMP-8 . CONCLUSION: This is the first demonstration in human subjects of the simultaneous reduction of excessive MMP activity with concomitant reduction in levels of collagen degradation fragments . The findings are potentially applicable to a wide variety of human diseases characterized by excessive collagenase activity. Bratisl Lek Listy, 1997 May, 98(5), 253 - 7 {Hematologic aspects of heart transplantation}; Goncalvesova E et al.; Heart transplantation is an accepted therapeutic method for end-stage heart failure . The aim of the presented paper is to provide a short review of haematologic problems of heart transplantation . Haemostatic disorders, cytopenias and lymphoproliferative diseases are the most frequent haematologic complications of this highly sophisticated procedure . Perioperative bleeding tendency is due to cardiopulmonary bypass, both qualitative and quantitative platelet disorders and hyperfibrinolysis are the main causes . Incidence of cytopenias (mono- and/or bi- and/or tricytopenia) reaches up to 70% . They are multifactorial as to etiology and coincidence with viral infection, antimicrobial and immunosuppressive therapy . Lymphoproliferative disease affects about 1.2% of patients during the first year after transplantation . Posttransplant lymphoproliferative diseases are highly variable as to manifestation and prognosis-ranging from indolent course to rapid, aggressive growth . Routine cytostatic therapy is generally ineffective . Crucial therapeutic measure is to turn off immunosuppressive therapy . (Tab . 3, Fig . 2, Ref . 41). J Biol Chem, 1997 Sep 19, 272(38), 23729 - 40 Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice; Garabedian EM et al.; The Paneth cell lineage is one of four epithelial lineages derived from the adult mouse small intestine's multipotent stem cell . Mature Paneth cells secrete antimicrobial peptides (cryptdins), growth factors, as well as two gene products, a secreted phospholipase A2 and matrilysin, that has been implicated as modifiers of adenoma formation in mice containing a mutation in the tumor suppressor Apc . Immature Paneth cells are located just above and below the cell layer, in intestinal crypts, that has been proposed to contain the multipotent stem cell . Paneth cells differentiate during a downward migration to the crypt base . The location and direction of Paneth cell migration, their high density and long residency time at the crypt base, and the nature of their secreted gene products, suggest that they may influence the structure and/or function of the stem cell niche . Paneth cell ablation can therefore be viewed as an experimental manipulation of the cellular microenvironment that purportedly contains the stem cell and its immediate descendants . Two types of ablation experiments were performed in transgenic mice . Nucleotides -6500 to +34 of the mouse cryptdin-2 gene (CR2) were used to express an attenuated diphtheria toxin A fragment . Light and electron microscopic immunohistochemical analyses of several pedigrees of postnatal day 28 to 180 animals established that ablation of Paneth cells is accompanied by an increase in the proportion of undifferentiated crypt base columnar cells . These cells normally co-exist with Paneth cells . The ablation does not produce a detectable effect on the proliferation or terminal differentiation programs of the other three lineages or on host-microbial interactions . The last conclusion is based on the ability of crypts to remain free of microbes detectable by Gram and Warthin-Starry stains and by retention of the normal crypt-villus distribution of components of the diffuse gut-associated lymphoid tissue . CR2-directed expression of simian virus 40 large T antigen also results in a loss of mature Paneth cells but produces a marked amplification of crypt cells having a morphology intermediate between Paneth and granule goblet cells . EM immunohistochemical analyses suggest that intermediate cells can differentiate to mature goblet cells but not to Paneth cells, as they migrate up the crypt-villus axis . Our findings suggest that (i) stemness in the crypt is not defined by instructive interactions involving the Paneth cell; (ii) expressing a Paneth cell fate may require that precursors migrate to the crypt base; (iii) antimicrobial factors produced by Paneth cells are not required to prevent colonization of small intestinal crypts; and (iv) this lineage does not function to maintain the asymmetric crypt-villus distribution of components of the diffuse gut-associated lymphoid tissue. Kekkaku, 1997 Aug, 72(8), 491 - 7 {In vivo activities of benzoxazinorifamycin KRM-1648, clarithromycin, and levofloxacin, or combination of KRM-1648 with diclofenac sodium against Mycobacterium avium infection induced in mice}; Akaki T et al.; We evaluated the in vivo therapeutic activities of benzoxazinorifamycin KRM-1648, clarithromycin (CAM) and levofloxacin (LVFX) against Mycobacterium avium infection induced in mice . Mice infected intravenously with M . avium (1.4 x 10(7)) were given KRM-1648 (20 mg/kg), CAM (10 mg/kg), or LVFX (5 mg/kg) alone, or combination of KRM-1648 with diclofenac sodium (1.25 mg/kg) by gavage, once daily, five times per week, from day 1 for up to 8 weeks . The bacterial loads in the lungs and spleens were determined by counting colony forming units of the organisms in the tissue homogenates of the visceral organs using 7H11 agar plates . Both KRM-1648 and CAM caused significant levels of bacteriological response in mice treated with these drugs, while LVFX exerted no appreciable therapeutic effect . The therapeutic efficacies of test antimicrobials were in the order, KRM-1648 > CAM > > LVFX . The combined use of diclofenac sodium with KRM-1648 did not affect the expression of therapeutic activity of KRM-1648 . This excludes the possibility that cyclooxygenase-dependent inflammatory reactions may be involved in the establishment of persistent bacterial growth of M . avium organisms at the sites of infection in mice . Furthermore, the present study showed that the parameters of in vitro antimicrobial activities of drugs such as MIC and MBC values are not useful in predicting their therapeutic outcome in M . avium-infected mice. Pharmazie, 1997 Aug, 52(8), 594 - 8 Synthesis and antimicrobial testing of thiazolinyl-, thiazolidinonyl-quinoxalines and 1,2,4-triazolo{4,3-a}quinoxalines; Habib NS et al.; Three novel series of quinoxaline derivatives namely 1-substituted amino-4-phenyl-1,2,4-triazolo{4,3-a}quinoxalines 3a-c, 2-{3,4,5-trisubstituted-2,3-dihydrothiazol-2-ylidene) hydrazono}-3-phenylquinoxalines 4a-j, 5a-e, and 2-{(3-substituted-4-oxothiazolidin-2-ylidene) hydrazone}-3-phenylquinoxalines 6a-e have been synthesized by cyclization of the key intermediates 2-substituted thiocarbamoylhydrazino-3-phenylquinoxalines 2a-e . The prepared compounds were tested in vitro for their antimicrobial activity. Pharmazie, 1997 Aug, 52(8), 585 - 9 Synthesis and antimicrobial activities of some new 2-substituted benzoxazole/benzothiazole derivatives; el-Shaaer HM et al.; In the search for new antimicrobial compounds, several new sulfur bearing heterobicyclic moieties (4-11) have been synthesized by acylation and alkylation of acetamide, thioacetamide and semicarbazide derivatives . The structure of the products was deduced from elemental analyses as well as spectral data (IR, 1H NMR and MS) . Significant antimicrobial activities were obtained for all new compounds especially against Fusarium oxysporum. Pharmazie, 1997 Aug, 52(8), 578 - 81 Synthesis and antimicrobial activity of N, N-dialkyl-2-substituted-5-diazo-imidazole-4-carboxamides; Varoli L et al.; A series of 2-substituted-5-diazoimidazole-4-carboxamides has been synthesized, and their antimicrobial activity has been tested in vitro . Some of the compounds show antifungal activity related to the presence of small groups on the 4-carbox-amido moiety, while the presence of substituents in position 2 was detrimental. J Clin Epidemiol, 1997 Aug, 50(8), 881 - 90 Antimicrobial treatment in acute maxillary sinusitis: a meta-analysis; de Bock GH et al.; OBJECTIVE: The aims of this study were to assess which antibiotic is most effective in the treatment of acute maxillary sinusitis in otherwise healthy adults and adolescents, and which has the fewest side effects . DESIGN: To assess the short-term effects of antimicrobial treatments, a meta-analysis was performed using Mantel-Haenszel procedures on 16 comparative, randomized studies with a total number of 3358 patients . No placebo-controlled studies were available . Antimicrobial treatments were categorized according to type, spectrum, beta-lactamase inhibition, and bactericidal effect . Outcomes were clinical cure, clinical success, and adverse events . RESULTS: When studies were analyzed separately, we found significant differences between cefpodoxim and cefaclor in relation to clinical cure, and between loracarbef and doxycycline in relation to clinical success . When data was pooled, sulphonamides were significantly more effective than penicillins in relation to clinical cure, and macrolids were more effective than penicillins in relation to clinical success, whereas cephalosporins caused significantly less adverse events than penicillins . When studies were stratified (standard classic meta-analysis), antibiotics with beta-lactamase inhibition offered significantly more clinical cures than antibiotics without beta-lactamase inhibition . However, this significant effect was only due to one study from Southern Europe, published before 1991 . CONCLUSION: Differences in outcome between antimicrobial treatments of acute sinusitis in otherwise healthy adults and adolescents appear to be small . Therefore, the cheapest antimicrobial treatment can be selected. Arch Med Res, 1997 Autumn, 28(3), 429 - 30 Achilles tendon rupture and fluoroquinolones use: report of two cases; de la Garza Estrada VA et al.; A report of two cases of fluoroquinolones-associated Achilles tendon rupture in two previously-healthy males is presented . Neither of them had any other predisposing condition for this complication . Both were used to strenuous physical activity . No other cause could be found in relation to their traumatic experience . Emphasis is placed on the necessity of identifying this potential and probably unusual complication of these widely-used antimicrobials. J S Afr Vet Assoc, 1997 Jun, 68(2), 40 - 4 Perceived causes, diagnosis and treatment of babesiosis and anaplasmosis in cattle by livestock farmers in communal areas of the central Eastern Cape Province, South Africa; Masika PJ et al.; Perceived causes, diagnosis and treatment of redwater (babesiosis) and gallsickness (anaplasmosis) in cattle by livestock farmers in communal areas of the central Eastern Cape Province were investigated by means of participatory methods, semi-structured interviews and a questionnaire survey . Most livestock owners relate the causes of these diseases to excessive grazing of lush green grass, which is thought to bring about an accumulation of bile in the body . The majority of livestock owners diagnose gallsickness and redwater on the basis of presenting signs and post mortem findings . Eighty nine percent of a total of 343 livestock owners participating in the study claimed to administer herbal remedies to treat the 2 tick-borne diseases; 75% of these combine herbal remedies with conventional medicines and 25% use herbal remedies only . Application of herbal remedies was reportedly aimed mainly at the removal of excess bile . However, some plant species used to prepare herbal remedies are reported to possess activities ranging from anti-inflammatory, analgesic, antimicrobial, anti-pyretic and purgative, and may be effective in the treatment of gallsickness and redwater . A lack of understanding of the causes and transmission of gallsickness and redwater, leading to ill-directed treatment, and widespread deviation from the directions of use when administering conventional medicines, were identified as problems that could be addressed by farmer training and the supply of appropriate information. Surg Neurol, 1997 Sep, 48(3), 284 - 7 Brain abscess in renal transplant recipients: report of three cases; Gupta SK et al.; BACKGROUND: Neurologic complications occur in about 30% of renal transplant patients, infections being the most common . We encountered three such patients and present our experience in the management of such cases . CLINICAL MATERIAL: Three cases of brain abscess in renal transplant recipients are reported . These patients presented from 9-60 months after the transplant . One patient had a pyogenic abscess; in the second the organism identified was Nocardia asteroides; in the third, a fungal infection was responsible . In two patients excision of the abscess was done, while in one repeated aspirations with intracavitary antibiotics were used . All received systemic antimicrobial therapy . CONCLUSIONS: Central nervous system (CNS) complications, specifically infections, are quite common in renal transplant recipients, but reports of brain abscesses in these patients are very rare . The treatment options for such patients are discussed. Compr Ther, 1997 Sep, 23(9), 575 - 82 Antibiotics update; Southern PM Jr; Some of the newer antimicrobial agents that have either appeared on the market, will probably soon appear, or that are being used in other parts of the world and are therefore worthy of our interest will be reviewed . The agents reviewed fall into the following four classes: antibacterial, antifungal, antiparasitic, and antiviral. Can Vet J, 1997 Sep, 38(9), 555 - 60 Evaluation of florfenicol for the treatment of undifferentiated fever in feedlot calves in western Canada; Booker CW et al.; A study was conducted in western Canada to evaluate the efficacy of florfenicol for the treatment of undifferentiated fever (UF) in feedlot calves . One hundred and twenty-five recently weaned, auction market derived, crossbred, beef steer calves suffering from UF were allocated to 1 of 2 experimental groups as follows: florfenicol, which was intramuscular florfenicol administered at the rate of 20 mg/kg body weight at the time of allocation (day 0) and again 48 h later; or control, which was intramuscular saline administered at the same volume as florfenicol at the time of allocation and again 48 h later . Eighty-four calves were allocated to the florfenicol group and 41 calves were allocated to the control group . Outcome measures describing animal health, body weight, and rectal temperature parameters were used to determine the efficacy of florfenicol for the treatment of UF . The 1st relapse of UF, 2nd relapse of UF, overall mortality, bovine respiratory disease mortality, and haemophilosis mortality rates were significantly (P < 0.05) lower in the florfenicol group than in the control group . Animals in the florfenicol group were significantly (P < 0.05) heavier at day 15 and day 45 than animals in the control group . The rectal temperature on days 1, 2, 3, and 4 of animals in the florfenicol group was significantly (P < 0.05) lower than in the control group . In addition, the change in rectal temperature from day 0 to day 4 was significantly (P < 0.05) different between the experimental groups . The results of this study demonstrate that florfenicol is an efficacious antimicrobial for the treatment of UF. Mol Mar Biol Biotechnol, 1997 Sep, 6(3), 248 - 59 Recombinant expression of the antimicrobial peptide polyphemusin and its activity against the protozoan oyster pathogen Perkinsus marinus; Pierce JC et al.; Polyphemusin is a broad-spectrum antimicrobial peptide isolated from hemocytes of the North American horseshoe crab Limulus polyphemus . To date the polyphemusin used for scientific analyses has been purified from the natural materials or obtained by chemical synthesis . We report here the recombinant expression in Escherichia coli, and subsequent purification, of a polyphemusin analogue (rLim1) . To prevent toxicity of the antimicrobial peptide in the highly susceptible E . coli host, we used a carboxy-terminal fusion protein cloning strategy provided by a maltose-binding protein (MBP) gene fusion system (New England Biolabs) . Antimicrobial activity of recombinant polyphemusin was similar to that seen with amidated native polyphemusin peptide . When rLim1 was tested for antibiotic activity against the apicomplexan protozoan oyster pathogen Perkinsus marinus, complete inhibition was observed at 12 micrograms/ml, and partial inhibition at 8 micrograms/ml. J Immunol, 1997 Sep 1, 159(5), 2468 - 75 Bridging of neutrophils to target cells by opsonized zymosan enhances the cytotoxicity of neutrophil-produced H2O2; Jiang X et al.; Hydrogen peroxide (H2O2) is a well-established cytotoxic agent released by activated neutrophils into the extracellular environment . However, a maximum of only 5 microM H2O2 was detected in the medium when 10(6) neutrophils/ml were activated with opsonized zymosan (OZ), more than 50-fold lower than the concentration of exogenous H2O2 required to produce equivalent killing of a cell line . In addition PMA-activated neutrophils were noncytotoxic, despite the capacity of PMA to generate two- to fourfold as much H2O2 for five times longer . The basis for this discrepancy was explored . NaN3 increased cytotoxicity to >90% only when neutrophils were activated with OZ due in part to inhibition of myeloperoxidase-mediated hydrolysis of H2O2, while catalase completely prevented cytotoxicity of OZ-activated neutrophils . These results indicate that H2O2 was solely responsible for the observed cytotoxicity . OZ-mediated cytotoxicity was prevented by intermittent agitation of the cultures or by the addition of soluble complement receptor type 1, suggesting that a physical association between neutrophils and target cells mediated by OZ was required to generate a cytotoxic environment . Significant numbers of neutrophil-target cell aggregates were observed by microscopic examination only under low hydrodynamic shear conditions . We conclude that the cytotoxic potency of H2O2 produced by neutrophils activated with OZ was due to a localized high concentration of H2O2 to which the target cells were exposed as a result of their labile adherence to OZ . This phenomenon may reflect a mechanism that neutrophils have acquired for maximizing the antimicrobial power of extracellular oxidants toward microbes that escape phagocytotosis. Acta Chem Scand, 1997 Sep, 51(9), 896 - 903 Acid-base behavior of quinolones in aqueous acetonitrile mixtures; Sanz-Nebot V et al.; Quinolones are a family of antibacterial agents that are used extensively in both human and veterinary clinics . Their antibacterial activity is pH-dependent, and therefore an examination of protonation equilibria in quinolone solutions is essential . pK-Values of nine quinolone antibacterials in acetonitrile-water mixtures containing 0, 10, 30, 40, 50 and 70%(w/w) acetonitrile were determined according to the rules and procedures endorsed by IUPAC . In order to obtain quinolone pK-values in any acetonitrile-water mixture up to 70%(w/w) acetonitrile, relationships between pK-values and different bulk properties (such as dielectric constant) and some microscopic parameters (such as solvatochromic parameters alpha, beta and pi*) were established . These relationships and the application of the preferential solvation theory of electrolytes in acetonitrile-water mixtures permit the interpretation of acid-base behaviour of these important antimicrobials in the widely used acetonitrile-water media. J Am Vet Med Assoc, 1997 Aug 15, 211(4), 419 - 27 Economic evaluation of risks to producers who use milk residue testing programs; Slenning BD et al.; OBJECTIVE: To evaluate the decision to test for milk antimicrobial residues in milk from dairy cows treated with procaine penicillin G (PPG) . DESIGN: Economic-decision analysis after stochastic simulation . SAMPLE POPULATION: 1,000 computer-simulated cows/model . PROCEDURE: Meta-analysis of the Food Animal Residue Avoidance Databank was used to generate PPG disappearance curves for cows given single PPG treatments, IM, of 6,600 U/kg (3,000 U/lb) of body weight or 26,400 U/kg (12,000 U/lb), and multiple treatments at 26,400 U/kg (12,000 U/lb), IM . These curves were entered into 1,000-replication stochastic pharmacokinetic models, generating population-level milk PPG profiles for each treatment group for each day after treatment, which were subjected to economic-decision analyses of feasibility of residue testing . The model was evaluated for changes in herd size, proportion of herd available for testing, milk production, test price, test sensitivity/specificity, and withdrawal periods . RESULTS: For both single-treatment groups, a 2-day withdrawal period avoided violative residues . However, nearly two thirds of the cows risked false identification for violative residues . For the multiple-treated group, nearly 40% had violative residues after a 5-day withdrawal period, and an additional 10 to 15% risked false identification for violative residues . Economic analysis yielded a decision against testing; mean cost was $2 (ie, 5% more than the mean cost of not testing) . CLINICAL IMPLICATIONS: Complex dynamics of current milk residue tests discourage practitioners from recommending procedures to clients . In general, increases in herd size, milk production, proportion of a herd available for testing, or milk price will increase the value of testing . Increasing test sensitivity decreases its desirability to producers. Ann Intern Med, 1997 Aug 15, 127(4), 267 - 74 Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections . A randomized, double-blind trial . The Texas Medical Center Catheter Study Group; Raad I et al.; BACKGROUND: Central venous catheters are a principal source of nosocomial bloodstream infections, which are difficult to control . OBJECTIVE: To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections . DESIGN: Multicenter, randomized clinical trial . SETTING: Five university-based medical centers . PATIENTS: 281 hospitalized patients who required 298 triple-lumen, polyurethane venous catheters . INTERVENTION: 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin . Untreated, uncoated catheters (n = 151) were used as controls . MEASUREMENTS: Quantitative catheter cultures, blood cultures, and molecular typing of organisms to determine catheter-related colonization and bloodstream infections . RESULTS: The group with coated catheters and the group with uncoated catheters were similar with respect to age, sex, underlying diseases, degree of immunosuppression, therapeutic interventions, and risk factors for catheter infections . Colonization occurred in 36 (26%) uncoated catheters and 11 (8%) coated catheters (P < 0.001) . Catheter-related bloodstream infection developed in 7 patients (5%) with uncoated catheters and no patients with coated catheters (P < 0.01) . Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization (P < 0.05) . No adverse effects related to the coated catheters or antimicrobial resistance were seen . An estimate showed that the use of coated catheters could save costs . CONCLUSIONS: Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections . The use of these catheters may save costs. Front Biosci, 1997 Aug 15, 2, e63 - 71 Oral antibiotics in the nineties: new drugs and new challenges in primary care; Bonomo RA et al.; The primary care physician is faced with a bewildering array of new oral antimicrobials to treat common infections . These agents promise to be extremely effective as replacements for time-honored drugs, as prophylaxis, and for the treatment of infections previously requiring prolonged intravenous therapy . The overuse of the newer macrolides, quinolones, and beta-lactam beta-lactamase inhibitors may prove to be ecologically and economically costly . It is feared that the selective pressure from these broad spectrum agents may burden society with an even greater problem of multiply resistant community-acquired pathogens . The specific therapeutic and economic advantages and disadvantages of each class should be considered and the decision to employ these agents should be highly individualized. Biochemistry, 1997 Aug 12, 36(32), 9799 - 806 Membrane permeabilization mechanisms of a cyclic antimicrobial peptide, tachyplesin I, and its linear analog; Matsuzaki K et al.; Tachyplesin I (T-SS), an antimicrobial peptide from Tachypleus tridentatus, has a cyclic antiparallel beta-sheet structure maintained by two disulfide bridges . The peptide effectively permeabilizes both bacterial and artificial lipid membranes . T-Acm, a linear analog peptide with the four SH groups protected by acetamidomethyl groups, exhibits a much weaker membrane-permeabilizing activity in spite of a greater disruption of the lipid organization {Matsuzaki, K., Nakayama, M., Fukui, M., Otaka, A., Funakoshi, S., Fujii, N., Bessho, K., & Miyajima, K . (1993) Biochemistry 32, 11704-11710} . To clarify the efficient permeabilization mechanism of T-SS, we studied the interactions of both peptides with liposomes and planar lipid bilayers . The cyclic peptide capable of spanning the bilayer (ca . 3 nm length) was found to form an anion-selective pore and translocate across the bilayer coupled with the pore formation . A cis-negative transmembrane potential facilitated the pore formation compared with the cis-positive potential . In contrast, the linear peptide failed to translocate . Instead, it impaired the membrane barrier by disrupting the lipid organization with morphological changes in the vesicles. FEBS Lett, 1997 Aug 11, 413(1), 45 - 9 The mouse genome encodes a single homolog of the antimicrobial peptide human beta-defensin 1; Huttner KM et al.; The cysteine-rich beta-defensin peptides are broad-spectrum bactericidal agents expressed in epithelial and myeloid tissues . The human beta-defensin-1 (hBD-1) gene maps adjacent to the human alpha-defensin cluster and is expressed in the respiratory, gastrointestinal and genitourinary tracts . Here, we characterize a mouse beta-defensin gene (mBD-1) which is: (1) closely related to hBD-1 both in sequence and gene organization; (2) expressed at high levels in the mouse kidney and at lower levels in brain, heart, lung, uterus, spleen, skeletal muscle, stomach, and small intestine; and (3) maps to mouse chromosome 8 at or near the location of the mouse alpha-defensin genes . These data indicate that mBD-1 is a close homolog of hBD-1, and suggest that analysis of its role in mouse host defense may provide significant insights into human epithelial innate immunity. Wien Klin Wochenschr, 1997 Aug 8, 109(14-15), 594 - 9 New developments in diagnostic and treatment of mycoplasma infections in humans; Bebear C et al.; Several methods can be used for the diagnosis of mycoplasmal human infections . Culture is not satisfactory for fastidious species, while serological procedures allow only a retrospective diagnosis . Recently, rapid methods have become available . Antigenic detection proposed for Mycoplasma pneumoniae lacks sensitivity . Hybridization based techniques include DNA probes and mainly DNA amplification . The main usefulness of the polymerase chain reaction (PCR) is the detection of fastidious organisms such as M . pneumoniae, M . genitalium, M . fermentans, M . penetrans, but PCR can also be used for characterization of the strains for epidemiological purposes, or for detection of antimicrobial resistance genes . The major advantage of PCR for detection is its very high sensitivity . However, until now, the major drawback of this technique has been the lack of commercial kits . When available, they should provide better standardization of the technique and, if available at a reasonable cost, become the major technique for the diagnosis of mycoplasma infections . The antibiotics used for the treatment of mycoplasmal infections belong to tetracyclines, macrolides-lincosamides and fluoroquinolones . These products are highly active in vitro against mycoplasmas . However, some of them have a differential activity according to the species, and acquired resistance has been reported, mainly in genital mycoplasmas . Most of mycoplasmal infections are cured by adapted antibiotics, but they may be difficult to cure in immunosuppressed patients. Health Policy Plan, 1997 Sep, 12(3), 234 - 9 Consequences of adult HIV infection for outpatient morbidity and treatment costs: a prospective study in a factory clinic in Tanzania; Kikumbih SN et al.; Most studies of the medical costs of HIV infection focus on the terminal stage of this chronic illness when the patients have developed AIDS or severe HIV disease and in-patient care dominates . Data are also needed on the medical costs during the prolonged phase of HIV infection preceding severe terminal illness and the effects it may have on the provision of outpatient care . The study population was derived from a cohort study of factory workers and their spouses in Tanzania . Morbidity and outpatient health services utilization are estimated for 1832 adults who on average had been enrolled for two years and utilized the study clinic . Among those who had been enrolled at least 2 years, 50 cases (HIV+ since enrollment) and 150 control (HIV- until last visit) were selected, matched by age, sex and income level to estimate expenditure on drugs by HIV status . There was an increase in morbidity during HIV infection: the incidence of clinical diagnoses was 30% higher among HIV-positive than among HIV-negative adults (p < 0.001) . HIV-infected adults also made more frequent use of the outpatient services (23% higher utilization) . Estimates of essential drug costs among the subsample showed a 15% increase for HIV infected adults compared to HIV-negative adults, caused by higher use of antibiotics and other antimicrobial drugs . The overall increase in morbidity, outpatient care services utilization and essential drug use due to HIV infection was limited, as HIV prevalence in this adult population was 11% . For example, the net proportion of all illness episodes attributable to HIV infection was 3.2% . Possible biases are discussed and suggest that our findings are a minimum estimate of the effect of adult HIV infection on outpatient care costs . There is a need for more studies in different settings to assess the impact of HIV infection on outpatient care in developing countriesPIP: Morbidity and outpatient health services utilization are estimated for 1832 adult factory workers and their spouses in Tanzania who had on average been enrolled at the study clinic for at least 2 years and used the clinic . A subsample of 50 cases HIV-positive since enrollment and 150 controls HIV-negative up to the most recent visit was selected, matched by age, sex, and income level to estimate expenditure on drugs by HIV status . An increase in morbidity was observed during HIV infection, with the incidence of clinical diagnoses 30% higher among HIV-positive than among HIV-negative adults . HIV-infected adults also used outpatient services 23% more often than did controls . Estimates of essential drug costs among the subsample showed a 15% increase for HIV-infected adults compared to HIV-negative adults . However, the net proportion of all illness episodes attributable to HIV infection was only 3.2% . These findings likely represent a minimum estimate of the effect of adult HIV infection on outpatient care costs . Proc Natl Acad Sci U S A, 1997 Aug 5, 94(16), 8801 - 6 A natural polymorphism in beta-lactamase is a global suppressor; Huang W et al.; A M182T substitution was discovered as a second-site suppressor of a missense mutation in TEM-1 beta-lactamase . The combination of the M182T substitution with other substitutions in the enzyme indicates the M182T substitution is a global suppressor of missense mutations in beta-lactamase . The M182T substitution also is found in natural variants of TEM-1 beta-lactamase with altered substrate specificity that have evolved in response to antibiotic therapy . The M182T substitution may have been selected in natural isolates as a suppressor of folding or stability defects resulting from mutations associated with drug resistance . This pathway of protein evolution may occur in other targets of antimicrobial drugs such as the HIV protease. Proc Natl Acad Sci U S A, 1997 Aug 5, 94(16), 8585 - 9 Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3; Lencer WI et al.; Salt and water secretion from intestinal epithelia requires enhancement of anion permeability across the apical membrane of Cl- secreting cells lining the crypt, the secretory gland of the intestine . Paneth cells located at the base of the small intestinal crypt release enteric defensins (cryptdins) apically into the lumen . Because cryptdins are homologs of molecules known to form anion conductive pores in phospholipid bilayers, we tested whether these endogenous antimicrobial peptides could act as soluble inducers of channel-like activity when applied to apical membranes of intestinal Cl- secreting epithelial cells in culture . Of the six peptides tested, cryptdins 2 and 3 stimulated Cl- secretion from polarized monolayers of human intestinal T84 cells . The response was reversible and dose dependent . In contrast, cryptdins 1, 4, 5, and 6 lacked this activity, demonstrating that Paneth cell defensins with very similar primary structures may exhibit a high degree of specificity in their capacity to elicit Cl- secretion . The secretory response was not inhibited by pretreatment with 8-phenyltheophyline (1 microM), or dependent on a concomitant rise in intracellular cAMP or cGMP, indicating that the apically located adenosine and guanylin receptors were not involved . On the other hand, cryptdin 3 elicited a secretory response that correlated with the establishment of an apically located anion conductive channel permeable to carboxyfluorescein . Thus cryptdins 2 and 3 can selectively permeabilize the apical cell membrane of epithelial cells in culture to elicit a physiologic Cl- secretory response . These data define the capability of cryptdins 2 and 3 to function as novel intestinal secretagogues, and suggest a previously undescribed mechanism of paracrine signaling that in vivo may involve the reversible formation of ion conductive channels by peptides released into the crypt microenvironment. Biochemistry, 1997 Aug 5, 36(31), 9540 - 9 Self-assembly of designed antimicrobial peptides in solution and micelles; Javadpour MM et al.; Hydrophobic interactions are responsible for stabilizing leucine zippers in peptides containing heptad repeats . The effects of substituting leucine by phenylalanine and alanine by glycine on the self-assembly of coiled-coils were examined in minimalist antimicrobial peptides designed to form amphipathic alpha-helices . The secondary structure of these peptides was monitored in solution and in diphosphocholine (DPC) micelles using circular dichroism spectroscopy . The leucine peptides (KLAKLAK)3 and (KLAKKLA)n (n = 3, 4) become alpha-helical with increasing concentrations of salt, peptide, and DPC . The aggregation state and equilibrium constant for self-association of the peptides were measured by sedimentation equilibrium . The glycine peptide (KLGKKLG)3 does not self-associate . The leucine peptides and phenylalanine peptides (KFAKFAK)3 and (KFAKKFA)n (n = 3, 4) are in a monomer-tetramer equilibrium in solution, with the phenylalanine zippers being 2-4 kcal/mol less stable than the equivalent leucine zippers . Thermodynamic parameters for the association reaction were calculated from the temperature dependence of the association constants . Leucine zipper formation has DeltaCp = 0, whereas phenylalanine zipper formation has a small negative DeltaCp, presumably due to the removal of the larger surface area of phenylalanine from water . Self-association of the peptides is coupled to formation of a hydrophobic core as detected using 1-anilino-naphthalene-8-sulfonate fluorescence . Carboxyfluorescein-labeled peptides were used to determine the aggregation state of (KLAKKLA)3 and (KLGKKLG)3 in DPC micelles . (KLAKKLA)3 forms dimers, and (KLGKKLG)3 is a monomer . Aggregation appears to correlate with the cytotoxicity of these peptides. Curr Opin Immunol, 1997 Aug, 9(4), 484 - 90 The T cell response against fungal infections; Romani L; A variety of pathological conditions, including impaired immune function, is believed to underlie host susceptibility to fungal infections and to determine both the severity and the characteristic of the associated pathology . Although the redundancy and the interdependence of antifungal responses may not favor the proper dissection and appreciation of individual effector mechanisms, the T helper type 1/type 2 paradigm of acquired immunity to fungi is proving essential for a better understanding of the host response from a regulatory perspective . The recent understanding of the importance of the different T helper cell subsets in fungal infections and the increasing appreciation of the reciprocal regulation between the innate, humoral, and adaptive immune systems in the development of optimal antimicrobial immunity have offered us new clues which may lead to an understanding of T cell dependent immunity to fungi. J Periodontol, 1997 Aug, 68(8), 713 - 9 Treatment of periodontal disease in diabetics reduces glycated hemoglobin; Grossi SG et al.; Periodontal disease is a common infection-induced inflammatory disease among individuals suffering from diabetes mellitus . The purpose of this study was to assess the effects of treatment of periodontal disease on the level of metabolic control of diabetes . A total of 113 Native Americans (81 females and 32 males) suffering from periodontal disease and non-insulin dependent diabetes mellitus (NIDDM) were randomized into 5 treatment groups . Periodontal treatment included ultrasonic scaling and curettage combined with one of the following antimicrobial regimens: 1) topical water and systemic doxycycline, 100 mg for 2 weeks; 2) topical 0.12% chlorhexidine (CHX) and systemic doxycycline, 100 mg for 2 weeks; 3) topical povidone-iodine and systemic doxycycline, 100 mg for 2 weeks; 4) topical 0.12% CHX and placebo; and 5) topical water and placebo (control group) . Assessments were performed prior to and at 3 and 6 months after treatment and included probing depth (PD), clinical attachment level (CAL), detection of Porphyromonas gingivalis in subgingival plaque and determination of serum glucose and glycated hemoglobin (HbA1c) . After treatment all study groups showed clinical and microbial improvement . The doxycycline-treated groups showed the greatest reduction in probing depth and subgingival Porphyromonas gingivalis compared to the control group . In addition, all 3 groups receiving systemic doxycycline showed, at 3 months, significant reductions (P < or = 0.04) in mean HbA1c reaching nearly 10% from the pretreatment value . Effective treatment of periodontal infection and reduction of periodontal inflammation is associated with a reduction in level of glycated hemoglobin . Control of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients. Immunopharmacology, 1997 Aug, 37(1), 35 - 41 Nitric oxide and antimicrobial activity of reactive oxygen intermediates; Marcinkiewicz J; It is well documented that nitric oxide contributes to the bactericidal activities of phagocytes . Murine activated neutrophils and macrophages produce both reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) . However, only neutrophils in the presence of myeloperoxidase, produce an antimicrobial agent, hypochlorous acid (HOCl) . Complex interactions of RNI (nitric oxide) with other antimicrobial agents of phagocytes are likely to exist, but these have not been clearly demonstrated . In this study, we treated bacteria (Escherichia coli) with the NO donor, S-nitrosoglutathione (GSNO) and hydrogen peroxide (H2O2) or HOCl . We found that exposure to H2O2 of the bacteria tested resulted in minimal toxicity . However the killing activities of H2O2 were potentiated by GSNO . On the contrary, the NO-donor completely abolished the bactericidal activity of HOCl . Our results indicate that NO-donating drugs in non toxic concentrations used for experimental purposes may strongly affect the cytotoxic activity of neutrophils and macrophages . We suggest that the similar interactions may exist at sites of inflammation. Zen