J Infect Chemother, 1999 Jun, 5(2), 110 - 123 Clinical evaluation methods for new antimicrobial agents to treat respiratory infections: Report of the Committee for the Respiratory System, Japan Society of Chemotherapy; Saito A et al.; The present report constitutes an attempt to improve and modify the existing clinical evaluation method for new antimicrobial agents to treat respiratory infections . One year ago, a general guideline on the clinical evaluation of antimicrobial agents to treat respiratory infections was drafted in Japanese, leaving scope for critical discussion, and this has been translated into English, as there were no major changes . In this report, respiratory infections have been discussed under the headings "acute respiratory tract infection" and pneumonia and acute exacerbation of chronic pulmonary diseases . Standardized criteria were set for the assessment of severity of infection and effectiveness of the antimicrobial agent in question . Severity was evaluated on the basis of a combined assessment of the severity of infection and severity of the clinical condition of the patients . Clinical effectiveness of the antimicrobial agent used was evaluated on the basis of clinical outcome as well as microbiological outcome of the trial . Body temperature, local pain, cough, change in sputum quality, peripheral white blood cell count, C-reactive protein level, and chest radiograph were used as the parameters for the evaluation . To maintain the quality of specimens to be examined, Geckler's classification of specimens was used . This report was constructed based on the analysis of large amounts of material collected over the years, incorporating internal and external factors concerning the present evaluation methods . The newly suggested standardized criteria for clinical evaluation of the new antimicrobial drugs are expected to be practiced properly hereupon and subjected to further improvement if necessary. J Food Prot, 2002 Jan, 65(1), 222 - 37 Process engineering variables in the spray washing of meat and produce; Pordesimo LO et al.; Recently, much attention has been focused on the safety of fruits and vegetables . Washing is a fundamental operation in the processing of produce . Aqueous spray energy can be, and often is, used to remove mineral, chemical, or biological contaminants from produce . A few advantages of spray washing over washing by dipping, soaking, or gravity rinse are increased energy directed to contaminants, reduced volume of water use and wastewater generation, and reduced water uptake by produce . The kinetic energy of the spray droplets produces the cleaning action . Increased spray pressure increases energy . If the energy is too great, produce may be physically damaged . If the energy is too little, the surface may not be cleaned . Indeed, studies on meat have shown that water pressures ranging from 1,379 to 2,070 kPa (200 to 300 psi) are effective in reducing microbial contamination, and a water flow rate of 7.5 liters/min is recommended . Water temperature >70 degrees C has been found to reduce bacterial counts in carcass tissue by 2 to 3 log CFU/cm2 . These levels are likely too high for the fragile produce; hence, the main function of spray washing in produce applications will probably shift to being a delivery system for antimicrobial agents . Several other equipment, process, and product variables are relevant to the optimization of such a system . Qualities of the spray, such as droplet spectrum, droplet velocity, angle of droplet impingement, number and orientation of nozzles, spray rate, and resident time of the produce in the sprayer, also can be manipulated to adjust the amount of energy directed to the surface . There is a need to scientifically investigate the effects of these processes and equipment parameters on the removal of microbiological contaminants on meats and produce . Such empirical investigations guided by the results from fundamental studies about produce surface characteristics and the mechanism of bacterial attachment to plant tissue surfaces would allow for the efficient development of spray washers that effectively decontaminate produce. Indian J Dent Res, 2001 Jul-Sep, 12(3), 127 - 32 The effects of extracts of chewing sticks (Salvadora persica) on healthy and periodontally involved human dentine: a SEM study; Almas K; The popularity and availability of chewing sticks (Salvadora persica) in the Asia, Middle East and Africa make them a commonly used oral hygiene tool in those societies . Salvador persica chewing stick called miswak is frequently used in Saudi Arabia . The antimicrobial effects of miswak has been well documented . The aim of this study is to find our the effect of aqueous extracts of miswak on healthy and periodontally involved human dentine with Scanning Electron Microscopy (SEM) in vitro . 25% aqueous extract of freshly prepared miswak solution was used for the study . Twelve human premolars teeth (6 healthy and 6 with periodontal disease) recently extracted for orthodontic and periodontal reasons were used . 24 SEM specimens were prepared and treated with miswak extract with different conditions e.g . soaking and burnishing with miswak extract . Soaking the healthy and periodontally diseased root dentine in miswak extract resulted in partial removal of smear layer and occlusion of dentinal tubules was observed in dentine specimens burnished with miswak solution . Further research is needed to evaluate the effect of aqueous extract of miswak on etched human dentine at higher concentrations. Tidsskr Nor Laegeforen, 2001 Dec 10, 121(30), 3538 - 43 {Microorganisms strike back--infectious diseases during the last 50 years}; Solberg CO; In the first half of the 20th century, improved living conditions, preventive measures, vaccines and antibiotics led to a marked reduction in morbidity and mortality from infectious diseases . It was predicted that the conquest of all infectious diseases was imminent . However, 50 years later, in 1999, they were still the major cause of disease worldwide, and caused nearly one third of all deaths (a total of 55.9 million) . The eradication of smallpox in the 1970s and the approaching eradication of poliomyelitis represent major achievements . The prevalence of measles, pertussis and tetanus neonatorum is also markedly reduced, but still 1.5 million children in developing countries die each year because of lack of vaccines . Malaria and tuberculosis are re-emerging . Tuberculosis and HIV/AIDS are the diseases with known aetiology that cause most deaths, altogether 5 million each year . Respiratory and gastrointestinal infections cause 6.5 million deaths annually . Infections in the immunocompromised host have become a "trade mark" of today's advanced medicine . Almost every year, new diseases related to new micro-organisms are described; over the last 30 years, approximately 40 new diseases/micro-organisms have been diagnosed . Among the best known are HIV/AIDS, peptic ulcer caused by Helicobacter pylori, Legionnaires' disease, borreliosis (Lyme disease), hepatitis C, gastroenteritis caused by rotavirus, and Ebola haemorrhagic fever . Antimicrobial resistance development of micro-organisms has become one of the major health problems worldwide; a number of preventive measures are being introduced. Phytother Res, 2002 Feb, 16(1), 94 - 5 Antimicrobial properties of star anise (Illicium verum Hook f); De M et al.; Star anise (Illicium verum Hook f) has been shown to possess potent antimicrobial properties . Chemical studies indicate that a major portion of this antimicrobial property is due to anethole present in the dried fruit . Studies with isolated anethole (compared with standard anethole) indicated that it is effective against bacteria, yeast and fungal strains . J Infect Dis, 2002 Jan 15, 185(2), 229 - 36 Epub 2002 Jan 03. In vitro therapeutic effect of epigallocatechin gallate on nicotine-induced impairment of resistance to Legionella pneumophila infection of established MH-S alveolar macrophages; Matsunaga K et al.; Epigallocatechin gallate (EGCg), a major form of tea catechins, has a variety of biological activities . Tobacco smoking, nicotine in particular, is one of the risk factors for respiratory infections . In the present study, a possible immunotherapeutic effect of EGCg on the nicotine-induced impairment of alveolar macrophages regarding antimicrobial activity, as well as immune function, was examined . The treatment of MH-S macrophages with nicotine significantly enhanced Legionella pneumophila replication in the cells and selectively down-regulated the production of interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-alpha induced by infection but did not alter IL-10 production . The EGCg treatment of nicotine-suppressed macrophages reconstituted the resistance to the infection . Furthermore, EGCg diminished the nicotine-induced inhibition of cytokine production . Experiments with TNF-alpha treatment, neutralization of cytokines with antibodies, and analysis of interferon (IFN)-gamma messenger RNA showed that the mechanism of the EGCg-induced recovery of anti-L . pneumophila activity impaired by nicotine may be due to the recovery of TNF-alpha and IFN-gamma production by the macrophages. Nature, 2002 Jan 24, 415(6870), 389 - 95 Antimicrobial peptides of multicellular organisms; Zasloff M; Multicellular organisms live, by and large, harmoniously with microbes . The cornea of the eye of an animal is almost always free of signs of infection . The insect flourishes without lymphocytes or antibodies . A plant seed germinates successfully in the midst of soil microbes . How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa . What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us? Biophys J, 2002 Feb, 82(2), 908 - 14 Sigmoidal concentration dependence of antimicrobial peptide activities: a case study on alamethicin; Chen FY et al.; The transition of the state of alamethicin from its inactive state to its active state of pore formation was measured as a function of the peptide concentration in three different membrane conditions . In each case the fraction of the alamethicin molecules occupying the active state, phi, showed a sigmoidal concentration dependence that is typical of the activities of antimicrobial peptides . Such a concentration dependence is often interpreted as due to peptide aggregation . However, we will show that a simple effect of aggregation cannot explain the data . We will introduce a model based on the elasticity of membrane, taking into consideration the membrane-thinning effect due to protein inclusion . The elastic energy of membrane provides an additional driving force for aggregation . The model produces a relation that not only predicts the correct concentration dependence but also explains qualitatively how the dependence changes with membrane conditions . The result shows that the membrane-mediated interactions between monomers and aggregates are essential for the strong cooperativity shown in pore formation. J Chemother, 2001 Dec, 13(6), 595 - 606 Efficacy of antiadhesive, antibiotic and antiseptic coatings in preventing catheter-related infections: review; Donelli G et al.; In recent years, central venous catheters (CVCs) are increasingly used in clinical practice . However, complications such as local or systemic infections are frequent for both temporary and indwelling vascular catheters . Annually, in the United States of America there are more than 200,000 cases of nosocomial bloodstream infections (BSIs), of which 90% are related to the use of an intravascular device . These infections are associated with increased morbidity and mortality, prolonged hospitalization and growing medical costs . Technological treatments of polymer surfaces including coating the catheter with antimicrobial substances may be promising tools for prevention of catheter-associated infections . A large number of surface-treated central venous catheters are now commercially available . In this paper the features and the clinical efficacy of different antimicrobial coatings are reviewed. Exp Mol Med, 2001 Dec 31, 33(4), 263 - 8 Free radical scavenging and antioxidant enzyme fortifying activities of extracts from Smilax china root; Lee SE et al.; The extract from Smilax china root has been used as medicinal remedy and reported to retain antimicrobial and antimutagenic acitivities . In this study, a possible presence of antioxidant activity of Smilax china root extract was investigated . Methanol extract (Me) revealed the presence of high 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (IC50 7.4 microg/ml) and protective property of cell's viability . Further fractionation with various solvent extraction and assay showed high levels of DPPH free radical scavenging activity in the ethyl acetate, butanol and water extracted fractions . In addition, V79-4 cells treated with Me of Smilax china root induced an increase of superoxide dismutase, catalase and glutathione peroxidase activities in a dose-dependent manner between 4-100 microg/ml . These results suggest that the medicinal component of the root of Smilax china extracts also contains antioxidant activity. AORN J, 2001 Dec, 74(6), 859 - 73 Is it time for brushless scrubbing with an alcohol-based agent? Gruendemann BJ, Bjerke NB. The practice of surgical scrubbing in perioperative settings is changing rapidly . This article presents information about eliminating the traditional scrub brush technique and using an alcohol formulation for surgical hand scrubs . Also covered are antimicrobial agents, relevant US Food and Drug Administration classifications, skin and fingernail care, and implementation of changes . The article challenges surgical team members to evaluate a new and different approach to surgical hand scrubbing. Adv Nutr Res, 2001, 10, 271 - 85 The antimicrobial function of milk lipids; Isaacs CE; Milk lipids serve not only as nutrients but as antimicrobial agents that constitute a defense system against microbial infections that occur at mucosal surfaces . The lipid fraction of milk develops antimicrobial activity in the gastrointestinal tract of suckling neonates as a result of lipolytic activity which converts milk triglycerides to antimicrobial fatty acids and monoglycerides . Antimicrobial milk lipids may be particularly important in protecting infants with an inadequate secretory immune response from infection . The lipid-dependent antimicrobial activity of milk is due to medium-chain saturated and long-chain unsaturated fatty acids and their respective monoglycerides released by lipases in the gastrointestinal tract . The antimicrobial activity of fatty acids and monoglycerides is additive and consequently it is their combined concentration that determines the lipid-dependent antimicrobial activity of milk . Microbial inactivation occurs rapidly by membrane destabilization . The antimicrobial activity of milk lipids can be duplicated using purified fatty acids and monoglycerides . It should be possible, therefore, to supplement banked human milk to provide lipid-dependent antimicrobial activity from the moment of ingestion (Schanler et al., 1986) . This could reduce the risk of viral transmission from mother to infant through milk . Milk lipids also could be adapted for use at mucosal surfaces other than those in the gastrointestinal tract to reduce vertical transmission of pathogens during birth. Tijdschr Diergeneeskd, 2002 Jan 1, 127(1), 2 - 6 {Maximum residue levels (MRL's) of veterinary medicines in relation to food safety . MRL's really do matter--the Benzaprocpen case}; Vaarkamp H; The importance of veterinary medicines and especially of antimicrobial agents is shown, not only as beneficial compounds for animal health and animal welfare but as risks as well, being potential sources of residues in food of animal origin, when after administration of veterinary medicines to the animals the withdrawal time in relation to the maximum residue limit (MRL) is not taken into account . Health for men and animal is of utmost importance and the quality of food is considered as an important health factor . Data are presented from a report, not made public previously, concerning a study dealing with plasma kinetics and forming of residues in young pigs of a long acting penicillin Benzaprocpen, which was formerly used in the Netherlands quite often in piglets with arthritis . Ten weeks after the last injection with these depot compounds at all injection sites penicillin G residues were present in quantities much greater than the allowed maximum residue limit of 50 micrograms/kg for benzylpenicillin . As a consequence it is impossible to use any longer this specific veterinary medicine in food producing animals and thus MRL's do really matter. Am J Health Syst Pharm, 2001 Dec 15, 58(24), 2381 - 95 Neuromuscular blockers in surgery and intensive care, Part 2; McManus MC; The historical development, pharmacology, pharmacodynamics, pharmacokinetics, clinical applications, pharmacologic basis for selection, adverse effects, and cost of neuromuscular blockers (NMBs) are discussed . The first NMB to be used was tubocurarine . During neurotransmission, acetylcholine is synthesized, stored in vesicles at the neuromuscular junction, released into the synapse, and bound to nicotinic receptors in the muscle end plate . For muscle contraction to occur, the impulse generated in a neuron's cell body must create an action potential that is chemically transmitted across the synapse . The postsynaptic nicotinic receptor at the neuromuscular junction is the major site of action of depolarizing and nondepolarizing NMBs . All NMBs have the potential for cross-reactivity at other nicotinic and muscarinic sites . Drug interactions most commonly occur between NMBs and inhalation anesthetics, certain antimicrobials, calcium-channel blockers, and anticholinesterases . When selecting an NMB, an agent's onset and duration of action must be considered . NMBs can be used on a short-term or long-term basis . Apart from cost, the choice of an NMB is made on the basis of its adverse-reaction profile, pharmacokinetics, and indications for use . Monitoring tools, their use, the rationale for their use, and the interpretation of the results they provide are unique . The patterns of peripheral nerve stimulation vary and elicit different characteristics of nondepolarizing neuromuscular blockade . The effectiveness of reversal agents is proportional to the degree of blockade . The mechanism of action of anticholinesterases involves inhibition of acetylcholinesterase . The expensive NMBs should be conserved for use in surgery, while the cheaper, long-acting {corrected} agents should be used in the intensive care unit . An understanding of the pharmacology, pharmacodynamics, and pharmacokinetics of NMBs will help health care providers gain expertise in the selection and use of these agents. Altern Med Rev, 2001 Dec, 6(6), 567 - 79 Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado; Williams JE; Viral diseases, including emerging and chronic viruses, are an increasing worldwide health concern . As a consequence, the discovery of new antiviral agents from plants has assumed more urgency than in the past . A number of native Amazonian medicines of plant origin are known to have antimicrobial and anti-inflammatory activity, although only a few have been studied for their antiviral properties and immunomodulating effects . Those most studied include: Sangre de Grado (drago) (Croton lechleri) in the Euphorbiaceae family and Una de Gato (Uncaria tomentosa) in the Rubiaceae family . This article reviews the chemical composition, pharmacological properties, state of current research, clinical use, and potential antiviral and immunomodulating activity of these and other plants from the Peruvian Amazon. J Med Assoc Thai, 2001 Oct, 84(10), 1467 - 76 Comparison of the resistance ratio and proportion methods for antimicrobial susceptibility testing of Mycobacterium tuberculosis; Tansuphasiri U et al.; This study compared two in vitro antimicrobial susceptibility methods for determining drug susceptibilities of Mycobacterium tuberculosis isolated from newly diagnosed pulmonary tuberculosis patients to four front-line drugs . Of 250 strains of M . tuberculosis tested, 74.4 per cent were susceptible by the resistance ratio method, with 72.0 per cent by the proportion method . The results showed high agreement for both methods (P<0.0001) and agreement rates to streptomycin, isoniazid, rifampicin and ethambutol were 96.8, 98.0, 94.8 and 96.8 per cent, respectively . For drug resistance patterns, both methods showed the highest resistance to one drug, followed by two, three, and four drugs, respectively . Of the single drug resistance, both methods gave the highest resistance to streptomycin, followed by resistance to isoniazid, rifampicin and ethambutol, respectively . The correlation between both methods for determining susceptibility of M . tuberculosis to four drugs was not statistically significantly different by Mc Nemar chi2 (p>0.05) . Thus, the resistance ratio method may be substituted . However, WHO recommended the use of the proportion method to be used for determining drug susceptibility of M . tuberculosis . The susceptibility testing result can be used as the guidance for proper treatment and is valuable for confirmation of drug resistance in patients showing unsatisfactory response to treatment, useful for identifying primary and acquired drug resistance trends in a community and for minimizing the spread of drug-resistant strains. Clin Infect Dis, 2002 Mar 1, 34(5), 628 - 33 Epub 2002 Jan 16. Drug prophylaxis for travelers' diarrhea; Rendi-Wagner P et al.; Travelers' diarrhea is the most common health impairment in persons visiting developing countries, affecting 20% to >50% of tourists . Although it is usually benign, travelers' diarrhea represents a considerable socioeconomic burden for both the traveler and the host country . The most common enteropathogens are enterotoxigenic and enteroaggregative Escherichia coli . Travelers' compliance with dietary precautionary measures is poor . Despite the excellent protection rates provided by antibiotics, routine administration of prophylaxis is currently not recommended because of potential adverse reactions . Of the various antibiotics that have been tested, quinolones are considered to be the first choice worldwide; however, quinolone-resistant pathogens are increasingly being isolated . Because it is frequently administered and provides only moderate protection, bismuth subsalicylate is not considered a recommendable option for prophylaxis in Europe, where it is rarely available anyhow . To date, no probiotic has been able to demonstrate clinically relevant protection worldwide . In conclusion, there is no satisfactory prophylactic option, and worldwide monitoring of antimicrobial susceptibility patterns and the search for novel antimicrobial agents, such as nonabsorbed antibiotics, and nonantibiotic medications should continue. Z Gastroenterol, 2002 Jan, 40(1), 11 - 4 Decreased prevalence of Helicobacter pylori infection in HIV patients with AIDS defining diseases; Lichterfeld M et al.; Various clinical studies indicated a lower prevalence of HP infection in HIV patients . The present study was initiated to determine whether the decreased frequency of HP infections in HIV patients might be associated with the stage of the underlying HIV disease or concomitant drug regimens the patients had received . 60 randomly selected HIV outpatients were stratified according to the stage of their HIV infection (CDC classification), their CD4 cell count and to the drug regimens they were given . Within these subgroups of patients, HP infection prevalence was separately investigated by serological and C13 breath testing . Data were compared to a reference population of 30 healthy volunteers.No difference in HP infection prevalence was found between the HIV infected patients in general and the reference cohort . A significantly lower proportion of HP infected individuals was observed among those HIV patients who had AIDS-defining diseases . Furthermore, a substantial but insignificant decrease of HP infection prevalence was noted in HIV patients with an extensive decline of CD4 cell count (< 100/microl) . HIV patients who had received antimicrobial or H2-antagonizing drugs within 12 months prior to the study commencement also were found to have a remarkably decreased frequency of HP infections independently of their CD4 cell count . No association between HP infection prevalence and patients age, sex, risk group and the type of their antiretroviral treatment was found.We concluded from these results that the decreased HP infection prevalence in HIV patients may, apart from frequent antibiotic treatment, be correlated to the stage of HIV-mediated immune suppression. Skin Pharmacol Appl Skin Physiol, 2002 Jan-Feb, 15(1), 1 - 6 Learning from leprosy: insights into contemporary immunology from an ancient disease; Modlin RL; Leprosy provides an ideal model to study immune responses in humans and in skin . Learning from leprosy, we have gained insight into mechanisms of host resistance and susceptibility to infection . New paradigms include the role of Th1/Th2 cytokines, the ability of CD1 to present nonpeptide antigens to T cells, the ability of microbial lipoproteins to stimulate antimicrobial activity in monocytes and the demonstration that T cells can mediate a direct antimicrobial activity through release of granulysin . Together, these findings provide a rationale for developing new strategies to treat and prevent infectious disease . Blood Purif, 2002, 20(1), 87 - 92 Prevention of hemodialysis catheter-related bloodstream infection using an antimicrobial lock; Quarello F et al.; Among currently available vascular access options for hemodialysis, central venous catheters show the poorest reliability, with frequent complications of thrombosis and stenosis impairing patency . The most serious problem, however, is catheter-related bloodstream infection (CRBI), which is typically a cause for removal of the catheter and protracted systemic antibiotic therapy . In our experience, a totally implanted device (Dialock, Biolink Corp.) seems to confer a better global protection against catheter-related infections than standard tunneled catheters, accounting for 0.97 vs . 4.75 infection episodes/1,000 catheter-days, respectively (p < 0.001) . Bloodstream infection rates, however, are not statistically different in the two groups (0.85 vs . 0.81 per 1,000 catheter-days; p = n.s.), indicating that the improvement is mainly related to local cutaneous infections . On the other hand, in the Sodemann experience, a new taurolidine-based lock solution (Neutrolin, Biolink Corp.) greatly reduced CRBI rates with both subcutaneous ports and tunneled catheters to 0.29 and 0.20 episodes/1,000 catheter-days, respectively . These promising results await further confirmation from ongoing clinical trials . Pharmazie, 2001 Dec, 56(12), 933 - 7 Reactions with pyrrolidine-2,4-diones, Part 4: Synthesis of some 3-substituted 1,5-diphenylpyrrolidine-2,4-diones as potential antimicrobial, anti-HIV-1 and antineoplastic agents; Shams el-Dine SA et al.; The condensation of 1,5-diphenylpyrrolidine-2,4-dione (1) with ethyl orthoformate yielded 3-ethoxymethylene-1,5-diphenylpyrrolidine-2,4-dione (2) . Reaction of the latter with hydrazine hydrate, secondary amines 7a-c or urea afforded the corresponding 3-substituted aminomethylene-1,5-diphenylpyrrolidene-2,4-diones 3, 8a-c or 9 . On the other hand, condensation of 3 with veratraldehyde (5a) yielded 3-{(3,4-dimethoxybenzylidene)hydrazinomethylene}-1,5-diphenylpyrrolidine- 2,4-dione (6) . Whereas, cyclization of 9 with the reactive malonate ester 11 produced 3-{(5-butyl-4-hydroxy-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-1-yl) methylene}-1,5-diphenylpyrrolidine-2,4-dione (12) . The condensation of some selected aromatic aldehydes 5a-c and addition of morpholine (7c) or piperidine (7d) to some of the resulting 3-arylidene-1,5-diphenylpyrrolidine-2,4-diones 13b, c gave the respective 3-substituted methyl-4-hydroxy-1,5-diphenyl-delta 3-pyrrolin-2-ones 14a-c . Selected members of the new series were screened for their in vitro antimicrobial, anti-HIV-1 and antineoplastic activities . Two compounds 14a, b showed pronounced inhibitory activities against Gram-positive bacteria; whereas, in the in vitro anti-HIV-1 screening, only one compound 13c displayed a moderate activity . However, in the antineoplastic screening protocol, the tested compounds were devoid of activity. Gynecol Obstet Fertil, 2001 Dec, 29(12), 924 - 41 {Treatment of genital infections in gynecology}; Pennehouat G et al.; Choice of antimicrobial agents and length of therapy of infections of the female genital tract and chemotherapy are presented with particular mention to their side effects . Clinical approach and antibiotic regimens of pelvic inflammatory diseases are discussed. Wien Klin Wochenschr, 2001 Dec 17, 113(23-24), 939 - 41 Amoxycillin, clarithromycin and either sucralfate or pantoprazole for eradication of Helicobacter pylori in duodenal ulcer (a randomized controlled trial); Vcev A et al.; BACKGROUND: Sucralfate enhances the anti-Helicobacter pylori activity of antimicrobials and has an inhibitory effect on H . pylori . AIM: To evaluate the efficacy and safety of one-week sucralfate-based eradication therapy for H . pylori infection in patients with duodenal ulcers, compared with treatment based on pantoprazole, in a randomized controlled multicenter study . METHODS: One hundred and twenty patients with active duodenal ulcers and H . pylori infection were treated with amoxycillin 1 g b.d . plus clarithromycin 500 mg b.d . for the first 7 days . Patients were randomly assigned to receive either sucralfate 1 g t.d.s . for 4 weeks (SAC group; n = 60) or pantoprazole (PAC group; n = 60) 40 mg b.d . for the first 7 days and 40 mg o.d . for the next 3 weeks . The patient's H . pylori status was determined by a urease test and histological investigation before the treatment, and again 4 weeks after cessation of all medication . RESULTS: One hundred and eleven patients completed the study . H . pylori infection was eradicated in 76.4% (42/55) of patients in the SAC group (ITT analysis: 70%, 95% CI: 58-80%) vs . 85.7% (48/56) of patients in the PAC group (ITT analysis: 80%, 95% CI: 70-89) (N.S.) . All ulcers had healed . There were no significant differences between the two regimens regarding the occurrence of adverse effects . CONCLUSION: Our study shows that one-week triple therapy with amoxycillin, clarithromycin and either pantoprazole or sucralfate are effective regimens to cure H . pylori infection in patients with duodenal ulcer. J Immunol, 2002 Feb 1, 168(3), 1490 - 5 Selective decrease in circulating V alpha 24+V beta 11+ NKT cells during HIV type 1 infection; van der Vliet HJ et al.; CD1d-restricted NKT cells express an invariant TCR and have been demonstrated to play an important regulatory role in a variety of immune responses . Invariant NKT cells down-regulate autoimmune responses by production of type 2 cytokines and can initiate antitumor and antimicrobial immune responses by production of type 1 cytokines . Although defects in the (invariant) Valpha24+Vbeta11+ NKT cell population have been observed in patients with cancer and autoimmune diseases, little is known regarding the protective role of Valpha24+Vbeta11+ NKT cells in human infectious disease . In a cross-sectional study in HIV-1-infected individuals, we found circulating numbers of Valpha24+Vbeta11+ NKT cells to be reduced, independent of CD4+ T cell counts, CD4:CD8 ratios, and viral load . Because a small minority of Valpha24+Vbeta11+ NKT cells of healthy donors expressed HIV-1 (co)receptors and the vast majority of Valpha24+Vbeta11+ NKT cells in HIV-1-infected individuals expressed the Fas receptor, the depletion was more likely due to Fas-mediated apoptosis than to preferential infection of Valpha24+Vbeta11+ NKT cells by HIV-1 . A longitudinal cohort study, in which patients were analyzed before seroconversion and 1 and 5 years after seroconversion, demonstrated that a large proportion of the depletion occurred within the first year postseroconversion . In this longitudinal study no evidence was found to support an important role of Valpha24+Vbeta11+ NKT cells in determining the rate of progression during HIV-1 infection. J Ethnopharmacol, 2002 Feb, 79(2), 165 - 8 In vitro antimicrobial activity of extracts and isolated constituents of Rubus ulmifolius; Panizzi L et al.; The antimicrobial activity on bacteria and fungi of increasing polarity extracts of Rubus ulmifolius and that of some isolated constituents, quercetin-3-O-beta-D-glucuronide; kaempferol-3-O-beta-D-glucuronide, gallic acid, ferulic acid and tiliroside was evaluated . The phenolic and tannins fractions showed an high antimicrobial activity. Int J Toxicol, 2001, 20 Suppl 4, 13 - 26 Final report on the safety assessment of PEG-25 propylene glycol stearate, PEG-75 propylene glycol stearate, PEG-120 propylene glycol stearate, PEG-10 propylene glycol, PEG-8 propylene glycol cocoate, and PEG-55 propylene glycol oleate; Johnson W Jr; Cosmetic Ingredient Review Expert Panel; The ingredients considered in this safety assessment are polyethylene glycol ethers of either propylene glycol itself, propylene glycol stearate, propylene glycol oleate, or propylene glycol cocoate . They function in cosmetic formulations as surfactant--cleansing agents; surfactant-solubilizing agents; surfactant--emulsifying agents; skin conditioning agents--humectant; skin-conditioning agents--emollient; and solvents . Those in current use are used in only a small number of cosmetic formulations . Some are not currently used . Polyethylene Glycol (PEG) Propylene Glycol Cocoates and PEG Propylene Glycol Oleates are produced by the esterification of polyoxyalkyl alcohols with lauric acid and oleic acid, respectively . Although there is no information available on the method of manufacture of the other polymers, information was available describing impurities, including ethylene oxide (maximum 1 ppm), 1,4-dioxane (maximum 5 ppm), polycyclic aromatic compounds (maximum 1 ppm), and heavy metals-lead, iron, cobalt, nickel, cadmium, and arsenic included (maximum 10 ppm combined) . In an acute oral toxicity study, PEG-25 Propylene Glycol Stearate was not toxic . An antiperspirant product containing 2.0% PEG-25 Propylene Glycol Stearate was nonirritating to mildly irritating to the eyes of rabbits . This product was also practically nonirritating to the skin of rabbits in single-insult occlusive patch tests . In a guinea pig sensitization test, PEG-25 Propylene Glycol Stearate was classified as nonallergenic at challenge concentrations of 25% and 50% in petrolatum . PEG-25 Propylene Glycol Stearate and PEG-55 Propylene Glycol Oleate were negative in clinical patch tests . Based on the available data, it was concluded that these ingredients are safe as used (concentrations no greater than 10%) in cosmetic formulations . Based on evidence of sensitization and nephrotoxicity in burn patients treated with a PEG-based antimicrobial preparation, the ingredients included in this review should not be used on damaged skin. Acta Anaesthesiol Belg, 2001, 52(4), 357 - 63 Interactions of neuromuscular blocking drugs; Cammu G; Many drugs interact with neuromuscular blocking drugs and often enhance the induced block; this is of clinical importance for volatile anaesthetics, antimicrobials, magnesium and some more specific drugs . Difficulty in reversing the block occurs with calcium-channel blockers and polymyxin . Phenytoin, carbamazepine and other anticonvulsants may cause resistance to neuromuscular blocking drugs . Moreover, clinically important interactions are found between individual neuromuscular blockers . Giving succinylcholine after a non-depolarizing neuromuscular blocking drug prolongs the onset of succinylcholine; when non-depolarizing drugs are administered after succinylcholine their effects are prolonged . The succinylcholine block is prolonged when the drug is administered during recovery from pancuronium or following neostigmine reversal . Drugs or diseases that decrease the activity of plasma cholinesterase may prolong a succinylcholine-induced block . Finally, liver dysfunction, renal failure, disturbances of acid-base balance, change in temperature and neurological diseases all have an effect on the profile of the neuromuscular blocking drugs; the response to an induced block may be altered in patients under intensive care and those with cancer . Although knowledge of the most important theoretical interactions of neuromuscular blocking drugs is favourable, the anaesthetist should be aware that pharmacological interactions can lead to an unpredictable induced neuromuscular block in many cases in daily clinical practice . Therefore anaesthetists should become familiar with the use of neuromuscular transmission monitoring in order to manage the block correctly. Semin Hematol, 2002 Jan, 39(1), 32 - 40 Improving immune reconstitution while preventing graft-versus-host disease in allogeneic stem cell transplantation; Cavazzana-Calvo M et al.; Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies or inherited disorders . Ex vivo T-cell depletion (TCD) of the graft and post-transplantation immunosuppression efficiently prevent the development of graft-versus-host disease (GVHD) . However, the consequence of these nonspecific approaches is a long-lasting immunodeficiency associated with increased disease relapse, graft rejection, and reactivation of viral infections . Donor lymphocyte infusion, to treat leukemic relapse after allogeneic HSCT, can cause severe GVHD . Several strategies are being optimized to specifically inactivate anti-host T cells while preserving antileukemic or antimicrobial immunocompetence, based on ex vivo or in vivo elimination of anti-host T cells or on the modulation of their anti-host activity . J Clin Psychopharmacol, 2002 Feb, 22(1), 71 - 81 Antimicrobial-induced mania (antibiomania): a review of spontaneous reports; Abouesh A et al.; The authors reviewed reported cases of antibiotic-induced manic episodes by means of a MEDLINE and PsychLit search for reports of antibiotic-induced mania . Unpublished reports were requested from the World Health Organization (WHO) and the Food and Drug Administration (FDA) . Twenty-one reports of antimicrobial-induced mania were found in the literature . There were 6 cases implicating clarithromycin, 13 implicating isoniazid, and 1 case each implicating erythromycin and amoxicillin . The WHO reported 82 cases . Of these, clarithromycin was implicated in 23 (27.6%) cases, ciprofloxacin in 12 (14.4%) cases, and ofloxacin in 10 (12%) cases . Cotrimoxazole, metronidazole, and erythromycin were involved in 15 reported manic episodes . Cases reported by the FDA showed clarithromycin and ciprofloxacin to be the most frequently associated with the development of mania . Statistical analysis of the data would not have demonstrated a significant statistical correlative risk and was therefore not undertaken . Patients have an increased risk of developing mania while being treated with antimicrobials . Although this is not a statistically significant risk, physicians must be aware of the effect and reversibility . Further research clearly is required to determine the incidence of antimicrobial-induced mania, the relative risk factors of developing an antimicrobial-induced manic episode among various demographic populations, and the incidence of patients who continue to have persistent affective disorders once the initial episode, which occurs while the patient is taking antibiotics, subsides . The authors elected to name this syndrome "antibiomania." Infect Immun, 2002 Feb, 70(2), 779 - 86 L-tryptophan-L-kynurenine pathway metabolism accelerated by Toxoplasma gondii infection is abolished in gamma interferon-gene-deficient mice: cross-regulation between inducible nitric oxide synthase and indoleamine-2,3-dioxygenase; Fujigaki S et al.; L-Tryptophan degradation by indoleamine 2,3-dioxygenase (IDO) might have an important role in gamma interferon (IFN-gamma)-induced antimicrobial effects . In the present study, the effects of Toxoplasma gondii infection on IDO were investigated by using wild-type and IFN-gamma-gene-deficient (knockout) (IFN-gamma KO) mice . In wild-type C57BL/6J mice, enzyme activities and mRNA levels for IDO in both lungs and brain were markedly increased and lung L-tryptophan concentrations were dramatically decreased following T . gondii infection . In contrast, these metabolic changes did not occur in T . gondii-infected IFN-gamma KO mice or in uninfected IFN-gamma KO mice . The levels of inducible nitric oxide synthase (iNOS) induction in infected IFN-gamma KO mice were high in lungs and low in brain compared to those in infected wild-type mice . The extent of increased mRNA expression of T . gondii surface antigen gene 2 (SAG2) induced in lungs and brain by T . gondii infection was significantly enhanced in IFN-gamma KO mice compared to wild-type mice on day 7 postinfection . Treatment with N-nitro-L-arginine methyl ester, an iNOS inhibitor, increased the levels of SAG2 mRNA in brain but not in lungs and of plasma L-kynurenine after T . gondii infection . This in vivo study provides evidence that L-tryptophan depletion caused by T . gondii is directly mediated by IFN-gamma in the lungs, where iNOS is not induced by IFN-gamma . This study suggests that there is an antitoxoplasma mechanism of cross-regulation between iNOS and IDO and that the expression of the main antiparasite effector mechanisms for iNOS and/or IDO may vary among tissues. Antimicrob Agents Chemother, 2002 Feb, 46(2), 471 - 7 Convulsant and subconvulsant doses of norfloxacin in the presence and absence of biphenylacetic acid alter extracellular hippocampal glutamate but not gamma-aminobutyric acid levels in conscious rats; Smolders I et al.; Fluoroquinolones are antibiotics with central excitatory side effects . These adverse effects presumably result from inhibition of gamma-aminobutyric acid (GABA) binding to GABA(A) receptors . This GABA antagonistic effect is greatly potentiated by the active metabolite of fenbufen, biphenylacetic acid (BPAA) . Nevertheless, it remains questionable whether GABA receptor antagonism alone can explain the convulsant activity potentials of these antimicrobial agents . The present study was undertaken to investigate the possible effects of norfloxacin, both in the absence and in the presence of BPAA, on the extracellular hippocampal levels of GABA and glutamate, the main central inhibitory and excitatory amino acid neurotransmitters, respectively . This in vivo microdialysis approach with conscious rats allows monitoring of behavioral alterations and concomitant transmitter modulation in the hippocampus . Peroral administration of 100 mg of BPAA per kg of body weight had no effect on behavior and did not significantly alter extracellular GABA or glutamate concentrations . Intravenous perfusion of 300 mg of norfloxacin per kg did not change the rat's behavior or the concomitant neurotransmitter levels in about half of the experiments, while the remaining animals exhibited severe seizures . These norfloxacin-induced convulsions did not affect extracellular hippocampal GABA levels but were accompanied by enhanced glutamate concentrations . Half of the rats receiving both 100 mg of BPAA per kg and 50 mg of norfloxacin per kg displayed lethal seizures, while the remaining animals showed no seizure-related behavior . In the latter subgroup, again no significant alterations in extracellular GABA levels were observed, but glutamate overflow remained significantly elevated for at least 3 h . In conclusion, norfloxacin exerts convulsant activity in rats, accompanied by elevations of extracellular hippocampal glutamate levels but not GABA levels, even in the presence of BPAA. Genes Chromosomes Cancer, 2002 Feb, 33(2), 213 - 6 Differentiation of follicular from mucosa-associated lymphoid tissue lymphoma by detection of t(14;18) on single-cell preparations and paraffin-embedded sections; Nomura K et al.; A 57-year-old woman was referred to the Kyoto Prefectural University of Medicine because of multiple polypoid lesions in the duodenum . On the basis of the histopathologic findings, mucosa-associated lymphoid tissue lymphoma had been diagnosed . The polypoid lesions did not show any improvement in spite of antimicrobial therapy for elimination of Helicobacter pylori . Because the disease remained stable during the clinical course, no other specific treatment was administered . We performed fluorescence in situ hybridization (FISH) analysis on a single-cell preparation obtained from the duodenal lesions, to assess the specific chromosome translocation . We identified BCL2/IGH fusion at a frequency of 83% . Two-color FISH was also performed on paraffin-embedded tissue sections, which demonstrated BCL2/IGH fusion-positive cells in neoplastic follicles . These findings, together with the CD10+ immunophenotyping of tumor cells, led to a diagnosis of primary follicular lymphoma of the duodenum . Interphase FISH with the IGH gene and oncogene probes is a rapid and powerful tool for assessing genomic changes in gastrointestinal lymphoma on single-cell preparations and tissue sections . This technique is particularly useful in view of the increasingly small core biopsy samples and needle aspirations obtained for diagnostic purposes . Med Electron Microsc, 2001 Sep, 34(3), 174 - 8 Expression of inflammatory cytokines and beta-defensin 1 mRNAs in porcine epithelial rests of Malassez in vitro; Liu F et al.; In the present study, we investigated the mRNA expression of inflammatory cytokines, including interleukin (IL)-1 alpha, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor (GM-CSF), and beta defensin 1 (BD-1), an antimicrobial peptide, in the epithelial rests of Malassez in vitro . A reverse transcription-polymerase chain reaction (RT-PCR) assay was performed in order to observe the expression of these mRNAs . The effect of lipopolysaccharide (LPS) on the mRNA expression was also studied by quantitative RT-PCR assay, with a LightCycler, using the double-stranded DNA dye SYBR Green I . The mRNAs of the four kinds of inflammatory cytokines and BD-1 were detected in the epithelial cells under normal culture conditions . Immunocytochemical staining showed the expression of CD14, a receptor for LPS, on the epithelial cells . The mRNA expressions of IL-1 alpha, IL-6, IL-8, and GM-CSF were upregulated by stimulation with LPS, in a dose- and time-dependent manner . Epithelial cells incubated with 1000 ng/ml of LPS for 6 h showed the most significant upregulation of the cytokine mRNAs . On the other hand, no obvious alteration of BD-1 expression by LPS stimulation was observed . The results indicated that the epithelial rests of Malassez may actively participate in the inflammatory response to bacterial infection, and that they play an important role in the defense mechanism of the radicular cyst. J Biol Chem, 2002 Apr 12, 277(15), 13106 - 14 Epub 2002 Jan 15. Structural elucidation of the specificity of the antibacterial agent triclosan for malarial enoyl acyl carrier protein reductase; Perozzo R et al.; The human malaria parasite Plasmodium falciparum synthesizes fatty acids using a type II pathway that is absent in humans . The final step in fatty acid elongation is catalyzed by enoyl acyl carrier protein reductase, a validated antimicrobial drug target . Here, we report the cloning and expression of the P . falciparum enoyl acyl carrier protein reductase gene, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast . Purified PfENR was crystallized, and its structure resolved as a binary complex with NADH, a ternary complex with triclosan and NAD(+), and as ternary complexes bound to the triclosan analogs 1 and 2 with NADH . Novel structural features were identified in the PfENR binding loop region that most closely resembled bacterial homologs; elsewhere the protein was similar to ENR from the plant Brassica napus (root mean square for Calphas, 0.30 A) . Triclosan and its analogs 1 and 2 killed multidrug-resistant strains of intra-erythrocytic P . falciparum parasites at sub to low micromolar concentrations in vitro . These data define the structural basis of triclosan binding to PfENR and will facilitate structure-based optimization of PfENR inhibitors. Immunopharmacol Immunotoxicol, 2001 Nov, 23(4), 617 - 26 Tolerance test in patients with multiple drug allergy syndrome; Nettis E et al.; Multiple Drug Allergy Syndrome (MDAS) is a frequent clinical condition characterized by reactions to more than one different class of antibiotics . Even if some studies have previously reported an increased rate of allergic reactions to drugs in patients with a history of antimicrobials and NSAIDs allergy, risk factors and pathogenesis of MDAS are still object of investigation . Moreover, in these subjects it is often difficult to prescribe a safe alternative antibiotic without a tolerance test . In this study we carried out 504 tests in 460 patients with a history of immediate adverse reactions to antibiotics . From the analysis of our results it emerges that risk factors for MDAS are female sex and intolerance to NSAIDs . Risk factors for positive tolerance test are male sex, intolerance to NSAIDs and a history of MDAS, respectively . In conclusion, it seems that tolerance test may represent a valid approach to detect a safe antibiotic in these patients. Immunopharmacol Immunotoxicol, 2001 Nov, 23(4), 585 - 95 Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients; Nettis E et al.; Urticaria and angioedema (UA) represent a syndrome that is frequently encountered in children and adults . However, although they are often associated (in up to 50% of some patient populations), these two clinical entities should not be considered synonymous because they have distinct clinical and histopathological characteristics . The frequency of UA in drug-induced pathologies is quite high Here we report a retrospective survey of 2287 patients, observed between 1988 and 1997 presenting one or more episodes of drug-induced UA . In 1,973 patients (86.2%) {639 (32.4%) males and 1,334 (67.6%) females} a specific drug responsible for UA was identified . Particularly over the last two years the frequency of drug-induced UA has tended to increase, being more prevalent in females and the majority of cases (576: 23.1%) occuring during the third decade of life . The most frequently involved drugs are anti-inflammatory (particularly acetylsalicylic acid) and antimicrobial agents (mainly beta-lactams). Microbiol Immunol, 2001, 45(11), 737 - 41 Menadione-catalyzed luminol chemiluminescent assay for the viability of Escherichia coli ATCC 25922; Yamashoji S et al.; Escherichia coli ATCC 25922 produced O2- in the presence of menadione, and O2- -dependent luminol chemiluminescence intensity was proportional to colony-forming unit (CFU) in the exponential phase . CFU was determined by using a 96-well plate at a range of 3 X 10(3) to 8 x 10(7) CFU /well (0.1 ml) after a 10-min incubation with menadione, followed by chemiluminescent assay for 5 s . After a 4-hr incubation of E . coli (10(5) CFU/0.1 ml) with menadione and an antimicrobial agent inhibiting the synthesis of peptidoglycan, protein, and DNA, the inhibitory concentration (IC) of the antimicrobial agent determined by menadione-catalyzed luminol chemiluminescent assay was in good agreement with minimal inhibitory concentration (MIC) of the NCCLS (National Committee for Clinical Laboratory Standard) method requiring 18 hr . Menadione-catalyzed luminol chemiluminescent assay is expected to be useful for the rapid determination of cell viability under the conditions of various cell growths and stresses. Pharmacotherapy, 2002 Jan, 22(1 Pt 2), 12S - 17S; discussion 30S-32S Optimizing economic outcomes in acute exacerbations of chronic bronchitis; Destache CJ; The treatment of community-acquired respiratory tract infections, such as acute exacerbations of chronic bronchitis (AECB), constitutes a huge socioeconomic burden . In most cases, an antimicrobial agent is advocated to lessen morbidity and prevent serious clinical sequelae . Use of antimicrobial agents for AECB, however, is controversial, as it is difficult to distinguish between bacterial and nonbacterial AECB, and only marginal benefits have been reported . Antimicrobial agents, however, have reduced relapse rates, prolonged the time between exacerbations, shortened the duration of symptoms, and reduced the need for hospitalization . Microbiologic resistance and individual patient characteristics play important roles in determining the most appropriate antimicrobial agent for patients with AECB . More research on the effect of resistant bacteria on antimicrobial response rates will enable physicians to prescribe economically rational antimicrobial therapy for this common infection. Acta Microbiol Immunol Hung, 2001, 48(3-4), 441 - 8 Sexual and enteric bacterial infections eliciting reactive arthritis; Ongradi J; In this review synonymous definitions of reactive arthritis are discussed first . Major clinical symptoms, their infectious etiology and epidemiology define post-dysenteric and post-veneral forms of reactive arthritis . Classical (smear, culture, biochemistry, antigen detection) and molecular (DNA and RNA detections) techniques are used in the routine microbial diagnosis that is retrospective in the majority of cases . In the pathomechanism of this disorder, HLA-B27 antigen positivity of patients is a frequent risk factor . Molecular mimicry between microbial and self-antigens, abnormal antigen presentation leading to incomplete CD8+ T lymphocyte activation might contribute to the persistence of microbial antigens that elicit clinical symptoms . Treatment is rarely successful with antimicrobial chemotherapy. Pediatr Infect Dis J, 2002 Jan, 21(1), 34 - 8 Plasma concentrations of defensins and lactoferrin in children with severe sepsis; Thomas NJ et al.; BACKGROUND: We hypothesized that systemic release of endogenous leukocyte-derived polypeptide antimicrobial defensins (polymorphonuclear leukocyte-specific) and lactoferrin (polymorphonuclear leukocyte and epithelial cell derived) occurs in nonneutropenic children with severe sepsis . METHODS: We performed a prospective cross-sectional and longitudinal study in a university children's hospital pediatric intensive care unit . Ninety-two consecutive children meeting criteria for sepsis and 14 critically ill children without sepsis (controls) were enrolled, and plasma defensins and lactoferrin concentrations were measured on Days 1 and 3 of sepsis . RESULTS: Nonneutropenic sepsis patients (n = 71) had increased defensins and lactoferrin plasma concentrations compared with critically ill control patients {defensins, 450 ng/ml vs . 150 ng/ml; lactoferrin, 332 ng/ml vs . 176 ng/ml (median values); P < 0.05} and neutropenic sepsis patients {n = 21; defensins, 450 ng/ml vs . 50 ng/ml; lactoferrin, 332 ng/ml vs . 20 ng/ml (median values); P < 0.05} . Neutropenic sepsis patients had similar plasma defensin concentrations and a decrease in plasma lactoferrin concentrations compared with control patients (P < 0.05) . Defensins and lactoferrin plasma concentrations correlated to total white blood cell and absolute neutrophil count (P < 0.05) . There was no association between plasma defensin concentration and organ failure or outcome; however, increased plasma lactoferrin concentrations were observed with the development of organ failure (P < 0.05) . CONCLUSION: These data suggest that increased circulating defensins and lactoferrin release are dependent in part on neutrophil count and might play a role in host defense in children with severe sepsis. Pediatr Infect Dis J, 2002 Jan, 21(1), 14 - 22 Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin; Saez-Llorens X et al.; BACKGROUND: Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci . PURPOSE AND DESIGN: A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy . RESULTS: A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen . Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; use of dexamethasone; history of seizures; and etiologic agents . No significant differences between trovafloxacin and the comparator, respectively, were detected in any of the following outcome measures: clinical success at 5 to 7 weeks after treatment (79% vs . 81%); deaths (2% vs . 3%); seizures after enrollment (22% vs . 21%); and severe sequelae (14% vs . 14%) . Only 4 of 284 children developed joint abnormalities up to 6 months after treatment, 1 (0.9%) child received trovafloxacin and 3 (3.1%) received the comparator regimen . None of the evaluable patients experienced significant abnormalities of liver function during treatment . One nonevaluable patient who received trovafloxacin for 5 days and ceftriaxone for 11 days was readmitted to the hospital with hepatitis of unknown etiology 1 day after discharge . The episode resolved with liver function tests returning to normal within 2 months . CONCLUSIONS: We conclude that trovafloxacin is an effective antibiotic for treatment of pediatric bacterial meningitis . These favorable results support further evaluation of fluoroquinolone therapy for children with meningitis or other serious bacterial infections. Am J Respir Crit Care Med, 2002 Jan 15, 165(2), 273 - 6 Closed-chest microdialysis to measure antibiotic penetration into human lung tissue; Herkner H et al.; The majority of bacterial lung infections are localized to the interstitial space fluid, which is therefore an important target site for antimicrobial chemotherapy . Direct measurement of interstitial concentrations of antimicrobial agents in human lung tissue would allow for a more informed approach to appropriate dosing of antimicrobial agents, but until now this was beyond technical reach . In this exploratory pharmacokinetic study, we measured the time versus concentration profile of cefpirome after a single intravenous dose administration of 2 g in the lung interstitial fluid by flexible microdialysis catheters, which were implanted during lung surgery for pulmonary tumors in five patients . Cefpirome concentrations in lung interstitial fluid were 66% of corresponding plasma values within the first 240 min, and exceeded minimal inhibitory concentrations of most relevant bacteria . The experimental procedure was well tolerated by the patients and no adverse events were observed . The present study provides evidence for the first time that closed chest microdialysis of the human lung is a feasible and safe method to measure lung concentrations in patients in vivo . The present data also corroborate the use of cefpirome as a valuable agent in the treatment of lung infections with most extracellular bacteria. Drug Discov Today, 2002 Jan 15, 7(2), 126 - 32 Combinatorial chemistry in anti-infectives research; Wijkmans JC et al.; The ever-increasing resistance to current anti-infective drugs has become a major concern to the medical community . As a result, research efforts have been stepped up with the ultimate goal to provide new, more effective and safer antimicrobial treatments that will overcome the resistance problem . In this context, advances in molecular biology, automation and combinatorial chemistry will play a crucial role in the timely introduction of these products onto the market . How the application of combinatorial techniques can impact anti-infectives research will be reviewed using illustrative examples. Curr Opin Immunol, 2002 Feb, 14(1), 87 - 95 The molecular basis of innate immunity in the horseshoe crab; Iwanaga S; During the past two decades, the molecular structures and functions have been established for various defense molecules, using horseshoe crab (Limulus) as a model animal . These defense molecules include clotting factors, proteinase inhibitors, lectins, antimicrobial peptides and other humoral factors found mainly in the hemolymph . These components of the cellular and humoral systems, which together comprise innate immunity, defend horseshoe crab effectively from invading microbes. Arch Androl, 2002 Jan-Feb, 48(1), 9 - 13 Spermicidal activity of seed oil of Pongamia glabra; Bandivdekar AH et al.; The medicinal properties of seed oil of Pongamia glabra are well known in traditional Indian medicine . It has antimicrobial activity against several organisms . It is used in the treatment of herpes and scabies and, systemically, it is also used in the treatment of dyspepsia with sluggish liver . The present study demonstrates that in vitro, Pongamia oil has strong spermicidal activity. Wien Med Wochenschr, 2001, 151(3-4), 66 - 72 {Antimicrobial therapy of febrile neutropenia--current developments}; Karthaus M et al.; Standard management of febrile neutropenia requires prompt administration of empirical, broad-spectrum, parenteral antibiotic therapy, since febrile neutropenia is associated with a significant risk of infectious complications and mortality . Although in-patient treatment is effective in up to 90%, hospitalization leads to excessive resource utilization . Over the last ten years chemotherapy for solid tumors has shifted out of the hospital setting into the ambit of community-based oncologists, and outpatient treatment with complex multidrug protocols has become more and more common . With the increase in the numbers of outpatients undergoing multidrug chemotherapy there has been a corresponding rise in the severity and duration of neutropenia and in the increase of febrile complications . Risk-assessment models have been developed that differentiate febrile patients with neutropenia according to their risk for infectious complications and/or mortality . Patients with neutropenia of short duration (< 7 days) and fever are at relatively low risk for complications if they have no concurrent comorbidities, and in these circumstances outpatient antibiotic treatment is an alternative to costly hospitalization . Drugs whose antimicrobial coverage and pharmacokinetics render them particularly suitable for outpatient treatment of febrile neutropenia include intravenous and oral quinolones and, for once-daily dosing, intravenous glycopeptides, ceftriaxone and intravenous aminoglycosides . Response rates of 60%-95% have been achieved with such regimens in clinical trials, with hospital admission avoided in 75%-95% of cases. Infection, 2001 Dec, 29(6), 337 - 41 Nocardial brain abscess: observation of treatment strategies and outcome in Switzerland from 1992 to 1999; Loeffler JM et al.; BACKGROUND: Brain abscesses caused by Nocardia spp . are rare, but life-threatening infections that are notoriously difficult to diagnose and treat and which occur mainly in immunocompromised patients . Standard treatment guidelines are not available . METHODS: A systematic search for nocardial brain abscesses from 1992 to 1999 was conducted in Switzerland for the comparison of clinical presentation, treatment strategies and outcome . RESULTS: Seven cases were found, for which data of six were available . In 4/6 patients antimicrobial therapy led to a decrease in the size of abscesses . Four of six patients died . The cause of death was likely due to underlying co-morbidities, rather than the nocardial infection . CONCLUSION: The finding that treatment was different in each case underscores the lack of therapeutic guidelines. Infection, 2001 Dec, 29(6), 326 - 31 The penetration of ciprofloxacin into human pancreatic and peripancreatic necroses in acute necrotizing pancreatitis; Adam U et al.; BACKGROUND: Antibiotic prophylaxis in necrotizing pancreatitis has recently gained acceptance . Published studies, however, used different antibiotic regimes and some antibiotics penetrated pancreatic tissue or pancreatic necroses only poorly . The aim of this study was to assess the penetration of ciprofloxacin (CIP) into necrotic pancreatic and peripancreatic tissue . PATIENTS AND METHODS: Serum, pancreatic necroses, peripancreatic fat tissue necroses and infected omental fluid levels of CIP were measured after 51 operations in 14 patients . RESULTS: The median penetration ratio of CIP was 137.5% (range 11-196%) in infected omental bursa fluid, 59.6% (3-214%) in pancreatic necroses and 67.1% (1-250%) in peripancreatic necroses . Chemotherapeutical ratios of CIP as a marker for antimicrobial potency were high against most relevant pathogens in necrotizing pancreatitis . CONCLUSION: Due to its antimicrobial spectrum and the good penetration into the relevant compartments, CIP may be useful in preventing local infection in necrotizing pancreatitis. J Clin Oncol, 2002 Jan 15, 20(2), 441 - 8 Granulocyte colony-stimulating factor in induction treatment of children with non-Hodgkin's lymphoma: a randomized study of the French Society of Pediatric Oncology; Patte C et al.; PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF; lenograstim) decreases the incidence of febrile neutropenia after induction courses in treatment of childhood non-Hodgkin's lymphoma (NHL) . PATIENTS AND METHODS: Patients were randomized to receive (G-CSF+) or not receive (G-CSF-) prophylactic G-CSF, 5 microg/kg/d, from day 7 until an absolute neutrophil count > or = 500/microL was sustained over 48 hours, after two consecutive induction courses of cyclophosphamide 1.5 or 3 g/m(2), vincristine 2 mg/m(2), prednisone 60 mg/m(2)/d x 5, doxorubicin 60 mg/m(2), high-dose methotrexate 3 or 8 g/m(2), and intrathecal injections (COPAD{M}) on protocols LMB89, LMT89, and HM91 of the French Society of Pediatric Oncology . RESULTS: One hundred forty-eight patients were assessable, 75 G-CSF+ and 73 G-CSF- . Although duration of neutropenia less than 500/microL was 3 days shorter in G-CSF+ patients (P = 10(-4)), incidence of febrile neutropenia (89% v . 93% in the first course, 88% v . 88% in the second course), durations of hospitalization and antimicrobial therapy, percentages of infections, mucositis, and transfusions were not significantly different . Although the percentage of G-CSF+ patients commencing the following course on day 21 was significantly higher (84% v 68% after the first and 57% v . 38% after the second course; P <.05), the median delay between the two courses was only 1 day less in G-CSF+ patients (median delay after first COPAD(M), 19 v . 20 days, P =.01; after second, 21 v . 22 days, P = not significant) . Remission and survival rates were similar in both arms . CONCLUSION: This study demonstrates that G-CSF did not decrease treatment-related morbidity, nor increase the dose-intensity in children undergoing COPAD(M) induction chemotherapy for NHL. FEMS Microbiol Lett, 2002 Jan 2, 206(1), 9 - 18 Current status of defensins and their role in innate and adaptive immunity; Raj PA et al.; Naturally occurring antimicrobial cationic polypeptides play a major role in innate and adaptive immunity . These polypeptides are found to be either linear and unstructured or structured through disulfide bonds . Among the structured antimicrobial polypeptides, defensins comprise a family of cysteine-rich cationic polypeptides that contribute significantly to host defense against the invasion of microorganisms in animals, humans, insects and plants . Their wide-spread occurrence in various tissues of these diverse organisms, and their importance in innate and adaptive immunity have led to their identification, isolation and characterization . A large volume of literature is available on defensins' occurrence, structural characterization, gene expression and regulation under normal and pathological conditions . Much has also been published regarding their antimicrobial, antiviral and chemoattractive properties, and their molecular and cellular interactions . In this review, we describe the current status of our knowledge of defensins with respect to their molecular, cellular and structural biology, their role in host defense, future research paradigms and the possibility of their utilization as a new class of non-toxic antimicrobial agents and immuno-modulators. Cell Mol Biol (Noisy-le-grand), 2001 Sep, 47(6), 987 - 95 Antibiotic resistant N . gonorrhoeae in Trinidad and Tobago; Castor D et al.; We tested the susceptibility patterns of 128 N . gonorrhoeae isolates to six antimicrobials; penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin and azithromycin, and examined whether certain demographic or behavioral factors related to antibiotic use increased the likelihood of infection by a resistant strain . There was a low rate of resistance to penicillin; penicillinase-producing and chromosomal-mediated penicillin resistant gonorrhea were estimated to be 0.8% . A much higher proportion of isolates were resistant to tetracycline (up to 15%) . All isolates were sensitive to spectinomycin, ciprofloxacin and ceftriaxone . However, less than 2% of isolates displayed intermediate resistance to both ciprofloxacin and ceftriaxone, and 9% exhibited intermediate resistance to spectinomycin . Patients who had obtained medication before attending the clinic and had taken all of the medication were more likely (p = 0.03) to be infected with a resistant strain of gonococcus . Also, patients who were asked by a clinic doctor to return for a test of cure during an earlier clinic visit, but who did not return were more likely to be infected with a resistant organism (p = 0.006) compared to those who returned at the doctor's request . These findings have important implications for antibiotic use and educational programs in Trinidad and Tobago. Expert Opin Investig Drugs, 2001 Aug, 10(8), 1575 - 99 American Society of Microbiology 101st General Meeting . 20-24 May 2001, Orlando, FL, USA; Discotto LF et al.; The application of sophisticated molecular biology, genetics and genomics has made possible the advanced analyses of microbial genes, the topology of DNA and chromosomes, and insight into the regulation of gene expression during all stages of the life cycle of microbes, both in vitro and in vivo . The struggle to control contagious pathogens continues world wide amidst resistance emergence to many classes of antimicrobial agents . Many hospital, research and community labs are applying themselves to a more thorough understanding of the molecular basis of this resistance . New drugs which improve on predecessor agents were presented . The following classes of antimicrobial agents were represented: quinolones, cephems, macrolides and natural products . New target opportunities against both lethal (essential) gene targets and virulence targets were presented throughout the conference . In addition, increasing attention to the involvement of microbial life forms in immune function and dysfunction were described in numerous presentations. Rev Neurol, 2001 Nov 16-30, 33(10), 925 - 7 {Perioperative antibiotic prophylaxis in neurological surgery}; Lacerda Gallardo AJ et al.; INTRODUCTION: Perioperative antibiotic prophylaxis is a current topic of interest . However, in neurosurgery there are no controlled studies or full reports to support its use . We have also observed that there is little consistency in the use of antibiotics in this type of surgery . This method has been used in other specialities, reducing the risk of postoperative sepsis . We therefore consider that it may be used in neurosurgery, bearing in mind certain specific aspects . OBJECTIVES: To find the postoperative sepsis in a consecutive group of patients in whom prophylaxis was used for neurosurgical operations . PATIENTS AND METHODS: We made a prospective, observational, descriptive study of 100 patients who needed neurosurgical operations and were given antimicrobial agents to prevent sepsis . The relation between intracranial and extracranial surgery, the use or not of these agents and the occurrence or not of sepsis was observed . The method was applied using the classification of the National Research Council of the USA . RESULTS . In spinal surgery, the method was used most and no difference was found with or without the use of antibiotics in cervical spinal surgery, with regard to the occurrence of sepsis . Exogenous factors played an important part in the development of sepsis unrelated to the surgical technique . CONCLUSIONS: The complications related to surgery were minimal . However, general complications occurred more frequently. Adv Biochem Eng Biotechnol, 2002, 75, 31 - 49 Biosynthesis of triterpenoid saponins in plants; Haralampidis K et al.; Many different plant species synthesise triterpenoid saponins as part of their normal programme of growth and development . Examples include plants that are exploited as sources of drugs, such as liquorice and ginseng, and also crop plants such as legumes and oats . Interest in these molecules stems from their medicinal properties, antimicrobial activity, and their likely role as determinants of plant disease resistance . Triterpenoid saponins are synthesised via the isoprenoid pathway by cyclization of 2,3-oxidosqualene to give primarily oleanane (beta-amyrin) or dammarane triterpenoid skeletons . The triterpenoid backbone then undergoes various modifications (oxidation, substitution and glycosylation), mediated by cytochrome P450-dependent monooxygenases, glycosyltransferases and other enzymes . In general very little is known about the enzymes and biochemical pathways involved in saponin biosynthesis . The genetic machinery required for the elaboration of this important family of plant secondary metabolites is as yet largely uncharacterised, despite the considerable commercial interest in this important group of natural products . This is likely to be due in part to the complexity of the molecules and the lack of pathway intermediates for biochemical studies . Considerable advances have recently been made, however, in the area of 2,3-oxidosqualene cyclisation, and a number of genes encoding the enzymes that give rise to the diverse array of plant triterpenoid skeletons have been cloned . Progress has also been made in the characterisation of saponin glucosyltransferases . This review outlines these developments, with particular emphasis on triterpenoid saponins. Eur J Clin Microbiol Infect Dis, 2001 Nov, 20(11), 820 - 3 European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori; Glupczynski Y et al.; A multicentre in vitro survey was carried out in 1998 in 22 European centres in order to assess the variation in the prevalence of Helicobacter pylori resistance . The susceptibility of 1,274 isolates to metronidazole, clarithromycin and amoxicillin was determined by the E test . The mean rate of resistance to metronidazole was 33.1% (95% CI, 7.5-58.9), to clarithromycin 9.9% (95% CI, 0-28.1) and to amoxicillin 0.8% (95% CI, 0-8.9) . Resistance to metronidazole was significantly higher in females (P<0.001), while resistance to clarithromycin was significantly higher in children and teens (P<0.05) . Resistance to both agents also tended to be higher in strains isolated from patients from southern European countries than in those isolated from patients from central or northern Europe . Overall, these results emphasize the need for further surveys of Helicobacter pylori sensitivity to antibiotics at a national and regional level. Adv Ther, 2001 Sep-Oct, 18(5), 205 - 15 Effects of common ophthalmic preservatives on ocular health; Noecker R; Preservatives are an important component of ophthalmic preparations, providing antimicrobial activity in the bottle and preventing decomposition of active drug . Often underrecognized, however, are the significant cytotoxic effects of preservatives associated with long-term therapy and especially use of multiple preserved drugs . The most common preservatives in ophthalmic preparations for glaucoma and surface eye disease-benzalkonium chloride (BAK), chlorobutanol, sodium perborate, and stabilized oxychloro complex (SOC)-were reviewed . Compared with other preservatives, SOC caused the least amount of damage to rabbit corneal epithelial cells . BAK has demonstrated cytotoxic effects in cell culture, as well as in animal and human studies . Physicians should consider treatment with new-generation preparations containing low-risk preservatives such as SOC, especially in patients receiving multiple ophthalmic medications. Crit Care Med, 2002 Jan, 30(1 Suppl), S58 - 63 Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug; Oberholzer A et al.; Interleukin (IL)-10 is a pleiotropic cytokine produced by both T cells and macrophages and possesses both anti-inflammatory and immunosuppressive properties . IL-10 circulates in the blood of patients with sepsis syndromes, and increased concentrations of IL-10 have been associated with an adverse clinical outcome . Experimental studies in rodents and primates have demonstrated that endogenously produced and exogenously administered IL-10 can reduce the magnitude of the inflammatory response and improve outcome, primarily in models of endotoxemic and bacteremic shock . However, endogenous IL-10 production and systemic administration can also exacerbate T-cell dysfunction, decrease T-cell apoptosis, reduce antimicrobial function, and increase mortality in other less acute bacterial models of sepsis or after thermal injury . Targeted delivery of IL-10 to individual tissues may obviate the adverse effects of systemic delivery . The potential anti-inflammatory properties of IL-10 will have to be carefully weighed against its immunosuppressive properties when considering its use in patients with acute inflammation and sepsis syndromes. J Leukoc Biol, 2002 Jan, 71(1), 154 - 62 NF-kappa B-mediated transcriptional regulation of human beta-defensin-2 gene following lipopolysaccharide stimulation; Tsutsumi-Ishii Y et al.; beta-Defensins are cationic peptides with broad-spectrum antimicrobial activities that contribute to innate host defense . Among human beta-defensins (hBDs), hBD-2 is up-regulated in epithelial tissues and mononuclear phagocytes in response to bacterial infection and proinflammatory cytokines . However, little is known about the molecular mechanism of hBD-2 gene regulation . Here, we investigated lipopolysaccharide (LPS)-mediated transcriptional regulation of the hBD-2 gene by focusing on the roles of NF-kappa B, STAT, and NF-IL-6 sites in mononuclear phagocytes using RAW264.7 cells, which are sensitive to LPS . Luciferase reporter analyses demonstrated that two NF-kappa B sites were essential for full LPS responsiveness of the hBD-2 gene . Further, both NF-kappa B sites were also crucial for basal transcriptional activity . In contrast, neither the NF-IL-6 nor STAT binding site was required for LPS-induced hBD-2 transcription . Electrophoretic mobility shift assay indicated that in unstimulated cells, NF-kappa B p50 homodimer bound to both NF-kappa B sites, whereas the p65-p50 heterodimer formed complexes with these sites following LPS stimulation . Together, these observations indicate that NF-kappa B plays an important role in the regulation of hBD-2 gene expression in response to LPS. Chin Med J (Engl), 2001 Apr, 114(4), 394 - 8 Infections caused by Flavimonas oryzihabitans; Qian K et al.; OBJECTIVE: To assess retrospectively the clinical characteristics and cell immune function of infections caused by Flavimonas oryzihabitans (F . oryzihabitans) . METHODS: We indentified 11 cases of F . oryzihabitans positive cultures from all microbial cultures collected in our hospital from November 1994 to December 1998 . Relevant clinical information was collected, including demographic data, underlying disease, and clinical manifestations of the F . oryzihabitans infections . Minimal inhibitory concentrations (MICs) of 15 antimicrobial agents against the 11 F . oryzihabitans isolates were determined . Cell immune function tests were determined by flow cytometry including T lymphocyte subsets (CD3, CD4, CD8 and ratio CD4/CD8) and NK cells (CD16 + 56) from peripheral blood . RESULTS: Six of these patients with infections caused by F . oryzihabitans were male, 5 were female and the mean age was 47.64 years (range, 5 to 69 years) . All but 1 patients had severe underlying diseases . 9 (81.8%) of these patients developed infection while hospitalization and 2 (18.2%) before hospitalization (Cases 2 and 5) . 8 (72.7%) of these patients manifested primary F . oryzihabitans bacteremia and one each (9.1%) had pleurisy, soft tissue infection and peritonitis . All these isolates were susceptible to amikacin, gentamicin and ciprofloxacin, but resistance to cefazolin, nitrofurantoin, penicillin and piperacillin . CD3, CD4, CD4/CD8 and CD16 + 56 value (mean +/- s) of these patients were significantly lower than normal values (P < 0.01) . The mean time of body temperature fell < or = 37 degrees C after antibiotic treatment in these patients was 3.5 days (range, 1 to 6 days) . All clinical symptom caused F . oryzihabitans after antibiotic treatment disappeared and all patients recovered . CONCLUSIONS: Infections caused by F . oryzihabitans was very few clinically, and relative to underlying diseases and the presence of foreign material . Immune function abnormality was among mostly factor for the F . oryzihabitans infections. Infect Dis Clin North Am, 2001 Dec, 15(4), 1205 - 26 Susceptibility testing . Phenotypic and genotypic tests for bacteria and mycobacteria; Louie M et al.; Genotypic-based methods hold promise for the rapid and accurate detection or confirmation of antimicrobial resistance; however, phenotypic methods will continue to have an advantage when resistance to the same antimicrobial agent may be caused by several different mechanisms . The diversity of genetic mechanisms may exceed the capabilities of current molecular technology . Genotypic assays have the ability to detect resistance but not susceptibility . Although resutls can be obtained rapidly, many molecular methods are labor-intensive, expensive, and lack standardization . Clinical studies will be required to validate the genotypic approach to detection of antimicrobial resistance . Molecular assays are also at risk for false-positive results because of contamination of specimens by other specimens that carry the DNA targeted for the assay, or carryover of amplified target DNA (amplicons) from a previous PCR assay during sample preparation . Detection of certain genetic resistance loci in clinical specimens must be interpreted with caution, because organisms in normal flora may also harbor the same loci . All these factors must be taken into consideration when introducing a genotypic method in the clinical laboratory . Other considerations include cost, turnaround time, and assay performance . It must be emphasized that the bedside assessment of the patient should always be considered in addition to the results of antimicrobial susceptibility tests (whether phenotypic or genotypic) so that the best outcome is assured for the patient. Am J Respir Crit Care Med, 2002 Jan 1, 165(1), 41 - 6 Role of serial routine microbiologic culture results in the initial management of ventilator-associated pneumonia; Hayon J et al.; Results of routine microbiologic cultures of specimens obtained before the onset of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients might help to identify the causative microorganisms and thus to select effective initial antimicrobial therapy . To test this hypothesis, we prospectively studied 125 consecutive VAP episodes for which the causative microorganisms were determined using bronchoscopic techniques . Upon entry into the study, each patient's hospital chart was reviewed and culture results of all previously obtained microbiologic specimens were recorded (mean number +/- SD per patient, 45 +/- 38) . A total of 220 microorganisms were cultured at significant concentrations (> or = 10(3)/10(4) colony-forming units {cfu}/ml) from bronchoscopic specimens and considered responsible for pneumonia . Of these 220 organisms, only 73 (33%) were recovered before VAP onset, sometimes from multiple sites in the same patient but mainly from prior respiratory secretion cultures (n = 53) . Also previously isolated were 342 organisms that were not responsible for VAP, making prospective identifications of the true pathogens difficult . Among the 102 episodes for which prior respiratory secretion culture results had been obtained (mean time before VAP onset, 8 +/- 9 d), all the organisms ultimately responsible for pneumonia were previously recovered from only 36 (35%) of these specimens . Based on these data, the contribution of routine microbiologic specimens in guiding initial antimicrobial therapy decisions for patients with suspected VAP appears limited. Biochim Biophys Acta, 2002 Feb 1, 1558(2), 171 - 86 General aspects of peptide selectivity towards lipid bilayers and cell membranes studied by variation of the structural parameters of amphipathic helical model peptides; Dathe M et al.; Model compounds of modified hydrophobicity (Eta), hydrophobic moment (mu) and angle subtended by charged residues (Phi) were synthesized to define the general roles of structural motifs of cationic helical peptides for membrane activity and selectivity . The peptide sets were based on a highly hydrophobic, non-selective KLA model peptide with high antimicrobial and hemolytic activity . Variation of the investigated parameters was found to be a suitable method for modifying peptide selectivity towards either neutral or highly negatively charged lipid bilayers . Eta and mu influenced selectivity preferentially via modification of activity on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) bilayers, while the size of the polar/hydrophobic angle affected the activity against 1-palmitoyl-2-oleoylphosphatidyl-DL-glycerol (POPG) . The influence of the parameters on the activity determining step was modest in both lipid systems and the activity profiles were the result of the parameters' influence on the second less pronounced permeabilization step . Thus, the activity towards POPC vesicles was determined by the high permeabilizing efficiency, however, changes in the structural parameters preferentially influenced the relatively moderate affinity . In contrast, intensive peptide accumulation via electrostatic interactions was sufficient for the destabilization of highly negatively charged POPG lipid membranes, but changes in the activity profile, as revealed by the modification of Phi, seem to be preferentially caused by variation of the low permeabilizing efficiency . The parameters proved very effective also in modifying antimicrobial and hemolytic activity . However, their influence on cell selectivity was limited . A threshold value of hydrophobicity seems to exist which restricted the activity modifying potential of mu and Phi on both lipid bilayers and cell membranes. Chin Med J (Engl), 2001 Jan, 114(1), 9 - 13 Cationic antimicrobial protein of Mr 37 kDa: a multifunctional inflammatory protein; Pereira HA; PURPOSE: To investigate the role of cationic antimicrobial protein of Mr 37 kDa (CAP37) a neutrophil-derived inflammatory mediator on endothelial cell function . DATA SOURCES: Endothelial cells used in this study were obtained from human lung microvessels and rat aorta . The latter was a kind gift of Dr . Paula Grammas . The mono-mac 6 cell line used in this study was the generous gift of Dr . H.W . Loms Ziegler-Heitbrock . STUDY SELECTION AND DATA EXTRACTION: Endothelial cell proteins kinase C activity was determined by measuring calcium- and phospholipid-dependent phosphorylation of histone . Endothelial cell migration was determined using Costar Transwell apparatus . Cell surface expression of adhesion molecules, ICAM-1 and PECAM-1 was determined using flow cytometry . RT-PCR was used to amplify the CAP37 from endothelial cells treated with LPS . RESULTS: We demonstrated that CAP37 which was originally identified as having potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions . CAP37 activated endothelial cell protein kinase C in a dose- and time-dependent fashion . Importantly CAP37 increased the adhesive properties of the endothelium for monocytes . CAP37 upregulated the well known adhesion molecules, ICAM-1 and PECAM-1 in a dose- and time-dependent manner . In addition, CAP37 promoted endothelial cell migration . Further investigations indicated that CAP37 was induced in endothelial cells in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 alpha as well as inflammatory mediators such as lipopolysaccharide . Unstimulated endothelial cells did not constitutively express CAP37 . The cDNA sequence of endothelial CAP37 was determined and found to be highly homologous to the sequence obtained for neutrophil-derived CAP37 . CONCLUSIONS: Our studies strongly suggest that CAP37 plays a pivotal role in monocyte-endothelial interactions and the transmigration of monocytes from the vasculature into extravascular tissues. Biochem Biophys Res Commun, 2002 Jan 11, 290(1), 204 - 12 Structural studies of porcine myeloid antibacterial peptide PMAP-23 and its analogues in DPC micelles by NMR spectroscopy; Park K et al.; PMAP-23 is a cathelicidin-derived antimicrobial peptide identified from porcine leukocytes . PMAP-23 was reported to show potent antimicrobial activity against Gram-negative and Gram-positive bacteria without hemolytic activity . To study the structure-antibiotic activity relationships of PMAP-23, two analogues by replacing Trp with Ala were synthesized and their tertiary structures bound to DPC micelles have been studied by NMR spectroscopy . PMAP-23 has two alpha-helices, one from Arg1 to Arg10 in the N-terminal region and the other from Phe18 to Arg23 in the C-terminal region . PMAP-1 (Trp(7)-->Ala) shows similar structure to PMAP-23, while PMAP-2 (Trp(21)-->Ala) has a random structure in the C-terminus . PMAP-2 was found to show less antibacterial and vesicle-disrupting activities than PMAP-23 and PMAP-1 {J . H . Kang, S . Y . Shin, S . Y . Jang, K . L . Kim, and K.-S . Hahm (1999) Biochem . Biophys . Res . Commun . 264, 281-286} . Trp(21) in PMAP-23 which induces an alpha-helical structure in the second alpha-helix is essential for the antibacterial activity of PMAP-23 . Also, the fluorescence data proved that Trp(21) at the second alpha-helix is buried deep into the phospholipid in the membrane . Therefore, it implies that Trp(21) in the second alpha-helix at the C-terminus of PMAP-23 may play an important role on the interactions with the membrane and the flexible region including two proline residues may allow this alpha-helix to span the lipid bilayer . (c)2002 Elsevier Science. Eur J Pharmacol, 2001 Sep 28, 428(1), 121 - 6 Differential uptake of grepafloxacin by human circulating blood neutrophils and those exudated into tissues; Niwa M et al.; The uptake of the antimicrobial quinolone agent, grepafloxacin, both by human circulating blood neutrophils and by those exudated into tissues, was evaluated in vitro by comparing the intracellular drug concentrations . In circulating blood neutrophils, the uptake of grepafloxacin was rapid and saturable at 37 degrees C . The uptake of grepafloxacin into circulating blood neutrophils was reduced by lowering the environmental temperature or by the presence of metabolic inhibitors, suggesting the involvement of an active transport mechanism . Furthermore, the uptake of grepafloxacin by tissue (salivary) neutrophils was also partially temperature-dependent and was significantly greater than that by circulating blood neutrophils, i.e . exudation of neutrophils into tissue results in a markedly enhanced transport mechanism for grepafloxacin . This phenomenon may be related to the higher defense activity against infection seen in exudated tissue neutrophils. Z Gastroenterol, 2001 Nov, 39(11), 911 - 8 Colonic fermentation as affected by antibiotics and acidic pH: Application of an in vitro model; Bender A et al.; Antimicrobial substances such as vancomycin or metronidazole suppress normal gut flora, thereby preventing physiological fermentation of colonic substrates that may promote mucosal inflammation . This study was designed to establish an in vitro model of microbial metabolism in the colon under control and disturbed conditions (acidic pH) to investigate specific effects of vancomycin and metronidazole on the production of short chain fatty acids (SCFA), which play a pivotal role in maintaining homeostasis in the colon . The experiments were carried out with the colon simulation technique (Cositec) representing an in vitro model for the semi-continuous incubation of defined colon contents . Inocula and fermentable substrates were sampled from cecal contents of fistulated pigs . Disturbed microbial metabolism was generated by reduction of pH in the fermentation vessels from 6.7 to 5.8 and 5.1 . In general, application of either vancomycin or metronidazole resulted in a significant decrease of SCFA production rates indicating substantial disturbance of the homeostasis of microbial metabolism . With low doses of vancomycin acetate and butyrate production rates were reduced and with high doses of the antibiotic propionate production was inhibited to a greater extent . Treatment with metronidazole inhibited butyrate production almost completely . Similarly, low pH caused a reduction in total SCFA production, which was mainly due to respective decrease of acetate synthesis . Metronidazole effects were not consistently changed at low pH . The Cositec system provides an excellent facility to test the effects of different antibiotics under defined conditions . In this study, both vancomycin and metronidazole affected microbial metabolism to a considerable extent . Both substances may thus be responsible for disturbances of colon function in vivo. Diagn Microbiol Infect Dis, 2001 Dec, 41(4), 171 - 5 Determining the value of antimicrobial surveillance programs; Jones RN et al.; Antimicrobial surveillance programs provide important information on the development of bacterial resistance mechanisms in different geographical regions . Data concerning these mechanisms and patterns of antimicrobial resistance allows the implementation of changes in antimicrobial prescribing practices and infection control interventions . The three most widely known global surveillance programs currently in active operation are: The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC), The SENTRY Antimicrobial Surveillance Program, and The Alexander Project . This presentation reviews these surveillance programs, using a set of key criteria in order to assess the significance of each program in monitoring the spread of antimicrobial resistance . The content of the MYSTIC Program monitors the in vitro performance of meropenem in hospital units in which this drug is actively prescribed . This distinguishes the MYSTIC Program from the other two major surveillance programs as it seeks to correlate antimicrobial resistance data, collected from high carbapenem usage institutions, with antimicrobial prescribing patterns over time . The MYSTIC Program and other assessed networks appear to be both valuable and complementary in their design and function. Vet Immunol Immunopathol, 2002 Jan 15, 84(3-4), 223 - 36 CpG oligodeoxynucleotides stimulate canine and feline immune cell proliferation; Wernette CM et al.; Oligodeoxynucleotides (ODNs) with unmethylated CpG dinucleotide motifs may be useful as non-specific immune system stimulants and adjuvants for protein or nucleic acid vaccines in humans and other primates . They may also be useful in cancer immunotherapy and in the modulation of allergic responses or mucosal immunity . To begin to determine the potential utility of CpG ODN technology in small animal veterinary medicine, we developed procedures to analyze the effects of CpG ODN on canine and feline blood, spleen and lymph node (LN) cells . We find that certain CpG ODN cause good lymphocyte proliferation (as monitored by {(3)H}-thymidine incorporation) in both canine and feline spleen and LN cells, but not in blood . This overall stimulatory effect of CpG ODN on spleen and LN cells is CpG dependent . The reverse sequences, GpC ODNs, do not cause significant lymphocyte proliferation in the cat; however, dogs are more sensitive to stimulation by the non-specific immune effects of the phosphorothioate backbone . We conclude that unmethylated CpG ODNs may also have potential uses as immune stimulants for vaccines and other antimicrobial agents in veterinary medicine for companion animals. Ann Intern Med, 2002 Jan 1, 136(1), 13 - 24 Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H . pylori antimicrobial resistance partnership (SHARP) study, 1993-1999; Meyer JM et al.; BACKGROUND: Pretreatment antimicrobial resistance has an important impact on the efficacy of many Helicobacter pylori treatment regimens . OBJECTIVE: To estimate the prevalence of H . pylori resistance to antimicrobials in the United States, to characterize risk factors associated with H . pylori antimicrobial resistance, and to explore the association between drug utilization and antimicrobial resistance patterns over time . DESIGN: Meta-analysis using patient-level data . SETTING: 20 nationwide trials of H . pylori eradication . PATIENTS: 3624 men and women, each of whom contributed one isolate . MEASUREMENTS: Rates of H . pylori resistance to clarithromycin, metronidazole, and amoxicillin, according to geographic region, age, sex, study year, ethnicity, ulcer status, test method, and study . RESULTS: Overall resistance to clarithromycin, metronidazole, and amoxicillin was 10.1% (95% CI, 9.1% to 11.1% {360 of 3571 patients}), 36.9% (CI, 35.1% to 38.7% {1063 of 2883 patients}), and 1.4% (CI, 1.0% to 1.8% {48 of 3486 patients}), respectively . In multivariable analyses, multiple risk factors were associated with resistance to individual agents . Clarithromycin resistance was significantly associated with geographic region (P = 0.050), older age (P < 0.001), female sex (P < 0.001), inactive ulcer disease (P < 0.001), and study (P = 0.010) . Metronidazole resistance was significantly associated with female sex (P < 0.001), earlier year of study enrollment (P = 0.036), Asian ethnicity (P < 0.001), use of an epsilometer test (P = 0.002), and study (P < 0.001) . Amoxicillin resistance was low and was not significantly associated with any risk factor . In the 1990s, when rates for use of oral macrolides and metronidazole were relatively stable, clarithromycin resistance rates were stable and metronidazole resistance rates varied . CONCLUSIONS: Clinicians should consider risk factors for antimicrobial resistance when deciding which patients should have susceptibility testing and when choosing appropriate H . pylori treatments in the empirical setting. Infect Control Hosp Epidemiol, 2001 Oct, 22(10), 656 - 60 Physician preferences for continuing medical education with a focus on the topic of antimicrobial resistance: Society for Healthcare Epidemiology of America; Brown TT et al.; OBJECTIVE: To determine the type of media preferred for continuing medical education (CME) and to assess the factors that affect physician preferences for CME in general and on the special topic of antimicrobial resistance . DESIGN: A voluntary survey of the membership of the Society for Healthcare Epidemiology of America, Inc . (SHEA) . METHODS: SHEA, in collaboration with other medical societies and with technical assistance from the Centers for Disease Control and Prevention, designed and mailed the survey to its membership . The survey included questions about media used, preferred, and of interest to try for CME delivery in general and on the topic of antimicrobial resistance in specific . The survey also included demographic and general questions, such as work environment, percentage of time in direct patient care, and experience treating patients with antimicrobial-resistant pathogens . RESULTS: 225 SHEA members completed the survey . The majority of physicians were in clinical practice (59%) and worked in a hospital (57%) . The median year of graduation from medical school was 1979 (range, 1951-1999) . CME subject matter (46%) was ranked as the most important factor affecting media preference . Journal articles (52%) were the most frequently used educational medium; local grand rounds (53%) and regional meetings (53%) were the most preferred media . CD-ROM (56%) and the Internet (46%) were selected as media of greatest interest to try . On the topic of antimicrobial resistance, the most frequently used and the preferred medium was journal articles (67% and 87%, respectively) . Most (94%) had received an educational update on current antimicrobial resistance issues within the past year . Stratification of the data by graduation date revealed no significant differences in the medical education media used most (F=0.59, degrees of freedom {dfl=4, P=.6715) or preferred by SHEA members in general or on the topic of antimicrobial resistance (F=1.99, df=4, P=.0982) . CONCLUSIONS: This study provides an understanding of how physicians learn, prefer to learn, and implement best practices for optimal patient outcomes in decreasing the spread of antimicrobial resistance. Infect Control Hosp Epidemiol, 2001 Oct, 22(10), 651 - 3 Application of the IDSA guidelines for the use of antimicrobial agents in neutropenic patients: impact on reducing the use of glycopeptides; Nucci M et al.; We evaluated the impact of applying the Infectious Diseases Society of America guidelines for febrile neutropenic patients in reducing the use of glycopeptides . Forty-five prior episodes of febrile neutropenia were compared to 97 episodes seen after application of the guidelines . Glycopeptide use was reduced from 73% to 43% of episodes (P=.0008), without changes in outcome. J Biomol NMR, 2001 Nov, 21(3), 191 - 208 Membrane-bound structure and alignment of the antimicrobial beta-sheet peptide gramicidin S derived from angular and distance constraints by solid state 19F-NMR; Salgado J et al.; The antimicrobial properties of the cyclic beta-sheet peptide gramicidin S are attributed to its destabilizing effect on lipid membranes . Here we present the membrane-bound structure and alignment of a derivative of this peptide, based on angular and distance constraints . Solid-state 19F-NMR was used to study a 19F-labelled gramicidin S analogue in dimyristoylphosphatidylcholine bilayers at a lipid:peptide ratio of 80:1 and above . Two equivalent leucine side chains were replaced by the non-natural amino acid 4F-phenylglycine, which serves as a highly sensitive reporter on the structure and dynamics of the peptide backbone . Using a modified CPMG multipulse sequence, the distance between the two 19F-labels was measured from their homonuclear dipolar coupling as 6 A . in good agreement with the known backbone structure of natural gramicidin S in solution . By analyzing the anisotropic chemical shift of the 19F-labels in macroscopically oriented membrane samples, we determined the alignment of the peptide in the bilayer and described its temperature-dependent mobility . In the gel phase, the 19F-labelled gramicidin S is aligned symmetrically with respect to the membrane normal, i.e., with its cyclic beta-sheet backbone lying flat in the plane of the bilayer, which is fully consistent with its amphiphilic character . Upon raising the temperature to the liquid crystalline state, a considerable narrowing of the 19F-NMR chemical shift dispersion is observed, which is attributed the onset of global rotation of the peptide and further wobbling motions . This study demonstrates the potential of the 19F nucleus to describe suitably labelled polypeptides in membranes, requiring only little material and short NMR acquisition times. Swiss Med Wkly, 2001 Oct 6, 131(39-40), 575 - 81 Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children's Hospital Basel; Bonhoeffer J et al.; OBJECTIVE: To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution . METHODS: Retrospective review of the medical records of those patients with a bacteriologically and/or radiologically confirmed diagnosis, hospitalised in the University Children's Hospital Basel, Switzerland between January 1980 and July 2000 . RESULTS: 90 patients (61% males), 4 weeks to 14 years of age, met the inclusion criteria . Median duration of disease prior to hospitalisation was 3 days (range 0-14); 88% were admitted during the first week after onset of complaints . 81 patients received no antimicrobial therapy prior to hospitalisation and are the subject of this presentation . ESR (1st hour in mm; median 36; range 11-124), CRP (mg/l; median 64; range 0-221) and WBC (x 10(9)/l; median 13; range 5-34) were elevated in 100%, 82% and 58% of patients, respectively . Blood cultures (BC) and/or tissue cultures (TC) were performed in 79 (98%) patients . Overall, bacteria were isolated from 53 patients (65%) with Staph . aureus as the most frequent organism (n = 31; 50%) . BC were performed in 67 patients and yielded 35 (52%) positive cultures; TC (n = 47) yielded 27 (57%) isolates . In 34 patients with both BC and TC performed, only 12 (35%) were positive in both tests . Diagnostic findings were observed in 23 (59%) of 39 plain radiographs, 31 (56%) of 55 sonograms, 39 (89%) of 44 99mTc-labeled bone scans and 4 (100%) of 4 MRI . 41 patients with diagnostic radiological findings had consecutive TC yielding 30 (73%) bacteriological isolates . Median duration of hospitalisation was 15 days (range 2-66) . CONCLUSION: Our data indicate that the diagnostic procedures of choice should be 1) early bone scan or MRI, 2) BC and 3) TC . Of supportive laboratory parameters, ESR and CRP were most valuable in our hands. Shokuhin Eiseigaku Zasshi, 2001 Oct, 42(5), 309 - 15 Identification of principal constituents in enzymatically hydrolyzed coix extract; Sugimoto N et al.; The structural elucidation of the main constituents in enzymatically hydrolyzed coix extract, a natural food preservative, was carried out . After peracetylation, five compounds, namely peracetylated forms of glucose, maltose, maltotriose, maltotetraose, and maltopentaose were isolated . The structures were determined by PFG HMQC and HMBC experiments . In addition, by using HPLC with an RI detector, the main components of this coix extract were identified as a mixture of oligosaccharides having one to seven glucose units coupled through alpha-(1-->4) linkages . Since this extract showed no antimicrobial activity, its preservative effect may be caused by its covering of the food surface, thereby blocking contact with air. J Ind Microbiol Biotechnol, 2001 Dec, 27(6), 393 - 8 Structure and mechanism of chalcone synthase-like polyketide synthases; Jez JM et al.; Polyketide synthases (PKS) produce an array of natural products with different biological activities and pharmacological properties by varying the starter and extender molecules that form the final polyketide . Recent studies of the simplest PKS, the chalcone synthase (CHS)-like enzymes involved in the biosynthesis of flavonoids, anthocyanin pigments, and antimicrobial phytoalexins, have yielded insight on the molecular basis of this biosynthetic versatility . Understanding the structure-function relationship in these PKS provides a foundation for manipulating polyketide formation and suggests strategies for further increasing the scope of polyketide biosynthetic diversity. J Cosmet Sci, 2001 Nov-Dec, 52(6), 369 - 75 A modified cup scrub method for assessing the antibacterial substantivity of personal cleansing products; Billhimer WL et al.; An improved in vivo method for evaluating the antibacterial substantivity or residual effectiveness of bar soaps and other personal cleansing products is presented . The effectiveness of an antibacterial bar soap containing 1.5% 3, 4, 4'-trichlorocarbanilide (TCC) versus its soap vehicle was evaluated under simulated conditions considered optimal for bacterial growth, proliferation, and possible infection . A washout period to clear the skin of any antimicrobial agents previously used was followed by a treatment period in which the subjects washed one of their forearms with the antibacterial soap and the other forearm with the soap vehicle . Either immediately or 24 hours following the final wash, three test sites on both forearms were inoculated with S . aureus and occluded with Hill Top Chamber patches . At intervals of 30 minutes, two hours and five hours, the patches were removed . The bacteria on the skin were harvested using the Williamson-Kligman scrub technique (1,2) to determine the number of surviving CFUs at each time period . The method successfully demonstrated that sufficient TCC had remained on the skin for 24 hours after the final wash to effectively inhibit the growth of S . aureuso on the skin for as long as five hours after inoculation. Biochem J, 2002 Jan 15, 361(Pt 2), 221 - 30 abf-1 and abf-2, ASABF-type antimicrobial peptide genes in Caenorhabditis elegans; Kato Y et al.; Two genes encoding the ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptide, abf-1 and abf-2, were identified in Caenorhabditis elegans . Recombinant ABF-2 exhibited potent microbicidal activity against Gram-positive