Pediatr Infect Dis J, 1998 Aug, 17(8 Suppl), S79 - 82 Potential infectious disease complications of upper respiratory tract infections; Gooch WM 3rd; Upper respiratory tract infections (URTIs), particularly otitis media and sinusitis, are prevalent among children . With recurrent URTIs there is an increased likelihood of sequelae . Suppurative complications associated with URTIs, although rare, must be treated rapidly to prevent serious morbidity and mortality . Further, increase in antimicrobial resistance may be accompanied by an increased risk for complications because infecting pathogens may be more difficult to eradicate. BMJ, 1998 Sep 5, 317(7159), 647 - 50 Antimicrobial resistance in developing countries; Hart CA et al.; PIP: In 1990, an estimated 78% of the world's total population lived in the developing world . Of the 39.5 million deaths in the developing world, 9.2 million were estimated to have been caused by infectious and parasitic diseases . 98% of child mortality occurs in the developing world, due mainly to infections . Based upon information gathered through searches of the Medline and Bath Information and Data Services computerized databases, discussions with colleagues, and personal experiences, the authors consider the progress and impact of bacterial resistance to antimicrobial drugs in the developing world . While antibiotics are important in developing countries, they are often scarce commodities which are affordable and therefore available to only the comparatively wealthy . Because the use of antibiotics is unregulated in many developing countries, antibiotics are often misused and overused . Such use has provoked the development of infectious agents which are resistant to antimicrobial drugs, such as strains of pneumococcal meningitis, tuberculosis, and typhoid fever . Levels of morbidity and mortality are increasing as a result . Better access to diagnostic laboratories is needed, as well as improved surveillance of the emergence of resistance, better regulation of antibiotics' use, and better education of the public, physicians, and veterinarians in the appropriate use of drugs . BMJ, 1998 Sep 5, 317(7159), 632 - 7 Are amoxycillin and folate inhibitors as effective as other antibiotics for acute sinusitis? A meta-analysis; de Ferranti SD et al.; OBJECTIVES: To examine whether antibiotics are indicated in treating uncomplicated acute sinusitis and, if so, whether newer and more expensive antibiotics with broad spectra of antimicrobial activity are more effective than amoxycillin or folate inhibitors . DESIGN: Meta-analysis of randomised trials . SETTING: Outpatient clinics . SUBJECTS: 2717 patients with acute sinusitis or acute exacerbation of chronic sinusitis from 27 trials . INTERVENTIONS: Any antibiotic versus placebo; amoxycillin or folate inhibitors versus newer, more expensive antibiotics . MAIN OUTCOME MEASUREMENTS: Clinical failures and cures . RESULTS: Compared with placebo, antibiotics decreased the incidence of clinical failures by half (risk ratio 0.54 (95% confidence interval 0.37 to 0.79)) . Risk of clinical failure among 1553 randomised patients was not meaningfully decreased with more expensive antibiotics as compared with amoxycillin (risk ratio 0.86 (0.62 to 1.19); risk difference 0.9 fewer failures per 100 patients (1.4 more failures to 3.1 fewer failures per 100 patients)) . The results were similar for other antibiotics versus folate inhibitors (risk ratio 1.01 (0.52 to 1.97)), but data were sparse (n=410) and of low quality . CONCLUSIONS: Amoxycillin and folate inhibitors are essentially as effective as more expensive antibiotics for the initial treatment of uncomplicated acute sinusitis . Small differences in efficacy may exist, but are unlikely to be clinically important. Eur Respir J, 1998 Aug, 12(2), 351 - 6 Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis; Plit ML et al.; Patients who have completed a treatment for severe pulmonary tuberculosis (TB) are often left with severe respiratory disability . There have been few prospective studies assessing the effect of treatment on lung function in such patients . The influence of antimicrobial chemotherapy on lung function was investigated over a six month period in patients with newly diagnosed pulmonary TB to test the hypothesis that treatment improves lung function, as well as to identify factors that may influence lung function outcome . Seventy-six patients were recruited into the study, of whom 74 completed the treatment programme . Forty-two were current smokers and 13 seropositive for the human immunodeficiency virus . Improvement in lung function occurred in 54% of patients, but residual airflow limitation or a restrictive pattern was evident in 28% and 24% of patients, respectively . The extent of lung infiltration (radiographic score) both at the outset and after chemotherapy was significantly and negatively related to forced expiratory volume in one second (FEV1) (% pred) (r=-0.41, and r=-0.46, respectively) . The post-treatment serum C-reactive protein and alpha1-protease inhibitor levels were negatively associated with FEV1 (% pred) (r=-0.30 and r=-0.35, respectively) . These findings demonstrate that, while antimicrobial chemotherapy may lead to improved lung function in patients with pulmonary tuberculosis, a large proportion of patients has residual impairment . The most significant factor influencing post-treatment lung function status, as measured by forced expiratory volume in one second (% predicted), is the pretreatment and post-treatment radiographic score, which acts as a marker of the extent of pulmonary parenchymal involvement in tuberculosis. J Antibiot (Tokyo), 1998 Jul, 51(7), 647 - 54 New types of liposidomycins that inhibit bacterial peptidoglycan synthesis and are produced by Streptomyces . II . Isolation and structure elucidation; Kimura K et al.; Various new liposidomycins were isolated from a culture of the strain Streptomyces sp . SN-1061M by changing medium components and they were classified into four types (I-IV) based on their structures . They were purified by butanol extraction, silica gel and LH-20 column chromatographies, and high performance liquid chromatography on ODS columns . Type (I) has the original structure which has sulfate and 3-methylglutaric acid moieties . Type (II) has no 3-methylglutaric acid moiety and type (III) has no sulfate moiety . Type (IV) has neither moiety . Type (III) and (IV) compounds, which have no sulfate moiety, exhibited more potent antimicrobial activity. J Antibiot (Tokyo), 1998 Jul, 51(7), 607 - 17 A-53930A and B, novel N-type Ca2+ channel blockers; Hisamoto M et al.; A-53930A, B and C, which inhibit N-type Ca2+ channels, were isolated from the culture broth of Streptomyces vinaceusdrappus SANK 62394 . A-53930A and B were new compounds which contained a carbamoyl group on the 6-hydroxyl group of the D-gulosamine part of streptothricin . A-53930C was identical to streptothricin B . A-53930A, B and C inhibited {125I}omega-conotoxin MVIIA binding to N-type Ca2+ channels (IC50= 0.17, 0.091 and 0.071 microM), but did not inhibit {3H}PN200-110 binding to L-type Ca2+ channels (IC50 > 50 microM) . These compounds also inhibited {3H}norepinephrine release from chick cerebral cortex synaptosomes (IC50=91.0, 20.6 and 39.5 microM), indicating these compounds selectively block N-type Ca2+ channels which are important for neurotransmitter release . It was also revealed that although A-53930C had antimicrobial activity against gram-negative and -positive bacteria and fungi, A-53930A and B showed weak activity only against gram-negative bacteria. World Health Organ Tech Rep Ser, 1998, 879, i - vi, 1-73 Evaluation of certain veterinary drug residues in food . Forty-eighth report of the Joint FAO/WHO Expert Committee on Food Additives; Evolution and phylogeny of defense molecules associated with innate immunity in horseshoe crab; Department of Biology, Faculty of Science, Kyushu University, Fukuoka 812-8581, JapanThis short review describes the molecular evolution and phylogeny of various defense molecules participating in the host defense of horseshoe crab . It is well known that invertebrate animals, which lack adaptive immune systems, have developed various defense systems, so called innate immunity, that respond to common antigens on the surface of potential pathogens . The systems include hemolymph coagulation, melanization, cell agglutination, antimicrobial action, active oxygen formation, and phagocytic action . Among them, hemolymph coagulation and phenoloxidase-mediated melanization, in addition to cell agglutination, are directly induced by foreign substances, that result in the engulfment of invading microbes . The immobilized invaders are finally killed by antimicrobial substances released mainly from many kinds of hemocytes . In the past two decades, we have investigated biochemically various defense molecules, using horseshoe crab as a model animal, and established extensively their molecular structures . These results now make it possible to discuss evolution and phylogeny of the defense molecules at a molecular level, in comparison with those derived from vertebrate animals . Here, the authors will describe the present state of our knowledge concerning molecules mainly associated with innate immunity. Aliment Pharmacol Ther, 1998 Aug, 12(8), 731 - 4 Short-term low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients; Pazzi P et al.; BACKGROUND: The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton-pump inhibitor pantoprazole as part of these regimens has not yet been widely tested . AIM: To evaluate the efficacy and tolerability of a 1-week low-dose pantoprazole-based triple therapy in patients with H . pylori-positive duodenal ulcer . METHODS: In an open single-centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H . pylori infection received pantoprazole 40 mg o.m . for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d . plus clarithromycin 250 mg b.d . H . pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4-6 weeks after the end of treatment, confirmed 4 weeks later by 13C-urea breath test . RESULTS: Sixty-six patients (93%) completed the trial and five patients were lost to follow-up . H . pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2-97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7-93.0%) . At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%) . Mild adverse events occurred in six patients (9.1%) . CONCLUSIONS: One-week low-dose pantoprazole-based triple therapy is a simple, effective and well-tolerated regimen for ulcer healing and H . pylori eradication in patients with duodenal ulcer. Bioessays, 1998 Jul, 20(7), 569 - 76 Oligoglucoside elicitor-mediated activation of plant defense; Ebel J; Plants have acquired defense mechanisms to counteract potential pathogens . One such strategy involves inducible defense reactions that are activated by elicitors, signaling compounds of diverse nature . For one class of elicitors, oligoglucosides, recent developments in the characterization and isolation of an oligoclucan-binding protein, a putative elicitor receptor, and isolation of a cDNA that encodes the binding protein are discussed . Furthermore, the discovery of a role for calcium in the elicitation process is described . Finally, the identification of polymerase chain reaction products whose sequences indicate that they encode cytochrome P-450-dependent enzymes with possible roles in the formation of phytoalexins, antimicrobial plant defense compounds, is reported . These advances may lay the foundation for the first characterization of a receptor and subsequent signaling events in oligoglucan elicitor perception by higher plants. Clin Nephrol, 1998 Aug, 50(2), 128 - 30 Nocardial brain abscess in a renal transplant recipient successfully treated with triple antimicrobials; Sabeel A et al.; Nocardia is a serious opportunistic infection in renal transplant recipients and nocardial brain abscess in these patients has a high mortality . In addition to antimicrobial therapy, treatment usually involves craniotomy and excision of the abscess . We describe a renal transplant recipient maintained on cyclosporine and prednisone developing Nocardia Asteroides brain abscess . After stereotactic aspiration of the abscess, successful treatment was achieved by triple therapy with trimethoprim sulfamethoxazole (TMP/SMX), ceftriaxone and amikacin . The allograft function remained stable . Long-term prophylaxis with TMP/SMX is necessary to prevent the relapse of nocardia. J Immunol, 1998 Sep 1, 161(5), 2383 - 90 Migration inhibitory factor induces killing of Leishmania major by macrophages: dependence on reactive nitrogen intermediates and endogenous TNF-alpha; Juttner S et al.; Macrophage migration inhibitory factor (MIF) is a product of activated T cells, anterior pituitary cells, and macrophages . MIF plays an important role in LPS-induced shock and delayed-type hypersensitivity . Furthermore, MIF exhibits a proinflammatory spectrum of action, promoting TNF-alpha production by macrophages, and counter-regulates glucocorticoid suppression of cytokine production . Here, we report that purified recombinant MIF activates murine macrophages to kill Leishmania major, with maximal effects at concentrations above 1 microg/ml . This MIF-mediated activation is specific, since it can be blocked completely by anti-MIF mAb . The MIF-mediated activation is dependent on TNF-alpha produced endogenously by macrophages, because the administration of anti-TNF-alpha antiserum markedly reduced the MIF effect . No MIF-mediated activation was observed in macrophages derived from TNF receptor p55 knockout mice, thus demonstrating the requirement of the smaller TNF receptor molecule for autocrine TNF-alpha signaling . A highly specific inhibitor of the inducible nitric oxide synthase (iNOS), L-N6-(1-iminoethyl)lysine, dihydrochloride, also inhibited the action of MIF, suggesting an important role for iNOS in the antiparasitic properties of MIF . In line with this, no MIF-mediated activation was detected analyzing macrophages derived from iNOS-deficient mice . The effect of MIF was blocked completely by the macrophage-deactivating cytokines IL-10, IL-13, and TGF-beta . Finally, the expression of MIF mRNA and protein was up-regulated in lymph nodes of mice during the first week after infection with L . major . MIF therefore represents a cytokine involved not only in the recruitment of proinflammatory cells during infection but also in the complex regulation of the antimicrobial activity of these cells. Dig Dis Sci, 1998 Aug, 43(8), 1708 - 13 Risk factors and prevention of early infection after implantation or revision of transjugular intrahepatic portosystemic shunts: results of a randomized study; Deibert P et al.; The aim of this study was to evaluate the efficacy of a single dose of a second-generation cephalosporine to prevent postinterventional infection and to identify risk factors for postinterventional infection in patients receiving implantation or revision of a transjugular intrahepatic portosystemic shunt (TIPS) . Eighty-four patients (105 transjugular interventions) were randomized receiving no antibiotic treatment (46 interventions) or 2 g cefotiam (56 interventions) given at the beginning of the procedure . Patients with overt infection or those receiving antibiotic treatment in the preceding two weeks were excluded . Groups were comparable with respect to biographic and medical data . Postinterventional infection was defined as an increase in WBC count (> or =15,000/microl), fever (> or =38.5 degrees C), or a positive blood culture . Infection occurred in 17% of the patients . Patients not receiving cefotiam had a slightly higher incidence of infection (20%) than patients treated with cefotiam (14%, NS) . Multivariate analysis demonstrated prognostic relevance for multiple stenting and periprocedural use of a central venous line . The clinical outcome of the patients was unaffected by cefotiam treatment . In conclusion, a single dose of intrainterventional cefotiam does not prevent postinterventional infection . This may be due to the antimicrobial spectrum and short half-time of cefotiam . Strict adherence to aseptic conditions during intervention and early removal of central venous lines may reduce the rate of post interventional infection considerably . Antibiotic prophylaxis with cefotiam does not seem to be useful since it will not influence outcome and costs. Ann Periodontol, 1998 Jul, 3(1), 262 - 75 Implications of oral infections on systemic diseases in the institutionalized elderly with a special focus on pneumonia; Limeback H; Systemic infection in the elderly patient living in a chronic care setting presents a significant burden to the health care system . The extent to which oral organisms cause systemic infections through hematogenous dissemination in the institutionalized elderly is still unknown . A more likely and common route of systemic infection by oral microorganisms is through aspiration of oropharyngeal fluids containing oral pathogenic microorganisms, which colonize the lower respiratory tract and cause pneumonia . Respiratory pathogens emerge in the dental plaque of elderly patients with very poor oral hygiene and severe periodontal disease . In the chronic care setting, aspiration of oropharyngeal fluids contaminated with these bacteria occurs in patients with diminished host defenses, resulting in bacterial pneumonia . This is also a problem in intensive care units in the hospital setting . In one study, pre-rinsing with a 0.12% chlorhexidine gluconate mouthwash significantly lowered the mortality rate from postsurgical pneumonia in patients undergoing open heart surgery . Selective digestive decontamination, a technique involving the topical application of antimicrobials to reduce the risk of colonization of the respiratory tract, has been used to reduce the incidence of nosocomial pneumonia in the acute care setting of hospitals . This technique has not been employed in the nursing home setting . Whether improving oral hygiene would also lower the risk in either of these settings has not been studied . A number of obstacles must be overcome in designing studies to investigate the relationship between oral infections and lung infections in the institutionalized elderly . Ethical issues must be addressed, and full collaboration of the medical team is required . Future studies should establish whether reducing the risk for pneumonia in the institutionalized elderly is possible through improved oral health. Intensive Care Med, 1998 Jul, 24(7), 663 - 72 Antithrombin III in patients with severe sepsis . A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis; Eisele B et al.; OBJECTIVES: To evaluate the safety and potential efficacy of antithrombin III (AT III) in reducing mortality in patients with severe sepsis . DESIGN: Prospective, randomized, placebo-controlled, double-blind, phase II, multicenter, multinational clinical trial . SETTING: Seven academic medical center intensive care units (ICU) in Belgium, Denmark, the Netherlands, Norway and Sweden . PATIENTS: 42 patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III or placebo . INTERVENTIONS: Patients received either an intravenous loading dose of 3000 IU AT III followed by a maintenance dose of 1500 IU every 12 h for 5 days or equivalent amounts of placebo . MEASUREMENTS AND RESULTS: All patients were evaluated for safety and for 30-day all-cause mortality . CONCLUSIONS: The administration of AT III was safe and well-tolerated . It was followed by a 39 % reduction in 30-day all-cause mortality (NS) . The reduction in mortality was accompanied by a considerably shorter stay in the ICU . Patients treated with AT III exhibited a better performance in overall severity of illness and organ failure scores (Acute Physiology and Chronic Health Evaluation II, multiple organ failure, organ system failure), which was noticeable soon after initiation of treatment . Patients treated with AT III demonstrated a better resolution of pre-existing organ failures and a lower incidence of new organ failures during the observation period . A meta-analysis comprising this and two other double-blind, placebo-controlled trials with AT III with a total of 122 patients suffering from severe sepsis confirms the positive trend . The results of the meta-analysis demonstrate a 22.9 % reduction in 30-day all-cause mortality in patients treated with AT III . Although still too small to be confirmative, the meta-analysis clearly points to the fact that a sufficiently powered phase III trial is warranted to prove whether AT III has a beneficial role in the treatment of severe sepsis. Microbios, 1998, 93(376), 169 - 78 Antimicrobial efficacy of preservative combinations in South African brown bread; McNaughton C et al.; Rope and mould spoilage decrease the shelf life of bread and may result in substantial monetary losses to producers . Five test bakes were carried out to determine the efficacy of sodium diacetate or vinegar in combination with calcium propionate, in inhibiting rope and mould spoilage of brown bread . Their effect on yeast activity was also evaluated . Baked loaves were stored at 30 degrees C and analysed for 6 days post-baking by duplicate plate counting, viable staining using 0.5% tetrazolium salt solution, mould-free shelf life determination and pH measurement . Changes in bacterial counts over time were used to rank treatments statistically . Vinegar combined with calcium propionate at 0.10% each achieved the longest rope-free shelf life, while 0.30% calcium propionate resulted in the longest mould-free shelf life . A combination of sodium diacetate and calcium propionate at 0.10% each showed the lowest reduction in yeast activity. J Appl Microbiol, 1998 Jul, 85(1), 132 - 40 Pyrithione biocide interactions with bacterial phospholipid head groups; Dinning AJ et al.; Sodium pyrithione and zinc pyrithione (NaPT and ZnPT, respectively) are antimicrobial agents widely used in both the cosmetics and fuel industries . They are also utilized in the mining industry because of their metal chelating properties . They have been shown to depolarize membrane electropotential in fungi and are also known to inhibit fungal and bacterial substrate transport processes . Recent work has shown that both pyrithiones cause the leakage of intracellular material (potassium ions and O.D.260 nm absorbing material) from exposed bacterial cells . The work here reports studies on the interactions between the pyrithiones and the bacterial phospholipid head group structures, at both a practical and a theoretical level, utilizing tube dilution neutralizer studies, scanning spectrophotometry and molecular modelling . The tube dilution neutralizer studies exhibited a decrease in minimum inhibitory concentration (MIC) for both pyrithiones in the presence of extracellular phosphatidyl-ethanolamine and EDTA . Scanning spectrophotometry exhibited the chelation of the central zinc atom from the ZnPT chelate by the addition of EDTA . Molecular modelling studies exhibited the chelation of the phosphatidyl-ethanolamine head group by ZnPT . Zinc pyrithione also exhibited an interaction with the ammonium tail of the head group structures . Sodium pyrithione exhibited electrostatic interactions with the phospholipid head groups in the molecular modelling studies. Rinsho Byori, 1998 Jul, 46(7), 719 - 27 {Evaluation of a newly developed broth microdilution test method to determine minimum inhibitory concentrations (MICs) of antimicrobial agents for mycobacteria}; Yamane N et al.; We developed a new broth microdilution antimycobacterial susceptibility test for determination of minimum inhibitory concentration (MICs) using an air-dried microplate containing serially diluted antimicrobial agents and the modified Middlebrook 7H9 broth . The eight agents included were streptomycin (SM), isoniazid (INH), rifampicin (RFP), ethambutol (EB), kanamycin (KM), levofloxacin (LVFX), sparfloxacin (SPFX) and clarithromycin (CAM) . Serial dilutions of the agents (128 micrograms/ml to 0.125 micrograms/ml) were prepared in microplates, and were reconstituted by inoculation of 0.2ml of cell suspensions (approximately 3 x 10(5) cells/ml) . The test plates were incubated at 36 degrees C in 5% CO2, and the growth endpoints were read visually after 5-day, 7-day and 10-day incubations . Four ATCC reference strains, Mycobacterium tuberculosis, M . avium, M . kansasii and M . intracellulare, were repeatedly tested at three sites . Of 480 determination against eight agents, 455 (94.8%), 470 (97.9%) and 455 (94.8%) of the MICs read after 5-day, 7-day and 10-day incubations fell within 3log2 dilutions, respectively . The MICs gradually elevated during the incubation, however those of 7-day incubation were highly precise and easily determined . A total of 160 clinical isolates of M . tuberculosis and 114 of nontuberculous mycobacteria were tested against eight agents . As for the primary drugs (SM, INH, RFP and EB), most isolates of M . tuberculosis were highly susceptible with MIC90, < or = micrograms/ml . Both LVFX and SPFX were also active . The MICs against nontuberculous mycobacteria distributed in a wide range, and the activities of RFP, LVFX, SPFX and CAM were more potent . These results demonstrate this newly developed test method to be a practical, rapid, quantitative and nonradiometric alternative for the determination of MICs in clinical mycobacteriology laboratories. Rinsho Byori, 1998 Jul, 46(7), 645 - 50 {Lyme disease}; Kawabata M; Lyme disease is a tick-borne disease, and recognized as a complex, multisystem disorder . An outbreak {correction of outback} of Lyme disease was first described in the United States in the 1970s . The presence of Borrelia burgdorferi, its causative agent, in the skin results in the development of characteristic expanding red skin lesions, erythema migrans (EM) . EM may be associated with cardiac abnormalities, meningitis, and cranial peripheral neuropathies . Arthritis, neurologic and skin manifestations may persist for several years and become chronic in a small percentage of patients . Studies on the classification of B . burgdorferi resulted in the identification of three closely related genospecies, and different clinical manifestation of Lyme disease have been correlated with the infecting genospecies . The diagnosis of Lyme disease should be based primarily on the clinical presentation, epidemiological information and serological tests . Antimicrobials are effective in the treatment of Lyme disease in most patients . Lyme disease is a zoonosis and endemic in areas where suitable mammalian reservoirs for B . burgdorferi and appropriate hosts for the tick vector are present . According to changes in the natural environment, the distribution of infected ticks and reservoirs is anticipated to expand. Am J Infect Control, 1998 Aug, 26(4), 406 - 12 Clinical efficacy of a chlorous acid preoperative skin antiseptic; Aly R et al.; BACKGROUND: Among the ways to reduce the incidence of iatrogenic infectious disease is the use of efficacious preoperative antiseptics . Iodophors and chlorhexidines, the chief presurgical disinfectants today, have various problems with practicality . A new preoperative skin antiseptic has been developed (Alcide Corporation, Redmond, Wash) that involves the mixture of a 0.1% sodium chlorite formulation and an activating preparation of 0.5% mandelic acid to produce chlorous acid and other antimicrobial degradation products . METHODS: Under clinical conditions, the antimicrobial effectiveness of this blended preparation was compared with a chlorhexidine gluconate scrub solution . Using a Latin-square randomization scheme, we treated 2 contralateral abdominal sites and 2 contralateral inguinal sites of healthy male and female volunteers with these antiseptics or the controls of vehicle or activator alone . Microorganisms were harvested and quantified by a standard cylinder-scrub technique . RESULTS: Of 85 volunteers (170 possible sites per test region) screened to meet the USA Food and Drug Administration baseline criteria on population densities of normal flora, 61 abnormal sites and 107 inguinal sites provided suitable data . Against chlorhexidine, the chlorous acid presurgical skin preparation produced superior but statistically equivalent reductions (P > .05) of each volunteer's normal flora at 10 minutes, 30 minutes, and 6 hours after treatment . As many as 4 log reductions were achieved, and activity persisted as long as 6 hours . Compared with chlorhexidine, the chlorous acid product has the practical advantages of a shorter scrub time, less foam, air drying (instead of wiping), and no perceivable residue . CONCLUSIONS: An activated chlorous acid product statistically matched the performance of chlorhexidine gluconate in reducing populations of resident flora on treated skin sites . With an easier and shorter application procedure and strong, long-term antimicrobial activity, the new halogenated antiseptic seems to be a useful and possible efficacious preoperative skin disinfectant. Biochemistry (Mosc), 1998 Jul, 63(7), 766 - 81 Inducible nitric oxide synthase in the liver: regulation and function; Taylor BS et al.; The inducible nitric oxide synthase (iNOS) gene is expressed by hepatocytes in a number of physiologic and pathophysiologic conditions affecting the liver including septic and hemorrhagic shock . The molecular regulation of iNOS expression is complex and occurs at multiple levels in the gene expression pathway . The cytokines TNF-alpha, IL-1beta, and INF-gamma synergistically activate iNOS expression in the liver, and the human iNOS gene was first cloned from cytokine-stimulated hepatocytes . iNOS expression requires the transcription factor NF-kappaB and is down-regulated by steroids, TGF-beta, the heat shock response, p53, and nitric oxide (NO) itself . In vivo, hepatic iNOS induction is differentially regulated from the typical acute-phase reactants and is not expressed as a mandatory component of the acute phase response . Thus, numerous mechanisms have evolved to regulate iNOS expression during hepatocellular injury . Studies of the effects of NO in the liver demonstrate that induced NO synthesis plays an important role in hepatocyte function and protects the liver during sepsis and ischemia reperfusion . Its cytoprotective role is best exemplified in a rodent model of endotoxemia . Here the addition of the nonspecific NOS inhibitors significantly increased hepatic damage . NO exerts a protective effect through its ability to prevent intravascular thrombosis by inhibiting platelet adhesion and neutralizing toxic oxygen radicals . NO also exerts a protective effects both in vivo and in vitro by blocking TNF-alpha-induced apoptosis and hepatotoxicity, in part by a thiol-dependent inhibition of caspase-3-like protease activity . These studies demonstrate the cytoprotective effects of NO in the liver and suggest hepatic iNOS expression functions as an adaptive response to minimize inflammatory injury . In addition, NO has anti-tumor effects as well as known mutagenic effects, is involved in the systemic vasodilatation of cirrhosis, and has potent antimicrobial properties. Eur J Pharmacol, 1998 Jul 17, 353(1), 97 - 103 1,5-Bis(4-amidinophenoxy)pentane (pentamidine) is a potent inhibitor of {3H}idazoxan binding to imidazoline I2 binding sites; Wood DH et al.; The aromatic diamidine 1,5-bis(4-amidinophenoxy)pentane (pentamidine) is used for treatment and prophylaxis of Pneumocystis carinii pneumonia in patients with Acquired Immune Deficiency Syndrome . Clinical use of pentamidine has been restricted by significant toxicity, that includes hypotension, and hypoglycemia . Although clinical toxicity is well described, the mechanisms are still poorly understood . Competitive binding analyses using {3H}idazoxan as the radioligand, and cirazoline to define non-specific binding, demonstrate that pentamidine binds to an imidazoline I2 binding site on rat liver membranes with a Ki of 1.4+/-0.22 nM . The Ki indicates that pentamidine inhibits radioligand binding at imidazoline I2 sites with an affinity approximating the most potent known ligands and may be related to pentamidine toxicity . Moreover, pentamidine analogs inhibit radioligand binding with a range of affinities that vary according to their structure . Two candidate drugs, Compounds 5 and 6, are more active than pentamidine in the corticosteroid-suppressed rat model of P . carinii pneumonia, yet have different affinities for the imidazoline I2 site (Ki 5 = 50.1+/-1.06 nM and Ki 6 = approximately 3500 nM) . Affinity for this site does not correlate with antimicrobial activity (r = 0.60; p = 0.09) or the calculated log of the octanol:water partition coefficient (ClogP) (r = -0.38; p = 0.22). Carbohydr Res, 1998 Jun, 309(1), 45 - 55 Chemical transformation of tylosin derivatives into neutral macrolides having a 3'-methoxyl group; Gotoh Y et al.; This paper describes the chemical transformation of the basic 16-membered macrolides, tylosin derivatives, into neutral macrolides having a 3'-methoxyl group . 2',4'-Di-O-acetyl-3,23-bis(O-tert-butyldimethylsilyl)mycaminosyltylon olide 9,20-bis(ethylene acetal) N-oxide (1b) was treated with Ac2O-pyridine in CH2Cl2 to afford the 3'-ketone 1c and the 3'-N-acetyl-3'-N-demethyl derivative 1d in 67 and 5% yield; respectively . Reduction of 1c with Zn(BH4)2 gave the 3'-alcohol 1e in 84% yield stereoselectively . O-Methylation of 1e with MeOTf and 2,6-di-tert-butylpyridine gave the 3'-methyl ether 1f in 49% yield in spite of the presence of the adjacent acetoxyl groups . Deprotection of 1f provided the desired neutral macrolide 1g . Similar synthetic routes were also used for transformation of the suitably protected 4'-deoxymycaminosyltylonolide 2b and desmycosin 3c into neutral macrolides having a 3'-methoxyl group . It was found that the mycinose moiety of a neutral macrolide plays an important role in its antimicrobial activity. J Chromatogr A, 1998 Jul 31, 815(2), 163 - 72 Analysis of recent antimicrobial agents in human biological fluids by high-performance liquid chromatography; Leveque D et al.; Our previous review on the liquid chromatographic (LC) analysis of anti-bacterial agents was published in 1990 in a special issue of the Journal of Chromatography . Eight years later, some new agents have been registered and numerous other are under clinical experiment . In spite of therapeutic problems encountered with certain bacterial pathogens, the development of novel drug candidates has slowed partially due to the need for identification of new bacterial targets and the cost of the research . The present overview updates the LC methods for the quantitations of recent antimicrobial agents (marketed and in clinical development) in human biological fluids . Consideration has been given to procedures permitting the determination of isomers and metabolites as well as methods regarding tissue extracts or liquid sampled from physiological sanctuaries . LC methods are available for the quantitation of almost all registered or investigated recent anti-infective drugs and some are applicable in routine practice . Nevertheless, few techniques have been validated for the determination in tissue extracts limiting the development of penetration studies. Cancer Treat Res, 1998, 96, 143 - 65 Role of the clinical microbiology laboratory in the diagnosis of infections; Thomson RB Jr et al.; The proper use and interpretation of clinical microbiology test results may be complicated but critical to the care of cancer patients . The microbiology laboratory director is often available to offer advice concerning the differential diagnosis, choice of specimens, as well as the optimal stains and cultures to facilitate diagnosis . Additionally, the rapid interpretation of Gram-stained smears provides useful, occasionally lifesaving, information relative to the etiologic diagnosis and empiric antimicrobial therapy . The microbiology laboratory director should also provide further interpretation of culture and antimicrobial testing results that allow the clinical service to focus on the most critical data . Person-to-person or telephone conversations discussing important laboratory information should be followed up by a written summary report placed in the patient's chart so all services involved share the same interpretation (Figure 2) . The clinical service has an important responsibility to communicate with the laboratory to optimize care of the patient with cancer . The laboratory compiles data collected from groups of patients that is available and useful to physicians . Review and discussion of test utilization is essential for cost-effective, quality health care . This may include analysis of blood cultures documenting an acceptable level of contamination, appropriate number collected per day, and sufficient blood volume per culture . In addition, information about changing resistance patterns or nosocomial transmission can be provided to the clinician . As patients with malignancies become more complex and their infections increasingly difficult to treat, regular interaction between the laboratory and clinician is likely to improve patient care. Med Klin (Munich), 1998 Jul 15, 93(7), 446 - 53 {Helicobacter eradication: an expensive Sisyphus task}; Wildgrube HJ; BACKGROUND: The benefits of eradicating H . pylori infection vary about the antimicrobial regimen . In contrast, comparing many clinical studies the overall outcomes seem independent of the kind of treatment . Therapy depends on accurate diagnosis . Therefore, the observed differences and correspondences can be caused by not obviously but systematic influences using noninvasive diagnostic tests . METHOD: Simulations concerning noninvasive tests with variable specificity and sensitivity were performed . The results were compared to the hypothetical estimate that 1/3 of the population of Germany were H . pylori infected . This group should be traced and checked again after a treatment with 90% efficacy . RESULTS: In comparison to the a priori conditions most decisions according to noninvasive tests were not valid . Both sensitivity and specificity differ significantly from 100%, therefore the accuracy was low . The differences between true positives and true negatives were unpredictably accelerated if the inclusion criteria depend on the poor sensitivity of the first test . For the second test which is commonly used regarding its specificity, there is a change in the statistical behavior . As a result, the homogeneity that is true and false negatives and positives of the non-infected or infected groups differed considerably . One of the examples was a procedure using a test with 79% specificity and 85% sensitivity . If the prevalence of the infection was 33% the simulations demonstrated a therapeutic effect of about 76.5% instead of a priori efficacy of 90% . Under these conditions 14% of the population become false positive . Furthermore, the simulations revealed a second effect . Using the same test with low accuracy twice the investigator got the impression of superior therapeutic considerations . The misleading conclusion was caused by diminished sensitivity if the specificity remained constant . Thus, neither serological tests nor the 13C-breathtests can be assumed as validated methods for both to screen infected people and to check the treatment . Furthermore, the noninvasive tests are not useful for the determination of the prevalence of H . pylori infection . The influence of variable sensitivity and specificity of a diagnostic test on the outcome of a clinical trial can become a bias or can be used to manipulate the outcome . CONCLUSION: The effect of a therapeutic regimen depends on the prevalence of the H . pylori infection . Because it is difficult to separate true positives, in clinical trials the main effects and interactions can be improved under the conditions used in "experimental design" . Some earlier results must be reevaluated because of the bias resulting from inadequate diagnostic tests. Clin Infect Dis, 1998 Aug, 27 Suppl 1, S135 - 40; discussion S141-2 Antibiotic resistance: lessons for the future; Moellering RC Jr; It is clear that emergence of resistant bacterial strains will continue to be a problem as long as clinicians use the currently available antimicrobial agents . Past and current policies for dealing with resistance have, at best, been only partially effective . Thus, novel approaches to the problem of antimicrobial resistance are badly needed . Development of novel "classic" antimicrobial agents, chemical modification of currently known agents to overcome resistance, and the development of potentiators of known antimicrobials represent three areas that have been partially exploited in the past and continue to represent fertile fields for additional investigation . In addition, a number of investigators are working to develop inhibitors of new bacterial targets and to develop inhibitors of genes relating to virulence or pathogenesis . Although the deployment of antisense nucleotides as antimicrobial agents is theoretically appealing, to date, it has not been possible to develop any of these agents for clinical use. J Nucl Med, 1998 Aug, 39(8), 1454 - 7 Gallium-67-citrate scanning of renal parenchymal malacoplakia; Houston TK 2nd et al.; The purpose of this article is to review the potential role of nuclear medicine scanning, especially with 67Ga, in the presumptive diagnosis and clinical management of patients with renal parenchymal malacoplakia (RPMP), a rare disease associated with coliform bacterial infection of the kidney and characterized by chronic unresolving inflammatory infiltrates containing von Hansemann macrophages in the renal parenchyma . METHODS: Published cases of RPMP were collected from the archival literature by searching the MEDLINE database and by reviewing bibliographic references contained in articles on malacoplakia . Data on the clinical features and radiographic evaluation of patients with RPMP were extracted from the clinical case reports . RESULTS: Forty-three cases of RPMP published over the past 20 yr were identified . Ten of the 43 patients (23%) had 67Ga scanning as a component of their diagnostic evaluation . In all 10 patients, renal uptake of 67Ga was classified as intense . Two of those 10 patients had serial 67Ga scanning performed to assess response to antibiotic treatment; both patients exhibited decreased uptake or complete resolution of abnormal renal uptake over time, a finding also exhibited by our patient . CONCLUSION: Intense renal uptake of 67Ga, typically in the clinical setting of fever, progressive renal failure and nephromegaly, strongly supports a diagnosis of RPMP . In those patients receiving prolonged antimicrobial therapy for RPMP, resolution of abnormal 67Ga uptake over time may provide an objective endpoint for treatment. Biochemistry, 1998 Aug 25, 37(34), 11949 - 52 A potent "fat base" nucleotide inhibitor of IMP dehydrogenase; Wang W et al.; Inosine monophosphate dehydrogenase (IMPDH) is a target for anticancer, antiviral, immunosuppressive, and antimicrobial chemotherapy . Thus, IMPDH inhibitors have great potential as chemotherapeutic agents . Here we show that imidazo{4,5-e}{1, 4}diazapine nucleotide (I) is a potent inhibitor of both human type II and Escherichia coli IMPDH . I is a slow-binding inhibitor . The values of Kd are 1.4 nM and 53 nM for human and E . coli IMPDH, respectively . Inhibition is reversible, as demonstrated by the recovery of activity upon denaturation and renaturation of the enzyme.I complex . I is not a substrate for IMPDH . I may form a covalent adduct with the active-site Cys of IMPDH . Such an adduct would serve as an analogue for an intermediate in the IMPDH reaction. Biochemistry, 1998 Aug 25, 37(34), 11856 - 63 Relationship of membrane curvature to the formation of pores by magainin 2; Matsuzaki K et al.; Magainin 2, an antimicrobial peptide from the Xenopus skin, kills bacteria by permeabilizing the cell membranes . We have proposed that the peptide preferentially interacts with acidic phospholipids to form a peptide-lipid supramolecular complex pore, which allows mutually coupled transbilayer traffic of ions, lipids, and peptides, thus simultaneously dissipating transmembrane potential and lipid asymmetry {Matsuzaki, K., Murase, O., Fujii, N., and Miyajima, K . (1996) Biochemistry 35, 11361-11368} . In this paper, we examined the effect of membrane curvature strain on pore formation . Magainin effectively forms the pore only in phosphatidylglycerol bilayers at low peptide-to-lipid ratios, well below 1/100 . In contrast, the permeabilization of phosphatidylserine, phosphatidic acid, or cardiolipin bilayers occurred at much higher peptide-to-lipid ratios (1/50 to 1/10) with some morphological change of the vesicles . The latter three classes of phospholipids are known to form hexagonal II structures under conditions of reduced interlipid electrostatic repulsions . Incorporation of phosphatidylethanolamine also inhibited the magainin-induced pore formation in the inhibitory order of dioleoylphosphatidylethanolamine > dielaidoylphosphatidylethanolamine . Addition of a small amount of palmitoyllysophosphatidylcholine enhanced the peptide-induced permeabilization of phosphatidylglycerol bilayers . Magainin greatly raised the bilayer to hexagonal II phase transition temperature of dipalmitoleoylphosphatidylethanolamine . These results suggest that the peptide imposes positive curvature strain, facilitating the formation of a torus-type pore, and that the presence of negative curvature-inducing lipids inhibits pore formation. Lett Appl Microbiol, 1998 Jun, 26(6), 407 - 11 Antibacterial activity of bovine lactoferrin and its peptides against enterohaemorrhagic Escherichia coli O157:H7; Shin K et al.; The antimicrobial activities of bovine lactoferrin (bLF), its pepsin hydrolysate (bLFH) and the active peptide lactoferricin B (LFcinB) against four clinical isolates of enterohaemorrhagic Escherichia coli O157:H7 were studied . The MICs against these isolates were 3 mg ml-1 for bLF, 0.1-0.2 mg ml-1 for bLFH and 8-10 micrograms ml-1 for LFcinB in 1% Bactopeptone broth . LFcinB killed these bacteria within 3 h at concentrations above 10 micrograms ml-1 . Transmission electron microscopy findings suggested that LFcinB acts on the bacterial surface and affects cytoplasmic contents . LFcinB was shown to influence the levels of verotoxins in the culture supernatant fluid of an E . coli O157:H7 strain . These results demonstrate that E . coli O157:H7 strains are susceptible to the antimicrobial effects of bLF and its peptides. Biochem J, 1998 Sep 1, 334 ( Pt 2), 321 - 3 The survival of ingested lactoferrin in the gastrointestinal tract of adult mice; Kuwata H et al.; Lactoferrin is an 80 kDa major protein component of mammalian colostral whey . The antimicrobial active centre of lactoferrin, lactoferricin (Lfcin), may also be an important determinant of the interaction between lactoferrin and specific receptors on lymphocytes . We have documented the survival in vivo of ingested lactoferrin in the gastrointestinal tract of adult mice by surface-enhanced laser desorption/ionization affinity MS . Various kinds of degraded lactoferrin fragments were detected as molecular-ion peaks corresponding to Lfcin after being captured by an affinity capture device, hydrolysis in situ and laser desorption/ionization . No evident molecular-ion peaks of Lfcin were observed upon analysis of faeces from mice fed commercial milk, whereas lactoferrin fragments containing the Lfcin region were detected at concentrations in the order of at least pmol/g in the faeces of mice fed milk enriched with lactoferrin at 40 mg/ml . These results suggest that ingested lactoferrin would survive transit through the gastrointestinal tract as partially degraded forms containing the receptor-binding region(s) as well as the antimicrobial active centre. Int J Antimicrob Agents, 1998 May, 10(2), 153 - 9 Prostatitis: US perspective; Schaeffer AJ; The diagnosis and management of prostatitis syndromes is a challenge to the clinician . Careful history and examination of the prostate fluid and quantitative segmented bacteriologic cultures will lead to proper categorization into the recognized forms of the prostatitis syndrome . Antimicrobial therapy is effective in the majority of men with acute and chronic bacterial prostatitis (CBP) . Fluoroquinolone agents appear to have an increasingly important role in this regard, although a randomized, prospective, double-blind study is still lacking . Alpha-1-selective blocking agents may relieve symptomatology of chronic pelvis pain syndrome (CPPS) . Other non-prostatic sources of voiding symptoms should be sought and ruled out, especially malignancy or inflammatory disorders. Int J Antimicrob Agents, 1998 May, 10(2), 107 - 17 Meropenem in elderly and renally impaired patients; Cunha BA; The safety profile of meropenem in the elderly (aged > 65 years, n=843) and/or renally impaired (creatinine clearance < 51 ml/min, n=436) was assessed by evaluating data from 26 phase III studies which compared the use of meropenem (0.5 or 1.0 g, i.v . every 8 h) with other antimicrobial agents in patients with bacterial infections . The overall pattern and frequency of adverse events following meropenem therapy in the elderly and/or renally impaired were similar to those in younger and/or non-renally impaired cohorts and to imipenem/cilastatin and injectable third generation cephalosporins . Both dosages of meropenem (0.5 and 1.0 g, i.v . every 8 h) were generally well tolerated . There was no clinically significant mean change in indicators of renal flux between baseline and the end of treatment in any patient sub-group . Importantly, meropenem-related seizures were rare (0.1%), even in patients with renal impairment . In summary, meropenem has an excellent safety profile and is therefore suitable for use in elderly and/or renally impaired patients. Int J Antimicrob Agents, 1998 May, 10(2), 95 - 105 The utility of aminoglycosides in an era of emerging drug resistance; Zembower TR et al.; As the problem of global antibiotic resistance continues to worsen, aminoglycosides have assumed increasing importance in clinical practice . Their broad antimicrobial spectrum, rapid bactericidal action, and ability to act synergistically with other drugs have made them especially useful in the treatment of serious nosocomial infections . However, as with other drugs, their overuse and misuse leads to the development of resistance in important microbial pathogens . The appropriate use of the aminoglycosides is essential to assure their continued efficacy . Therefore, physicians must familiarize themselves with both the clinical indications and the limitations of these drugs if they are to remain efficacious in the years to come. Lab Invest, 1998 Aug, 78(8), 949 - 55 Nitric oxide synthases in Kaposi's sarcoma are expressed predominantly by vessels and tissue macrophages; Weninger W et al.; Kaposi's sarcoma (KS) is a tumor of presumed vascular origin frequently found in patients with AIDS . Recent data suggest that the development of KS is linked with the presence of a newly recognized herpesvirus, human herpesvirus type 8 . Nitric oxide (NO), a messenger molecule with vasoactive, antitumor, and antimicrobial effects, is produced by three isoforms of nitric oxide synthases (NOS) . In the present report, we investigated the expression of NOS isoforms in KS . By NADPH-diaphorase histochemistry, NOS activity was detectable in endothelia and CD45+ cells within KS lesions . Reactivity for endothelial NOS (eNOS) was found in blood vessel endothelia; however, eNOS reactivity was negative in KS spindle cells in 12 of 17 tumors, and moderately positive in the other 5 lesions . In contrast to KS, tumor cells in three hemangiomas and one angiosarcoma were strongly positive for eNOS . Inducible NOS (iNOS) was absent from KS tumor cells but was found regularly in CD45+, HLA-DR+ cells within the lesions . In five KS-derived spindle cell cultures, neither eNOS nor iNOS proteins were detectable . The sporadic expression of eNOS by KS spindle cells in vivo and the absence of eNOS protein from KS spindle cells in tissue cultures argue against the possibility that the cells are derived from blood vessel endothelia . The consistent expression of iNOS by CD45+, HLA-DR+ cells within KS lesions strongly suggests that leukocyte-derived NO participates in the pathology of this tumor. Sex Transm Dis, 1998 Aug, 25(7), 350 - 2 Comparative in vitro susceptibility of a tetracycline-resistant Chlamydia trachomatis strain isolated in Toulouse (France); Lefevre JC et al.; BACKGROUND AND OBJECTIVES: We recently reported the first isolation of a tetracycline-resistant Chlamydia trachomatis strain in Toulouse from a woman treated with tetracycline . To characterize this isolate, its in vitro susceptibility was compared with those of 34 other C . trachomatis isolates recovered in Toulouse . STUDY DESIGN: The susceptibilities of C . trachomatis strains were determined in terms of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) using McCoy cells in 96-well microdilution plates, with an inoculum of 5.10(3) to 1.10(4) inclusion-forming units/ml . The antimicrobial agents tested were tetracycline, azithromycin, erythromycin, ofloxacin, and pristinamycin . RESULTS: No difference was observed between the MICs and MBCs except for the tetracycline . Tetracycline-resistant strain MIC and MBC were > 64 micrograms/ml, although < 1% of the bacterial population showed resistance . For the other isolates, the MIC of tetracycline was < or = 0.25 microgram/ml . The antibiotics other than tetracycline were active in vitro against all strains . CONCLUSIONS: These results show that the tetracycline resistance observed in Toulouse differs from the "heterotypic resistance" described previously in the United States in multiresistant C . trachomatis isolates . They confirm that the resistance we observed may be a new phenomenon. J Food Prot, 1998 Aug, 61(8), 1018 - 22 Characteristics of the LacTek test as applied to tissue samples: assessment of performance using incurred field samples; Mitchell JM et al.; The Lactek test, marketed for antimicrobial residue detection in milk, was validated for the detection of antimicrobial residues in tissues . A previous study found that the LacTek test could confidently identify tissue samples spiked with antimicrobial residues . However, the test could not reliably distinguish violative from nonviolative spiked samples relative to Canadian maximum residue limits (MRLs) . The objectives of this study were to assess and compare the performance of the LacTek tests for beta-lactams, tetracyclines, gentamicin, and sulfamethazine on samples containing naturally incurred residues by running the test in parallel with the standard microbial inhibition test (MIT) presently used for the routine testing of tissues at our facility and to assess the agreement with high pressure liquid chromatographic (HPLC) determinative methods . Parallel testing with the official MIT found that the Lactek tests could be confidently used for testing tissue samples containing incurred residues . Among 1,008 MIT-positive samples, the LacTek test found that 90% contained beta-lactams and/or tetracyclines . A further 7.3% of violative residues could not be identified to an antimicrobial class . In addition, 9% of samples testing negative on the MIT were found to contain an antimicrobial residue by the LacTek tests . Comparative testing with HPLC methods found that there was very good agreement between the two tests and that most violations were due to penicillin G and oxytetracycline . Although the LacTek test cannot be used to distinguish violative from nonviolative residue levels, it does offer several advantages over the present MIT . These include speed, ease of use, the ability to identify residues to a specific class, and an improved sensitivity at the MRL level for the most commonly found antimicrobials in tissue. Tuber Lung Dis, 1997, 78(3-4), 195 - 203 rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo; Johnson BJ et al.; SETTING: Low-dose recombinant human interleukin 2 (rhuIL-2) adjunctive immunotherapy in multidrug resistant tuberculosis (MDR-TB) patients . OBJECTIVE: Evaluation of the effects of daily versus pulse-administered rhuIL-2 compared to placebo . DESIGN: MDR-TB patients on best available antituberculous chemotherapy received rhuIL-2 for 30 consecutive days (daily therapy), or for 5 days followed by a 9-day 'rest', for three cycles (pulse therapy) . Placebo control patients received diluent . The cumulative total dose of rhuIL-2 given to each patient in either rhuIL-2 treatment group was the same . Patient immunologic, microbiologic, and radiologic responses were compared . RESULTS: The three treatment schedules induced different results . Immune activation was documented in patients receiving daily rhuIL-2 therapy . Numbers of CD25+ and CD56+ cells in the peripheral blood were increased in these patients, but not in patients receiving pulse rhuIL-2 or placebo . In addition, 5/8 (62%) patients receiving daily rhuIL-2 demonstrated reduced or cleared sputum bacterial load while only 2/7 (28%) pulse rhuIL-2 treated and 2/8 (25%) controls showed bacillary clearance . Chest radiographs of 7/12 (58%) patients receiving daily rhuIL-2 indicated significant improvement over 6 weeks . Only 2/9 (22%) pulse rhuIL-2-treated patients and 5/12(42%) placebo controls showed radiologic improvement . CONCLUSION: Daily low dose rhuIL-2 adjunctive treatment stimulates immune activation and may enhance the antimicrobial response in MDR-TB. Anticancer Res, 1998 Jul-Aug, 18(4C), 3133 - 8 Methoxy- and methyl-, methoxy-5,6,11-trimethyl-6H-indolo {2,3-b}quinolinium derivatives as novel cytotoxic agents and DNA topoisomerase II inhibitors; Kaczmarek L et al.; New members of the cytotoxic indolo{2,3-b}quinoline family, with a methyl groups at N-5, N-6 (their presence stabilizes the positive charge of the molecule), were prepared using a modified Graebe-Ullmann reaction . The derivatives obtained were well soluble in water in a non-pH-dependent manner . They displayed strong antimicrobial activity against Gram-positive bacteria and pathogenic fungi (the MIC values fall between 0.0025 and 0.12 mM) and highly selective cytotoxicity in vitro against different human cancer cell lines: colon adenocarcinoma SW 707, lung carcinoma A 549, transitional cell carcinoma Hu 1703, and oral epidermoid carcinoma KB, in the range of 0.01 to 3.0 microM . They also stimulated the formation of topoisomerase-II-mediated DNA cleavage at concentration from 0.04 to 0.5 microM . These observations correspond well with the ability of the tested compounds to increase the melting temperature of calf thymus DNA (delta Tm being between 13 degrees C and 22 degrees C). Boll Chim Farm, 1998 Jun, 137(6), 186 - 90 {Preliminary study on the chemical constituents and #microbiologic activity of Asphodelus microcarpus (Salzm . et Viv.)}; Bonsignore L et al.; The extracts of the aerial parts and tubers of Asphodelus microcarpus (Liliacee) were studied . The fatty acids, the sugars and some anthraquinone glycosides were determined by means of GC/FTIR, GC/MS and HPLC . The antimicrobial activity of essential oil of aerial parts against blastomycetes, Gram-positive and Gram-negative bacteria was evaluated. Infect Immun, 1998 Sep, 66(9), 4222 - 8 Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue; Krisanaprakornkit S et al.; Human beta-defensin-1 (hBD-1) is a member of the family of small cationic antimicrobial peptides that have been identified in several mucosal epithelia . Because human gingival epithelium is a site that is constantly challenged by oral microorganisms, we examined the expression of hBD-1 in human gingival epithelial and fibroblast cell cultures and tissue samples . Cell cultures were challenged with cell wall extracts of Porphyromonas gingivalis or Fusobacterium nucleatum, Escherichia coli lipopolysaccharide, tumor necrosis factor alpha, or phorbol myristate acetate . hBD-1 mRNA was detected in unstimulated and stimulated cultures by reverse transcription (RT)-PCR using several primer sets specific for hBD-1 . Gingival epithelial cells, but not gingival fibroblasts, expressed a product of the predicted size for hBD-1 mRNA . The sequence of the PCR product was identical to that of hBD-1 . hBD-1 mRNA expression was not significantly modulated by any of the stimulants tested . Human gingival tissues from noninflamed and inflamed sites were also analyzed by RT-PCR . hBD-1 mRNA was expressed in all tissue samples . The relative expression of hBD-1 mRNA was similar in noninflamed and inflamed tissues obtained from each of four patients undergoing treatment for periodontitis . However, the relative expression of hBD-1 mRNA varied in gingival biopsies obtained from 15 different normal individuals, and the relative hBD-1 expression was unrelated to interleukin-8 expression . Our findings show the constitutive expression of hBD-1 mRNA in cultured epithelial cells and gingival tissues but not gingival fibroblasts . These findings suggest that expression of hBD-1 may play a role as part of the innate host defenses in maintaining normal gingival health. Int J Tuberc Lung Dis, 1998 Aug, 2(8), 621 - 6 In vitro activity of antimicrobial combinations against clinical isolates of susceptible and resistant Mycobacterium tuberculosis; Bergmann JS et al.; SETTING: University of Texas Medical Branch, Clinical Microbiology Laboratory . OBJECTIVE: To evaluate in vitro the activity of rifabutin plus each of four other antimicrobial agents: isoniazid, amoxicillin/clavulanate, sparfloxacin and clarithromycin, against five susceptible (S-MTB) and five multidrug-resistant (MDR-TB) clinical isolates of Mycobacterium tuberculosis . DESIGN: The antimicrobial activity of each two-drug combination was assessed by macrodilution checkerboard technique using Bactec 460 and classified as synergistic, additive, or antagonistic, using the fractional inhibitory concentration index . RESULTS: For S-MTB, rifabutin + amoxicillin/clavulanate, rifabutin + isoniazid, rifabutin + sparfloxacin and rifabutin + clarithromycin acted synergistically against four, three, one and one isolate, respectively; clarithromycin + rifabutin was additive for one isolate . None of the combinations were antagonistic against S-MTB . For MDR-TB, rifabutin + amoxicillin/clavulanate, rifabutin + isoniazid, rifabutin + sparfloxacin and rifabutin + clarithromycin acted synergistically against one, one, one and two isolates, respectively, and additively against two, one, one and two isolates, respectively . Rifabutin + amoxicillin/clavulanate, rifabutin + isoniazid, and rifabutin + clarithromycin were antagonistic against one, two and two MDR-TB isolates, respectively . CONCLUSION: Certain drug combinations acted synergistically against MDR-TB; however, the clinical predictive value of these in vitro experiments is unknown. J Antibiot (Tokyo), 1997 Jul, 50(7), 546 - 50 9-Hydroxycrisamicin A, a new cytotoxic isochromanquinone antibiotic produced by Micromonospora sp . SA246; Yeo WH et al.; 9-Hydroxycrisamicin A, a new cytotoxic isochromanquinone antibiotic, was isolated from a soil microorganism SA246 which was identified as Micromonospora sp . The molecular formula of 9-hydroxycrisamicin A was determined as C32H22O13 based on the HRFAB-MS analysis, and the structure was determined by various NMR experiments . 9-Hydroxycrisamicin A showed weak antimicrobial activity against Gram-positive bacteria and strong cytotoxic activity against some human cancer cell lines such as SK-OV-3 (ovarian), HCT15 (colon), SK-MEL-2 (melanoma), A549 (lung), XF498 (central nervous system) with ED50 of 0.47-0.65 microgram/ml. J Dairy Sci, 1998 Jul, 81(7), 1896 - 903 Identification of lactoferrin complexes in bovine mammary secretions during mammary gland involution; Wang H et al.; Part of the antimicrobial activity of lactoferrin resides in its ability to bind to bacteria . The complexing of lactoferrin with other proteins could alter its activity . This study identified the presence of lactoferrin complexes in mammary secretions during mammary gland involution and determined the proportion of free and complexed lactoferrin in mammary secretions . Mammary secretions were collected from Holstein cows on d 7, 14, and 21 of involution . Proteins were fractionated from defatted, filtered mammary secretions by sucrose density gradient ultracentrifugation and by gel filtration chromatography . Proteins contained in separated fractions were identified by SDS-PAGE . The presence of lactoferrin was confirmed by immunoblot analysis . Lactoferrin was present as complexed forms of high molecular mass in mammary secretions at each day of involution . The majority of lactoferrin was present in complexes of higher molecular mass rather than as monomers . A majority of lactoferrin existed in fractions of approximately 250 kDa, although peaks of lactoferrin at 150, 300, and 800 kDa were also found . The presence of lactoferrin complexes may result from interactions with casein or immunoglobulins or from the formation of lactoferrin multimers in the secretions . The interaction of lactoferrin with other proteins in mammary secretions during involution may affect the antimicrobial properties of lactoferrin. Clin Infect Dis, 1998 Aug, 27 Suppl 1, S125 - 30 Consequences of increasing resistance to antimicrobial agents; Acar JF et al.; The correlation between in vitro bacterial susceptibility results and clinical outcome has been debated for many years . Bacterial resistance traits are more significantly correlated with failure of therapy than is an organism's susceptibility to an antimicrobial agent . We review the situations that have supported the clinical relevance of in vitro bacterial resistance . Those situations include: emergence, during therapy, of a new resistance marker not known before; selection of a resistant mutant or acquisition of a resistance gene during therapy; failure to recognize or take into account a new resistance mechanism; and superinfection with resistant bacteria . More information should be obtained in the future by performing studies oriented toward bacteriologically documented clinical failures and by better communication between microbiologists and physicians to correlate the in vitro data with host status, the pharmacokinetics of the antimicrobial agent, and the bacteriologic and clinical outcome. J Food Prot, 1998 Jun, 61(6), 742 - 56 Antimicrobial drug residues in milk and meat: causes, concerns, prevalence, regulations, tests, and test performance; Mitchell JM et al.; This paper presents a historical review of antimicrobial use in food animals, the causes of residues in meat and milk, the types of residues found, their regulation in Canada, tests used for their detection, and test performance parameters, with an emphasis on immunoassay techniques . The development of residue detection methods began shortly after the introduction of antimicrobials to food animal production in the late 1940s . From initial technical concerns expressed by the dairy industry to the present public health and international trade implications, there has been an ongoing need for reliable, sensitive, and economical methods for the detection of antimicrobial residues in food animal products such as milk and meat . Initially there were microbial growth inhibition tests, followed by more sensitive and specific methods based on receptor binding, immunochemical, and chromatographic principle . An understanding of basic test performance parameters and their implications is essential when choosing an analytical strategy for residue testing . While each test format has its own attributes, none test will meet all the required analytical needs . Therefore the use of a tiered or integrated system employing assays designated for screening and confirmation is necessary to ensure that foods containing violative residues are not introduced into the food chain. Biochemistry, 1998 Aug 18, 37(33), 11516 - 23 Interactions of phenol and m-cresol in the insulin hexamer, and their effect on the association properties of B28 pro --> Asp insulin analogues; Whittingham JL et al.; Insulin's natural tendency to form dimers and hexamers is significantly reduced in a mutant insulin B28 Pro --> Asp, which has been designed as a monomeric, rapid-acting hormone for therapeutic purposes . This molecule can be induced to form zinc hexamers in the presence of small phenolic derivatives which are routinely used as antimicrobial agents in insulin preparations . Two structures of B28 Asp insulin have been determined from crystals grown in the presence of phenol and m-cresol . In these crystals, insulin exists as R6 zinc hexamers containing a number of phenol or m-cresol molecules associated with aromatic side chains at the dimer-dimer interfaces . At the monomer-monomer interfaces, the B28 Pro --> Asp mutation leads to increased conformational flexibility in the B chain C termini, resulting in the loss of important intermolecular van der Waals contacts, thus explaining the monomeric character of B28 Asp insulin . The structure of a cross-linked derivative of B28 Asp insulin, containing an Ala-Lys dipeptide linker between residues B30 Ala and A1 Gly, has also determined . This forms an R6 zinc hexamer containing several m-cresol molecules . Of particular interest in this structure are two m-cresol molecules whose binding disrupted the beta-strand in one of the dimers . This observation suggests that the cross-link introduces mechanical strain on the B chain C terminus, thereby weakening the monomer-monomer interactions. Arch Otolaryngol Head Neck Surg, 1998 Aug, 124(8), 921 - 5 A combination of amoxicillin and clavulanate every 12 hours vs every 8 hours for treatment of acute bacterial maxillary sinusitis; Seggev JS et al.; OBJECTIVE: To compare the safety and efficacy of a combination of amoxicillin and clavulanate potassium given orally every 12 hours (amoxicillin, 875 mg; clavulanate, 125 mg) with that given every 8 hours (amoxicillin, 500 mg; clavulanate, 125 mg) for the treatment of patients with acute bacterial maxillary sinusitis . DESIGN: Multicenter double-blind randomized double-dummy controlled trial . SETTING: Physicians' offices and ambulatory care clinics . PATIENTS: One hundred seventy patients at least 18 years of age with acute bacterial maxillary sinusitis who could be treated with an oral antimicrobial agent were randomized, and data from 134 were suitable for evaluation . Four patients were withdrawn from this study because of adverse effects . INTERVENTIONS: Patients received a combination of amoxicillin and clavulanate orally every 12 hours (amoxicillin, 875 mg; clavulanate, 125 mg) or every 8 hours (amoxicillin, 500 mg; clavulanate, 125 mg) for 14 days . MAIN OUTCOME MEASURE: Clinical success at the end of therapy . RESULTS: Clinical success at the end of therapy was similar for the 2 treatment groups, 93% and 88% of patients in the every 12-hour and every 8-hour groups, respectively (P = .76; 95% confidence interval, -4.0% to 15.6%) . Clinical success rates at follow-up 2 to 4 weeks after the end of therapy were also similar in the 2 groups . Adverse events related to treatment were reported with similar frequency in the 2 groups . CONCLUSION: Amoxicillin and clavulanate given every 12 hours is as effective and as safe as administration every 8 hours for the treatment of acute bacterial maxillary sinusitis. Aust Crit Care, 1998 Mar, 11(1), 16 - 9 Biopatch--a new concept in antimicrobial dressings for invasive devices; Roberts B et al.; A randomised controlled trial (RCT) was conducted to assess the reduction in the rate of catheter-related infections associated with the Biopatch dressing (Johnson & Johnson Medical Inc., Arlington, Texas, USA) used for insertion-site management of central venous catheters (CVCs) placed in the intensive care unit . Patients having a CVC placed were randomly assigned to receive either a Biopatch keyhole dressing to the occlusive Opsite IV 3000 (Smith and Nephew Medical Ltd., Hull, UK) (experimental group) or the Opsite IV 3000 alone (control group) . There was a very low colonisation rate of CVC tip and skin exit-site swabs in both the experimental group (6 of 17) and the control group (5 of 16) . No statistical difference was found between the two groups with regard to CVC or exit-site colonisation . A calculated sample size of 11,000 would be required to statistically demonstrate a 10 per cent reduction in CVC infection rate using the new Biopatch dressing . A much larger RCT would be required to demonstrate the efficacy of this new device. Eur J Clin Microbiol Infect Dis, 1998 Apr, 17(4), 219 - 34 Moraxella catarrhalis: clinical significance, antimicrobial susceptibility and BRO beta-lactamases; McGregor K et al.; Moraxella catarrhalis is an important pathogen of humans . It is a common cause of respiratory infections, particularly otitis media in children and lower respiratory tract infections in the elderly . Colonisation of the upper respiratory tract appears to be associated with infection in many cases, although this association is not well understood . Nosocomial transmission is being increasingly documented and the emergence of this organism as a cause of bacteremia is of concern . The widespread production of a beta-lactamase enzyme renders Moraxella catarrhalis resistant to the penicillins . Cephalosporins and beta-lactamase inhibitor combinations are effective for treatment of beta-lactamase producers, and the organism remains nearly universally susceptible to the macrolides, fluoroquinolones, tetracyclines and the combination of trimethoprim and sulfamethoxazole . Two major beta-lactamase forms, BRO-1 and BRO-2, have been described on the basis of their isoelectric focusing patterns . The BRO-1 enzyme is found in the majority of beta-lactamase-producing isolates and confers a higher level of resistance to strains than BRO-2 . The BRO enzymes are membrane associated and their production appears to be mediated by chromosomal determinants which are transmissible by an unknown mechanism . The origin of these novel proteins is unknown. Med Clin (Barc), 1998 Jun 27, 111(3), 92 - 8 {Adverse drug reaction surveillance in pediatric and adult patients in an emergency room}; Munoz MJ et al.; BACKGROUND: Adverse drug reactions (ADR) in the pediatric emergency room of a tertiary care hospital in Spain are described and compared with the adult ward . METHODS: Identification of cases was carried out through review of admission diagnoses and selection of those included in a previous list of diagnoses considered as possible ADR, that were thereafter verified . RESULTS: During 25 months, in 47.107 pediatric consultations were detected 451 cases as suspicious of ADR (0.96%) . The ADR was moderate in 29 and serious in 1, being hospitalized 4 . In adults, there were 68,431 consultations, and 704 cases detected (1.03%); moderate 218, serious 34 and mortal 1, being hospitalized 101 . The most common reactions were dermatological (43.9% in children, 19.5% in adults) and of digestive nature (28.5 and 36.6%, respectively) . The drugs most frequently involved in children were antimicrobials (49.5%), drugs used in respiratory illnesses (19.9%), non-steroid anti-inflammatory drugs (NSAID) (10.4%) and vaccines (9.2%); only two recently marketed products were involved . In adults, drugs involved were NSAID (28.2%), cardiovascular drugs (15.9%), antimicrobials (14.5%) and drugs active in digestive system (11.1%) . There were 10 cases of hypoglycemia in diabetic adults, probably by interaction of hypoglycemic agents with angiotensin-converting enzyme inhibitors, and 7 cases of gastrointestinal hemorrhage associated with ketorolac, that generated an alert; 12 recently marketed products were involved . CONCLUSIONS: Intensive monitoring in emergency ward measures ADR problem, estimates underreporting, but it has a moderate value to generate alert or to survey new products. AORN J, 1998 Aug, 68(2), 239 - 41, 243-4, 247-51 Testing a new alcohol-free hand sanitizer to combat infection; Dyer DL et al.; Universal precautions require that perioperative health care personnel wash their hand before and after all patient contact . Time constraints, however, can make adhering to universal precautions, including proper hand washing, difficult . Some perioperative health care workers, therefore, routinely use rise-free hand sanitizers to supplement normal hand washing . This study evaluated immediate and persistent antimicrobial effectiveness of two alcohol--containing hand sanitizers and a novel surfactant, allantoin, benzalkonium chloride (SAB) hand sanitizer using a federally approved effectiveness protocol . Results indicate that all three products were equally effective after a single application . After repeated use, the alcohol-containing sanitizers did not meet federal performance standards, and the alcohol-free sanitizer did . These properties and others illustrated in this article indicate that the nonflammable, alcohol-free SAB hand sanitizer is the most favorable of the rise-free hand sanitizer formulas for normal hand washing. Biochem Biophys Res Commun, 1998 Aug 10, 249(1), 202 - 6 Wide-spectrum antibiotic activity of synthetic, amphipathic peptides; Tiozzo E et al.; PGYa and PGAa are synthetic, amphipathic, alpha-helical peptides that were designed using a novel "sequence template" approach . Their antimicrobial activity was tested against several pathogenic clinical isolates, most of which were multiply resistant to conventional antibiotics . PGYa appeared to be more active towards Gram-positive species (MIC = 0.5-4 microM), towards such Gram negative species as P . aeruginosa, X . maltophilia, E . coli, K . pneumoniae and S . enteritidis (MIC = 1.4 microM), and towards the filamentous fungus A . niger (MIC = 8 microM) . Conversely, PGAa showed the greater activity towards three Candida species (MIC = 2.16 microM) . The peptides were shown to have a bactericidal activity, resulting in a decrease of viability for both Gram-positive and -negative bacteria of 3-6 logs within 60 min . Scanning electron microscopy of S . aureus and E . coli treated with PGYa shows considerable roughening and blebbing of the bacterial surfaces providing conclusive evidence that the peptide is membrane active. J Photochem Photobiol B, 1998 May 15, 43(2), 164 - 71 Singlet molecular oxygen-mediated photo-oxidation of tetracyclines: kinetics, mechanism and microbiological implications; Miskoski S et al.; Members of the biologically active series tetracyclines (TCs) suffer visible light-promoted photodynamic degradation to different extents, depending on their respective chemical structures and reaction conditions (solvent polarity and pH) . The photo-oxidation is accompanied by a partial loss of the antimicrobial power . The photodamage is very fast in the alkaline pH range and less aggressive . although not negligible in kinetic terms, in the physiological pH region . Photo-oxidation quantum efficiencies, evaluated for eight TC derivatives, through singlet molecular oxygen {O2(1Delta(g))} phosphorescence detection, spectrophotometric and polarographic methods, range from 0.12 to 0.65 as upper limits in alkaline medium . The photo-oxidation essentially proceeds via a O2(1Delta(g)) mediated process, with rose bengal or eosine as dye-sensitizers, Nevertheless, as a minor reactive pathway,the excited triplet state of the dye sensitizers interacts with TCS in a competitive process with O2(1Delta(g) generation . The O2(1Delta(g)-mediated photo-oxidation of TCs appears to be a plausible mechanism to account for their phototransformations in biological media, in the presence of visible-absorbing pigments . In both highly and moderately polar media, the quenching of the excited oxygen species is mainly represented by a reactive interaction . It is exerted by the TC molecule through a cooperative effect from the different contributions of several nuclear and extranuclear O2(1Delta(g)-sensitive substituents, as discussed in detail in this paper . The TC lower than 0.03 in the most favourable cases . Nevertheless, the TC photoproduct, formed through direct irradiation, efficiently generates O2(1Delta(g) with Phi(Delta)=0.24 . This important finding constitutes the first direct evidence of Type II sensitization by TC photoproducts, and could contribute to the elucidation of the mechanism of TC phototoxicity. J Clin Microbiol, 1998 Sep, 36(9), 2784 - 5 Antimicrobial susceptibility of Helicobacter pylori determined by the E test using tetrazolium egg yolk agar; Valdez Y et al.; Metronidazole and tetracycline E tests were compared to an agar dilution method for the antimicrobial susceptibility testing of Helicobacter pylori . Sixteen strains were tested by using tetrazolium egg yolk (TEY) agar . The characteristic E test inhibition ellipse was clearer on TEY agar than on standard blood agar and gave results comparable to those of the agar dilution test . The use of TEY medium is preferable to that of blood agar medium in E test MIC determinations for H . pylori. Vet Clin North Am Food Anim Pract, 1998 Jul, 14(2), 257 - 77 Nutrition and disease; Nagaraja TG et al.; Mortality from digestive diseases in feedlot cattle is second only to that from respiratory diseases . Acidosis and bloat are the major digestive disorders and are likely to continue because of ongoing attempts to improve the efficiency of beef production by feeding more grain and less roughage . Subacute acidosis is probably the most prevalent form of acidosis in feedlots and is difficult to diagnose because of the absence of overt clinical signs . Ruminal changes in subacute acidosis are not as dramatic as those in acute acidosis . Also, the subacute form is not severe enough to induce systemic acidosis . Ruminal acidosis is also a predisposing factor for many other ailments in feedlot cattle such as laminitis, polioencephalomalacia, sudden death syndrome, and liver abscesses . Control of acidosis is achieved largely by sound nutritional management . Antimicrobial compounds (i.e., ionophores and nonionophores), have become management tools to impart stability to ruminal fermentation, modulate feed intake, and control acidosis . Bloat in feedlot cattle can be of free gas or frothy type . Frothy bloat is more common but is rarely the reason for bloat deaths . The economic impact of bloat results mainly from decreased animal performance . The etiology of bloat is complex and is the result of interactions between three major groups of factors: animal, dietary, and microbial . Presently, an effective method to control frothy bloat in feedlot cattle is not available . Ionophore antibiotics, particularly monensin, have been shown to be effective in decreasing the incidence and severity of bloat in cattle. Crit Rev Immunol, 1998, 18(4), 327 - 57 Role of gamma delta T lymphocytes in immune response in humans and mice; Salerno A et al.; T lymphocytes recognize antigen through the T cell receptor . T cells expressing the gamma delta T cell receptor have been found in many species . Whereas murine alpha beta T cells are concentrated in the lymphoid organs, gamma delta T cells represent only a minor population in the adult thymus and peripheral lymphoid organs (less than 5% of the population) . However, murine gamma delta cells predominate in epidermis, in epithelial layers of small intestine, in lung, and in female reproductive organs . In contrast, human gamma delta cells predominate in lymphoid organs . Despite extensive progress in the molecular characterization of the gamma delta T cell receptor and its genes, the physiological role of gamma delta T cells has remained elusive for many years . It is becoming now clear that, in contrast to alpha beta cells that recognize peptide/MHC complexes, gamma delta T cells appear to recognize unprocessed proteic antigens and, in humans, also a class of widely represented nonproteic antigens containing critical phosphate moieties . Similarly, it is now known that gamma delta cells can perform a vast array of immune effector functions and appear to play important roles in antimicrobial immunity as well as in chronic inflammatory reactions. Biochem Biophys Res Commun, 1998 Jul 30, 248(3), 904 - 9 Antileukoprotease in human skin: an antibiotic peptide constitutively produced by keratinocytes; Wiedow O et al.; Antileukoprotease (ALP), also known as mucous protease inhibitor or secretory leukoprotease inhibitor, resembles one of the major antiproteases present in human body fluids . It is capable of preventing proteolytic degradation of extracellular matrix proteins by neutrophil-derived serine proteases . ALP was isolated from human callus and detected in supernatants of cultured human primary keratinocytes . ALP mRNA was constitutively expressed in keratinocytes and the expression was not significantly affected by TNF alpha or Interferon gamma stimulation . In microbicidal assays recombinant ALP exhibited antimicrobial activity against several human skin associated microorganisms like P . aeruginosa, S . aureus, S . epidermidis, and C . albicans, indicating that ALP may actively participate in mechanisms allowing homeostasis of bacterial and yeast colonization on human skin . Thus, ALP represents a major soluble serine protease inhibitor and antimicrobial agent expressed in human skin and seems to contribute to the high resistance of the epidermis against proteolysis and infections. J Neurol Neurosurg Psychiatry, 1998 Aug, 65(2), 209 - 12 Spinal epidural abscess: the importance of early diagnosis and treatment; Mackenzie AR et al.; OBJECTIVES: To remind clinicians of the dangers of delayed diagnosis and the importance of early treatment of spinal epidural abscess . METHODS: A review of the literature on spinal epidural abscess and a comparison of the published literature with local experience . RESULTS: Imaging with MRI or CT enables early diagnosis of spinal epidural abcess and optimal therapy is surgical evacuation combined with 6-12 weeks (median 8 weeks) of antimicrobial chemotherapy . Clinical features are fever, pain, and focal neurological signs and may be associated with preceding and pre-existing bone or joint disease . The commonest aetiological organism is S aureus . CONCLUSION: Early diagnosis and appropriate early antimicrobial chemotherapy with surgery is associated with an excellent prognosis. Clin Chem, 1998 Aug, 44(8 Pt 1), 1680 - 4 Early detection of peritonitis in continuous ambulatory peritoneal dialysis patients by use of chemiluminescence: evaluation of diagnostic accuracy by receiver-operating characteristic curve analysis; Dalaman G et al.; Continuous ambulatory peritoneal dialysis (CAPD) is now a widely accepted treatment for end-stage renal disease . However, the high incidence of peritonitis is a major complication of CAPD . Polymorphonuclear leukocytes (PMNs) play a major role in antimicrobial response of the host . During phagocytosis, the PMNs undergo a striking increase in oxidative metabolism, known as the respiratory burst, and emit light as chemiluminescence (CL) . CL is thus a sensitive measure of PMN oxidative potential and correlates well with antimicrobial activity . In view of the observation of increased susceptibility to infection in CAPD patients, we have studied lucigenin- and luminol-enhanced CL in peritoneal fluids of these patients and assessed the diagnostic accuracy of these tests by ROC curve analysis . ROC curves showed diagnostic accuracies for both tests that were superior to counts of PMNs in the dialysis fluid (P <0.001) . At selected cutoff values of 150000 cpm/vial for lucigenin CL and 600000 cpm/vial for luminol CL, sensitivities were 100% . Specificities for lucigenin and luminol CL were 89% and 80%, respectively . Our results suggest that CL measurements can be used as an early marker for the presence of infection in CAPD patients. Eur Respir J, 1998 Jul, 12(1), 57 - 63 Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells; Takizawa H et al.; Erythromycin and its fourteen-member macrolide analogues have attracted attention for their efficacy in bronchial asthma . However, their mechanisms of action remain unclear . We evaluated the effects of the macrolide antibiotics on endothelin-1 (ET-1) expression in normal and transformed human bronchial epithelial cells, one of the sources of this potent bronchoconstrictor important in the pathogenesis of asthma . Human bronchial epithelial cells were obtained from the resected bronchi, and the effect of several antimicrobial and antiasthmatic drugs on the production and messenger ribonucleic acid (mRNA) levels of ET-1 was evaluated . Bronchoepithelial cells were also isolated from the mucosa of asthmatic patients under fibreoptic bronchoscopy, and the modulating effects of the drugs were studied . Erythromycin and clarithromycin uniquely suppressed mRNA levels as well as the release of ET- at therapeutic and non-cytotoxic concentrations (percentage inhibition of ET-1 protein release: 26.4+/-5.22% and 31.2+/-7.45%, respectively, at 10(-6) M) . Furthermore, erythromycin and clarithromycin inhibited ET-1 expression in bronchoepithelial cells from patients with chronic, stable asthma . A glucocorticosteroid, dexamethasone, also inhibited ET-1 expression . In contrast, theophylline, salbutamol and FK506 had no effect on ET-1 production . Our findings demonstrated that these fourteen-member macrolide antibiotics had an inhibitory effect on endothelin-1 expression in human bronchial epithelial cells . Moreover, this new mode of action may have some relevance to their clinical efficacy in bronchial asthma. Ann Emerg Med, 1998 Aug, 32(2), 214 - 23 Medical preparedness for a terrorist incident involving chemical or biological agents during the 1996 Atlanta Olympic Games; Sharp TW et al.; During the 1996 Centennial Olympic Games in Atlanta, Georgia, unprecedented preparations were undertaken to cope with the health consequences of a terrorist incident involving chemical or biological agents . Local, state, federal, and military resources joined to establish a specialized incident assessment team and science and technology center . Critical antimicrobials and antidotes were strategically stockpiled . First-responders received specialized training, and local acute care capabilities were supplemented . Surveillance systems were augmented and strengthened . However, this extensive undertaking revealed a number of critical issues that must be resolved if our nation is to successfully cope with an attack of this nature . Emergency preparedness in this complex arena must be based on carefully conceived priorities . Improved capabilities must be developed to rapidly recognize an incident and characterize the agents involved, as well as to provide emergency decontamination and medical care . Finally, capabilities must be developed to rapidly implement emergency public health interventions and adequately protect emergency responders. Aliment Pharmacol Ther, 1998 Feb, 12 Suppl 1, 123 - 8 Review article: Practical management issues for the Helicobacter pylori-infected patient at risk of gastric cancer; Tytgat GN; The public health implications of H . pylori infection are considerable in view of the universality of the infection and its attributable risk in cancer causation . Education of the population as to hygiene and nutrition are prerequisites . Total testing/screening and treatment of the infected population, although cost-effective, appears impractical given the current costs of effective antimicrobial treatment, difficulties with compliance, possibilities of side-effects and especially induction of resistance, and the potential for re-infection . A useful vaccine, probably the best hope, is years away from clinical applicability . Current recommendations focus on a selective test and treatment approach which concentrates on asymptomatic individuals at enhanced risk (gastric cancer families; recognized premalignant lesions such as atrophy, intestinal metaplasia, dysplasia, adenomatous polyps); (hypo)achlorhydria, spontaneous or drug-induced; immunodeficiency; ethnic groups; individual demand and wishes . Clinicians will need to establish their individual set of guidelines regarding 'test and treat' of asymptomatic individuals until the outcome of desperately needed clinical trials becomes available. J Antimicrob Chemother, 1998 Jul, 42(1), 107 - 11 The effect of intravenous-to-oral switch guidelines on the use of parenteral antimicrobials in medical wards; Laing RB et al.; The effect of an intravenous (i.v.)-to-oral switch policy on antibiotic prescribing in general medical wards was examined . Three audits, each of 2 months' duration, were carried out to examine the duration of i.v . therapy and length of patient stay . The first audit (S1) was performed before the introduction of switch guidelines, the second (S2) after guidelines had been placed in patient case-notes and the third (S3) after the guidelines had been introduced into the drug charts . The duration of i.v . therapy was significantly shorter in the S3 group (mean = 3.7 days) than in the S2 or S1 groups (mean 4.4 and 4.35 days, respectively) (P < 0.05) . There was no significant difference in the length of patient stay between the three audit periods but the stay was significantly shorter in 81 switched patients (mean duration = 8.9 days) than in matched controls (mean duration = 12.6 days) (P = 0.01) . Fewer patients with respiratory infection were treated for > 24 h with i.v . antimicrobials in the S3 audit period (75/549) than in the S2 (85/372) and S1 audits (83/326) (P < 0.01) . The introduction of switch guidelines to drug charts reduces the length of i.v . therapy . Switched patients spend less time in hospital than their matched controls. J Antimicrob Chemother, 1998 Jul, 42(1), 13 - 28 Photodynamic antimicrobial chemotherapy (PACT); Wainwright M; Whereas the photodynamic therapy (PDT) of cancer has recently shown rapid clinical acceptance, photodynamic antimicrobial chemotherapy (PACT)--which predates the related cancer regimen--is not widely appreciated . Like PDT, PACT utilizes photosensitizers and visible or ultraviolet light in order to give a phototoxic response, normally via oxidative damage . Currently, the major use of PACT is in the disinfection of blood products, particularly for viral inactivation, although more clinically-based protocols are being developed, e.g . in the treatment of oral infection . The technique has been shown to be effective in vitro against bacteria (including drug-resistant strains), yeasts, viruses and parasites . A wide range of photosensitizers, both natural and synthetic, is available with differing physicochemical make-up and light-absorption properties . PACT is proposed as a potential, low-cost approach to the treatment of locally occurring infection. Dent Clin North Am, 1998 Jul, 42(3), 543 - 60 Periodontics in the next millennium; Vandersall DC; This article prognosticates where periodontology will be in the next millennium . The forecasting of such events is wrought with confusion because such predictions are shadowed by bias, dogmatism, prejudice, experiences, and opinions from either a closed or open mind . The results of the survey from 101 periodontists reflect opinions from varied backgrounds, years of clinical experience, and individual levels of success or failure . The responses cannot be tested for accuracy or duplicated by another survey except to wait out the test of time for the year 2025 . Clinicians will be challenged to make decisions on accepting new techniques and concepts as these are brought into the therapeutic fold of periodontics . The clinician will be met with new possibilities as a paradigm shift is inevitable for periodontal practice in the next millennium . After all, who would have thought in the 1960s, the soft tissue augmentation era, that 22 years later in 1982, the regeneration of the lost attachment apparatus (alveolar bone, cementum, and periodontal ligament) would become a reality . This survey strongly suggests that by the end of the first quarter of the twenty-first century, local delivery of antimicrobials, growth and differentiation factors, and root biomodification agents will have a major impact on the practice of periodontics . One thing is certain, in the next millennium, considering the responses from this survey, a new era in periodontics will be here . By the year 2025, the research, development, and dissemination of new periodontal knowledge will be beyond the imagination from what was considered usual and customary for the twentieth century. Aust Vet J, 1998 Jul, 76(7), 460 - 4 Pneumonia associated with Mycoplasma spp in three cats; Foster SF et al.; Mycoplasma spp were isolated in pure culture from bronchoalveolar lavage specimens from three cats with clinical, cytological and radiographic signs of bronchopneumonia or suppurative bronchitis . Predisposing factors were not identified in the first case, the second cat had oesophageal hypomotility, while the third cat had been exposed to cigarette smoke and had advanced periodontal disease . Respiratory signs resolved promptly and completely in all cases following antimicrobial therapy directed against mycoplasmas . Mycoplasma spp are possible causes of lower respiratory tract disease in cats and this should be considered when selecting empirical therapy for feline airway disease and pneumonia . In some situations mycoplasmas may behave as primary lower respiratory tract pathogens in cats. New Microbiol, 1998 Jul, 21(3), 269 - 73 A protein kinase inhibitor from A431 subline overexpressing TGF alpha possesses antimicrobial activity; Pogrebnoy PV et al.; During the last decade the key role of antimicrobial peptides in innate immunity has been argued . They were found in plants and in different phylogenic groups of animals (insects, amphibia, and even in mammals) . We report the production of a human peptide antibiotic that was previously characterized as an EGF receptor tyrosine kinase inhibitor in epidermoid carcinoma A431/1522 cell subline overexpressing TGF alpha . It is a 3 kDa hydrophobic cationic peptide cytotoxic for different species of Gr+ and Gr- bacteria in micromolar concentration range, and demonstrating slight fungicidal activity. Braz J Med Biol Res, 1998 Jun, 31(6), 785 - 91 Toxic, antimicrobial and hemagglutinating activities of the purple fluid of the sea hare Aplysia dactylomela Rang, 1828; Melo VM et al.; The antimicrobial, hemagglutinating and toxic activities of the purple fluid of the sea hare Aplysia dactylomela are described . Intact or dialyzed purple fluid inhibited the growth of species of Gram-positive and Gram-negative bacteria and the action was not bactericidal but bacteriostatic . The active factor or factors were heat labile and sensitive to extreme pH values . The fluid preferentially agglutinated rabbit erythrocytes and, to a lesser extent, human blood cells, and this activity was inhibited by the glycoprotein fetuin, a fact suggesting the presence of a lectin . The fluid was also toxic to brine shrimp nauplii (LD50 141.25 micrograms protein/ml) and to mice injected intraperitoneally (LD50 201.8 +/- 8.6 mg protein/kg), in a dose-dependent fashion . These toxic activities were abolished when the fluid was heated . Taken together, the data suggest that the activities of the purple fluid are due primarily to substance(s) of a protein nature which may be involved in the chemical defense mechanism of this sea hare. Immunol Lett, 1998 Jun, 62(2), 59 - 66 Insect immunity: evolutionary roots of the mammalian innate immune system; Vilmos P et al.; The innate immune system of vertebrates was considered as a survival of ancient antimicrobial systems that have become obsolescent by the emergence of adaptive immunity . Despite the fact that innate immunity lacks the elegance of genetic recombination mechanism to produce trillions of specific clones of immune cells and shows no memory, that view is out of date . Today, the innate immune system is rather regarded to be essential to the function of adaptive immunity by dictating the conduct of the acquired immune response {1} with the help of cytokines, complement, lectin receptors, antigen-reactive T-lymphocytes and B7.1, B7.2 proteins on B cells {2} . This review focuses on recent studies of insect immunology and summarises the currently known similarities between the innate immune system in insects and in vertebrates. Am J Physiol, 1998 Jun, 274(6 Pt 1), G1011 - 7 Effects of Helicobacter pylori gastritis on gastric secretion in healthy human beings; Feldman M et al.; Helicobacter pylori gastritis is common, but effects on gastric secretion are not well understood . We measured basal and pentagastrin-stimulated gastric acidity, pepsin activity, and fluid output, as well as serum gastrin concentrations and H . pylori antibody levels, before and after treatment of H . pylori gastritis in 28 men and women . Subjects were studied before and 1 and 3 mo after a course of bismuth, metronidazole, and tetracycline . Elimination of H . pylori gastritis, accomplished in 14 subjects, increased basal and pentagastrin-stimulated gastric acidity (by 15 meq/l) and basal acid output significantly (by 2.1 meq/h 1 mo after therapy) . Elimination of H . pylori had an opposite effect on pepsin secretion, significantly decreasing pepsin output by 30% . Elimination of H . pylori significantly reduced nonparietal fluid output by 35%, without affecting fluid output from parietal cells . Serum gastrin and H . pylori antibody levels declined significantly after elimination of H . pylori . None of these changes was observed in 14 subjects whose H . pylori gastritis was resistant to antimicrobial therapy . In summary, eradication of H . pylori infection increases gastric acidity by reducing nonparietal gastric secretion from peptic and other cells. Support Care Cancer, 1998 Jul, 6(4), 396 - 401 Prognostic significance of febrile episodes in lung cancer patients receiving chemotherapy; Rikimaru T et al.; The prognostic significance of neutropenic fever in lung cancer patients receiving chemotherapy with or without radiotherapy was investigated . Male patients and patients with squamous cell lung cancer had a higher incidence of febrile episodes than female patients and patients with other cell types, but the differences were not significant . Patients with a poor performance status had a significantly higher incidence of febrile episodes . An indwelling central venous catheter was an important risk factor for febrile episodes, indicating that bacteremia was one of the major causes of fever . The median survival time of the patients who developed febrile episodes during chemotherapy was significantly shorter than that of patients without fever (6.1 vs 12.0 months), whether or not cases of early death within 3 months were excluded (8.9 vs 13.1 months) . The prevention of infectious complications during anticancer treatment by the use of rh G-CSF and the early initiation of antimicrobial chemotherapy, although the results are inconclusive, may be worthwhile. Digestion, 1998 Jul-Aug, 59(4), 321 - 5 Triple therapy with omeprazole, amoxicillin and clarithromycin is effective against Helicobacter pylori infection in gastric ulcer patients as well as in duodenal ulcer patients . Results of a randomized controlled trial in Japan; Habu Y et al.; BACKGROUND/AIMS: There have been few reliable published studies permitting assessment of therapeutic regimens for Helicobacter pylori infection in gastric ulcer (GU) patients . The aim of the present study was to evaluate the efficacy of omeprazole-based dual and triple therapy regimens, both including clarithromycin, for the cure of H . pylori infection in active GU and duodenal ulcer (DU) patients . The study was conducted in Japan, a country in which GU is more prevalent than DU . METHODS: Two hundred and thirty-four consecutive peptic ulcer patients (GU: n = 124; DU: n = 103; GDU: n = 7) suffering from H . pylori infection were randomly treated with either omeprazole 20 mg b.i.d . + amoxicillin 500 mg q.i.d . + clarithromycin 400 mg b.i.d . (OAC) or with omeprazole 20 mg b.i.d . + clarithromycin 400 mg b.i.d . (OC) for 14 days . H . pylori infection was evaluated by histology and culture from antral and corpus biopsies 6 weeks after completing antimicrobial therapy . RESULTS: Follow-up data were available in 202 patients . The cure rates of H . pylori infection in GU patients were 83.9% (47/56) with OAC and 59 . 2% (29/49) with OC . Corresponding rates in DU patients were 91.5% (43/47) and 70.5% (31/44), respectively . The cure rates with OAC were significantly higher than those with OC (p < 0.001, chi2 test) . The cure rates in GU patients were lower than those in DU patients for both regimens, but these differences were not statistically significant . Side effects were generally mild and did not interfere with compliance . One patient in the OAC group and 2 patients in the OC group complained of severe side effects that led to therapy discontinuation . CONCLUSIONS: Triple therapy with omeprazole, amoxicillin and clarithromycin is a safe and effective regimen for the cure of H . pylori infection in GU patients as well as in DU patients . We recommend this triple regimen as a first-line treatment in all patients with peptic ulcers associated with H . pylori infection in Japan. J Endod, 1998 Jun, 24(6), 432 - 4 Chemical stability of heated sodium hypochlorite endodontic irrigants; Gambarini G et al.; Several previous studies have investigated the advantage of temperature on tissue-dissolving and antimicrobial properties of sodium hypochlorite . However, it is known that the chemical stability of sodium hypochlorite is adversely affected by exposure to high temperature . The purpose of this study was to investigate the effect of heating sodium hypochlorite to 50 degrees C on the stability of the solution . An iodometric titration test was used to evaluate the decomposition rates of heated and nonheated solutions over 30 days . Results showed that all specimens exhibited a minimal, gradual degradation versus time . However, no statistically significant difference (p < 0.05) was noted between the two groups . After 30 days, both heated and non-heated solutions maintained high available chlorine content and pH values consistent with excellent tissue-dissolving and antibacterial properties. J Endod, 1998 Jul, 24(7), 472 - 6 Antimicrobial activity of 2.5% sodium hypochlorite and 0.2% chlorhexidine gluconate separately and combined, as endodontic irrigants; Kuruvilla JR et al.; Sodium hypochlorite irrigant is known to be toxic to periapical tissues . Chlorhexidine gluconate, a safer and effective antimicrobial irrigant, is not known to dissolve pulpal tissues . To obtain their optimal properties, their combined action within the root canal was evaluated . Ten single rooted nonvital anterior teeth were irrigated using either 2.5% sodium hypochlorite alone, 0.2% chlorhexidine gluconate alone, 2.5% sodium hypochlorite and 0.2% chlorhexidine gluconate combined within the root canal, or 0.9% saline, respectively . Microbiological samples for culture and Gram's staining were taken before and proceeding irrigation . This study indicates that the use of sodium hypochlorite and chlorhexidine gluconate combined within the root canal resulted in the greatest percentage reduction of postirrigant positive cultures . This may be due to formation of "chlorhexidine chloride," which increases the ionizing capacity of the chlorhexidine molecule . This reduction was significant compared to use of sodium hypochlorite alone but not significant compared to use of chlorhexidine gluconate alone. Front Biosci, 1998 Aug 05, 3, d865 - 76 Interaction of mycobacterial glycolipids with host cells; Vergne I et al.; Mycobacteria elaborate a great variety of glycolipids of rather exotic structure . Some of these lipids are abundant cell envelope components and are exposed on the bacterial surface . These comprise the species-specific phenolic glycolipids, glycopeptidolipids, sulfatides, and lipooligosaccharides, and the ubiquitous phosphatidylinositolmannosides . Because pathogenic mycobacterial species are facultative intracellular parasites that infect and reside in host cells, some of them may represent potential virulent factors as they have been shown to inhibit both macrophage antimicrobial activities and lymphoproliferation . These biologic activities may derive, at least in part, from the modulation of the cell functions through the interactions between host membranes and these surface-exposed lipids whose structures are different from those of mammalian cell membrane components . In few cases purified glycolipids have been shown to profoundly affect the physical and functional properties of biologic membranes . Therefore, the enzymes involved in the biosynthesis of the biologically active glycolipids represent potential drug targets . However, definite proofs of their implication in the mycobacterial pathogenicity are lacking . Mutants unable to elaborate defined glycolipids are needed. Biochem J, 1998 Aug 15, 334 ( Pt 1), 99 - 105 Identification and characterization of the antimicrobial peptide corresponding to C-terminal beta-sheet domain of tenecin 1, an antibacterial protein of larvae of Tenebrio molitor; Lee KH et al.; An active fragment was identified from tenecin 1, an antibacterial protein belonging to the insect defensin family, by synthesizing the peptides corresponding to the three regions of tenecin 1 . Only the fragment corresponding to the C-terminal beta-sheet domain showed activity against fungi as well as Gram-positive and Gram-negative bacteria, whereas tenecin 1, the native protein, showed activity only against Gram-positive bacteria . CD spectra indicated that each fragment in a membrane-mimetic environment might adopt a secondary structure corresponding to its region in the protein . The leakage of dye from liposomes induced by this fragment suggested that this fragment acts on the membrane of pathogens as a primary mode of action . A comparison between the structure and the activity of each fragment indicated that a net positive charge was a prerequisite factor for activity . To the best of our knowledge this is the first report in which the fragment corresponding to the beta-sheet region in antibacterial proteins, which consists of alpha-helical and beta-sheet regions, has been identified as a primary active fragment. Am J Hematol, 1998 Aug, 58(4), 293 - 7 Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy; Griggs JJ et al.; The purpose of