J Pediatr Surg, 1998 May, 33(5), 756 - 8 Junctional epidermolysis bullosa: diagnosis and management of a patient with the Herlitz variant; Goldstein AM et al.; A case of Herlitz-type epidermolysis bullosa (EB) is reported . The baby was born after a normal, full-term pregnancy with blisters on his extremities . Over the next several months, progressive skin sloughing involving 95% of his body surface area developed, including gastrointestinal, laryngeal, tracheobronchial, and corneal involvement . The diagnosis of junctional EB, Herlitz type, was made using clinical, electron microscopic, and immunohistochemical criteria . Despite meticulous wound care, aggressive nutritional support, and continuous antimicrobial therapy, the baby died at 9 months of age . This report discusses the presentation, complications, and management of this unusual and tragic disease. Kidney Int, 1998 Jun, 53(6), 1792 - 4 Treatment of infected tunneled venous access hemodialysis catheters with guidewire exchange; Robinson D et al.; Cuffed venous access catheters have become commonplace for hemodialysis access . The major complications of these catheters are catheter thrombosis, catheter fibrin sheathing and infection . When catheter associated bacteremia occurs treatment with antimicrobial therapy alone has been unsuccessful in providing acceptable cure rates . Failed antimicrobial therapy exposes the patient to the risks of prolonged bacteremia, while the alternative, catheter replacement at a new site can lead to central venous stenosis and compromise future long-term upper extremity access . Catheter guidewire exchange when the tunnel tract is clinically not infected theoretically allows the preservation of future access sites and yields a higher treatment success rate while avoiding temporary non-cuffed access placement . We report a series of 23 cases of hemodialysis patients with tunneled cuffed catheters and bacteremia related to the catheter who were treated with the exchange of a new catheter over a guidewire combined with three weeks of systemic antibiotics . Patients eligible for the study required no evidence of tunnel tract infection and defervescence within 48 hours of antimicrobial therapy . Technique failure was defined as repeat infection from any organism within 90 days of catheter exchange . Four patients (18%) redeveloped bacteremia within 90 days of the exchange . The bacteremias developed at 4, 19, 63 and at 74 days days after the exchange . Guidewire exchange in combination with intravenous antibiotics in cases of catheter related bacteremia has an acceptable rate of treatment success and is a viable treatment option in a carefully selected patient population. Biochim Biophys Acta, 1998 Apr 24, 1402(3), 250 - 60 A chemically modified tetracycline inhibits streptozotocin-induced diabetic depression of skin collagen synthesis and steady-state type I procollagen mRNA; Craig RG et al.; Wasting of connective tissues including skin, bone, and cartilage have been closely associated with elevated matrix metalloproteinase (MMP) activity and depressed collagen content in the streptozotocin (STZ)-induced diabetic rat, while tetracyclines have been reported to normalize total body weight, skin hydroxyproline and collagen content in this model, in part through inhibition of MMPs . In the present study, we report the effect of CMT-1, a chemically modified tetracycline that lacks antimicrobial properties but retains divalent cation binding and MMP inhibitory activity, on diabetic skin collagen synthesis and steady-state levels of procollagen alpha 1(I) mRNA . Male, 4-month old Sprague-Dawley rats received a single injection of 75 mg/kg STZ or citrate vehicle alone and diabetic status was confirmed by positive glucosuria . Some diabetic animals received 10 mg/day of CMT-1 by oral gavage and, 28 days after STZ treatment, body weight, blood glucose values and the in vivo rates of skin collagen production were measured using the pool-expansion technique . Steady-state levels of procollagen alpha 1(I) mRNA were analyzed 21 days after STZ treatment by hybridization of total RNA with a 32P labelled cDNA to rat type I procollagen alpha 1(I) mRNA in a dot-blot assay . STZ treatment was found to significantly depress body weight, skin collagen hydroxyproline content, the in vivo rate of collagen production, and hybridizable levels of type I procollagen alpha 1(I) mRNA . CMT-1 administered daily to STZ-treated rats inhibited the diabetic depression of these parameters but had little or no effect on non-diabetic controls or on STZ-induced hyperglycemia . Thus, in addition to the inhibition of MMP mediated extracellular collagen degradation, these results suggest CMT-1 also acts to inhibit diabetic connective tissue breakdown in STZ-induced diabetes by increasing both steady-state levels of type I procollagen mRNA and collagen synthesis through mechanism(s) that are independent of the antibacterial properties of tetracyclines. Rheum Dis Clin North Am, 1998 May, 24(2), 305 - 22 Gonococcal arthritis; Cucurull E et al.; Disseminated gonococcal infection is the most common systemic complication of acute gonorrhea and occurs in 0.5% to 3.0% of patients with untreated mucosal infection . It is also the most common cause of septic arthritis in patients less than 30 years of age . Fortunately, the incidence of gonorrhea is decreasing dramatically in the United States and Western Europe, although it is still high in developing countries . Increasing resistance to antibiotics requires continuous surveillance of antimicrobial susceptibilities to determine the efficacy of current therapeutic measures. Rheum Dis Clin North Am, 1998 May, 24(2), 287 - 304 Septic arthritis in children; Shetty AK et al.; Because of its seriousness, septic arthritis should be considered early in the differential diagnosis of any child presenting with joint inflammation . Physicians who care for children should be aware of the early signs and symptoms of septic arthritis and be aggressive about establishing the diagnosis so that treatment is not delayed . Early orthopedic consultation and a low threshold for performing arthrocentesis are prudent . Prolonged and appropriate antimicrobial therapy is warranted to achieve optimal results. J Biol Chem, 1998 Apr 24, 273(17), 10463 - 9 In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila; Nicolas E et al.; The dorsoventral regulatory gene pathway (spatzle/Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila . This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-kappaB during the inflammatory response in mammals . Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response . We observe that the cactus gene is up-regulated in response to immune challenge . Interestingly, the expression of the cactus gene is controlled by the spatzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated . We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge . This degradation is also dependent on the Toll signaling pathway . Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response. Rheumatol Int, 1998, 17(5), 175 - 80 Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis; Nordstrom D et al.; Tetracyclines exert, independently of their antimicrobial activity, anti-collagenolytic effects by inhibiting activities of human interstitial collagenases and by preventing the oxidative activation of latent pro-collagenases . We tested the clinical response to a 3-month doxycycline in concert with collagenase activity in 12 rheumatoid arthritis (RA) patients . Patients received 150 mg/day of doxycycline for 3 months . Clinical assessments at zero, six and 12 weeks comprised classification of the functional class, joint score index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS) of pain, pain disability index, comprehensible psychopathological rating scale (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and Western blots . Significant reductions were seen in joint score index (P < 0.01), pain VAS (P < 0.05) and some CPRS parameters . Furthermore, collagenase activities measured from saliva by quantitative SDS-PAGE electrophoresis were significantly reduced during the 12-week intervention (P < 0.01) . Western blots demonstrated intact 75-80 kDa enzyme protein (classic neutrophil collagenase), but also a newly discovered mesenchymal, less glycosylated 40-55 kDa MMP-8 subtype of fibroblast/chondrocytic origin . These results indicate that the documented favourable clinical response may in part be due to in vivo inhibition of classic neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline . This anti-collagenolytic doxycycline effects is mediated through inhibition of the enzyme activity and not through degradation of the enzyme, which may have contributed to the reportedly reduced tissue destruction, as has been seen in clinical studies concerning RA as well as reactive arthritis. J Chemother, 1998 Apr, 10(2), 91 - 6 Immunopharmacology of oral betalactams; Periti P; Among the oral beta-lactam antibiotics only cefaclor has demonstrated a consistent in vitro and in vivo immunopharmacological effect which favors phagocytic chemotaxis and antimicrobial potential by inducing a T-helper 1 or pro-inflammatory response . Together with cefpimizole, cefaclor significantly reduces the minimum bactericidal concentration (MBC) against some bacterial species when cultured together with a suspension of polymorphonuclear leukocytes, as opposed to some other oral beta-lactams, co-amoxiclav and cefixime, which do not show this effect . The pro-inflammatory component of cefaclor's activity explains the clinical success of this antibiotic in a high percentage of cases, even when laboratory tests indicate in vitro resistance by the pathogen. J Chemother, 1998 Apr, 10(2), 83 - 90 Selecting antibacterial agents for the control of surgical infection: mini-review; Periti P et al.; An analysis of the recent literature on the control of surgical infections confirms the role of antimicrobial agents which guarantee valid perioperative antisepsis in both clean and clean-contaminated surgery . Current chemotherapy is able to check serious postoperative infectious complications by reducing the risk of septic shock with use of a glycopeptide-aminoglycoside-betalactam combination together with anti-inflammatory drugs. Exp Parasitol, 1998 May, 89(1), 103 - 12 Plasmodium gallinaceum: differential killing of some mosquito stages of the parasite by insect defensin; Shahabuddin M et al.; We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites . Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites . The defensins affected the oocysts in a time-dependent manner . Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito . When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced . Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8 . The oocysts were swollen or had extensive internal vacuolization . The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro . Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility . In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium. Poult Sci, 1998 May, 77(5), 765 - 9 Sodium lactate affects sensory and objective characteristics of tray-packed broiler chicken breast meat; Williams SK et al.; The objective of this study was to determine the antimicrobial properties of sodium lactate solutions adjusted to various pH values . The effectiveness of sodium lactate increases with increased concentrations; however, there are off-flavor development problems associated with increasing concentrations of sodium lactate above 2.0% . This study evaluated the effects of 2% sodium lactate treatments, adjusted to various pH values, on sensory characteristics, instrumental texture, and microbial populations of tray-packed broiler breast meat . Breast meat was treated with either tap water (pH 7.85) or 2% sodium lactate solutions (pH 7.30, 5.50, 5.00, 4.50, and 4.00) and stored at 2 +/- 1 C for 12 d . Approximately 15% of the panelists reported acidic aftertastes in samples treated with pH 5.00 sodium lactate solutions, and 10% of the panelists reported slight sodium or metallic off-flavor in all samples treated with sodium lactate . Instrumental texture measurements were similar (P > 0.05) for all treatments . Sodium lactate (pH 7.30 and 5.50) enhanced (P < 0.05) cooking yields and retarded the growth of spoilage bacteria (pH 5.50 and 5.00) . Due to the development of severe discoloration and intense acidic off-odors and -flavors, testing was not conducted on samples treated with pH 4.50 and 4.00 sodium lactate solutions. Food Addit Contam, 1998 Feb-Mar, 15(2), 162 - 70 Contamination of animal feedingstuffs with undeclared antimicrobial additives; Lynas L et al.; A study was carried out on 397 feedingstuffs and 11 premixes on which 161 (39.5%) were declared free of medication and 247 (60.5%) were medicated . These were subjected to analysis for the presence of antibiotics . Of the 247 medicated feeds 87 (35.2%) contained undeclared antimicrobials of which 59 (23.9%) were at a concentration sufficient to allow quantification by HPLC . Of the 161 unmedicated feeds 71 (44.1%) were shown to contain detectable antimicrobials of which 42 (26.1%) contained concentrations which could be quantified by HPLC . The most frequently identified contaminating antimicrobials were chlortetracycline (CTC) (15.2%), sulphonamides (6.9%), penicillin (3.4%) and ionophores (3.4%) . Four samples (ionophores--3, sulphadimidine--1) contained therapeutic concentrations and one sample a supra-therapeutic concentration (monensin) . The remainder were sub-therapeutic . All the contaminating concentrations of sulphadimidine detected were sufficient to cause violative tissue residues if fed to animals immediately prior to slaughter. Infect Immun, 1998 Jun, 66(6), 2426 - 33 Differential gene expression in response to adjunctive recombinant human interleukin-2 immunotherapy in multidrug-resistant tuberculosis patients; Johnson BJ et al.; Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with multidrug chemotherapy to patients with multidrug-resistant tuberculosis (MDR TB) induces measurable changes in in vitro immune response parameters which are associated with changes in the clinical and bacteriologic status of the patients . To determine the molecular basis of these changes, we have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and differential display technology . During rhuIL-2 treatment of MDR TB patients, decreased levels of gamma interferon (IFN-gamma) mRNA in peripheral blood mononuclear cells (PBMC) relative to baseline levels were observed . However, at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD), the expression of cellular IFN-gamma and IL-2 mRNAs was increased during rhuIL-2 therapy . Levels of other cytokine mRNAs were not significantly affected by rhuIL-2 administration . Using differential-display RT-PCR, we identified several genes expressed at the DTH skin test site which were up- or down-regulated during rhuIL-2 treatment . Cytochrome oxidase type I mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as was heterogeneous nuclear ribonuclear protein G mRNA . CD63, clathrin heavy chain, and beta-adaptin mRNAs, all of which encode proteins associated with the endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL-2 administration . The differential effects of IL-2 were confirmed in vitro by using PBMC obtained from PPD-positive individuals stimulated with Mycobacterium tuberculosis and IL-2 . The differential expression of genes may provide a surrogate marker for leukocyte activation at a mycobacterial antigen-specific response site and for the development of an enhanced antimicrobial response which may result in improved outcomes in MDR TB patients. J Rheumatol, 1998 May, 25(5), 975 - 82 Functional sites of chemically modified tetracyclines: inhibition of the oxidative activation of human neutrophil and chicken osteoclast pro-matrix metalloproteinases; Sorsa T et al.; OBJECTIVE: We studied the relative ability of 6 different chemically modified non-antimicrobial analogs of tetracycline (CMT) to inhibit human and chicken matrix metalloproteinases (MMP) in vitro . The ability of tetracycline and its analogs to inhibit MMP appears to depend on the Ca++/Zn++ binding site at C11 (carbonyl oxygen) and C12 (OH group) of the molecule, which is lacking in CMT-5, the pyrazole derivative of tetracycline . This significant property of CMT-5 was used to differentiate between the effects of CMT on already active MMP versus the oxidative activation of latent MMP (pro-MMP) . METHODS: Cultured chicken osteoclast conditioned medium and purified human neutrophil progelatinase (MMP-9) and pro-collagenase (MMP-8) were assayed for proteinase activities using gelatin and collagen, respectively . The pro-MMP were activated either by preincubation with 1 mM aminophenylmercuric acetate (APMA) or 100 microM sodium hypochlorite (NaOCI) . CMT were added either to the preincubation mixtures together with NaOCl or after activation of pro-MMP with NaOCl . RESULTS: All CMT tested, except CMT-5, inhibited APMA or NaOCl activated pro-MMP . However, CMT-5 (like the other CMT), inhibited the oxidative activation of pro-MMP by NaOCl when added together by scavenging the reactive oxygen species . The degradation of type-I collagen by chicken osteoclast conditioned medium was probably due to MMP-2 and/or MMP-13 . CONCLUSION: Oxidative activation of pro-MMP may be crucial during soft tissue/bone destruction in the inflammatory diseases, including the arthritides . Our results indicate that the Ca++/Zn++ binding site of CMT is not essential for inhibition of the oxidative activation of pro-MMP. South Med J, 1998 May, 91(5), 464 - 6 Chromobacterium violaceum infection; Midani S et al.; Chromobacterium violaceum infection is confined to the tropical and subtropical areas, with almost all reported cases occurring in the Southeast . The most common feature of this infection is sepsis, followed by cutaneous involvement and liver abscesses . Treatment consists of surgical drainage of purulent collections and appropriate antimicrobial therapy, such as chloramphenicol, gentamicin, imipenem, trimethoprim-sulfamethoxazole, or ciprofloxacin . Although C violaceum infection is rare, it is potentially fatal and remains an important entity for clinicians to suspect and treat appropriately. J Antimicrob Chemother, 1998 Apr, 41(4), 467 - 80 Clinical trials of antibacterial agents: a practical guide to design and analysis . Statisticians in the Pharmaceutical Industry Working Party; Smith C et al.; Guidelines on the conduct of clinical trials of antibacterial agents produced by the US Food and Drug Administration, the British Society for Antimicrobial Chemotherapy, the Infectious Diseases Society of America and a European Working Party have been reviewed . Although very informative, these guidelines provide limited practical guidance on the design and statistical aspects of phase III studies of antimicrobial agents . This paper describes the differences between antibacterial trials and clinical studies in other therapeutic areas with regard to subjective endpoints, dual clinical and bacteriological endpoints, frequent protocol violations and difficulty of using placebo controls . The importance of a detailed protocol and planned analysis strategy is emphasized . The choice of comparator agents, practical issues with the blinding of trial materials and the documentation of patients excluded from study entry are discussed . The use of different patient groups and different endpoints in analyses are described . The principles of equivalence and their application to trials of antibacterial agents are discussed, together with an approach to calculating sample size . A variety of statistical analyses of results are compared for different situations indicating some of the problems that can arise . Different methods of presentation of study data are included with emphasis on regulatory submissions rather than scientific publications . Some graphical presentations are recommended and issues regarding data across different studies are discussed. Adv Exp Med Biol, 1998, 434, 213 - 35 Maillard reaction and food processing . Application aspects; Chuyen NV; The Maillard reaction occurs widely in food and biological systems . This contribution reviews the relation between the Maillard reaction and food processing, particularly its contribution to flavor formation, antioxidative effects, desmutagenic activity and the improvement of protein functional properties . Proteins modified by glucose, and melanoidins are important components of foodstuffs while the reactions of amino acids or peptides with glucose or dicarbonyl compounds produce various kinds of flavor components . Melanoidins and Amadori rearrangement products play an important role in providing antioxidative effects, both in vitro and in vivo . Melanoidins also exhibit desmutagenic activity against carcinogenic compounds . Protein-polysaccharide conjugates, prepared by Maillard reaction at mild conditions, increase the emulsifying activity, as well as antioxidative and antimicrobial effects of the original proteins. J Clin Pharmacol, 1998 Jan, 38(1), 90 - 3 Levofloxacin does not alter cyclosporine disposition; Doose DR et al.; Certain fluoroquinolones have been shown to elevate the serum concentrations of the immunosuppressant cyclosporine . It is thus important to investigate the potential interaction between levofloxacin, a new fluoroquinolone antimicrobial agent, and the pharmacokinetics of cyclosporine . Twelve healthy subjects (6 men, 6 women) were enrolled in and completed a placebo-controlled, randomized, double-blind, two-phase crossover study . Subjects were given a single oral 10-mg/kg dose of cyclosporine solution during multiple-dose twice-daily oral treatment with placebo or 500 mg of levofloxacin . Blood cyclosporine concentrations were measured for 48 hours after each cyclosporine dose for pharmacokinetic evaluation . Cyclosporine pharmacokinetic parameters were comparable and not significantly different in the absence and presence of levofloxacin . Results of this study suggest that a clinically important pharmacokinetic interaction between levofloxacin and cyclosporine is unlikely to occur during concurrent therapy. Dent Clin North Am, 1998 Apr, 42(2), 263 - 83 Controlled local delivery of antimicrobials in the treatment of periodontitis; Killoy WJ et al.; Five local delivery systems with five different antimicrobial agents have been discussed . All are capable of delivering high concentrations of their antimicrobial to the site of the periodontal infection . Although only one system, tetracycline fiber, is available in United States, two other systems, chlorhexidine chip and doxycycline polymer, may be available in the near future . Two other systems, metronidazole gel and minocycline ointment, are available in other countries . Data from pertinent studies were presented as were techniques for using the various systems . Indications for the use of the products were also discussed . In selecting the appropriate delivery system, the clinician has to weigh the efficacy of the products, ease of use, availability, and cost . Although local delivery systems do not replace existing periodontal therapies, they do have a place in the treatment of periodontitis and offer the dentist additional methods to aid in the control of periodontal diseases. Dent Clin North Am, 1998 Apr, 42(2), 245 - 62 Pharmacologic management of periodontal diseases using systemically administered agents; Mariotti A et al.; Since the establishment of bacteria-laden plaque as a causative agent in gingivitis, the search for specific bacteria that induce different types of periodontitis has generated extensive research . In contrast to many other microbial-induced disorders, the specific periodontal pathogen(s) has not been identified to date . Therefore, the search for an effective systemic agent to prevent the loss of attachment through the selective reduction of known periodontal pathogens has remained elusive . It is not surprising then that antibiotics are not used solely to manage periodontal diseases but rather as an adjunct to the mechanical debridement of root surfaces in select periodontal diseases . Further, the sole use of antibiotics in patients with adult periodontitis (or those who exhibit signs of inflammation but are periodontally stable) has shown little benefit and only increases the chance of microbial resistance to antibiotics . Despite these limitations, considerable progress in antibiotic therapy has delivered regimens that enhance the effectiveness of conventional therapy . In contrast to traditional antimicrobial therapy, new treatment modalities have begun to focus on modulating the responses of host cells to bacteria rather than modulating only the bacteria . Current drugs used to regulate host cells inhibit the cyclooxygenase pathway, reduce the activity of metalloproteinases, or inactivate bone resorptive cells (see Table 1) . Although these drugs offer great potential to modulate a variety of mammalian cells, a notable and consequential limitation of these agents is a lack of specificity . Inflammation, bone metabolism, and connective tissue metabolism are two-edged swords; all are necessary for the homeostasis of the tissue, but some or all may also be involved in the pathologic destruction of that same tissue . Hence, drugs that inhibit destruction of the connective tissue in one site of the periodontium also interfere with wound healing at another . As a result of these limitations, the efficacy, safety, and cost-effectiveness of the long-term use of these agents is unknown . Preliminary results of treatment with these drugs are promising, and future generations of host-modulating drugs will provide clinicians with additional agents to help improve the success rate of periodontal treatment for patients . Antibiotics remain an important adjunctive therapy in the treatment of periodontal diseases, and the use of host modulating drugs as supplemental agents in the management of periodontal diseases continues to grow . As more knowledge is gained about the causes of periodontal diseases, new drugs that are potent, effective, site specific, and safe can be delivered at optimal times by simply having the patient take a few tablets . Considering the dramatic progress in the past decade in understanding the cause and pharmacologic management of periodontal diseases, the twenty-first century holds great promise for the development of magic bullets. Zhonghua Yi Xue Za Zhi, 1997 Feb, 77(2), 91 - 3 {Polymerase chain reaction in the detection of patients infected by Chlamydia trachomatis after treatment}; Wang H et al.; OBJECTIVE: To investigate the value of polymerase chain reaction (PCR) for follow-up patients infected by Chlamydia trachomatis . METHODS: Follow-up specimens were collected from 30 patients . Chlamydia trachomatis positive were detected by PCR and direct fluorescence assay test (DFA) in the 30 patients before therapy . 15 patients were treated with minocycline (100 mg twice daily) for 10 days, and 15 patients were treated with 1.0 g of azithromycine as a single oral dose . RESULTS: After 1-2 weeks of antimicrobial therapy, all patients had negative DFA for Chlamydia trachomatis, but 9 had positive Chlamydia trachomatis DNA as detected by PCR . CONCLUSIONS: The 9 specimens were not confirmed to livae viable organisms of Chlamydia trachomatis . The debris of nonviable Chlamydia trachomatis DNA was excluded from urinogenital tract at about one month. Croat Med J, 1998 Mar, 39(1), 28 - 32 Recovery of respiratory functional defects after war injuries to the chest; Ilic N et al.; AIM: Assessment of lung function before, during, and after surgical treatment of war injuries to the chest, and comparison of conservative and operative surgical approach . PATIENTS AND METHODS: A retrospective study of 439 patients with war injuries to the chest inflicted during the wars in Croatia and Bosnia and Herzegovina was performed . Patients were classified by injury mechanism and by physiologic scoring on admission, according to the cardiovascular-respiratory elements of the Injury Severity Score (ISS) . "Conservative" surgical treatment with chest tube drainage, appropriate fluid therapy, and antimicrobial and atelectasis prophylaxis was performed in 358 (81.5%) and operations in 81 (18 . 5%) patients . Blood gases were analyzed before, during, and after surgical treatments . Pulmonary function was assessed after the stabilization of patients' clinical condition and 3-6 months after the injury . RESULTS: On admission, blood gas profiles showed slight to moderate hypoxemia with consecutive hypercapnia related to the severity of injuries . Surgical treatment left a minimum degree restrictive disorder of ventilation without an obstructive pattern . Definitive repair of lung function presented with normalization of blood gas data, and significantly improved restrictive pattern (p<0.05) . There was no difference in definitive lung function between conservatively and operatively treated patients . Mortality was 2% . CONCLUSION: The success of surgical resuscitation was related to ISS scoring . Recovery of respiratory function defects after the injury was not significantly related to the mechanism of injury or the patient's condition at arrival . The recovery of lung function was similar in conservatively and operatively treated patients. Med Care, 1998 May, 36(5), 646 - 60 Influence of the NIH Consensus Conference on Helicobacter pylori on physician prescribing among a Medicaid population; Thamer M et al.; OBJECTIVES: In February 1994, an National Institutes of Health (NIH) Consensus Development Conference panel unequivocally recommended antimicrobial therapy to eradicate Helicobacter pylori in the treatment of peptic ulcer disease . The goal of this study was to determine if these recommendations resulted in a change in physician prescribing among an underserved population . METHODS: Computerized Pennsylvania Medicaid data from January 1993 through February 1996 were used to evaluate prescribing patterns in the year before and 2 years after the NIH conference . An interrupted time series model, based on 12,737 outpatient peptic ulcer disease encounters, assessed the impact of the conference in influencing physician prescribing . RESULTS: The prescription of antimicrobial agents for the treatment of peptic ulcer disease significantly increased across the study period, from 6.5% in January 1993 to 10.2% in February 1996 . Similarly, the prescription rate for the proton pump inhibitor, omeprazole, significantly increased from 9.4% in January 1993 to 25.6% in February 1996 . Neither trend, however, could be attributed to the NIH Consensus Development Conference . Stratification by physician specialty, ulcer type, nonsteroidal anti-inflammatory drug use, and patient demographics did not affect these results . The traditional treatment approach, using H2-receptor antagonists, remained the preferred pharmacotherapy (72% of all prescriptions) . CONCLUSIONS: Two years after the highly publicized NIH conference on the eradication of Helicobacter pylori, antimicrobial agents were not widely prescribed among the Pennsylvania Medicaid population . In treating this underserved population, physicians do not appear to be using recommendations developed by an NIH expert panel based on recent scientific advances. Boll Chim Farm, 1998 Feb, 137(2), 43 - 7 Synthesis of some new biologically active 2,3-disubstituted quinazolin-4-ones; Abdel-Rahman TM; The facile synthesis of 2-(2'-4-anisoylvinyl)-3-arylquinazolin-4-ones (2a, b) involves the condensation of 2-toluidine or 4-phenylenediamine with the corresponding 2-{2'-(4-anisoylvinyl)}-4H-3,1-benzoxazine-4-one (1) . Reaction of compound 2 with aldehydes, bromine, alcohols, hydrazine hydrate, urea and thiourea are discussed . The former structure of the products have been characterized by elemental analysis and spectral data . Preliminary screening of some selected compounds for antimicrobial activity is reported. Subcell Biochem, 1998, 29, 321 - 41 Biosynthesis and regulation of coronatine, a non-host-specific phytotoxin produced by Pseudomonas syringae; Bender CL et al.; Many P . syringae pathovars are known to produce low-molecular-weight, diffusible toxins in infected host plants . These phytotoxins reproduce some of the symptoms of the relevant bacterial disease and are effective at very low concentrations . Phytotoxins generally enhance the virulence of the P . syringae pathovar which produces them, but are not required for pathogenesis . Genes encoding phytotoxin production have been identified and cloned from several P . syringae pathovars . With the exception of coronatine, toxin biosynthetic gene clusters are generally chromosomally encoded . In several pathovars, the toxin biosynthetic gene cluster also contains a resistance gene which functions to protect the producing strain from the biocidal effects of the toxin . In the case of phaseolotoxin, a resistance gene (argK) has been utilized to engineer phaseolotoxin-resistant tobacco plants . Although P . syringae phytotoxins can induce very similar effects in plants (chlorosis and necrosis), their biosynthesis and mode of action can be quite different . Knowledge of the biosynthetic pathways to these toxins and the cloning of the structural genes for their biosynthesis has relevance to the development of new bioactive compounds with altered specificity . For example, polyketides constitute a huge family of structurally diverse natural products including antibiotics, chemotherapeutic compounds, and antiparasitics . Most of the research on polyketide synthesis in bacteria has focused on compounds synthesized by Streptomyces or other actinomycetes . It is also important to note that it is now possible to utilize a genetic rather than synthetic approach to biosynthesize novel polyketides with altered biological properties (Hutchinson and Fujii, 1995; Kao et al., 1994; Donadio et al., 1993; Katz and Donadio, 1993) . Most of the reprogramming or engineering of novel polyketides has been done using actinomycete PKSs, but much of this technology could also be applied to polyketides synthesized by Pseudomonas when sufficient sequence information is available . It is important to note that Pseudomonas produces a variety of antimicrobial compounds from the polyketide pathway, including mupirocin (pseudomonic acid) (Feline et al., 1977), pyoluteorin (Cuppels et al., 1986), and 2-4 diacetylphloroglucinol (Phl) (Bangera and Thomashow, 1996) . Pseudomonic acid is valued for its pharmaceutical properties as an antibiotic (Aldridge, 1992), whereas pyoluteorin and Phl have antifungal properties (Howell and Stipanovic, 1980; Keel et al., 1992) . A thorough understanding of the biosynthetic pathway to polyketide phytotoxins such as coronatine may ultimately lead to the development of novel compounds with altered biological properties . Thus, specific genes in the biosynthetic pathways of P . syringae phytotoxins could be deployed in other systems to develop new compounds with a wide range of activities. Antimicrob Agents Chemother, 1998 May, 42(5), 1290 - 2 Susceptibilities of neonatal respiratory isolates of Ureaplasma urealyticum to antimicrobial agents; Matlow A et al.; Twenty-one neonatal respiratory isolates of Ureaplasma urealyticum were serotyped, and their susceptibilities to ciprofloxacin, gentamicin, chloramphenicol, erythromycin, azithromycin, and doxycycline were tested . Most patient strains were Ureaplasma urealyticum bv . parvum . Chloramphenicol, doxycycline, and azithromycin had the lowest MICs . This data may be useful when designing prophylactic or therapeutic trials of antibiotics for chronic lung disease of the newborn. Antimicrob Agents Chemother, 1998 May, 42(5), 1239 - 44 Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk; Lampe MF et al.; The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority . Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure . To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk . C . trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times . Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted . A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C . trachomatis after 120 min of contact with the organism . The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity . On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell . Lipid activity was unaffected by the presence of 10% human blood or alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in the vagina . Our results suggest that these lipids, especially 2-O-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C . trachomatis . Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress. J Antibiot (Tokyo), 1997 Nov, 50(11), 926 - 31 Formamicin, a novel antifungal antibiotic produced by a strain of Saccharothrix sp . I . Taxonomy, production, isolation and biological properties; Igarashi M et al.; Formamicin, an antifungal antibiotic, was isolated from the cultured broth of an actinomycete strain . The strain was isolated from a soil collected at Setagaya-ku, Tokyo, Japan, and identified as Saccharothrix sp . MK27-91F2 . Formamicin was extracted with acetone from cultured mycelia and purified by silicagel and Sephadex LH-20 column chromatographies and CPC (Centrifugal liquid-liquid Partition Chromatography) . Formamicin showed strong antimicrobial activity against phytopathogenic fungi. J Antibiot (Tokyo), 1997 Nov, 50(11), 900 - 5 Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis . I . Taxonomy, fermentation, isolation and antimicrobial activities; Matsumoto N et al.; A new structural class of the antibiotic, epoxyquinomicins A, B, C and D were isolated from the culture broth of the strain MK299-95F4, which was related to Amycolatopsis sulphurea . Antimicrobial activity of epoxyquinomicins A and B were weak against Gram-positive bacteria, and epoxyquinomicins C and D showed almost no antimicrobial activity and no cytotoxicity . All these antibiotics showed improvement of collagen induced arthritis in vivo. J Biochem (Tokyo), 1998 Apr, 123(4), 675 - 9 Purification, primary structure, and antimicrobial activities of bovine apolipoprotein A-II; Motizuki M et al.; We purified an antimicrobial protein of 76 residues, denoted bovine antimicrobial protein-1 (BAMP-1), from fetal calf serum using hydrophobic chromatography, gel filtration, and reverse-phase high-performance liquid chromatography . The amino acid sequence of BAMP-1 was similar to that of human apolipoprotein A-II (apo A-II), a major component of high-density lipoprotein (HDL), and the amino acid composition was almost identical to that of a previously reported candidate for bovine apo A-II . BAMP-1 was recovered from the post-HDL fraction, but not from the HDL fraction of the serum and was associated with a small amount of triglycerides (5%, w/w) . These results suggest that BAMP-1 is the bovine homologue of apo A-II and is present in almost free form in serum . BAMP-1 showed a weak growth-inhibitory activity against Escherichia coli and yeasts tested in phosphate-buffered saline (PBS). Biofizika, 1998 Mar-Apr, 43(2), 186 - 8 {Antioxidant properties of plant extracts}; Bol'shakova IV et al.; Investigation of antioxidant properties of some plants was carried out . A group of plants exhibited antimicrobial activity was studied in detail . Efficiency of plants as antioxidants was tested by the influence of their extracts on the yield of photochemiluminescence of Gly-Trp solutions . Antioxidant properties were examined under conditions when their own absorption was minimized . Riboflavin as additional sensitizer was used in this experiment for superoxide generation . The antioxidant effect was evaluated with regard to single dose of plant extracts and their concentration in human organism . The effect decreases in the following consequence: Hypericum perforatum > Potentilla erectra > Ledum palustre > Plantago major > Salvia officinalis > Chamomilla recutita > Arctostaphylos uva. Afr Dent J, 1995, 9, 25 - 9 Saliva and salivary gland alterations in HIV infection: a review; Matee MI et al.; HIV-1 can be recovered sporadically from whole saliva and individual salivary gland secretions, but the concentration of virus, when present, is low . Saliva possesses antiviral activity, and although virus may be found in the mouth, the mouth is not a transmission route of HIV-1 . After HIV-1 infection, salivary gland function is altered . Flow rates may decrease, and certain electrolytes and anti-microbial proteins are elevated . A proportion of patients develop severe salivary gland disease . Most patients, however, maintain adequate salivary gland function and retain ability to produce antimicrobial proteins in saliva. Clin Chem, 1998 May, 44(5), 1129 - 40 Laboratory guidelines for monitoring of antimicrobial drugs . National Academy of Clinical Biochemistry; Hammett-Stabler CA et al.; Few antimicrobial drugs meet the requirements for therapeutic drug monitoring . Those that are monitored include the aminoglycosides (gentamicin, tobramycin, and amikacin), chloramphenicol, and in some cases, vancomycin . For these drugs, there is evidence of a relationship between serum concentration, efficacy, and/or the incidence of adverse or toxic events . Monitoring begins with the appropriate timing of collection and continues through the analytical process to the integration of all data used to guide the clinician's next decision. Clin Ther, 1998 Mar-Apr, 20(2), 244 - 56 Cefdinir versus cephalexin for the treatment of skin and skin-structure infections . The Cefdinir Adult Skin Infection Study Group; Tack KJ et al.; Because of increasing resistance to older antimicrobial agents, newer drugs need to be evaluated for the treatment of skin and skin-structure infections (SSSIs) . This double-masked, randomized, comparative, multicenter study enrolled patients aged 13 years or older with SSSIs to receive either cefdinir 300 mg BID or cephalexin 500 mg QID for 10 days . Nine hundred fifty-two patients (474 in the cefdinir group and 478 in the cephalexin group) took part, primarily white males between 18 and 65 years of age . There were two follow-up visits, with efficacy determined at the test-of-cure visit, 7 to 16 days posttherapy . Many patients were not microbiologically assessable, primarily because of negative cultures at study admission . Patients who required surgical intervention (e.g., incision and drainage) at the site of infection more than 24 hours after the initiation of drug therapy were defined as treatment failures . Significantly more isolated pathogens were resistant to cephalexin than to cefdinir . In the 178 efficacy-assessable cefdinir-treated patients, the rate of pathogen eradication was 93% (200/215), and the rate of successful clinical response was 88% (157/178), compared with 89% (221/247) and 87% (177/204), respectively, in the 204 efficacy-assessable cephalexin-treated patients . Using confidence-interval analysis, the microbiologic and clinical response rates of the cefdinir-treated patients were statistically equivalent to those of the cephalexin-treated patients . At the follow-up visits, patients were questioned about any adverse events occurring since their previous visit . Any untoward symptom occurring during or within 2 days after completion of drug treatment was considered an adverse reaction if the investigator judged it to be definitely, probably, or possibly related to the study drug . One hundred twenty-three (26%) cefdinir-treated patients and 77 (16%) cephalexin-treated patients experienced at least one adverse reaction, a statistically significant difference . Study drug was discontinued for adverse reactions in 20 (4%) cefdinir-treated patients and 13 (3%) cephalexin-treated patients; in the two groups, 10 and 7 patients, respectively, were discontinued for diarrhea . Cefdinir taken BID was as effective as cephalexin taken QID in the treatment of mild-to-moderate SSSIs and was well tolerated by most patients . The increased antibacterial activity of cefdinir must be balanced against the higher rate of diarrhea seen in patients treated with this drug. Am J Pathol, 1998 May, 152(5), 1247 - 58 Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract; Quayle AJ et al.; This study describes the novel localization of the antimicrobial peptide human intestinal defensin-5 (HD-5) in female genital tract epithelia . Using a 3' rapid amplification of cDNA ends (RACE) protocol, HD-5 was cloned from a vaginal epithelial cell RNA preparation, and its identity was confirmed by sequencing . Tissue samples from multiple donors were subsequently screened for HD-5 expression by reverse transcription polymerase chain reaction . HD-5 message was invariantly expressed by normal vagina and ectocervix and inflamed fallopian tube, but variably expressed by normal endocervix, endometrium, and fallopian tube (60, 64, and 29% of specimens, respectively) . Expression in endometrium was the highest during the early secretory phase of the menstrual cycle . Using immunohistochemistry and confocal microscopy, HD-5 peptide was localized in the upper half of the stratified squamous epithelium of the vagina and ectocervix, with the intensity of cellular staining increasing toward the lumen . In positive endocervix, endometrium, and fallopian tube specimens, HD-5 was located in apically oriented granules and on the apical surface of a proportion of columnar epithelial cells . Using Western blot analysis, secreted HD-5 was detected in cervicovaginal lavages, with the highest concentrations found during the secretory phase of the menstrual cycle . We hypothesize that HD-5 is an intrinsic component of the female urogenital innate immune defense system and that its expression may be modulated by hormonal and proinflammatory factors. Biochem Biophys Res Commun, 1998 Apr 28, 245(3), 764 - 73 Bactericidal domain of lactoferrin: detection, quantitation, and characterization of lactoferricin in serum by SELDI affinity mass spectrometry; Kuwata H et al.; Lactoferricin is a bioactive peptide fragment (3196 Da) derived from lactoferrin (80 kDa) that contains the bactericidal domain and the lymphocyte receptor-binding domain of lactoferrin . Although lactoferricin has been produced from lactoferrin by proteolytic digestion in vitro, its natural occurrence and distribution in vivo are still not clear, in part because of the absence of a suitable detection means . Surface-enhanced laser desorption/ionization (SELDI) was used to detect and characterize lactoferricin by affinity mass spectrometry . Human, porcine, and bovine lactoferricin in unfractionated serum samples were found to bind specifically to ligands presenting a terminal n-butyl group . SELDI was used to detect and quantify each species of lactoferricin in a manner that was independent of the presence of intact lactoferrin, partially degraded lactoferrin, and lactoferrin peptides containing the lactoferricin peptide sequence . The limit of detection of bovine lactofericin in serum was as low as 200 pg/ml . The FKCRRWQWR-homoserine/-homoserine lactone moiety of bovine lactoferricin, which includes the complete antimicrobial center (i.e., RRWQWR), was shown to be responsible for interaction with the n-butyl group . The SELDI procedure defined here is the only molecular recognition tool known to date that is capable of distinguishing the multi-functional lactoferricin domain located within structurally related but distinct forms of lactoferrin and its metabolic fragments . Enabling the direct quantitation of lactoferricin produced in vivo opens new opportunities to evaluate lactoferrin function. J Fr Ophtalmol, 1997, 20(10), 749 - 52 {Toxoplasmic chorioretinitis complicated by retinal detachment}; Frau E et al.; PURPOSE: To describe and analyse relationship between chorioretinal toxoplasmosis and retinal detachment . PATIENTS AND METHODS: Seven immunocompetent patients examined and treated between November 1992 and March 1996, with ocular toxoplasmic retinochoroiditis and retinal detachment . RESULTS: Of the 7 patients examined, 5 had active retinochoroiditis and 2 had typical inactive scars . Of the patients with active focus 3 had giant retinal tears, one had a posterior retinal tear and one had a retinal tear located at the edge of an atrophic scar . Of the patients with inactive lesions, one had tractional retinal detachment and the other presented with a complete retinal detachment, multiples tears and PVR . Five patients were treated by corticosteroid without antitoxoplasmic drug before they were referred . The seven patients underwent endo-ocular surgery with silicon oil or long actic gas tamponade . Three patients developed PVR and redetachment of the retina and two patients underwent further surgery . Good anatomical result was obtained in 6 patients . CONCLUSION: Retinal detachment associated with toxoplasmic retinochoroiditis is rare . However it represents a serious complication . Steroid administrated to salvage vision may then worsen the clinical course, these may be justified to reduce hypersensitivity to toxoplasma antigen, but they should be combined with an antimicrobial agent. Q Rev Biol, 1998 Mar, 73(1), 3 - 49 Antimicrobial functions of spices: why some like it hot; Billing J et al.; Although spices have been important for centuries in food preparation throughout the world, patterns of spice use differ considerably among cultures and countries . What factors underlie these differences? Why are spices used at all? To investigate these questions, we quantified the frequency of use of 43 spices in the meat-based cuisines of the 36 countries for which we could locate traditional cookbooks . A total of 4578 recipes from 93 cookbooks was analysed . We also complied information on the temperature and precipitation in each country, the ranges of spice plants, and the antibacterial properties of each spice . These data were used to investigate the hypothesis that spices inhibit or kill food-spoilage microorganisms . In support of this is the fact that spice plant secondary compounds are powerful antimicrobial (i.e., antibacterial and antifungal) agents . As mean annual temperatures (an indicator of relative spoilage rates of unrefrigerated foods) increased, the proportion of recipes containing spices, number of spices per recipe, total number of spices used, and use of the most potent antibacterial spices all increased, both within and among countries . Likewise, the estimated fraction of bacterial species inhibited per recipe in each country was positively correlated with annual temperature . Several alternative hypotheses were considered--that spices provide macronutrients, disguise the taste and smell of spoiled foods, or increase perspiration and thus evaporative cooling; it also is conceivable that spice use provides no benefits . However, none of these four alternatives was well supported by our data . The proximate reason spices are used obviously is to enhance food palatability . But the ultimate reason is most likely that spices help cleanse foods of pathogens and thereby contribute to the health, longevity and reproductive success of people who find their flavors enjoyable. Am Surg, 1998 May, 64(5), 402 - 7 Impact an anatomical site on bacteriological and clinical outcome in the management of intra-abdominal infections; Wilson SE et al.; The clinical and bacteriological results of treatment for 429 patients who had intra-abdominal infection were analyzed to determine whether the anatomical origin of peritonitis influenced outcome . All patients had received effective broad spectrum antimicrobial therapy and operation in four multicenter trials . The diagnoses of infection were categorized into three sites: upper gastrointestinal tract, complicated appendicitis, and lower gastrointestinal tract . Clinical response rates were excellent for complicated appendicitis and were lowest for infections related to the upper gastrointestinal tract . Bacteriological response rates were also lower for upper gastrointestinal tract organisms and were highest for isolates associated with complicated appendicitis . There were no deaths in the 213 patients who had infection associated with appendicitis . Seven deaths occurred in the 86 patients (81%) with an upper gastrointestinal site of infection, and nine deaths occurred in the 130 patients (6.5%) with lower gastrointestinal site of infection . Mortality was related to recurrent intra-abdominal infection after an unsuccessful primary operation and a serum albumin less than 25 g/l . Clinical trails of antimicrobials for intra-abdominal infection should consider stratification of patients according to these three levels of alimentary tract perforation when the site is known preoperatively . Patients who have infection secondary to previous surgery or who are malnourished represent a higher risk group even with appropriate antibiotics. J Formos Med Assoc, 1998 Apr, 97(4), 266 - 70 One-week proton pump inhibitor-based triple therapy eradicates residual Helicobacter pylori after failed dual therapy; Sheu BS et al.; The purposes of this study were to assess the efficacy of a 1-week proton pump inhibitor (PPI)-based triple therapy after failure of dual therapy in Helicobacter pylori eradication, and to compare the effectiveness of clarithromycin and metronidazole in this regimen . Between January 1996 and March 1997, 67 patients with persistent H . pylori infection after a 2-week course of dual therapy (amoxicillin plus omeprazole) were enrolled . They were randomly assigned to receive amoxicillin (1000 mg twice daily) and omeprazole (20 mg twice daily) plus either metronidazole (500 mg twice daily) or clarithromycin (250 mg twice daily) . Endoscopy was performed in each patient to assess the status of H . pylori using the rapid urease test (CLOtest) and the histologic findings before dual therapy, after dual therapy, and after triple therapy . H . pylori isolates were tested for antibiotic resistance when triple therapy failed . The 1-week triple therapy was well tolerated in both groups with no adverse effects severe enough to cause withdrawal from the trial . Residual H . pylori was eradicated in 94% (33/35) of patients in the clarithromycin group and 84% (27/32) in the metronidazole group; the difference was not statistically significant . All seven patients in whom triple therapy failed were infected with metronidazole-resistant isolates and two also had clarithromycin-resistant isolates . This 1-week triple therapy is safe and effective in eradicating residual H . pylori after dual therapy failure . Failure of the rescue regimen is related to antimicrobial agent resistance . Because of the high metronidazole resistance rate in Taiwan, clarithromycin appears to be more promising than metronidazole for the control of H . pylori. J Nat Prod, 1998 Apr, 61(4), 548 - 50 Agelasines H and I, 9-methyladenine-containing diterpenoids from an Agelas sponge; Fu X et al.; Two new diterpenes possessing a 9-methyladeninium substituent, agelasines H (5) and I (6), along with five related known ones, 1-4 and 7, were isolated from a sponge, Agelas sp . The structures of the new compounds were determined from spectral data . Compounds 2-4, 6, and 7 exhibited varying degrees of antimicrobial activity. Endocrinology, 1998 May, 139(5), 2253 - 64 Novel sites of adrenomedullin gene expression in mouse and rat tissues; Cameron VA et al.; Adrenomedullin (AM) was originally identified in pheochromocytoma tissue and was characterized as a hypotensive peptide . The tissue distribution and cellular localization of AM messenger RNA (mRNA) were determined in mouse and rat tissues by in situ hybridization . Three probes were used: two nonoverlapping probes to the pro-AM N-terminal 20 peptide (PAMP) and AM peptide regions of mouse pro-AM, and a larger complementary DNA (cDNA) probe spanning both the PAMP- and AM peptide-coding regions . The most intense expression of AM mRNA was in endometrium and epithelial cells lining the uterus and mouse adrenal medulla . Moderate levels of expression were detected in kidney glomerulus and cortical distal tubules, ovarian corpus luteum and follicles, epithelial cells lining the bronchioles, cardiac atrium and ventricle, posterior pituitary (particularly in female rats), stomach, small intestine (microvilli, mucosa and submucosa), spleen, and pancreas . Lower levels were observed in pulmonary alveoli, anterior pituitary, and submandibular gland . No expression was detected in the testis, thymus, skeletal muscle, or liver . The localization of AM mRNA in epithelial cells lining the uterus, bronchioles, and gastrointestinal tract indicates novel roles for AM, possibly as an antimicrobial agent . The strong expression of AM in uterus, ovary, and posterior pituitary suggests that AM plays a role in female reproduction. Biochim Biophys Acta, 1998 Mar 13, 1370(2), 218 - 34 The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles; Selinsky BS et al.; The ability of the shark antimicrobial aminosterol squalamine to induce the leakage of polar fluorescent dyes from large unilamellar phospholipid vesicles (LUVs) has been measured . Micromolar squalamine causes leakage of carboxyfluorescein (CF) from vesicles prepared from the anionic phospholipids phosphatidylglycerol (PG), phosphatidylserine (PS), and cardiolipin . Binding analyses based on the leakage data show that squalamine has its highest affinity to phosphatidylglycerol membranes, followed by phosphatidylserine and cardiolipin membranes . Squalamine will also induce the leakage of CF from phosphatidylcholine (PC) LUVs at low phospholipid concentrations . At high phospholipid concentrations, the leakage of CF from PC LUVs deviates from a simple dose-response relationship, and it appears that some of the squalamine can no longer cause leakage . Fluorescent dye leakage generated by squalamine is graded, suggesting the formation of a discrete membrane pore rather than a generalized disruption of vesicular membranes . By using fluorescently labeled dextrans of different molecular weight, material with molecular weight </=4000 g/mol is released from vesicles by squalamine, but material with molecular weight >/=10,000 is retained . Negative stain electron microscopy of squalamine-treated LUVs shows that squalamine decreases the average vesicular size in a concentration-dependent manner . Squalamine decreases the size of vesicles containing anionic phospholipid at a lower squalamine/lipid molar ratio than pure PC LUVs . In a centrifugation assay, squalamine solubilizes phospholipid, but only at significantly higher squalamine/phospholipid ratios than required for either dye leakage or vesicle size reduction . Squalamine solubilizes PC at lower squalamine/phospholipid ratios than PG . We suggest that squalamine complexes with phospholipid to form a discrete structure within the bilayers of LUVs, resulting in the transient leakage of small encapsulated molecules . At higher squalamine/phospholipid ratios, these structures release from the bilayers and aggregate to form either new vesicles or squalamine/phospholipid mixed micelles . Eur Respir J, 1998 Jan, 11(1), 104 - 11 Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis; Ashitani J et al.; Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins . Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB) . Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults . The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects . DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls . In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8 . Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells . In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8 . Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF . Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease. AIDS Res Hum Retroviruses, 1998 Apr, 14 Suppl 1, S5 - 10 Heterosexual transmission of human immunodeficiency virus type 1 (HIV): interactions of conventional sexually transmitted diseases, hormonal contraception and HIV-1; Plummer FA; The interactions between HIV-1 and other viral sexually transmitted infections (STI) are complex . The presence of ulcerative and nonulcerative STD increase susceptibility of exposed individuals to HIV-1 infection by several folds . In HIV-1 infected individuals, STD increase genital tract shedding of HIV-1 and enhance the infectivity of these individuals . STD have also recently been shown to increase plasma viremia either directly or through altering the cytokine milieu, which may both increase infectivity and result in more rapid HIV-1 disease progression . HIV-1 infection in turn has effects on susceptibility to other STD as well as increasing the serverity of some infections and possibly reducing the response to antimicrobial therapy . In addition, other potential risk factors for sexual transmission of HIV-1, such as hormonal contraception in women and lack of circumcision in men, may operate partly through effects on enhancing susceptibility to STD . The mutual enhancement of transmission of HIV-1 and other STD that has fueled HIV-1 epidemics worldwide, offers the opportunity for intervention . The effectiveness of this approach has recently been demonstrated in a trial in Mwanza, Tanzania, where provision of effective treatment for STD resulted in a 40% decline in HIV-1 incidence . The implementation of effective STD management may do much to slow the spread of HIV-1. Br J Dermatol, 1998 Mar, 138(3), 467 - 76 Patch testing with preservatives, antimicrobials and industrial biocides . Results from a multicentre study; Schnuch A et al.; Preservatives are biologically reactive substances, and their allergenic potential has been known for a long time . This study examined the role of different preservatives in a large number of patients with suspected allergic contact dermatitis . Patch test data and data from the patients' history were collected from the 24 departments participating in the Information Network of Departments of Dermatology from 1 January 1990 to 31 December 1994 . Patch test data from 28,349 patients tested with preservatives of the standard series (SS), from 11,485 patients tested additionally with a preservative series (PS), and from 1787 patients tested with an industrial biocide tray (IB) were evaluated . Sensitization rates (standardized) of the SS preservatives were all > 1%, with thiomersal rating highest (5.3%), the parabens lowest (1.6%), and the remainder (chlormethylisothiazolinone/methylisothiazolinone, formaldehyde and methyldibromoglutaronitrile/phenoxyethanol (MDBGN/PE)) in the range of 2% . The most important allergens of the PS were, in women, alkylaminobenzoate (contained in milking fat) (2.5%), MDBGN/PE (2.2%), benzalkonium chloride (1.8%), chloracetamide (1.4%), diazolidinyl urea (1.3%), octylgallate (1.2%) and Bronopol (1.1%) . In men rates differed only with regard to alkylaminobenzoate (0.9%) . Patients tested with the IB series reacted most often to methylene-bis-thiocyanate (5%), but with a reaction index of -0.7, many reactions were most probably false positives . A further seven preservatives, mostly formaldehyde-releasers used in cutting fluids, gave sensitization rates of between 1% and 3% . Glutaraldehyde, not contained in the series but often tested additionally, showed a remarkable increase in sensitization during the study period . Health care personnel were frequently affected . Altogether, this study identified areas of concern within the different groups of preservatives . The overall impact of most of the preservatives on public health seems to be low, but for diagnostic reasons preservatives must be included in patch test series. Br J Cancer, 1998 Apr, 77(8), 1294 - 9 Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost; Lee SM et al.; In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor (G-CSF, filgrastim) following peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23 consecutive patients aged less than 60 years with poor-prognosis, high-grade non-Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between May 1993 and September 1995 . Patients were randomized to receive either PBPC alone (n = 12) or PBPC+G-CSF (n = 11) after HDCT with busulphan and cyclophosphamide . G-CSF (300 microg day{-1}) was given from day +5 until recovery of granulocyte count to greater than 1.0 x 10(9) l(-1) for 2 consecutive days . The mean time to achieve a granulocyte count > 0.5 x 10(9) l(-1) was significantly shorter in the G-CSF arm (9.7 vs 13.2 days; P<0.0001) as was the median duration of hospital stay (12 vs 15 days; P = 0.001) . In addition the recovery periods (range 9-12 vs 11-17 days to achieve a count of 1.0 x 10(9) l{-1}) and hospital stays (range 11-14 vs 13-22 days) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median . There were no statistically significant differences between the study arms in terms of days of fever, documented episodes of bacteraemia, antimicrobial drug usage and platelet/red cell transfusion requirements . Taking into account the costs of total occupied-bed days, drugs, growth factor usage and haematological support, the mean expenditure per inpatient stay was pound sterling 6500 (range pound sterling 5465-pound sterling 8101) in the G-CSF group compared with pound sterling 8316 (range pound sterling 5953-pound sterling 15,801) in the group not receiving G-CSF, with an observed mean saving of 1816 per patient (or 22% of the total cost) in the G-CSF group . This study suggests that after HDCT and PBPC rescue, the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay . Furthermore, and despite the additional costs for G-CSF, these clinical benefits are not translated into increased health care expenditure. J Antimicrob Chemother, 1998 Mar, 41 Suppl B, 29 - 35 Synergic interactions of macrolides and proton-pump inhibitors against Helicobacter pylori: a comparative in-vitro study; Malizia T et al.; Thirty-eight clinical strains of Helicobacter pylori were isolated from patients with chronic gastritis and gastroduodenal ulceration, and their susceptibility to macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin) in combination with proton-pump inhibitors (lansoprazole and omeprazole) and bismuth subcitrate was assayed . Chequerboard titration was used to analyse the results of antimicrobial interactions and showed that the activity of macrolides was enhanced by combining them with lansoprazole, omeprazole or, to a lesser extent, bismuth subcitrate . While the interactions between erythromycin and the proton-pump inhibitors or bismuth subcitrate were always additive, the combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H . pylori strains, respectively . These results may, in part, account for the enhanced clinical efficacy of macrolides administered with proton-pump inhibitors in the treatment of H . pylori-associated diseases. Aust Vet J, 1998 Jan, 76(1), 25 - 31 Role of prokinetic drugs for treatment of postoperative ileus in the horse; Dart AJ et al.; All horses undergoing coeliotomy for an acute abdominal crisis are at risk of developing ileus and should receive therapy aimed at promoting gastrointestinal function by restoring fluid and electrolyte balance . Adequate analgesia and prevention against peritonitis, bacteraemia and endotoxaemia should be provided . Horses that at the time of surgery have a strangulating or non-strangulating small intestinal obstruction should be considered to be at greater risk of developing a persistent ileus that is refractory to treatment than those horses with lesions involving the large intestine . In horses considered to be at greater risk of developing a persistent ileus, the use of prokinetic agents should be considered . Agents that may be used to improve gastrointestinal motility include adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists, somatostatin analogues and local anaesthetics . There are limited studies into the use of these agents in the horse . Until further research provides more information on motility disorders following intestinal surgery and the efficacy of prokinetic agents in this species, only selective use of some of these drugs can be recommended. Chem Biol, 1998 May, 5(5), 293 - 8 A ligand-mediated dimerization mode for vancomycin; Loll PJ et al.; BACKGROUND: Vancomycin and related glycopeptide antibiotics exert their antimicrobial effect by binding to carboxy-terminal peptide targets in the bacterial cell wall and preventing the biosynthesis of peptidoglycan . Bacteria can resist the action of these agents by replacing the peptide targets with depsipeptides . Rational efforts to design new agents effective against resistant bacteria require a thorough understanding of the structural determinants of peptide recognition by vancomycin . RESULTS: The crystal structure of vancomycin in complex with N-acetyl-D-alanine has been determined at atomic resolution . Two different oligomeric interactions are seen in the structure: back-to-back dimers, as previously described for the vancomycin-acetate complex, and novel face-to-face dimers, mediated largely by the bound ligands . Models of longer, naturally occurring peptide ligands may be built by extension of N-acetyl-D-alanine . These larger ligands can form an extensive array of polar and nonpolar interactions with two vancomycin monomers in the face-to-face configuration . CONCLUSIONS: A new dimeric form of vancomycin has been found in which two monomers are related in a face-to-face configuration, and bound ligands comprise a large portion of the dimer interface . The relative importance of face-to-face and back-to-back dimers to the antimicrobial activity of vancomycin remains to be established, but face-to-face interactions appear to explain how increased antimicrobial activity may arise in covalent vancomycin dimers. Eur J Biochem, 1998 Apr 1, 253(1), 221 - 8 Solution structure of the antimicrobial peptide ranalexin and a study of its interaction with perdeuterated dodecylphosphocholine micelles; Vignal E et al.; Ranalexin, a 20-residue peptide isolated from the skin of the bullfrog Rana catesbeiana displays antimicrobial activity . This peptide contains two cysteine residues in positions 14 and 20 linked by a disulphide bridge . Ranalexin was chemically synthesised and close antimicrobial activities were measured for the reduced and oxidised forms . The solution structure of ranalexin was determined by using circular dichroism, proton NMR spectroscopy and molecular modelling techniques . The reduced and oxidised forms of ranalexin are mainly unstructured in water but display an alpha-helical structure spanning residues 8-15 and 8-17, respectively, in a trifluoroethanol/water mixture (3:7, by vol.) . Ranalexin was found to interact with micelles of dodecylphosphocholine and to adopt a similar helical structure . Moreover, slow-exchanging amide protons located on the same side of the helix suggest that the hydrophobic face of the helix lies on the micelle surface . Hydrophobic residues of the poorly structured N-terminal part which are important for the biological activity are also involved in the interaction with micelles . Taken together, the results suggest that the disulphide bond does not strongly affect either the conformation or the antimicrobial activity of ranalexin. Med Hypotheses, 1998 Mar, 50(3), 219 - 26 Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation; Romanovsky AA et al.; Entering both the old dispute (whether fever is adaptive or maladaptive) and its more recent modification (whether hypothermia is protective or detrimental in systemic inflammation), we suggest a new solution . We hypothesize that fever and hypothermia represent two different strategies of fighting systemic inflammation, each developed as an adaptive response to certain conditions, and each beneficial under these conditions . The antimicrobial and immunostimulating benefits of a high body temperature could be easily offset by its high energy cost . Fever, therefore, is protective only when there is no immediate threat of a substantial energy deficit . Hypothermia, on the other hand, constitutes a response aimed at energy conservation and, as such, is beneficial exactly under the conditions of a substantial energy deficit . The two thermoregulatory responses represent two complementary strategies of survival in systemic inflammation: fever ensures the active attack against the pathogen; hypothermia secures the defense of the host's vital systems . The importance of each response's contribution to the whole campaign depends on the severity of the pathogenic insult, premorbid pathology, and current conditions (stress, nutrition, ambient temperature, etc.). Neurol Clin, 1998 May, 16(2), 419 - 47 Infections of the nervous system; Pruitt AA; Epidemiologic trends causing infections of the nervous system remain a significant source of morbidity and mortality one half-century after the introduction of penicillin . This article outlines common causes of bacterial meningitis, aseptic meningitis syndrome, encephalitis, abscess, spinal cord syndromes, and cranial and peripheral nerve problems . Recommendations for diagnostic evaluation and both empiric and definitive antimicrobial therapy are offered; controversial management issues are also discussed . The protean manifestations of varicella-zoster virus and Lyme diseases are outlined . In addition, special considerations in the immunocompromised host, including organ transplant recipients, cancer patients, and HIV-positive persons are explained, and antimicrobial therapy is discussed. Am J Gastroenterol, 1998 Apr, 93(4), 562 - 8 Cost-effectiveness of noninvasive testing and treatment strategies for H . pylori infection in children with dyspepsia; Vakil N et al.; OBJECTIVE: We sought to model the cost-effectiveness of endoscopy, noninvasive testing and treatment strategies for Helicobacter pylori infection in children with recurrent abdominal pain in two health care systems, those of the United States and Finland . METHODS: Initial serological testing and treatment was compared to empirical treatment with antimicrobials, endoscopy with rapid urease testing, and 13C urea breath testing . Key assumptions and ranges were obtained from the published literature . Costs were determined for the acquisition of various tests and actual reimbursement figures were used for procedural costs . RESULTS: The disease management costs were very similar for both endoscopy ($643.00) and serology ($646.00) in the United States . In Finland, endoscopy ($173.00) was less expensive than serology ($192.00) . The 13C urea breath test was the most expensive procedure in the United States . Sensitivity analysis demonstrated that serological testing became the preferred path if its cost was < $42 in the United States . Empirical treatment of children with dyspepsia was not cost-effective in either country . Sensitivity analysis showed that when prevalence of infection was > 53% in children with recurrent abdominal pain, empirical therapy with endoscopy reserved for failures was the optimal path . CONCLUSIONS: In developed countries like the United States and Finland, significant cost savings are unlikely with an initial test and treat strategy based on serology . Noninvasive testing and treatment of H . pylori infection can be cost-effective in populations with highly prevalent rates of infection. Am J Gastroenterol, 1998 Apr, 93(4), 553 - 61 How do clinicians practicing in the U.S . manage Helicobacter pylori-related gastrointestinal diseases? A comparison of primary care and specialist physicians; Breuer T et al.; OBJECTIVES: We sought to examine the extent to which physicians recognize H . pylori as a causal agent in peptic ulcer disease or as a potential cofactor in other gastrointestinal diseases, and to observe how this knowledge has influenced diagnostic and therapeutic practices . METHODS: We used a national mail survey in the U.S . between February and May of 1996, querying 5994 U.S . physicians (family/general practitioners {FPs}, internists {IMs}, and gastroenterologists) selected at random from three different membership databases of professional associations . RESULTS: The response rate was 52% . More than 95% of physicians who treat symptoms empirically would prescribe acid suppressant therapy rather than anti-H . pylori therapy . Between 43% and 66% of physicians, varying in frequency by medical specialty, would treat the infection in H . pylori-positive patients with nonulcer dyspepsia . In confirmed peptic ulcer disease, between 88% and 100% of physicians would treat the H . pylori infection, depending on the physician group and whether or not the presentation of an ulcer was recurrent . Although 103 distinct anti-H . pylori regimens were reported, 89% of the gastroenterologists and 70% of the primary care physicians (PCPs) used combinations of antimicrobials with reported cure rates of at least 80% . CONCLUSIONS: General knowledge regarding H . pylori-associated diseases was widespread among primary care physicians and gastroenterologists . However, anti-H . pylori therapies judged ineffective were reported as the first choice regimen by 5% of gastroenterologists and 18% of primary care physicians . Gastroenterologists appear to implement the latest scientific developments in the field rapidly whereas PCPs manifest a delayed response, due to either insufficient knowledge or to other factors influencing their approach to treatment. Mil Med, 1998 Apr, 163(4), 198 - 201 Biological warfare training: infectious disease outbreak differentiation criteria; Noah DL et al.; The threat of biological terrorism and warfare may increase as the availability of weaponizable agents increases, the relative production costs of these agents decrease, and, most importantly, there exist terrorist groups willing to use them . Therefore, an important consideration during the current period of heightened surveillance for emerging infectious diseases is the ability to differentiate between natural and intentional outbreaks . Certain attributes of a disease outbreak, although perhaps not pathognomonic for a biological attack when considered singly, may combine to provide convincing evidence of intentional causation . These potentially differentiating criteria include proportion of combatants at risk, temporal patterns of illness onset, number of cases, clinical presentation, strain/variant, economic impact, geographic location, morbidity/mortality, antimicrobial resistance patterns, seasonal distribution, zoonotic potential, residual infectivity/toxicity, prevention/therapeutic potential, route of exposure, weather/climate conditions, incubation period, and concurrence with belligerent activities of potential adversaries. Folia Med (Plovdiv), 1997, 39(4), 93 - 7 Acute renal failure--etiologic and therapeutic considerations . A five-year experience at a single institution; Dimitrakov D et al.; In the present study we highlight the epidemiology, etiologic spectrum, and evaluation of ARF in adults . We then expand on the pathophysiologic mechanisms of renal failure and discuss the rationale for current therapeutic strategies in ARF patients . A total of 79 patients (45 male, female 34), aged 18-75 years (median age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years (January 1990 through October 1995) . Emergency hemodialysis sessions following an acute anuric episode were instituted in 39 cases (49.3% of all patients) . The median number of hemodialysis procedures per patient treated at our institution was 3.2 +/- 1.9 . The total number of acute interstitial nephritis-associated ARF was 40 . In 30 of them (75%) the acute renal insult included a combination of several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted from a combined therapeutic regimen and in the remaining 5 (12.5%) from the application of a single drug . Acute interstitial nephritis developed in 2 patients following a viral infection . In the hemodialysis-treated ARF group 12 patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented with renal impairment for an unspecified period of time preceding the development of overt ARF . In a subset of this group of patients, ARF occurred in 7 patients (17.95%) following an urologic intervention, in 8 patients (20.51%) as a consequence of thermal or mechanical trauma or intoxication and in 3 cases (7.69%) it resulted from fever of unknown origin . Three patients with postoperative peritonitis and 4 other (10.26%) with postoperative complications were encountered in our series . No cases of septic abortion-related or obstetric-related ARF were recorded . 92.3% of all hemodialysis-treated patients seen at our Institution had received a combination of antibiotics and only 2 patients had been pre-treated with a single antimicrobial agent . Our results underscore the strong tendency towards diversity in the etiologic spectrum of clinical entities causing ARF and the increase in the number of acute interstitial nephritis . These factors highlight the importance of precise dosing and administration of drugs, especially antibiotics, as well as the duration of antibiotic treatment. Rev Rhum Engl Ed, 1998 Mar, 65(3), 181 - 6 Iliopsoas bursopathies . A review of twelve cases; Ginesty E et al.; Synovial cysts are far less common at the hip than at the knee and usually occur in patients whose hip cavity communicates with the iliopsoas bursa . We report 12 cases of enlargement of the iliopsoas bursa, nine men and three women, with a mean age of 48 years . The six patients with septic bursitis had severe symptoms similar to those seen in septic arthritis of the hip . Chronic pain with or without a palpable inguinal swelling was the main symptom in the six remaining patients, some of whom had compression of neighboring structures making the diagnosis more difficult . Ultrasonography is the best first-line investigation in patients with an inguinal swelling . Computed arthrotomography with examination of the synovial fluid or magnetic resonance imaging should be performed as a confirmatory diagnostic test . Our series provides evidence of the efficacy of appropriate antimicrobial therapy in septic cases and of corticosteroid injections into the bursa or hip cavity in nonseptic cases. Langenbecks Arch Chir Suppl Kongressbd, 1997, 114, 953 - 5 {Aspects of calculated and controlled antibiotic therapy}; Rodloff AC; Strategies for selection of antimicrobial agents may include estimation of the most appropriate agent (empirical therapy), or planned escalation or de-escalation therapy . Severe and life-threatening infections such as peritonitis have a particularly poor prognosis if the initial therapy fails . Hence, in these cases a de-escalation therapy employing broad spectrum agents with proven high efficacy should be employed, and selection pressure arguments and cost considerations should be immaterial . After 48 to 72 hours, this initial therapy should be reconsidered (de-escalated to less powerful agents), especially in light of the microbiological test results. Oral Microbiol Immunol, 1997 Dec, 12(6), 366 - 71 In vitro antimicrobial susceptibility of periodontopathic Actinobacillus actinomycetemcomitans to roxithromycin and erythromycin; Piccolomini R et al.; The in vitro minimal inhibitory concentrations (MIC) and minimal bactericidal concentration (MBC) of roxithromycin and erythromycin against Actinobacillus actinomycetemcomitans were evaluated . Sixty-seven different A . actinomycetemcomitans isolated from periodontal pockets of 101 subjects with different forms of early-onset and adult periodontitis and three reference strains of A . actinomycetemcomitans (ATCC 29522, ATCC 29523, and NCTC 9710) were included in this study . Erythromycin showed poor in vitro activity against A . actinomycetemcomitans; roxithromycin, on the contrary, exhibited good in vitro activity . Moreover, roxithromycin showed the best in vitro antimicrobial activity against 17 serotype a and 12 serotype c subpopulations of A . actinomycetemcomitans; against 38 serotype b subpopulation of A . actinomycetemcomitans, roxithromycin was consistently active . Roxithromycin exhibited MBC values usually equal to, or one-fold higher than MIC values . All the MBC values of erythromycin were three- to four-fold higher than the respective MIC result . Since roxithromycin is characterized by high concentrations in serum and good penetration and diffusion into gingival tissue, it could be expected to pass into the gingival crevicular fluid at levels sufficiently high to inhibit A . actinomycetemcomitans in vivo . These data indicate that roxithromycin might be a potential candidate for therapeutic trials in patients with A . actinomycetemcomitans-associated periodontitis. Haematologica, 1998 Mar, 83(3), 231 - 6 Prior treatment with alpha-interferon does not adversely affect the outcome of allogeneic BMT in chronic phase chronic myeloid leukemia; Zuffa E et al.; BACKGROUND AND OBJECTIVE: Controlled clinical trials have shown that Interferon-alpha (IFN-alpha) is able to control myeloid proliferation and to suppress the Ph+ clonal hemopoiesis in early chronic phase chronic myeloid leukemia (CML): a growing number of patients are treated with this agent from diagnosis . However, if a CML patient has an HLA-identical sibling, bone marrow transplant (BMT) represents the best choice of treatment . Since IFN-alpha is known to modify the immunologic response and to increase marrow fibrosis, information is needed on the outcome of patients transplanted after IFN-alpha treatment . DESIGN AND METHODS: We analyzed retrospectively 32 Ph+ CML patients submitted to BMT in the last 6 years in Institute "Seragnoli" . All the patients were in 1st chronic phase, their median age was 37 years, the donors were HLA-identical (27/32) or 1 Ag-mismatched (5/32) siblings . Big BuCy was the conditioning regimen employed for all and GVHD prophylaxis was based on CsA in 4 patients and Csa+MTX in 28 patients; all patients received homogeneous pre and post-transplant supportive care, antimicrobial and antiviral prophylaxis . These patients were divided into 2 groups according to the treatment before BMT: 16 received IFN from diagnosis to BMT (mean dose 6.9 MU/daily) for at least 6 mos (mean 23 mos, range 8-75) and 16 received chemotherapy alone (hydroxyurea {HU}) . RESULTS: Hematological recovery was comparable in the two groups: time to 0.5 x 10(9)/L PMN was 20.5 days (range 11-32) in the IFN group and 20 days (range 10-32) in the HU group; time to 50 x 10(9)/L platelets was 28 days (range 20-117) in the IFN group and 27 days (range 20-112) in the HU group . The incidence of acute GVHD was not different in the two groups for any grade of the disease; in patients who survived more than 100 days, chronic GVHD occurred in the two groups with the same frequency . Seven patients died of transplant related mortality (TRM), 4 in the IFN group and 3 in the HU group . Hematological relapse was observed in only one case in the HU group; no cytogenetic relapse occurred . Disease free survivals at 7 years are 61% and 72%, respectively; the difference is not significant . INTERPRETATIONS AND CONCLUSIONS: Notwithstanding the low number of patients included in this study, the data reported here confirm that prior treatment with alpha-IFN does not adversely affect transplant outcome. Int J Antimicrob Agents, 1998 Feb, 9(4), 239 - 53 Subgingival controlled release of antimicrobial agents in the treatment of periodontal disease; Southard GL et al.; Local drug delivery of antimicrobics by sustained release delivery systems can be used to treat periodontal disease . Advantages of these systems may include biodegradation of the system, maintaining high levels of antibiotic in the gingival crevicular fluid (GCF) for a sustained period of time and ease of use with high patient acceptance . This review will identify human in vivo clinical and microbiological studies . Sustained release formulations, application methods, clinical results and microbiological effects are discussed. Folia Microbiol (Praha), 1998, 43(1), 7 - 14 Biological effects of macrotetrolide antibiotics and nonactic acids; Zizka Z; Published results as well as patent applications on biological effects of macrotetrolides and nonactic acids are reviewed . Their antimicrobial, antiprotozoan (coccidiostatic), antiparasitic (anthelminthic), insecticidal and acaricidal (miticidal) effects and also newly described immunosuppressive and plant growth stimulating activities are described . Both theoretical papers and practical applications including the effects of macrotetrolides on the environment are included; a particular target organism and precise dosage (e.g . LD50) are reported, in agreement with the original papers . It appears that macrotetrolides and their homologs are very prospective bioactive compounds that find application in agriculture, forestry, human and veterinary medicine while their negative effects on the environment are restricted to a minimum (biological quality of soil and water etc.). J Gen Virol, 1998 Apr, 79 ( Pt 4), 731 - 40 Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression; Wachinger M et al.; Antimicrobial peptides are effectors of innate immunity, providing their hosts with rapid non-specific defence against parasitic invaders . In this report, the effects are assessed of two well-characterized antimicrobial amphipathic peptides (melittin and cecropin) on human immunodeficiency virus 1 (HIV-1) replication and gene expression in acutely infected cells at subtoxic concentrations . Production of infectious, cell-free virus was inhibited in a dose-dependent manner, with ID50 values in the range 0.9-1.5 microM for melittin and 2-3 microM for cecropin . Analysis of the effect of melittin on cell-associated virus production revealed decreased levels of Gag antigen and HIV-1 mRNAs . Transient transfection assays with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that melittin has a direct suppressive effect on activity of the HIV LTR . HIV LTR activity was also reduced in human cells stably transfected with retroviral expression plasmids for the melittin or cecropin gene . It is concluded that antimicrobial peptides such as melittin and cecropin are capable of inhibiting cell-associated production of HIV-1 by suppressing HIV-1 gene expression. Clin Exp Metastasis, 1998 Apr, 16(3), 217 - 25 Chemically modified tetracyclines inhibit human melanoma cell invasion and metastasis; Seftor RE et al.; Recent work has shown that chemically modified tetracyclines (CMTs) are potent inhibitors of matrix metalloproteinase (MMP) activity, both in vitro and in vivo, which is distinct from their antimicrobial activities (Golub et al . Crit Rev Oral Biol Med, 2, 297-321, 1991; Ryan et al . Curr Opin Rheumatol, 8, 23847, 1996) . The process of tumor cell invasion requires MMP-mediated degradation of extracellular matrix barriers as a key step in the metastasic cascade . In this study, we examined the effect(s) of doxycycline and CMTs on extracellular levels of gelatinase A and B activity from a highly invasive and metastatic human melanoma cell line C8161, and correlated these observations with changes in the cells' biological behavior in an in vitro invasion assay and in an in vivo SCID mouse model . The results indicate that coincident with the ability of these compounds to differentially suppress extracellular levels of gelatinase activity, C8161 cells treated with doxycycline, CMT-1, CMT-3, or CMT-6 were less invasive in vitro in a dose-dependent manner (3-50 microg/ml) . Furthermore, data derived from the in vivo model indicate that SCID mice dosed orally with CMT-1 or CMT-3 contained a reduced number of lung metastases following i.v . injection of C8161 cells via tail vein inoculation . These observations suggest that careful screening of different CMTs could lead to the identification of compounds which suppress the formation and magnitude of metastases associated with certain cancers, and if used as an adjunct to other treatment regimes, lead to greater efficacy in the treatment of metastatic cancers. Burns, 1997 Nov-Dec, 23(7-8), 608 - 14 Cryopreserved cadaveric allografts for treatment of unexcised partial thickness flame burns: clinical experience with 12 patients; Eldad A et al.; Partial thickness burns (PTB) usually heal within 3 weeks . Prevention of infection and desiccation of the wounds are crucial for optimal healing . Early tangential excision of the burn eschar and allografting prevent deepening of the burns, and are therefore advocated for treatment with the best functional and aesthetic results . For superficial partial thickness burns (SPTB) conservative use of topical antimicrobial agents with frequent dressing changes are implemented . We compared the conservative treatment for PTBs and SPTBs to grafting cryopreserved cadaveric allografts with no prior excision . Twelve patients with flame PTB areas were allografted after mechanical debridement without excision of the burn wounds . The allografts were cadaveric skin cryopreserved by programmed freezing and stored at -180 degrees C for 30-48 months . Matching burns for depth and area were treated with silver sulfadiazine (SSD) one to two times daily until healing or debridement and grafting were required . It was found that 80 per cent of the cryopreserved allografts adhered well and 76 per cent of the treated areas healed within 21 days, whereas only 40 per cent of the SSD-treated burns healed within 21 days . Partial thickness burns can be treated successfully with viable human allografts (cryopreserved cadaveric skin) with no prior surgical excision . The burn wounds heal well within 3 weeks . For deep partial thickness burns (DPTB) treatment with allografts has no advantage if they have not been previously excised. Br Poult Sci, 1998 Mar, 39(1), 42 - 6 Effectiveness of two fluoroquinolones for the treatment of chronic respiratory disease outbreak in broilers; Sumano LH et al.; 1 . Chronic respiratory disease (CRD) caused by Mycoplasma synoviae in association with Escherichia coli is the disease most frequently encountered in poultry in Mexico . 2 . Differences of antimycoplasmal activity, pharmacokinetics and cost among fluoroquinolones were the impetus for this clinical evaluation of efficacy of enrofloxacin and norfloxacin-nicotinate in broilers with CRD . 3 . A total of 99,600 broilers, naturally infected with M . synoviae and E . coli, were treated with enrofloxacin (10 mg/kg/d for 3 d) (n = 49,800) or norfloxacin-nicotinate (20 mg/kg/d for 3 d) (n = 49,800) . 4 . Based on survivor analysis, there were no significant differences of efficacy of the 2 drugs . Survivor probabilities were above 0.99 . 5 . These results indicate that enrofloxacin and norfloxacin-nicotinate are efficacious for treatment of CRD . Questions remaining to be answered by other studies include: public health concern about the use of fluoroquinolones for the treatment of CRD; clinical superiority of one of these drugs on the basis of an attribute other than antimicrobial activity, such as cost:benefit ratio or ability to prevent bacterial resistance . 6 . Clinical efficacy is not a relevant variable in assessing whether norfloxacin-nicotinate or enrofloxacin should be used for the treatment of CRD associated with E . coli in broilers. Sci Prog, 1998, 81 ( Pt 1), 35 - 68 Plants under attack II; Strange RN; In many diseases of plants there is a well defined genetic relationship between host and pathogen, the host possessing resistance genes and the pathogen possessing avirulence genes . Where these are cognate their products interact and trigger a variety of resistance responses, resulting in an incompatible interaction . Where they are not cognate the pathogen is not recognised and invades the host causing a compatible interaction . A few resistance genes and a larger number of avirulence genes have been cloned and this information has afforded us new perspectives of the recognition phenomenon itself and the means by which virulent pathogens avoid being recognised . Mechanisms of resistance range from preformed antimicrobial compounds to a series of components that are induced as a response to microbial challenge . Most of these induced reactions are preceded by and may be triggered by an oxidative burst which results in the cross-linking of cell wall proteins and also causes the death of one to several cells . This localized death of host cells, termed the hypersensitive response, provides an explanation for resistance to obligate parasites which require living host tissue but not for resistance to facultative parasites which colonise dying or dead tissue . However, the hypersensitive response appears to be intimately involved with several other defence responses such as the synthesis and accumulation of phytoalexins, lignification and the production of hydrolase enzymes that attack the invader . Salicylic acid has proved fundamental to the effecting of these defence responses and also to the phenomenon of systemic acquired resistance whereby a previous challenge from a pathogen induces the expression of enhanced resistance to a second challenge by the same or another organism . Despite these sophisticated defences plants still succumb to attack . Two of the weapons to which they are vulnerable and which are produced by many successful pathogens are toxins and enzymes . In some instances an understanding of these has pointed to novel methods of control supplementary to that obtained by conventional breeding for resistance. Indian J Exp Biol, 1997 Nov, 35(11), 1233 - 6 Effect of mycotoxins isolated from Penicillium nigricans on glucose-6-phosphate dehydrogenase; Majumder UK et al.; A new mycotoxin product (NMP) was isolated from the culture of mutated wild strain of P . nigricans which is less toxic and has sterol derivative . NMP (LD50 > 1 g/kg) showed antimicrobial and antineoplastic activities and does not affect the hematological parameters like RBC count and hemoglobin . It maintained normal blood glucose level by increasing the enzyme activity of glucose-6-phosphate dehydrogenase (EC-1.1.1.49; G-6-PDH) by 30% . It also maintained the normal ion balance in the blood of mice . NMP decreased Km value of glucose-6-phosphate dehydrogenase and thus increased substrate affinity of the enzyme . Reduction of toxicity of NMP has been well explained by higher activity of G-6-PDH which is highly specific for production of NADPH. Rev Hosp Clin Fac Med Sao Paulo, 1997 Jul-Aug, 52(4), 209 - 16 {Antibiotic prophylaxis in oncologic surgery}; Velasco E et al.; Perioperative antibiotic administration can decrease surgical morbidity, shorten hospitalization, while lowering the overall costs attributable to infections . Its use in surgery is widespread and often inappropriate . In this study, the authors evaluate the guidelines for selection and use of prophylactic antibiotics in surgical cancer patients at the Hospital of Cancer in Rio de Janeiro, Brazil . During 36 non-consecutive months, 1681 cancer patients submitted to surgical procedures were prospectively followed-up by members of the Hospital Infection Control Committee . The overall surgical site infection (SSI) and mortality rates were 17.7% and 4.8% respectively . Prophylactic antibiotics were used in 1262 elective surgeries (75.1%), and their use was not considered to be in accordance with the recommended protocol in 37.6% of the cases . The inadequate antimicrobial prophylaxis resulted in higher incidence of SSI than did prophylaxis in according to the protocol (21.7% vs . 16.4, Relative Risk 1.32; 95% Confidence Internal 1.05-1.67; p0.01) . This study calls the attention for the need of a more strict and determined educational program in order to provide mechanisms for an adequate administration of prophylactic antibiotics to patients submitted to high-risk surgeries. Med Klin (Munich), 1998 Mar 15, 93(3), 165 - 9 {Quantitative cultures in diagnosis of pneumonia--a method for routine practice?}; Ewig S et al.; Quantitative cultures of respiratory secretions represent a valid technique for the diagnosis of ventilator-associated pneumonia . Contamination, colonization and true infection can be differentiated with a reasonable specificity using established cut-offs of bacterial colony counts . Quantitative investigations provide local epidemiological databases as a framework for empirical antimicrobial policies and may also prove helpful in the guidance of individual antimicrobial therapy . Another reasonable indication is HIV-associated pneumonia . However, the use of this technique in routine practice is hampered by the high expertise and experience that will be necessary to be successfully used . Nevertheless, in view of the need to identify bacterial susceptibility patterns, at least large treatment centers should routinely use this most powerful diagnostic technique. Schweiz Rundsch Med Prax, 1998 Mar 18, 87(12), 403 - 12 {Sensitivity of bacteria to therapeutic drugs (Zurich 1996)}; Wust J et al.; This paper describes the frequency of susceptibility of Gram-negative and Gram-positive bacteria against antibacterial agents . The data are based on all susceptibility tests performed in 1996 at the Department of Medical Microbiology of the University of Zurich and at the private medical laboratory "medica" in Zurich . The evaluation of the results from 1975 to 1996 shows that susceptibilities against the antimicrobial agents tested have not changed markedly in this period with few exceptions . The tables may be a help for the physician in his decision for a "calculated chemotherapy" of bacterial infections. Biochemistry, 1998 Mar 24, 37(12), 4288 - 98 Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin; Hwang PM et al.; The solution structure of bovine lactoferricin (LfcinB) has been determined using 2D 1H NMR spectroscopy . LfcinB is a 25-residue antimicrobial peptide released by pepsin cleavage of lactoferrin, an 80 kDa iron-binding glycoprotein with many immunologically important functions . The NMR structure of LfcinB reveals a somewhat distorted antiparallel beta-sheet . This contrasts with the X-ray structure of bovine lactoferrin, in which residues 1-13 (of LfcinB) form an alpha-helix . Hence, this region of lactoferricin B appears able to adopt a helical or sheetlike conformation, similar to what has been proposed for the amyloidogenic prion proteins and Alzheimer's beta-peptides . LfcinB has an extended hydrophobic surface comprised of residues Phe1, Cys3, Trp6, Trp8, Pro16, Ile18, and Cys20 . The side chains of these residues are well-defined in the NMR structure . Many hydrophilic and positively charged residues surround the hydrophobic surface, giving LfcinB an amphipathic character . LfcinB bears numerous similarities to a vast number of cationic peptides which exert their antimicrobial activities through membrane disruption . The structures of many of these peptides have been well characterized, and models of their membrane-permeabilizing mechanisms have been proposed . The NMR solution structure of LfcinB may be more relevant to membrane interaction than that suggested by the X-ray structure of intact lactoferrin . Based on the solution structure, it is now possible to propose potential mechanisms for the antimicrobial action of LfcinB. Am J Vet Res, 1998 Apr, 59(4), 464 - 7 Clinical and microbiological effects of controlled-release local delivery of minocycline on periodontitis in dogs; Hayashi K et al.; OBJECTIVE: To evaluate the clinical and microbiological efficacy of minocycline in a subgingival local delivery system as an adjunct to tooth scaling and root planing in dogs with periodontal disease . ANIMALS: Nine 4- to 7-year-old Beagles with periodontitis . PROCEDURE: After scaling of teeth and root planing, 2 treatment and 1 or 2 control sites were selected for each dog: treated sites (n = 18) received minocycline hydrochloride periodontal formulation and control sites (n = 12) received ointment base (no minocycline) . Gingival crevicular fluid was collected at a baseline (prior to treatment) and at week 4 . Clinical and microbiological effects were evaluated and compared among sites . RESULTS: In minocycline-treated sites, clinical indices were significantly decreased at week 4, compared with those at baseline . Minocycline-treated sites were associated with a significant decrease in gingival crevicular fluid, probing depth, and bleeding on probing values, compared with those for control sites at week 4 . Compared with that for control sites, total bacteria count in periodontal pockets of minocycline-treated sites had an obvious tendency to decrease by week 4 . Proportions of Porphyromonas and Fusobacterium spp were significantly decreased at week 4, compared with proportions at control sites and with pretreatment (baseline) values . CONCLUSIONS: When used as an adjunct to tooth scaling and root planing, minocycline periodontal formulation stimulated favorable clinical and antimicrobial responses. Curr Eye Res, 1998 Apr, 17(4), 348 - 62 Identification, origins and the diurnal role of the principal serine protease inhibitors in human tear fluid; Sathe S et al.; PURPOSE: Previous work identified polymorphonuclear leukocyte (PMN) elastase as the major caseinolytic entity in tears collected after overnight eye closure . This study was designed to identify the principal serine protease inhibitors (serpins) in tears and to determine their function in the regulation of PMN cell proteases on eye closure . METHODS: Reflex and closed eye tear samples were collected by microcapillary tube and centrifuged . After reflex and closed eye supernatants (R and C) were fractionated by HPLC, samples were subjected to casein zymography and reverse zymography . Western blots were utilized to screen tears and HPLC fractions for elastase, cathepsin G and proteinase-3 and to obtain semi-quantitative data on alpha 1-protease inhibitor (alp1), alpha 1-antichymotrypsin (alpha 1-Achy), secretory leukocyte protease inhibitor (SLPI), elafin and alpha 2-macroglobulin (alpha 2-M) as well as associated complexes and products . To confirm specificity of reactivity, samples were immunoprecipitated for a given protease or serpin and screened for the coprecipitation of interacting species . RESULTS: Although R fluid contains no caseinolytic activity, it contains low levels of serpin-like activity principally in the form of SLPI (5-10 ng/microliter) . Lesser amounts of alpha 2-M, alpha 1-Achy and alp1 (approximately < 1-3 ng/microliter) are also evident . C fluid is associated with very high levels of PMN cell proteases along with a approximately 5-20-fold increase in the concentrations of all of the above inhibitors . Trace levels of elafin were also detected . The concentrations of rapid reacting inhibitors exceeded that of proteases, with SLPI, alpha 1-Achy and alp1 being the principal functional entities . In atypical samples, complexes of elastase and alpha 2-M were also encountered . CONCLUSIONS: SLPI, a known antimicrobial agent and an elastase and cathepsin G inhibitor, is the principal serpin in R fluid . C fluid is associated with a marked increase in the concentrations of an array of rapid reacting serpins capable of inhibiting all known PMN cell serine proteases . In the normal closed eye, the concentration of rapid reacting inhibitors always exceeds that of proteases with C fluid also containing a functional reserve of the slow reacting inhibitor alpha 2-M. Crit Care Clin, 1998 Apr, 14(2), 283 - 308 Antibiotic use in the critical care unit; Ambrose PG et al.; The antimicrobial management of patients in