Clin Infect Dis, 1995 Feb, 20(2), 443 - 4 Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient; Tebas P et al.; Mycobacterium chelonae (formerly known as M . chelonae subspecies chelonae) is a rapidly growing mycobacterium that can cause disseminated infections, especially in immunocompromised hosts . The bacterium is typically resistant to antimicrobial agents; less than 20% of M . chelonae isolates are susceptible to trimethoprim-sulfamethoxazole, doxycycline, erythromycin, or ciprofloxacin . Findings in a recent study suggested that clarithromycin may be the drug of choice for the treatment of cutaneous (disseminated) disease due to M . chelonae . We describe a 60-year-old heart transplant patient with disseminated M . chelonae infection for whom monotherapy with clarithromycin failed because of the rapid development of resistance to the drug. Clin Infect Dis, 1995 Feb, 20(2), 363 - 71 Outcome for hospitalized patients with fever and neutropenia who are infected with the human immunodeficiency virus; Hambleton J et al.; We conducted a retrospective cohort study to evaluate the occurrence of bacteremia and associated mortality among hospitalized patients who were seropositive for the human immunodeficiency virus (HIV) and who developed fever and neutropenia following antineoplastic chemotherapy or for other reasons . Review of medical records revealed 224 episodes in 142 patients . Of these episodes, 57% occurred following antineoplastic chemotherapy, and 43% occurred under other circumstances . Members of the chemotherapy group had significantly less-advanced HIV disease, a lower mean absolute-neutrophil-count nadir, and a shorter duration of hospitalization . There was no difference between the two groups in the frequency of bacteremia or mortality due to all causes when they were compared by multivariate analysis . Statistically significant univariate and multivariate predictors of bacteremia included sepsis syndrome and concurrent infection . Predictors of mortality included sepsis syndrome, concurrent infection, bacteremia, and antimicrobial therapy . This study suggests that the cause of neutropenia in HIV-seropositive patients is not a predictor of the outcome of fever and neutropenic episodes . Instead, clinical presentation and concomitant illnesses have a greater impact on outcome for a patient. Clin Pharmacokinet, 1995 Feb, 28(2), 143 - 60 The importance of pharmacokinetic/pharmacodynamic surrogate markers to outcome . Focus on antibacterial agents; Hyatt JM et al.; Pharmacokinetic/pharmacodynamic surrogate relationships have been used to describe the antibacterial activity of various classes of antimicrobial agents . Studies that have evaluated these relationships were reviewed to determine which of these surrogate markers were further dependent on antimicrobial class . The fluoroquinolone and aminoglycoside agents exhibit concentration-dependent killing . Studies have demonstrated that peak serum concentration: minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC): MIC ratios are important predictors of outcome for these antimicrobial agents . Area under the inhibitory concentration-time curve (AUIC24) {i.e . AUC24/MIC} is a useful parameter for describing efficacy for these agents, while an adequate peak concentration: MIC ratio seems necessary to prevent selection of resistant organisms . For beta-lactam antibiotics, the duration of time that the serum concentration exceeds the MIC (T > MIC) was the significant pharmacokinetic/pharmacodynamic surrogate in cases where the bacterial inoculum was low, or where very sensitive organisms were tested . However, in studies using more resistant organisms or larger inoculum sizes there is some concentration-dependence to the observed effect . Studies using reasonable dosage intervals have demonstrated covariance between T > MIC and AUC/MIC ratio for beta-lactam antibiotics . Since glycopeptide antibiotics display relatively slow but concentration-independent killing, and are cell wall active agents similar to beta-lactams, it has been presumed that T > MIC is the important pharmacokinetic surrogate related to efficacy for these agents . Some studies have shown that a concentration multiple of the MIC may be necessary for successful outcome with vancomycin . AUIC24 may prove to be an important pharmacokinetic surrogate if both time and concentration are indeed important parameters . To select an appropriate antimicrobial agent, the clinician must consider many patient-specific as well as organism-specific factors . Utilisation of known pharmacokinetic/pharmacodynamic surrogate relationships should help to optimise treatment outcome. Intern Med, 1995 Feb, 34(2), 96 - 9 Severe hyponatremia and hyperkalemia induced by trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia; Noto H et al.; An antimicrobial agent trimethoprim-sulfamethoxazole (Tmp-Smx) does not usually cause electrolyte disturbances at regular doses, and few cases of Tmp-Smx-induced electrolyte imbalance have been reported in the English-language literature to date . Recently, however, we treated two patients with Pneumocystis carinii pneumonia who developed severe hyponatremia and hyperkalemia on administration of high-dose Tmp-Smx . These electrolyte disturbances were attributable to the direct effect of Tmp-Smx on the renal distal tubules, were reversible, and corrected by infusion of a sodium-enriched and potassium-free liquid . Therefore, it is suggested that even after electrolyte disturbances have occurred, high-dose Tmp-Smx therapy may be continued for severe infectious diseases under appropriate electrolyte correction. Antimicrob Agents Chemother, 1995 Feb, 39(2), 445 - 52 Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer . The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer; Cometta A et al.; Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients . Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory . Thus, new antibiotics with better activity against gram-positive bacteria should be tested . The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients . A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy . The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05) . The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group . A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05) . A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02) . This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients . Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds. Antimicrob Agents Chemother, 1995 Feb, 39(2), 301 - 7 Antimicrobial activities of amphiphilic peptides covalently bonded to a water-insoluble resin; Haynie SL et al.; A series of polymer-bound antimicrobial peptides was prepared, and the peptides were tested for their antimicrobial activities . The immobilized peptides were prepared by a strategy that used solid-phase peptide synthesis that linked the carboxy-terminal amino acid with an ethylenediamine-modified polyamide resin (PepsynK) . The acid-stable, permanent amide bond between the support and the nascent peptide renders the peptide resistant to cleavage from the support during the final acid-catalyzed deprotection step in the synthesis . Select immobilized peptides containing amino acid sequences that ranged from the naturally occurring magainin to simpler synthetic sequences with idealized secondary structures were excellent antimicrobial agents against several organisms . The immobilized peptides typically reduced the number of viable cells by > or = 5 log units . We show that the reduction in cell numbers cannot be explained by the action of a soluble component . We observed no leached or hydrolyzed peptide from the resin, nor did we observe any antimicrobial activity in soluble extracts from the immobilized peptide . The immobilized peptides were washed and reused for repeated microbial contact and killing . These results suggest that the surface actions by magainins and structurally related antimicrobial peptides are sufficient for their lethal activities. Ther Drug Monit, 1995 Feb, 17(1), 101 - 3 Time course of appearance of ofloxacin in human scalp hair after oral administration; Uematsu T et al.; The time course of appearance of antimicrobial ofloxacin (OFLX) in human scalp hair was monitored in three healthy male volunteers after the oral administration of 100 mg OFLX three times daily for 2 consecutive days . Hair samples were collected from each subject by plucking several strands of frontal hair every day from 1 till 16 days after administration . A single hair was dissolved in 1 M NaOH to extract OFLX by chloroform, and the drug was measured by high-performance liquid chromatography and fluorescence detection . OFLX started to appear in the hair 1 to 3 days after administration and reached the maximal level approximately 4 to 9 days, remaining at almost the same level thereafter . This finding suggests the slow transfer of OFLX from hair follicle cells to hair matrix may be due to the slow dissociation of OFLX from bound melanin. Postgrad Med J, 1995 Feb, 71(832), 71 - 8 Immunotherapy in the management of sepsis; Fagan EA et al.; The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation . Early deaths are related primarily to the acute effects of the systemic inflammatory response . Later deaths are related more closely to the consequences of multiple organ dysfunction . Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response . Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. Tuber Lung Dis, 1995 Feb, 76(1), 51 - 8 Therapeutic effect of KRM-1648 with various antimicrobials against Mycobacterium avium complex infection in mice; Saito H et al.; A new benzoxazinorifamycin, KRM-1648 (KRM), was studied for its therapeutic efficacy in combination with other antimicrobials against Mycobacterium avium complex infections in mice . When M . intracellulare-infected (intravenously) mice were given KRM, clarithromycin (CAM), sparfloxacin (SPFX), or ethambutol (EB) each alone or in combination, by gavage, once daily 6 times per week (streptomycin {SM} was given subcutaneously twice per week) from day 1, KRM + CAM exhibited combined efficacy in terms of reducing the incidence of gross lung lesions and the bacterial loads in the lungs and spleens . The addition of either EB or EB + SPFX to KRM + CAM increased the efficacy . Moreover, the multi-drug regimen of KRM + CAM + EB + SPFX or ofloxacin {OFLX}) was more efficacious than rifampicin (RMP) + CAM + EB + SPFX (or OFLX) . In M . avium infection, KRM + clofazimine was the most efficacious among two-drug combinations tested followed by KRM + SM . KRM + CAM was considerably less effective against M . avium than against M . intracellulare infection . KRM + EB and KRM+OFLX failed to show such a combined effect. J Antibiot (Tokyo), 1995 Feb, 48(2), 158 - 61 New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . VII . Structure determination of brominated lachnumon and mycorrhizin A derivatives; Stadler M et al.; The structure determination of lachnumon B1 (16) and lachnumon B2 (17), brominated derivatives of lachnumon (1), as well as mycorrhizin B1 (18) and mycorrhizin B2 (19), brominated derivatives of mycorrhizin A (3), is described . The compounds, which exhibit similar antimicrobial and nematicidal activity as their chlorinated analogues, were isolated from extracts of cultures of the ascomycete Lachnum papyraceum to which CaBr2 had been added . The structures were elucidated by spectroscopic methods. J Antibiot (Tokyo), 1995 Feb, 48(2), 154 - 7 New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . VI . Structure determination of non-halogenated metabolites structurally related to mycorrhizin A; Stadler M et al.; The structure determination of four new biologically active non-halogenated metabolites isolated from submerged cultures of the ascomycete Lachnum papyraceum is described . The compounds are structurally related to the antibiotic mycorrhizin A: (l'Z)-Dechloromycorrhizin A (12), a stereoisomer of dechloromycorrhizin A (5) previously isolated from the same fungus, as well as papyracon A (13), papyracon B (14) and papyracon C (15) containing an exocyclic double bond . The amounts of the latter three increased significantly when CaBr2 was added to the culture medium . The structures were determined by spectroscopic methods. J Antibiot (Tokyo), 1995 Feb, 48(2), 149 - 53 Metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . V . Production, isolation and biological activities of bromine-containing mycorrhizin and lachnumon derivatives and four additional new bioactive metabolites; Stadler M et al.; Eight novel bioactive metabolites were isolated from submerged cultures of the ascomycete Lachnum papyraceum (Karst.) Karst, when CaBr2 was added to the cultures after the onset of secondary metabolism . Four of these metabolites (16 to 19) are bromo analogues of mycorrhizin A and lachnumon, while (l'Z)-dechloromycorrhizin A (12) and the papyracons A (13), B (14), and C (15) are non-halogenated compounds structurally related to the mycorrhizins . All compounds exhibited antimicrobial, cytotoxic, nematicidal and phytotoxic activities . The brominated mycorrhizins and lachnumons were found to be slightly less active than the chlorine-containing compounds . All mycorrhizin derivatives were mutagenic in the Ames test, suggesting DNA-alkylating properties. Arch Dis Child, 1995 Feb, 72(2), 165 - 6 Non-tuberculous mycobacterial lymphadenopathy; Clark JE et al.; The surgical and antimicrobial treatment of non-tuberculous mycobacterial lymphadenopathy in 17 children was reviewed . Node excision was curative, but most nodes were still incised leaving discharging lesions . Standard antituberculous treatment was unhelpful, but a new macrolide/quinolone combination appeared to be effective in three cases. Kekkaku, 1995 Feb, 70(2), 97 - 101 {In vitro antimycobacterial activity of a new quinolone, T-3761}; Tomioka H et al.; We evaluated the in vitro antimicrobial activity of T-3761 and ofloxacin against representative pathogenic mycobacteria by the agar dilution method, using 7H11 agar medium . T-3761 showed appreciable antimicrobial activity against Mycobacterium tuberculosis (MIC90: 3.13 micrograms/ml), M . kansasii (MIC90: 6.25 micrograms/ml) and M . fortuitum (MIC90: 3.13 micrograms/ml), whereas the agent was not active against M . marinum (MIC90: 25 micrograms/ml), M . scrofulaceum (MIC90: 50 micrograms/ml), M . avium (MIC90: > 100 micrograms/ml), M . intracellulare (MIC90: > 100 micrograms/ml), M . chelonae subsp . abscessus (MIC90: > 100 micrograms/ml) and M . chelonae subsp . chelonae (MIC90: 50 micrograms/ml) . The in vitro antimicrobial activity of T-3761 against M . fortuitum was a little more potent than that of ofloxacin, whereas the activity of T-3761 against the other mycobacteria was slightly inferior to that of ofloxacin . The antimycobacterial activity of T-3761 against M . tuberculosis H37Rv (MIC in vitro: T-3761 = 3.13 micrograms/ml, OFLX = 0.78 micrograms/ml) phagocytosed in murine peritoneal macrophages was less active than that of ofloxacin, when the macrophages were cultured in RPMI-1640 medium containing 1 microgram/ml or 10 micrograms/ml of these agents for up to 5 days . The activity of 10 micrograms/ml of T-3761 was equivalent to that of 1 microgram/ml of ofloxacin. J Appl Bacteriol, 1995 Feb, 78(2), 134 - 41 Methylchloroisothiazolone-induced growth inhibition and lethality in Escherichia coli; Chapman JS et al.; Exposure of log phase Escherichia coli cells to inhibitory levels of 5-chloro-2-methyl-isothiazolin-3-one (MCI) results in rapid bacteriostasis and a delayed onset of bactericidal activity . Inhibition of respiration occurs within the same time frame as bacteriostasis, and is followed by a decline in intracellular ATP levels . In vitro and in vivo experiments suggest that growth inhibition is the result of selective inhibition of particular targets, with succinate dehydrogenase being identified as a possible target . Such selectivity was not anticipated from this highly reactive molecule . MCI-induced lethality is positively correlated with a loss of reduced protein sulphydryls (r2 = 0.79) . A greater than equimolar loss of reduced protein sulphydryls, compared with the number of MCI molecules added, and a reduction in killing by MCI after induction of the OxyR regulon suggest that free radical generation may have a role in the antibacterial activity of MCI . We present an examination of the in vivo effects of MCI exposure on bacterial cells, and evidence that the isothiazolones exhibit selectivity in their cellular targets and antimicrobial effects. Endod Dent Traumatol, 1995 Feb, 11(1), 6 - 9 Observation of bacteria and fungi in infected root canals and dentinal tubules by SEM; Sen BH et al.; The aim of this study was to observe the root canal flora and possible penetration of microorganisms into dentinal tubules in teeth with necrotic pulps . Ten infected maxillary and mandibular molars with periapical lesions were extracted and fixed in 2.5% phosphate-buffered glutaraldehyde solution for nine days . After separation from the crowns, longitudinal grooves were cut in the roots, and they were split into two halves . The specimens were prepared for SEM . The root canals and the dentinal tubules of the fractured dentin were scanned systematically from the cervical to the apical area of the root . Cocci and rods were seen in 6 specimens . Penetration of bacteria into the dentinal tubules ranged from 10 to 150 microns . In 4 specimens, the root canals were heavily invaded by yeasts . The antimicrobial effect of routinely used endodontic disinfectants also on yeasts may be considered in persistent root canal infections. Immunol Lett, 1995 Feb, 45(1-2), 117 - 21 Functional alterations of human blood monocytes after exposure to various nickel compounds in vitro: an effect on the production of hydrogen peroxide; Zeromski J et al.; It is generally known that nickel, a metal with distinct carcinogenic properties, can significantly alter the functioning of host defense mechanisms and impair various components of the immune system . In the present study the influence of 3 nickel salts on the production of hydrogen peroxide (H2O2) by human monocytes was examined in in vitro culture . Highly purified, resting and PMA-stimulated normal human monocytes were cultured with subtoxic concentrations of nickel subsulfide nickel sulfate, nickel acetate and manganese chloride . A portion of the cells was cultured with nickel-manganese salt mixture . Following culture cells were tested in an in vitro functional assay for H2O2 production . It has been shown that all nickel salts, used in micromole concentrations, suppressed H2O2 formation both in resting and PMA-stimulated monocytes, while it was not the case when manganese chloride was used for cell cultures . The strongest suppressive effect was manifested by nickel sulfate . The cells subjected to nickel-manganese mixture displayed H2O2 production similar to that of control ones . These results show that nickel salts in micromole concentrations exert a suppressive effect on oxygen-dependent antimicrobial system of human monocytes and manganese prevents this effect. Eur J Oral Sci, 1995 Feb, 103(1), 8 - 10 Calprotectin levels in oral fluids: the importance of collection site; Cuida M et al.; Calprotectin is a major protein of granulocytes and monocytes with antimicrobial properties, and is released during activation or cell death . In the present study the levels of calprotectin in various oral fluids were analyzed in 12 healthy adults using different collection devices . Parotid saliva, stimulated whole saliva and "mucosal transudate" were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) . The results showed mean concentrations of 3.2, 22.0 and 40.9 mg/l in the respective oral fluids, illustrating great variation of calprotectin levels between different oral fluids . The results are in accordance with the composition of these saliva samples; the lowest calprotectin level was obtained in parotid saliva, which contains the purest secretion . These findings illustrate the importance of careful sampling procedures . The levels of salivary calprotectin are markedly influenced by the site of collection. Boll Chim Farm, 1995 Feb, 134(2), 80 - 4 Novel diarylsulphide derivatives as potential cytotoxic agents; el-Subbagh HI et al.; A series of diarylsulphides bearing amino, acetamido, sulphonamido, benzamido or arylideneamino synthons have been synthesized and evaluated for their antimicrobial and cytotoxic activities . Some of the tested compounds proved to possess a remarkable activity . The detailed synthesis, spectroscopic and biological data are reported. Boll Chim Farm, 1995 Feb, 134(2), 77 - 9 Synthesis and antimicrobial activity of some new carbazoles, indazoles, quinolines, quinazolines and naphthalenes from 3-methyl-5-phenyl-6-benzylidene-2-cyclohexene-1-one; El-Ablak FZ et al.; Reaction of the title compound (1) with phenylhydrazine using the Fisher indole synthesis, resulted in the formation of the carbazole derivative (2) . Condensation of (1) benzaldehyde afforded the 6-benzylidene derivative (3) . Treatment of compound (3) with some hydrazines and hydrazides resulted in the formation of the indazoles (4) . Michael addition of some active methylene components with (3) gave quinolines (5) and naphthalenes (7) . The reaction of (3) with urea and thiourea gave the uraciles (6) . The newly synthesized compounds were screened for antibacterial activity. Rev Med Chil, 1995 Feb, 123(2), 185 - 91 {Comparison of 2 treatment schemes to eradicate Helicobacter pylori}; Hoffenberg P et al.; INTRODUCTION: Anti secretory drugs, antimicrobials and bismuth salts are used with variable success to eradicate Helicobacter pylori . AIM: To assess the effectiveness and rates of reinfection of two therapeutic modalities H pylori infection in adult patients with duodenal ulcer or non ulcer dyspepsia . METHODS: During upper gastrointestinal endoscopy, 5 antral and 2 fundic biopsies were obtained and sent for microbiological and anatomopathological study . Patients infected with Helicobacter pylori were randomly assigned to receive during two weeks omeprazole 20 mg od plus amoxicillin 500 mg tid (group A) or bismuth subsalicylate 260 mg bid, metronidazole 250 mg tid and amoxicillin 500 mg tid (group B) . A new endoscopy with antral and fundic biopsies was performed to all patients four weeks after discontinuing treatment and six months later to those in whom H pylori was eradicated . RESULTS: Eighty patients (40 in each treatment group) completed the treatment and follow up . H pylori was eradicated in 22 patients of group A (55%) and 28 of group B (70%) . Minor adverse effects were reported by 5 patients in group A (12%) and 11 in group B (27.5%) . Six months later, reinfection was documented in 12 patients of group A and 8 of group B (54% and 30% of those with successful treatment respectively) . Ten of twenty five patients with duodenal ulcer had reinfections, but there was only one ulcer relapse . CONCLUSIONS: These two treatment modalities have similar results. Int J Immunopharmacol, 1995 Feb, 17(2), 91 - 102 Adjuvants, endocrines and conserved epitopes; factors to consider when designing "therapeutic vaccines"; Rook GA et al.; Research into immunity to complex intracellular parasites has recently placed emphasis on the identification of peptide sequences recognised by T-cells, often with the dual objectives of finding species-specific protective epitopes, and of understanding selection of Th1 versus Th2 response patterns . In this review it is suggested that although such work is interesting, it will not achieve these objectives, which must, however, be addressed before we can design the new generation of therapeutic vaccines which may eventually replace antimicrobial drugs in the treatment of infection . First, we suggest that the balance of Th1 to Th2 lymphocyte activity is not determined by epitopes, but rather by adjuvant effects of microbial components which we have barely begun to define, and local endocrine effects mediated by conversion of prohormones into active metabolites by enzymes in lymph node macrophages . Cytokines play a role as mediators within these pathways . In chronic disease states there is a tendency for T-cell function to shift towards Th2 . We describe immunopathological consequences of this tendency, including a putative role for agalactosyl IgG, and review evidence for involvement of changes in the endocrine system, brought about not only by the cytokine-hypothalamus-pituitary-adrenal axis, but also by direct actions on peripheral endocrine organs of excess levels of cytokines such as TNF alpha, TGF beta and IL-6 . We summarise evidence that the epitopes that are targets for protective cell-mediated responses to complex organisms are usually not species specific . In tuberculosis, cellular responses to species-specific components appear to be associated with immunopathology rather than protection . Finally, we discuss how application of these principles has led to remarkable results in the immunotherapy of tuberculosis, including multidrug-resistant disease. Alcohol Clin Exp Res, 1995 Feb, 19(1), 11 - 6 Effects of ethanol on cellular immunity to facultative intracellular bacteria; Jerrells TR et al.; Alcohol abuse has been associated with an increase in infectious diseases caused by pathogenic and opportunistic microorganisms . Study results obtained from this laboratory and other laboratories have shown that consumption of large amounts of ethanol is associated with numerous changes in the immune system . The purpose of this article is to report findings obtained from this laboratory, as well as review those obtained from other laboratories, from experiments designed to evaluate the effects of ethanol on various components of antimicrobial host-defense mechanisms . The effects of ethanol on various aspects of immunity obtained with the use of in vivo and in vitro model systems are reviewed as they pertain to antimicrobial defenses . All current data would support the suggestion that ethanol affects both the development of an antigen-specific immune response and the effector mechanisms of the cellular immune response . Findings obtained from animal models show that ethanol prevents the formation of granulomas in infected tissues, perhaps by inhibiting the response of macrophages to T-cell cytokines . Data obtained from this laboratory also support the suggestion that the inability of the immune system to control the intracellular growth of microorganisms results in an exaggerated inflammatory response that is responsible for at least a part of the tissue damage. Pharm World Sci, 1995 Jan 27, 17(1), 1 - 11 Liposomes as delivery systems in the prevention and treatment of infectious diseases; Bergers JJ et al.; Research on the potential application of liposomes in the prevention and treatment of infectious diseases has focussed on improvement of the therapeutic index of antimicrobial drugs and immunomodulators and on stimulation of the immune response to otherwise weak antigens in vaccines composed of purified micro-organism subunits . In this review current approaches in this field are outlined . The improved therapeutic index of antimicrobial drugs after encapsulation in liposomes is a result of enhanced drug delivery to infected tissue or infected cells and/or a reduction of drug toxicity of potentially toxic antibiotics . Liposomal encapsulation of immunomodulators that activate macrophages aims at reducing the toxicity of these agents and targeting them to the cells of the mononuclear phagocyte system in order to increase the nonspecific resistance of the host against infections . Studies on the immunogenicity of liposomal antigens have demonstrated that liposomes can potentiate the humoral and cell mediated immunity to a variety of antigens. Schweiz Rundsch Med Prax, 1995 Jan 24, 84(4), 98 - 105 {sensitivity of bacteria to chemotherapeutic agents (Zurich, 1993)}; Wust J et al.; This paper describes the incidence of Gram-negative and Gram-positive bacteria susceptible to antibacterial agents . The data are based on all susceptibility tests performed at the Department of Medical Microbiology of the University of Zurich . The evaluation of the results from 1987 to 1993 shows that susceptibilities against the antimicrobial agents tested have not changed markedly in this period with few exceptions . The tables may be of help to the physician in his decision for a 'calculated chemotherapy' of bacterial infections. J Biol Chem, 1995 Jan 20, 270(3), 1048 - 56 The role of amphipathicity in the folding, self-association and biological activity of multiple subunit small proteins; Perez-Paya E et al.; The effect that altering amphipathicity has on the folding process and self association of melittin, a small model protein, has been investigated using single amino acid substitutions of lysine 7, a residue distant from the contact residues involved in the hydrophobic core of tetrameric melittin . While substitutions of such a residue were not expected to interfere with the packing process, the largest alterations in the potential overall amphipathicity of melittin were found to prevent the folding into an alpha-helical conformation to occur and, in turn, to prevent the self association . Amphipathic alpha-helices were found to be a key determining feature in the early folding process of the self association of peptides and protein segments . Those substitutions, which prevented the inducible amphipathic folding ability, were also found to result in a loss in hemolytic and antimicrobial activity . These results, combined with studies of the binding to artificial liposomes and to polysialic acids, indicate that the losses in activity were due to an initial inability to be induced into an amphipathic alpha-helix and to self associate . Ultimately, melittin's self association is proposed to be required to penetrate the carbohydrate barrier present in biological membranes. JAMA, 1995 Jan 18, 273(3), 214 - 9 Trends in antimicrobial drug prescribing among office-based physicians in the United States; McCaig LF et al.; OBJECTIVE--To assess changes in oral antimicrobial drug prescribing by office-based physicians from 1980 through 1992, with emphasis on the treatment of otitis media and sinusitis and on the possible impact of demographic variables on such use . DESIGN--The National Ambulatory Medical Care Survey is a sample survey of office-based physicians in the United States conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention . SETTING--Physicians' offices . PATIENTS OR OTHER PARTICIPANTS--Physicians sampled for the 1980, 1985, 1989, and 1992 National Ambulatory Medical Care Surveys, which included groups of 2959, 5032, 2540, and 3000 physicians, respectively . Sample physicians responding in 1980, 1985, 1989, and 1992 reported data for 46,081, 71,594, 38,384, and 34,606 sample office visits, respectively, including information on antimicrobial drug prescribing . MAIN OUTCOME MEASURE--Trends in the antimicrobial drug prescription rates . RESULTS--From 1980 through 1992, increasing prescribing measured by the annual drug prescription rate per 1000 population, was found for the more expensive, broad-spectrum antimicrobial drugs, such as the cephalosporins; decreasing rates were observed for less expensive antimicrobial drugs with a narrower spectrum, such as the penicillins . No trend was found for trimethoprim-sulfamethoxazole, the erythromycins, or the tetracyclines . During the decade, an increasing trend in the visit rate to office-based physicians for otitis media was observed, while the visit rate for sinusitis among adults was found to be higher in 1992 than in each of the other study years . CONCLUSIONS--The increased use of broader-spectrum and more expensive antimicrobial drugs have implications for all patients because of the impact on health care costs and the potential for the emergence of antimicrobial resistance . The data suggest that the incidence of otitis media and sinusitis is increasing. Med J Aust, 1995 Jan 16, 162(2), 95 - 7 Upper gastrointestinal tract; Crotty B et al.; Drug therapy for upper gastrointestinal disease in the elderly must be moderated by the likelihood of increased sensitivity to the side effects of drugs . For example, in the frail elderly with helicobacter-associated duodenal ulcers, maintenance therapy with an H2-receptor antagonist or omeprazole may be preferable to attempting to eradicate Helicobacter pylori with the current antimicrobial regimens. J Am Vet Med Assoc, 1995 Jan 15, 206(2), 206 - 9 Comparison of clinical signs, diagnostic findings, organisms isolated, and clinical outcome in dogs with bacterial pneumonia: 93 cases (1986-1991); Jameson PH et al.; Medical records were reviewed for 93 dogs with bacterial pneumonia from which transtracheal aspiration samples were obtained for culturing of Mycoplasma spp and aerobic bacteria . On the basis of culture results, there were 65 Mycoplasma-positive dogs, including 7 dogs for which only Mycoplasma spp were isolated, and 28 Mycoplasma-negative dogs . Most dogs were > 5 years old, and differences in breed or gender distribution among the 3 groups of dogs were not detected . Hematologic and serum biochemical analysis results did not differ significantly between Mycoplasma-positive and Mycoplasma-negative dogs . Fifty-three of 93 (57%) dogs had a concurrent medical problem that may have predisposed them to developing bacterial pneumonia as a sequelae to aspiration or immunosuppression . Mycoplasma-positive dogs were significantly (P < 0.005) more likely to have > 1 species of bacteria isolated from their transtracheal aspiration samples . Clinical outcome was favorable when antimicrobials were selected on the basis of antimicrobial susceptibility results for the other bacterial isolates and not on results of the antimicrobial activity against Mycoplasma spp . It could not be determined whether Mycoplasma spp were primary pathogens or only opportunists. J Am Vet Med Assoc, 1995 Jan 15, 206(2), 203 - 5 Contamination and infection of fractures resulting from gunshot trauma in dogs: 20 cases (1987-1992); Doherty MA et al.; Medical records of 20 dogs with gunshot fractures were reviewed to determine the prevalence of preoperative contamination and postoperative osteomyelitis . Fractures were repaired primarily by application of a bone plate (n = 16) or external fixator (n = 2) in buttress fashion or application of interfragmentary screws and pins (n = 2) . In 17 dogs, an autogenous bone graft was also used . Results of bacteriologic culture of swab specimens obtained intraoperatively for 15 of the 16 dogs that received antimicrobials preoperatively and for all 4 dogs that did not receive antimicrobials preoperatively were negative . Three dogs developed osteomyelitis at 6, 8, and 10 weeks following surgery; for all 3, results of bacteriologic culture of specimens obtained intraoperatively had been negative . Fracture healing was uncomplicated in the remaining dogs (mean follow-up time, 23 months; range, 2 to 58 months) . Despite the potential for contamination associated with gunshot trauma, results indicated a low prevalence of preoperative fracture contamination and postoperative osteomyelitis . These results imply either a low contamination rate or treatable contamination of the perifracture area. Contemp Intern Med, 1995 Feb, 7(2), 47 - 54, 57-60 Current recommendations for community-acquired pneumonia; Esposito AL; The question of which antimicrobial agents to use is compounded by the imprecision of presenting signs and symptoms and the limitations of diagnostic tests . The use of empiric therapy is explored along with suggested management if treatment fails. JAMA, 1995 Jan 4, 273(1), 41 - 5 Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women; Hooton TM et al.; OBJECTIVE--To determine the efficacy, safety, and costs associated with four different 3-day regimens for the treatment of acute uncomplicated cystitis in women . DESIGN--A prospective randomized trial with a cost analysis . STUDY POPULATION--Women with acute cystitis attending a student health center . INTERVENTIONS--Treatment with 3-day oral regimens of trimethoprim-sulfamethoxazole, 160 mg/800 mg twice daily, macrocrystalline nitrofurantoin, 100 mg four times daily, cefadroxil, 500 mg twice daily, or amoxicillin, 500 mg three times daily . RESULTS--Six weeks after treatment, 32 (82%) of 39 women treated with trimethoprim-sulfamethoxazole were cured compared with 22 (61%) of 36 treated with nitrofurantoin (P = .04 vs trimethoprim-sulfamethoxazole), 21 (66%) of 32 treated with cefadroxil (P = .11 vs trimethoprim-sulfamethoxazole), and 28 (67%) of 42 treated with amoxicillin (P = .11 vs trimethoprim-sulfamethoxazole) . Persistence of significant bacteriuria was less common with trimethoprim-sulfamethoxazole (3%) and cefadroxil (0%) compared with nitrofurantoin (16%; P = .05 vs trimethoprim-sulfamethoxazole) and amoxicillin (14%; P = .11 vs trimethoprim-sulfamethoxazole) . Persistence of bacteriuria was associated with amoxicillin-resistant strains in the amoxicillin group but nitrofurantoin-susceptible strains in the nitrofurantoin group . Trimethoprim-sulfamethoxazole was more successful in eradicating Escherichia coli from rectal cultures soon after therapy and from urethral and vaginal cultures at all follow-up visits compared with the other treatment regimens . Adverse effects were reported by 16 (35%) of 46 patients receiving trimethoprim-sulfamethoxazole, 18 (43%) of 42 receiving nitrofurantoin, 12 (30%) of 40 receiving cefadroxil, and 13 (25%) of 52 receiving amoxicillin . The mean costs per patient were less with trimethoprim-sulfamethoxazole ($114) and amoxicillin ($131) compared with nitrofurantoin ($155) and cefadroxil ($155) . CONCLUSIONS--A 3-day regimen of trimethoprim-sulfamethoxazole is more effective and less expensive than 3-day regimens of nitrofurantoin, cefadroxil, or amoxicillin for treatment of uncomplicated cystitis in women . The increased efficacy of trimethoprim-sulfamethoxazole is likely related to its antimicrobial effects against E coli in the rectum, urethra, and vagina. Asepsis, 1995 3RD-4TH QUART, 17(2), 14 - 20 Forum: trauma and infection: considerations for patient and health care professional; Ziglar MK et al.; Trauma and infection are leading causes of morbidity, mortality and health care expenditures despite remarkable advances in treatment over the past two decades . Numerous research studies report that in those trauma patients who survive the initial injury, infections account for over one-third of the deaths . While the immediate resuscitation of trauma patients is based on the principles of management for restoring airway, breathing, and circulation, long-term survival requires prevention of infection . Additionally, infection of the health care professional has long been known as a possible complication of caring for acutely ill and injured patients . This article reviews the risk of infection, the pathogenesis of infection, prevention, antimicrobial therapy and infection control for health care professionals. J Calif Dent Assoc, 1995 Jan, 23(1), 57 - 9 Necrotizing ulcerative periodontitis in an HIV patient; Gowdey G et al.; This case report emphasizes: aggressive HIV-related periodontal lesions can be managed by general practitioners using standard scaling and root planing procedures in combination with proper antibiotic and antimicrobial pharmaceuticals; these lesions can be managed over long periods of time with adequate home care and professional recall; motivation from both the dental team and the patient can translate into a very rewarding result which can improve the quality of life for persons who experience the extreme consequences of HIV-associated dental disease. Eur J Cardiothorac Surg, 1995, 9(9), 528 - 30 Homograft replacement of fungal endocarditic pulmonary valve; Tolan M et al.; Right-sided infective endocarditis is uncommon but is increasingly seen as a reflection of the prevalence of drug abuse, chronic intravenous catheters and associated congenital malformations . Isolated pulmonary valve endocarditis has rarely been reported and there has been only one previous report of isolated pulmonary valve fungal endocarditis . This resolved with antimicrobials . We describe a case of isolated mycotic pulmonary valve endocarditis resistant to existing anti-fungal chemotherapy, which necessitated pulmonary valve resection and replacement with a homograft. J Clin Gastroenterol, 1995, 21 Suppl 1, S169 - 73 Helicobacter pylori detected deep in gastric glands: an ultrastructural quantitative study; Taniguchi Y et al.; To determine the presence of Helicobacter pylori deep in the gastric glands and in the parietal cell canaliculi, biopsied specimens from 15 patients were observed by electron microscopy . In the specimens, 818 H . pylori and 1,846 parietal cells were detected . Most of the H . pylori (93.9%, 768/818) were present on the mucosal surface . However, a few organisms (50/818, 6.1%) were detected deep in the mucosa . The mean number of H . pylori per specimen was 2.13 (32/818, 3.9%) and 1.20 (18/818, 2.2%), deep in the gland and in the parietal cell canaliculi, respectively . All appeared morphologically intact . Although the combination of culture and histology from biopsy tissues is usually used for isolation of H . pylori in most laboratories, such organisms are considered difficult to detect with conventional methods and to dislodge with antimicrobial therapy . Therefore, H . pylori present deep in the mucosa are suggested to be one of the factors in recrudescence after eradication therapy . In addition, H . pylori in the parietal cell canaliculi may affect parietal cell function or alter gastric physiology. Acta Neurochir (Wien), 1995, 137(1-2), 78 - 84 Intracranial mycotic infections in neurosurgical practice; Jamjoom AB et al.; Intracranial mycotic infections requiring neurosurgical intervention are being diagnosed more frequently . This study is a review of 17 cases of intracranial mycotic infections that were treated in a neurosurgical unit in Saudi Arabia over an 8-year period . A primary focus of infection was identified in 41% of patients while 18% of patients had a predisposing factor . Forty-seven percent of patients presented with a brain abscess (solitary 29%, multiple 18%) while 35% had a granuloma . 18% meningitis and ventriculitis and 12% hydrocephalus . The Aspergillus species and Ramichloridium machenziei were the commonest pathogens . Following the appropriate surgical and antimicrobial treatment, the mortality rate was 41% and there was evidence of residual disease at follow-up in 18% . The reason for a fatal outcome was failure to consider a fungal aetiology and to obtain a tissue diagnosis early-because of late referral (2 cases), as well as failure to respond to antimycotic therapy (4 cases) and rupture of the internal carotid artery due to Aspergillus arteritis (one case) . It is concluded that an early tissue diagnosis is crucial in the management of intracranial mycotic infection so that the appropriate surgical and antimycotic treatment can be started early. Curr Top Med Mycol, 1995, 6, 47 - 71 Treatment of eumycetoma and actinomycetoma; Welsh O et al.; Mycetoma is a chronic disease caused by aerobic actinomycetes and eumycetes which mainly affects the lower extremities . It predominates among farm workers in tropical, subtropical and adjacent zones . Clinically it is characterized by a firm swelling with abscesses and fistulae discharging pus that contains granules or grains of the causal agent . Their color, size, consistency and histopathology contribute to their identification . Cultures and metabolic studies determine the disease's etiology . Eumycete and actinomycete antigens can be used serologically to diagnose and predict prognosis of the disease . Many different antimicrobials and antifungal drugs have been used with varying degrees of success . Trimethoprim-sulfamethoxazole alone or together with diamino-diphenyl-sulfone is the treatment of choice for actinomycetoma . Amikacin is used for severe cases, unresponsive to previous treatment, and for those in danger of dissemination to adjacent organs . Surgery is seldom used for actinomycetoma . In eumycetoma a combination of medical treatment and surgery is advised . Small eumycetomas are easily surgically removed . Ketoconazole at a dosage of 400 mg/day is the medical treatment of choice for eumycetoma caused by M . mycetomatis . The therapeutic response to itraconazole varies . Fluconazole has been unsuccessful in the treatment of eumycetoma but amphotericin B has shown good to poor therapeutic response. Intervirology, 1995, 38(3-4), 206 - 13 Nitric oxide inhibits Epstein-Barr virus DNA replication and activation of latent EBV; Kawanishi M; Nitric oxide (NO), a mediator of biological functions, has antimicrobial activity against a variety of pathogens including viruses . Effects of NO donors on EBV replication in two EBV lytic systems, Raji cells infected with P3HR-1 virus and P3HR-1 cells activated with TPA plus n-butyrate, were studied . S-nitroso-N-acetylpenicillamine (SNAP), which generates NO when placed in an aqueous solution, and 3-morpholinosydnonimine (SIN-1), which liberates NO and O2-, resulting in the formation of peroxynitrite, were used as NO donors . Immunoprecipitation analysis showed that in superinfected Raji cells, SNAP inhibited EBV late protein synthesis but not EBV early protein expression . Analysis of the structure of EBV DNA termini demonstrated that SNAP suppressed the amplification of EBV DNA in superinfected Raji cells at a dose which did not affect synthesis of EBV early proteins required for EBV DNA replication . In TPA plus n-butyrate-treated P3HR-1 cells, SNAP inhibited synthesis of both early and late proteins of EBV . Northern blot analysis of RNA expressed in TPA plus n-butyrate-treated P3HR-1 cells demonstrated that expression of EBV immediate-early mRNAs coded from BZLF1 and BRLF1 genes was inhibited by SNAP . SIN-1 showed no or little effect on EBV replication in both cell systems . Cell viability and cellular protein synthesis were not affected by either NO donor under the conditions used . These findings suggest that NO prevents EBV replication by inhibiting EBV DNA amplification during the lytic phase of the life cycle as well as by blocking activation of the latent EBV genome . The mechanism for inhibiting of EBV replication by NO was discussed in relation to the role of NO in EBV latency in vivo. Med Tr Prom Ekol, 1995, (10), 35 - 7 {Antimicrobial means for individual protection used by medical personnel in emergency situations}; Selov AV et al.; For protection of medical staff from infections during emergencies, the authors recommend individual antimicrobial means--medical gowns and special suits protecting skin against extremely dangerous causal agents, surgical masks and individual means with autonomous air supply for lower intake of bacteria. Microbios, 1995, 84(339), 79 - 85 Presence of sterile hyphae in moulds: relationship with inhibitory activity; Calvo MA et al.; The relationship involving the presence of sterile hyphae in moulds and their inhibitory activity on 34 micro-organisms was investigated . From the results it was evident that antimicrobial activity varied when morphological changes were observed in the cultures. J Enzyme Inhib, 1995, 9(4), 263 - 75 Belactins A and B, new serine carboxypeptidase inhibitors produced by Actinomycete . I . Taxonomy, production, isolation and biological activities; Murakami S et al.; Belactins A and B, new inhibitors of serine carboxypeptidase were discovered in the fermentation broth of Saccharopolyspora sp . MK19-42F6 . They were purified by ethyl acetate extraction, silica gel chromatography, Sephadex LH20 chromatography, Capcellpak C18 SG120 reversed phase HPLC and centrifugal partition chromatography (CPC) following their inhibitory activity against carboxypeptidase Y (CP-Y) . The inhibition constants (Ki) of belactins A and B against CP-Y are 0.14 and 0.27 microM respectively . Belactins A and B have highly specific inhibitory activities for CP-Y among various peptidases, have no antimicrobial activities at 100 micrograms/ml and have low toxicities. J Clin Dent, 1995, 6 Spec No, 84 - 8 Effect of a stabilized stannous fluoride dentifrice on plaque acid (toxin) production; White DJ et al.; A Plaque Glycolysis and Regrowth Method (PGRM) has been used to examine the effects of single brushing with a new stabilized stannous fluoride dentifrice on plaque acid production . Plaque samples collected 45 minutes after subject toothbrushing were compared with samples collected prior to toothbrushing for glycolytic activity (pH reduction in incubation media), and the composition and proportion of acids produced during metabolism (capillary electrophoresis) . Subjects brushed with both active SnF2 and placebo dentifrices in a cross-over design . Acetic and lactic acid were found to be produced during PGRM metabolism . SnF2 dentifrice was observed to significantly inhibit plaque glycolysis, reducing the pH drop associated with acid production . and specifically inhibiting both lactic acid and acetic acid production . Control dentifrice had a modest inhibitory effect on acid production, primarily inhibiting acetic acid production . SnF2 dentifrice inhibited lactic acid production more effectively than control dentifrice, and this effect appeared to be related to SnF2 specificity in metabolic inhibition, as opposed to the components of control dentifrice, namely ionic fluoride and surfactant . These experimental results support the in vivo antimicrobial activity of SnF2 formulated in a new stabilized matrix (currently marketed as Crest Gum Care), and demonstrate the utility of the PGRM method in elucidating specific mechanisms of action for antimicrobial agents. J Clin Dent, 1995, 6 Spec No, 80 - 3 Antimicrobial effects of a stabilized stannous fluoride dentifrice in reducing plaque acid production--a single-brushing PGRM study; Liang N et al.; A Plaque Glycolysis and Regrowth Method (PGRM) has been used to evaluate the in vivo antimicrobial activity of a new stabilized stannous fluoride dentifrice in comparison to a control dentifrice (Regular Crest, containing NaF) and a second commercial dentifrice containing SnF2 . In the method, plaque collected from subjects prior to toothbrushing served as control for subsequent plaque samples collected following toothbrushing with assigned formulations . Inhibition of plaque metabolic activity was determined by the comparative acidogenicity of normalized plaque samples as contrasted with control plaques incubated similarly . Results from a sixteen-person cross-over study demonstrated that the improved stabilized stannous fluoride dentifrice significantly reduced plaque metabolism of sucrose in comparison to both placebo and commercial SnF2 dentifrice formulations following a single toothbrushing with 2.5 grams of dentifrice for over 90 minutes following treatment . These results support the strong antimicrobial activity of the stabilized stannous fluoride dentifrice, currently marketed as Crest Gum Care, in inhibiting plaque metabolism/acid production following in vivo toothbrushing. J Clin Dent, 1995, 6 Spec No, 71 - 9 Effects of nine weeks' use of a new stabilized stannous fluoride dentifrice on intrinsic plaque virulence expressed as acidogenicity and regrowth: a modified PGRM study; Kasturi R et al.; A new stabilized stannous fluoride dentifrice, currently marketed as Crest Gum Care has been examined for its effects on intrinsic plaque metabolic and regrowth activity and effects on plaque resistance to SnF2 throughout nine weeks of toothbrushing . Subjects brushed their teeth 1 X, 2 X or 3 X/day with stabilized stannous fluoride dentifrice or placebo dentifrice for nine weeks, presenting in the morning on weeks 3, 6-9 for plaque sampling . Following nine weeks, subjects were crossed-over and repeated the experiment on their alternative assigned product (active SnF2/placebo) . Sampled dental plaques were evaluated for standardized glycolysis and regrowth activity using the "Plaque Glycolysis and Regrowth Method" (PGRM) . Following the second nine-week treatment period, subjects concluding either placebo or SnF2 toothbrushing participated in a single-treatment PGRM experiment using stabilized stannous fluoride dentifrice . Toothbrushing with stabilized stannous fluoride dentifrice in this experiment produced significant and sustained reductions in both plaque glycolytic and regrowth activity as compared to placebo treated plaques . In the concluding single-brushing PGRM experiment, SnF2 dentifrice was shown to produce equal inhibitory actions in plaque from subjects completing stannous fluoride or placebo treatments . This result confirmed that nine weeks toothbrushing with stabilized stannous fluoride dentifrice produced no development or resistance of plaque to SnF2 inhibition . These results support the strong in vivo antimicrobial actions of the stabilized stannous fluoride dentifrice, Crest Gum Care. J Clin Dent, 1995, 6 Spec No, 59 - 70 A new Plaque Glycolysis and Regrowth Method (PGRM) for the in vivo determination of antimicrobial dentifrice/rinse efficacy towards the inhibition of plaque growth and metabolism--method development, validation and initial activity screens; White DJ et al.; A new method, the Plaque Glycolysis and Regrowth Method (PGRM), is described for the evaluation of antimicrobial effects on plaque metabolism in vivo . The method relies on the experimental observation that in vivo sampled dental plaques, collected from different quadrants of the dentition, produce equivalent rates of metabolic activity and regrowth when similarly dispersed and normalized into incubation media . In applications of the technique to antimicrobial evaluations, overnight fasted dental plaque is collected from a non-treated quadrant of the dentition along the gingival margin . Topical formulations are used in vivo . Following this, dental plaques are collected from other dentition quadrants at extended times, allowing for the back diffusion, clearance and natural intraoral deactivation of antimicrobials within the oral cavity . In vivo treated and non-treated plaque samples are subsequently tested for metabolic and regrowth activity under controlled and standardized conditions in vitro following normalization for biomass . The technique thus combines the necessary biological factors important to the legitimate evaluation of antimicrobial effects in vivo, while benefiting from the improved precision and control provided by in vitro assessment of plaque activity . In this paper evidence is presented validating the PGRM method, and initial activity screens of commercial antimicrobial mouthrinses and toothpastes, including a new stabilized stannous fluoride dentifrice, are described. Drug Metabol Drug Interact, 1995, 12(2), 161 - 9 Synthesis of 3-methyl-4-{(2,4-dihydro-4-substituted-3H-1,2,4-triazole-3-thione-5-yl) phenylhydrazono}-5-isoxazolone and evaluation of their antimicrobial activities; Komurcu SG et al.; 3-Methyl-4-{(2,4-dihydro-4-substituted-3H-1,2,4-triazole-3-thione-5-yl) phenylhydrazono}-5-isoxazolone derivatives have been synthesised . The structure of these compounds was determined using spectral data and elemental analyses . These compounds were tested for antimicrobial activity. Drug Metabol Drug Interact, 1995, 12(2), 145 - 50 Synthesis and antimicrobial activity of some new 1-{4-(4-fluorobenzoylamino)-benzoyl}-4-substituted thiosemicarbazides; Durgun BB et al.; 1-Aroyl-4-substituted thiosemicarbazides were obtained by the addition of 4-(4-fluorobenzoylamino)benzoylhydrazine to methyl, ethyl, propyl, allyl, cyclohexyl, phenyl and phenethyl isothiocyanates . The structures of the synthesized compounds were confirmed using UV, IR, 1H-NMR (for compounds 4c, 4g) and mass (for compounds 4b, 4c, 4g) spectral methods together with elemental analyses . None of the synthesized compounds has been reported previously. Scand J Infect Dis, 1995, 27(5), 499 - 502 Analysis of restriction fragment length polymorphism and ribotyping of multiresistant Stenotrophomonas maltophilia isolated from persisting lung infection in a cystic fibrosis patient; Wust J et al.; A cystic fibrosis patient was infected by Stenotrophomonas maltophilia over at least 15 months . The bacteria became increasingly resistant to antimicrobial agents . Determination of restriction fragment length polymorphism and ribotyping showed that resistance was due to changes in that S . maltophilia rather than to infection by another strain. World Health Organ Tech Rep Ser, 1995, 855, 1 - 59 Evaluation of certain veterinary drug residues in food . Forty-third report of the Joint FAO/WHO Expert Committee on Food Additives; Clinical perspectives of granulocyte transfusions: efficacy to date; Department of Pathology and Pediatrics, University of Iowa College of Medicine, Iowa City 52242-1182, USAThe literature pertaining to the use of granulocyte transfusions as treatment for progressive bacterial, yeast, and fungal infections in severely neutropenic patients is reviewed . Efficacy in treating bacterial infections that are unresponsive to antimicrobial therapy is well established--especially if bone marrow failure does not recover rapidly and neutropenia is persistent . The role of therapeutic granulocyte transfusions for yeast and fungal infections has potential merit, but current data are incomplete and findings are inconsistent . The possibility of greater success has been raised by use of recombinant granulocyte colony stimulating factor to greatly increase the yield of neutrophils collected from normal donors. Scand J Gastroenterol Suppl, 1995, 210, 82 - 4 Sucralfate affects the susceptibility of Helicobacter pylori to antimicrobial agents; Slomiany BL et al.; BACKGROUND: Infection with Helicobacter pylori is regarded as a primary factor in the pathogenesis of gastric disease, and successful therapies now include a combination of antiulcer drugs with antimicrobial agents . In this study, we investigated the effect of sucralfate and omeprazole on the vitro anti-H . pylori activity of metronidazole, erythromycin, tetracycline, and amoxycillin . METHODS: Aliquots of H . pylori culture were transferred to the wells containing different concentrations of antibiotics either alone or in the presence of various doses of sucralfate and omeprazole and incubated for 3 days for MIC evaluation . RESULTS: The assays in the absence of sucralfate and omeprazole gave MIC value 0.10 mg/l for erythromycin, 0.12 mg/l for amoxycillin, 0.15 mg/l for tetracycline, and 14 mg/l for metronidazole . Inclusion of sucralfate evoked a 28% enhancement in the MIC of metronidazole, 2.5-fold in tetracycline, 8-fold in erythromycin, and 2-fold in amoxycillin . In the presence of omeprazole, the MIC of erythromycin improved 4-fold, tetracycline 1.6-fold, and amoxycillin, 2-fold . CONCLUSIONS: The results demonstrate that sucralfate enhances the anti-H . pylori activity of antibiotics and that this effect is comparable to that of omeprazole. Annu Rev Microbiol, 1995, 49, 277 - 304 Peptides as weapons against microorganisms in the chemical defense system of vertebrates; Nicolas P et al.; The innate immunity of vertebrates to microbial invasion is arbitrated by a network of host-defense mechanisms involving both the long-lasting highly specific responses of the cell-mediated immune system and a nonspecific chemical defense system based on a series of broad-spectrum antimicrobial peptides that are analogous to those found in insects . Vertebrate antibiotic peptides secreted by nonlymphoid cells of the mucosal surfaces of the respiratory and gastrointestinal tracts as well as by the granular glands of the skin reportedly cause the lysis of numerous pathogenic microorganisms, including viruses, gram-positive and gram-negative bacteria, protozoa, yeasts, and fungi, as well as of cancer cells . Antimicrobial peptides isolated from vertebrates have three characteristic properties: They are relatively small (20-46 amino acid residues), basic (lysine- or arginine-rich), and amphipathic . Although these peptides differ widely in length and amino acid sequences, they may be grouped in four broad families based on characteristic structural features . Although the precise mechanism of action of these peptides remains to be defined, their microbicidal effect very likely results from their capacity to form channels or pores within the microbial membrane in order to permeate the cell and impair its ability to carry out anabolic processes . This secondary, chemical immune system provides vertebrates with a repertoire of small peptides that are promptly synthesized upon induction, easily stored in large amounts, and readily available for antimicrobial warfare. Pathobiology, 1995, 63(2), 93 - 9 Interferon-gamma-induced downregulation of CD4 inhibits the entry of human immunodeficiency virus type-1 in primary monocytes; Dhawan S et al.; We have previously shown that the treatment of monocytes with interferon-gamma (IFN-gamma) prior to exposure with human immunodeficiency virus type-1 (HIV) results in complete inhibition of HIV infection of monocytes . In the present report, we have extended this study to obtain information on the mechanism(s) underlying IFN-gamma-induced inhibition of HIV infection of monocytes . To examine the effect of IFN-gamma on HIV entry, the first event in the infectious cycle of the virus, we amplified HIV-gag sequences in the genomic DNA and RNA of IFN-gamma treated monocytes, and found no evidence for the presence of either proviral DNA or HIV RNA sequences . These results were consistent with the absence of intracellular HIV particles either in the latent or actively replicating state as determined by flow-cytometric analysis of these cells . Furthermore, no HIV-induced cytopathic effects, such as multinucleated giant cell formation or cell death, were observed in IFN-gamma-treated monocytes after their exposure to HIV . Stimulation of IFN-gamma-treated monocytes 6 days postinfection with tumor necrosis factor-alpha (TNF-alpha), which is known to augment HIV replication in the infected cells, did not result in the induction of the HIV indicating the absence of latent HIV infection in IFN-gamma-treated monocytes . Treatment of monocytes with IFN-gamma, TNF-alpha, or with a combination of the two agents which is known to induce antimicrobial free radical nitric oxide (NO2- in the murine system did not induce NO2- production human monocytes suggesting the antiviral activity of IFN-gamma to be independent of NO2(-)-mediated killing of HIV or HIV-infected monocytes.(ABSTRACT TRUNCATED AT 250 WORDS) Drugs, 1995, 49 Suppl 2, 159 - 63 Fluoroquinolone toxicities . An update; Lietman PS; The main types of adverse effects associated with quinolones are uncommon and reversible and vary in frequency among different agents . Phototoxicity appears more frequent with lomefloxacin than with some other quinolones . Three mechanisms have been proposed to explain the neurotoxic effects, including rare proconvulsant activity, associated with quinolone therapy . Arthropathy remains a dilemma for paediatricians deciding whether to use quinolones in growing children . Importantly, the experience with temafloxacin, which has now been withdrawn from the market, emphasises the need for thorough postmarketing surveillance . Nonetheless, it should be remembered that the fluoroquinolones as a group are effective and very well tolerated antimicrobial drugs. Oncol Res, 1995, 7(5), 213 - 25 Difloxacin reverses multidrug resistance in HL-60/AR cells that overexpress the multidrug resistance-related protein (MRP) gene; Gollapudi S et al.; In this study, we have examined the in vitro chemosensitizing activity of difloxacin, a quinolone antimicrobial agent, in the multidrug-resistant human myeloid leukemia HL-60/AR cell line . HL-60/AR cells were found to overexpress multidrug resistance-associated protein (MRP) mRNA as compared to HL-60 cells . Difloxacin, in a concentration-dependent manner, increased the sensitivity of HL-60/AR cells to daunorubicin, adriamycin, and vincristine, and partially corrected the altered drug transport . In addition, difloxacin corrected subcellular distribution of adriamycin by inducing redistribution of the drug from the perinuclear region to the nucleus in HL-60/AR cells . The chemosensitizing effect of difloxacin was observed at clinically achievable concentrations . We conclude that difloxacin is an effective chemosensitizer of MRP-associated multidrug-resistant tumor cells and is a potential candidate for clinical use to reverse multidrug resistance. J Clin Lab Anal, 1995, 9(5), 308 - 19 Myelin- and microbe-specific antibodies in Guillain-Barré syndrome; Terryberry J et al.; We surveyed the frequency of reported infections and target autoantigens in 56 Guillain Barre syndrome (GBS) patients by detecting antibodies to myelin and microbes . Sulfatide (43%), cardiolipin (48%), GD1a (15%), SGPG (11%), and GM3 (11%) antibodies were the most frequently detected heterogenous autoantibodies . A wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps-specific IgG (66%), adenovirus-specific IgG (52%), varicella-zoster virus-specific IgG (46%), and S . pneumoniae serotype 7-specific IgG (45%) were the most prevalent . Our results indicate that polyclonal expansion of physiologic and pathologic antibodies and/or molecular mimicry likely occurs following infection and is related to other autoimmune factors in the etiology of GBS . Although no single definitive myelin-specific autoantibody was identified, our results suggest a unique pattern of reactivity against autoantigens. Prog Clin Biol Res, 1995, 392, 567 - 79 Monophosphoryl lipid A as a prophylactic for sepsis and septic shock; Gustafson GL et al.; The ability of monophosphoryl lipid A (MLA) to provide prophylactic protection against septic shock was evaluated in a mouse model of induced endotoxin hypersensitivity . Treatments of hypersensitized animals with low doses of MLA attenuated endotoxin lethality and endotoxin-mediated liver damage . These effects were related to the ability of MLA to suppress accumulation of TNF-alpha and IFN-gamma in the bloodstream of animals . MLA treatments had only a modest effect in suppressing the accumulation of nitrate in the bloodstream . This implied that MLA did not suppress induction of macrophage and hepatocyte nitric oxide synthetases that contribute to antimicrobial defense and protect against endotoxin-mediated liver damage . The MLA treatments did not appear to compromise inflammatory defenses against local infection since locally recruited leukocytes remained responsive to endotoxin after hypersensitivity had been attenuated . In agreement with these findings, other studies have shown that the induction of endotoxin tolerance by MLA parallels the induction of resistance of animals to lethal challenges with either Gram negative or Gram positive bacteria . As predicted from preclinical studies, human trials of the clinical form of MLA (MPL-immunostimulant) have confirmed that MLA could attenuate systemic responses to endotoxin in normal volunteers, including the attenuation of blood cytokine accumulation and attenuation of symptomatic responses. Med Tr Prom Ekol, 1995, (8), 33 - 5 {Use of products made of antimicrobial materials in the prevention of foot mycoses}; Sedov AV et al.; Field trials were conducted to evaluate effectiveness of mycoses prophylaxis gained by use of antimicrobial insoles and foot-binding with fungicide agents . The trials involved 100 novice soldiers . Bacteriology and bacterioscopy studies diagnosed 47 soldiers as having subclinical mycosis of feet . Using antimicrobial insoles and foot-binding caused considerably lower occurrence of pathogenic fungi in the skin samples; using antimicrobial insoles with regular foot-binding resulted in no changes of the skin microflora . The authors recommend wide application of antimicrobial stuff with fungicide agents for prophylaxis of feet mycosis. Infect Control Hosp Epidemiol, 1995 Jan, 16(1), 7 - 11 Multidrug-resistant Mycobacterium tuberculosis in an HIV dental clinic; Cleveland JL et al.; OBJECTIVE: To investigate possible transmission of multidrug-resistant tuberculosis (MDR-TB) in a dental setting . DESIGN: A retrospective, descriptive study of dental workers (DWs), patients, and practice characteristics . PATIENTS: Two dental workers (DW1 and DW2) with acquired immunodeficiency syndrome and MDR-TB . SETTING: A hospital-based (Hospital X) human immunodeficiency virus (HIV) dental clinic in New York City . METHODS: To identify dental patients with tuberculosis (TB), patients treated in the dental clinic at Hospital X during 1990 were cross-matched with those listed in the New York City Department of Health Tuberculosis Registry . Mycobacterium tuberculosis isolates from both DWs and from dental patients with TB were tested for antimicrobial susceptibility and typed by restriction fragment length polymorphism (RFLP) analysis . Infection control practices were reviewed . RESULTS: M tuberculosis isolates infecting DW1 and DW2 were resistant to isoniazid and rifampin and had identical RFLP patterns . DW1 and DW2 worked in close proximity to each other in a small HIV dental clinic in Hospital X during 1990 . Of 472 patients treated in the dental clinic in 1990, 41 (8.7%) had culture-proven M tuberculosis infection . Of these 41, 5 had isolates with resistance patterns similar to both DWs; however, for four available isolates, the RFLP patterns were different from the patterns of the DWs . Sixteen of the 41 patients received dental treatment while potentially infectious . Dental patients were not routinely questioned about TB by dental staff, nor were all dental staff screened routinely for TB . No supplemental environmental measures for TB were employed in the dental clinic in 1990 . CONCLUSIONS: Our investigation suggests that MDR-TB transmission may have occurred between two DWs in an HIV dental clinic . Opportunities for transmission of TB among dental staff and patients were identified . TB surveillance programs for DWs and appropriate infection control strategies, including worker education, are needed to monitor and minimize exposure to TB in dental settings providing care to patients at risk for TB. Biopolymers, 1995, 37(2), 105 - 22 Structure-activity studies on magainins and other host defense peptides; Maloy WL et al.; Host defense peptides are widely distributed in nature, being found in species from bacteria to humans . The structures of these peptides from insects, horseshoe crabs, frogs, and mammals are known to have the common features of a net cationic charge due to the presence of multiple Arg and Lys residues and in most cases the ability to form amphipathic structures . These properties are important for the mechanism of action that is thought to be a nonreceptor-mediated interaction with the anionic phospholipids of the target cell followed by incorporation into the membrane and disruption of the membrane structure . Host defense peptides have been shown to have broad spectrum antimicrobial activity, able to kill most strains of bacteria as well as some fungi, protozoa, and in addition, many types of tumor cells . Specificity for pathogenic cells over host cells is thought to be due to the composition of the cell membranes, with an increased proportion of anionic phospholipids making the pathogen more susceptible and the presence of cholesterol making the host membranes more resistant . Structure-activity relationship studies have been performed on insect cecropins and apidaecins, horseshoe crab tachyplesins and polyphemusins, and the frog magainins, CPFs (caerulein precursor fragments) and PGLa . In general, changes that increased the basicity and stabilized the amphipathic structure have increased the antimicrobial activity; however, as the peptides become more hydrophobic the degree of specificity decreases . One magainin-2 analogue, MSI-78, has been developed by Magainin Pharmaceuticals as a topical antiinfective and is presently in clinical trials for the treatment of infected diabetic foot ulcers. Enferm Infecc Microbiol Clin, 1995 Jan, 13(1), 23 - 32 {Comparative study of the prevalence of hospital infections at a Valencia county hospital}; Morales Suarez-Varela MM et al.; BACKGROUND: Nosocomial infections presently imply a 10-day average prolongation of hospital stay per infection, with an important increase in mortality and costs . A comparison is made between the prevalence of nosocomial infections, microorganisms isolated and antimicrobial agents used in the Arnau de Vilanova Hospital (Valencia, Spain), and those corresponding to other hospitals of similar characteristics in the triple-province Valencia Community . METHODS: Cross-sectional epidemiological study, reflecting the prevalence of hospital infections globally and in each of services . RESULTS: The global prevalence of hospital infections was 6.08% . Services with greatest prevalence are Intensive Care, Internal Medicine and Surgery . Respiratory tract and postoperative wound infections were the most frequent presentations . CONCLUSIONS: Global prevalence was slightly less than in the Valencian Community for 1992 (8.28%), with a predominance of gram-negative over gram-positive germs, in contrast with the results reported globally for the Valencia an hospitals. J Periodontol, 1995 Jan, 66(1), 69 - 74 Antimicrobial susceptibility of periodontopathic bacteria associated with failing implants; Sbordone L et al.; The aim of this study was to examine the subgingival microflora associated with failing implants, and to determine their susceptibility to commonly used antibiotics in periodontal therapy and dental practice . Thirteen partially edentulous patients with 19 failing implants were selected . Clinical examination included probing depth, attachment level, gingival index, plaque index, and radiographic analyses . Two subgingival plaque samples were taken from each failing implant and analyzed for microbial composition . Fusobacterium nucleatum, Porphyromonas gingivalis, and Prevotella intermedia were the prevalent cultivable microflora . Antimicrobial susceptibility of isolates was determined by the agar dilution technique . Antibacterial activity of penicillin G, amoxicillin, amoxicillin-clavulanate, and the combination amoxicillin-metronidazole was significantly higher than with other antibiotics tested . These data indicated that the commonly-used antibiotics were highly effective against bacteria isolated around failing implants, which would suggest the use of these antibiotics to control peri-implant infections. J Periodontol, 1995 Jan, 66(1), 47 - 51 The effect of a single application of subgingival antimicrobial or mechanical therapy on the clinical parameters of juvenile periodontitis; Unsal E et al.; Twenty-six (26) patients, 18 female and 7 male, aged 16 to 25 years (mean age 19.03 +/- 2.2 years) previously diagnosed as suffering from localized juvenile periodontitis were randomly assigned to one of the following treatment groups: 9 patients acted as controls; 8 received subgingival chlorexidine gel; and 9 had subgingival tetracycline paste application . All treatment modalities resulted in a pronounced improvement in PI, GI, and GI-S by 12 weeks (P < 0.001) . The mean probing depths also decreased, but there were no significant differences found between the three groups . However, when the interproximal sites of the 3 groups were examined separately from the buccal and lingual sites, it was found that there was a significant (P < 0.05) difference between the probing depths, with the control group showing the greatest reduction of 2.58 mm and the chlorhexidine group showing the least reduction of 1.37 mm . It was concluded that a single application of topical subgingival tetracycline did not result in any short-term improvement over that achieved by standard non-surgical therapy in the clinical parameters of these localized juvenile periodontitis patients. Klin Padiatr, 1995 Jan-Feb, 207(1), 19 - 23 {Neurological complications in infectious endocarditis}; Groll A et al.; Despite considerable progress in both diagnostic studies and therapeutic management serious complications of infectious endocarditis have become rather more common . Next to intracardiac complications arterial embolization to the central nervous system is the second most common life-threatening event, which might lead to infarction, hemorrhage, mycotic aneurysm and/or metastatic infection with a wide spectrum of neurological symptoms and an overall very poor prognosis . The most effective prevention of neurological complications is the early diagnosis of infectious endocarditis with isolation of the infecting agent and adequate antimicrobial chemotherapy in combination with well-timed cardiosurgical measures . Computed tomography and cerebral angiography is mandatory in any patient with neurological symptoms to check the need for a neurosurgical intervention as well as in patients assigned for anticoagulation for cardiac reasons. J Appl Bacteriol, 1995 Jan, 78(1), 39 - 46 The antimicrobial activity of hexapeptides derived from synthetic combinatorial libraries; Blondelle SE et al.; A series of peptides identified through the use of synthetic hexapeptide combinatorial libraries (represented by the formula Ac-RRWWCO-NH2) were examined for their antimicrobial activity against five different micro-organisms . Their toxicity was also evaluated in an in vitro haemolytic assay . The peptides showed activity against the five micro-organisms, although higher activities were found against Gram-positive bacteria . Both growth inhibition and cell viability assays were carried out to demonstrate the bactericidal activities of these peptides against two of the micro-organisms tested . The dimeric cystine forms of these peptides were shown to have biological activities identical to the monomeric forms. Bull Group Int Rech Sci Stomatol Odontol, 1995 Jan-Feb, 38(1-2), 45 - 50 Comparative study of heat release of various cement base materials during their setting; Panagiotouni E et al.; An ideal cement base material in order to protect the pulpal tissue from several external irritations (microbial, mechanical, thermal, galvanic and osmotic irritations) must present the following requirements: to attach or bond to the residual dentin, to be biocompatible, to present suitable physicomechanical, antimicrobial and optical properties, to be color stable, easy to use and rapid to set . Thermal phenomena developed during the mixing and setting are a factor influencing the biocompatibility properties of these materials . Cement base materials are used under various types of filling materials (amalgams, composite resins, gold and porcelain inlays) and are placed in contact with the dentin that contains exposed dentinal tubules . The purpose of this study was to investigate the possible exothermic reaction of these materials and to measure the developing temperatures for a time period from their mixing up to the completion of their setting . We studied the following types of cement base materials: a) Zinc oxide eugenol cement, b) Zinc phosphate cement, c) Zinc polycarboxylate cement and d) Glass ionomer cement both light- and self-cured . From the obtained results we observed that ZOE cements developed the lowest temperatures ranging from 32.8 degrees C to 37 degrees C, while Zinc phosphate cements developed the highest temperatures ranging from 44.4 degrees C to 52 degrees C . The other two types of materials Zinc polycarboxylate and Glass ionomer cements developed biocompatible temperatures ranging from 38 degrees C to 40.8 degrees C, which usually do not cause deteriorations and harms to the pulp . We concluded that the ZOE cements presented the best thermal behaviour followed by Zinc polycarboxylate and Glass ionomer cements . Hence, these materials can be safely used without causing any pulpal response. Aust Fam Physician, 1995 Jan, 24(1), 49 - 53, 56 Antibiotics for common respiratory infections; Christiansen K; One of the most common reasons for prescribing antibiotics is an infection in the respiratory tract . There are a large number of antimicrobial agents available, some of long standing and others relatively new to the market . The rationale for the choice of agent, including emerging resistances, spectrum of activity, antibiotic pharmacokinetics, adverse reactions and cost, is discussed for the various sites of infection. Ann Hematol, 1995 Jan, 70(1), 59 - 60 Microangiopathic hemolytic anemia and severe thrombocytopenia in Brucella infection; Di Mario A et al.; A case of Brucella septicemia presenting at the onset as a severe microangiopathic hemolytic anemia with coexisting dramatic hemorrhagic syndrome (severe epistaxis, gross hematuria, and skin purpura) is reported . A hemogram showed severe thrombocytopenia, anemia, and leukopenia . Bone marrow morphology showed the typical features associated with Brucella infection: numerous histiocytes with signs of activation, multiple granulomata, giant cells, and hemophagocytosis . After appropriate antimicrobial therapy, the clinical and hematological status of the patient improved, and he is alive and well 1 year later with disappearance of all hematological abnormalities. J Allergy Clin Immunol, 1995 Jan, 95(1 Pt 1), 52 - 9 Extrathoracic and intrathoracic airway responsiveness in sinusitis; Bucca C et al.; BACKGROUND: Asthma associated with sinusitis is supposed to be sustained by bronchoconstrictive reflexes originating in extrathoracic airway (EA) receptors . OBJECTIVE: The study was designed to evaluate the relationship between EA responsiveness and bronchial responsiveness in sinusitis . METHODS: We performed histamine inhalation challenge in 106 patients with chronic sinusitis, during disease exacerbation and after treatment with antimicrobials and nasal flunisolide (100 micrograms daily) for 2 weeks . Forced expiratory volume in 1 second (FEV1) and maximal mid-inspiratory flow (MIF50) were the respective indexes of bronchial and EA narrowing; the histamine concentrations causing a 20% fall in FEV1 (PC20) and 25% drop in MIF50 (PC25MIF50) were used as thresholds of bronchial and EA responsiveness . Thresholds of 8 mg/ml or less were assumed to indicate bronchial hyperresponsiveness (B-HR) or EA hyperresponsiveness (EA-HR) . RESULTS: During sinusitis exacerbation 76 patients had EA-HR, which in 46 was associated with B-HR . The values of PC20 were closely related with those of PC25MIF50 (p < 0.001) . EA-HR and B-HR were strongly associated with pharyngitis . After treatment, mean PC25MIF50 and PC20 were significantly increased (p < 0.001) . The improvement of PC25MIF50 was closely related to that of PC20 (p < 0.001) and to the decrease in neutrophils in nasal lavage (p < 0.05) . EA-HR reversed in 58 patients and improved in 10; B-HR reversed in 29 and improved in 12 . CONCLUSIONS: Our findings suggest that in sinusitis, B-HR may be sustained by constrictive reflexes originating in pharyngeal receptors, made hypersensitive by seeding of the inflammatory process. Med Clin North Am, 1995 Jan, 79(1), 53 - 77 Infectious emergencies in patients with diabetes mellitus; Smitherman KO et al.; Although it remains controversial as to whether diabetics have an overall increased incidence of infection as compared to nondiabetics, several potentially life-threatening infections do appear to be uniquely associated with diabetes . These infections generally occur in older diabetics with less than optimal glucose control . For each entity, selected symptoms and signs may suggest the diagnosis but confirmation of via tissue biopsy with culture and histopathology or radiography is usually necessary . Management typically require both antimicrobial treatment and surgery. Cancer Chemother Pharmacol, 1995, 35(3), 188 - 90 Vinblastine and erythromycin: an unrecognized serious drug interaction; Tobe SW et al.; Vinblastine and erythromycin are among the most commonly used chemotherapeutic and antimicrobial agents, respectively . No interaction between the two has ever been reported . Towards the end of a phase I study of vinblastine plus oral cyclosporin (to reverse multidrug resistance), three patients also received erythromycin to raise their cyclosporin levels . All developed severe toxicity consistent with a much higher vinblastine dose than was actually given . This apparent potentiation of vinblastine toxicity has not been previously described. Drugs Exp Clin Res, 1995, 21(1), 17 - 22 Imipenem and immune response: in vitro and in vivo studies; Pasqui AL et al.; Imipenem is a new beta-lactam antibiotic endowed with very high antimicrobial activity; it is used in severe infections which often occur in those conditions characterized by impairment of the immune system . The aim of this study was to evaluate the effect of imipenem on some immune functions, both in vitro and in vivo . The authors studied the effect in vitro of three different drug concentrations (15, 30 and 60 mg/l) on polymorphonuclear leucocyte (PMN) phagocytosis and superoxide anion production, as well as on lymphomonocyte proliferative response and cytokine production . Preincubation of PMN with the highest dosages (30 and 60 mg/l) was found to increase phagocytosis evaluated via both cytofluorimeter and chemiluminescence, while no effect was detected on superoxide anion production or on lymphomonocyte tests . In the in vivo study, the authors administered imipenem/cilastatin (1500 mg/day) to 15 elderly and diabetic patients, in whom both PMN functions (phagocytosis and superoxide anion production) and lymphocyte tests (CD3, CD4, CD8, CD19, IL2 and sIL2R serum levels) were studied before and on the 3rd and 7th days of treatment . The drug assimilation did not modify the lymphocyte parameters, whereas it increased PMN superoxide anion production and phagocytosis which were depressed in basal conditions . In the former case, such increase was slight and insignificant, whereas in the latter it was significant. Scand J Infect Dis, 1995, 27(1), 39 - 43 Endotoxin, interleukin-6 and phospholipase-A2 as markers of sepsis in patients with hematological malignancies; Rintala E et al.; The concentrations of endotoxin, interleukin-6 (IL-6) and group II phospholipase-A2 (PLA2-II) were measured in serum or plasma during cytotoxic chemotherapy, fever of unknown origin and sepsis in 56 patients with hematological malignancies and during sepsis and viral infections in 22 non-hematological patients . High concentrations of IL-6, PLA2-II and endotoxin were detected in sepsis, the levels being similarly elevated in hematological and non-hematological patients . The levels of IL-6 and PLA2-II correlated closely with that of C-reactive protein (CRP) . The levels of PLA2-II and IL-6 declined earlier than the level of CRP during the course of antimicrobial treatment . The levels of IL-6 also rose earlier than the level of CRP . The ability of IL-6 and PLA2-II and endotoxin to discriminate between sepsis and other causes of fever was comparable to that of CRP . IL-6 and PLA2-II are, together with CRP, valuable tools for the detection of sepsis in patients with hematological malignancies who undergo cytotoxic medication . Endotoxin is not suitable for routine laboratory diagnosis of sepsis. Scand J Infect Dis, 1995, 27(1), 23 - 7 Human nocardiosis in northern Italy from 1982 to 1992 . Northern Italy Collaborative Group on Nocardiosis; Farina C et al.; We conducted a retrospective survey of nocardiosis in 9 city hospitals in northern Italy from 1982 to 1992 . The medical records of 30 patients with documented nocardiosis were reviewed . Microbiological data included morphology, biochemical characteristics, serology and in vitro susceptibility testing . The 29 isolates (1 case was diagnosed on the basis of serological results) were Nocardia asteroides (n = 25) and Nocardia farcinica (n = 4) . Predisposing factors including immunosuppression for organ transplant rejection prophylaxis, lung disease (silicotuberculosis and pulmonary fibrosis), solid tumours and hematological malignancies, and AIDS . Three patients had no identified risk factors . 20 cases of pulmonary nocardiosis were observed . Sites of infection in patients without previous pulmonary involvement were: brain abscesses, soft tissues, pericardium, blood, and cerebrospinal fluid . Most strains tested were susceptible to amikacin and imipenem . Resistance to several antimicrobial agents was found, particularly erythromycin, fosfomycin, pefloxacin, sulphonamides and trimethoprim . Antimicrobial chemotherapy included sulphonamides, amikacin, ceftriaxone, imipenem and minocycline . 21 patients survived, although 2 relapsed transiently . Nocardiosis appears to be more common than generally realised by physicians in northern Italy . The local species distribution and disease spectrum are similar to those described elsewhere . Nocardiosis should be part of the differential diagnosis in patients with pulmonary infiltrates or brain abscess, particularly those with predisposing factors. Virchows Arch, 1995, 426(3), 301 - 5 Reaction of human lungs to aspirated animal fat (ghee): a clinicopathological study; Annobil SH et al.; We report the clinical findings and pathological lung changes in four children following a cultural practice of forced feeding with animal fat (ghee) during infancy . The clinical presentation was of acute or chronic chest infection which failed to respond to antimicrobial therapy . The radiographic features ranged from extensive bronchopneumonia to collapse/consolidation and bronchiectasis . The light microscopy findings included diffuse mononuclear interstitial pneumonia, intraalveolar desquamation of pneumocytes, lipid granuloma formation, lung atelectasis and bronchiectasis . In the two children with longstanding reactions, the striking feature was the minimal lipid engulfment by the macrophages, the continuation of the mononuclear interstitial pneumonia, bronchiectasis and minimal lung fibrosis . In these two older children, the lung lymphatics were probably the main channels for drainage of the aspirated ghee. J Biomater Sci Polym Ed, 1995, 6(9), 833 - 44 Degradation behaviour of ionic stepwise polyaddition polymers of medical interest; Ferruti P et al.; The aim of this presentation is to review some of our recent work mostly on poly(amidoamine)s (PAAs) and some other families of polymers structurally related to PAAs of medical interest . PAAs are obtained by stepwise polyaddition of primary monoamines, or bis secondary amines, to bisacrylamides . There are several other ter-amino polymers structurally related to PAAs, such poly(amido phosphine)s (PAPs), poly(ester-amine)s (PEAs), poly(ketone-amine)s (PKAs), poly(amidothioeteramine)s (PATAs) poly(esterthioether amine)s (PTEAs), and poly(sulphone thioetheramine)s (PSTAs) . Most of the PAAs exhibit heparin complexing ability . PAAs are also being considered as soluble carriers for delivering anti-cancer drugs . Some of these polymers have been studied as antimicrobial agents . PAAs with different structures degrade at different rates under physiological conditions . The degradation rate is also strongly influenced by pH . The quaternarized PATAs and PTEAs are reasonably stable over a period of some days, but ultimately degrade to oligomeric products, while the quaternized PAAs do rapidly degrade. J Antimicrob Chemother, 1995 Jan, 35(1), 31 - 52 Assessment of therapeutic potential by means of a probability model of antimicrobial action; Schalkowsky S et al.; The probability model of antimicrobial action is based on the definition of bactericidal activity as the probability, q, that any cell in the population will be killed during a division interval . Bacteriostatic activity is defined as a change in the division intervals (generation times) of the cells . A simplified, homogeneous model is used which assumes that, at a constant concentration of the drug, all cells have the same kill probability and the same generation times . Birth-death analysis techniques require that the combined bacteriostatic and bactericidal effects of the drug (they are not mutually exclusive) are accounted for . Moreover, to suitably reflect the combined effect, the rate of change of the viable population, i.e . the slope of a kill curve (activity), needs to be expressed not in terms of exposure time, but in units of drug-free generations (DFGs), obtained by dividing exposure time by a measured DFG time interval (growth rate) . A Discrete MIC (DMIC) is defined as the zero slope kill curve, coinciding with the horizontal axis and dividing population change into a restrained (subinhibitory) growth region, below the DMIC, and population reduction above it . At the DMIC, the probability of a cell being killed is 0.5, resulting in no change from the initial inoculum concentration, since half the cells are killed but the remaining cells double . The DMIC is found to be a measure of bactericidal activity only, even though bacteriostatic activity may also be present . An antibiotic-organism activity profile includes measurement of the DMIC, rate of change of activity at the DMIC and normalized activity at a number of clinically relevant drug concentrations . An overall, quantitative efficacy value over a dosing interval can be obtained from the activity profile and expressed as the number of DFGs which are needed to achieve a 99.9% reduction of the viable population at the site of infection . These reference efficacy values can be used to derive interpretive standards (break-points) based upon a quantitative relationship between laboratory measurements and population reduction at the site of infection . Model-derived measures of efficacy also provide a basis for assessing drug combination activity, including quantitative criteria of synergy and antagonism. J Antimicrob Chemother, 1995 Jan, 35(1), 149 - 54 Heat stability of the antimicrobial activity of sixty-two antibacterial agents; Traub WH et al.; Sixty-two antimicrobial agents, including several combinations, were examined for stability at 56 degrees C for 30 min and 121 degrees C for 15 min, respectively . A microtiter broth dilution MIC test and an agar disk diffusion test served to test each chemo-agent for residual antimicrobial activity . Eleven drugs were partially heat-labile (MICs raised four- to eight-fold after autoclaving) and 26 drugs were heat-labile (MICs raised > or = 16-fold following autoclaving); the remainder proved heat-stable (MICs raised < or = two-fold after autoclaving) . Surprisingly, the beta-lactams, azlocillin, aztreonam, mezlocillin, and oxacillin, were remarkably heat-stable. J Ind Microbiol, 1995 Jan, 14(1), 41 - 5 Fungal colonization of air filters for use in heating, ventilating, and air conditioning (HVAC) systems; Simmons RB et al.; New and used cellulosic air filters for HVAC systems including those treated with antimicrobials were suspended in vessels with a range of relative humidities (55-99%) and containing non-sterile potting soil which stimulates fungal growth . Most filters yielded fungi prior to suspension in the chambers but only two of 14 nontreated filters demonstrated fungal colonization following use in HVAC systems . Filters treated with antimicrobials, particularly a phosphated amine complex, demonstrated markedly less fungal colonization than nontreated filters . In comparison with nontreated cellulosic filters, fungal colonization of antimicrobial-treated cellulosic filters was selective and delayed. Lett Appl Microbiol, 1995 Jan, 20(1), 14 - 8 Antifungal effects of Allium sativum (garlic) extract against the Aspergillus species involved in otomycosis; Pai ST et al.; Otomycosis due to saprophytic keratolytic fungi represents a small percentage of clinical external otitis . Although there are certain antibacterial and antifungal agents available, they usually are very caustic, potentially ototoxic and cannot be used if the ear drum is perforated . Garlic is utilized as a folk medicine in many countries for its antimicrobial and other beneficial properties . In response to a lack of otic preparations, the authors studied the efficacy of garlic extracts against the fungi belonging to the genus Aspergillus which are the most common cause of this infection . Aqueous garlic extract (AGE) and concentrated garlic oil (CGO) along with various commercial garlic supplements and pharmaceutical prescriptions were used in an in-vitro study . AGE and especially CGO were found to have antifungal activity . These agents showed similar or better inhibitory effects than the pharmaceutical preparations and demonstrated similar minimum inhibitory concentrations. Ann Pharm Fr, 1995, 53(2), 86 - 9 {Limiting tests of benzyle halides or heavy alkyles in tensioactive and antimicrobial quaternary ammonium salts}; Willemot J; As working material at the final stage of the synthesis of tensioactive and antimicrobial quaternary ammoniums salts, the alcoyles halides residuums have been let aside . The author developed limiting tests about these impurities particularly on the benzododecinium bromide . Four alternative methods are thus proposed. Am J Surg Pathol, 1995, 19 Suppl 1, S37 - 43 Helicobacter pylori and gastric carcinogenesis; Correa P; Recent epidemiologic evidence indicates that Helicobacter pylori infection increases the risk for gastric carcinoma . Infection with H . pylori leads to chronic gastritis, which usually persists for life unless treated with antimicrobial drugs . Because the great majority of gastritis patients never develop neoplasias, research concerning those who do may provide clues about carcinogenesis . In affluent populations, H . pylori infection leads to nonatrophic gastritis, predominantly involving diffusely the antrum (diffuse antral gastritis), the basic lesion seen in patients with duodenal ulcer, which has not been associated with increased risk for gastric carcinomas . In populations with high gastric cancer risk, H . pylori infection is associated with multifocal atrophic gastritis, which frequently advances to intestinal metaplasia, occasionally to dysplasia, and rarely to carcinoma . H . pylori infection increases the rate of proliferation of the gastric epithelial cells and decreases the gastric secretion of ascorbic acid, processes that may modulate the process of carcinogenesis . Infection with H . pylori is characterized by infiltration of lymphocytes, polymorphonuclear leukocytes, and macrophages in the gastric mucosa . There is considerable interest in investigating oxygen radicals originating in white blood cells and the possibility that they induce mutations with carcinogenic potential in the gastric epithelium. Pharmacotherapy, 1995 Jan-Feb, 15(1 Pt 2), 9S - 14S Bacterial resistance mechanisms to beta-lactam antibiotics: assessment of management strategies; Dudley M; Several mechanisms render antimicrobials inactive; one of these, beta-lactamase hydrolysis of beta-lactam antimicrobials, is a common and serious problem resulting in loss of antimicrobial activity . Resistance in gram-negative organisms may be caused by chromosomally or plasmid-mediated beta-lactamases . Chromosomally mediated resistance may result from exposure to inducer compounds (induction) or by selection of stably derepressed mutants . Plasmids are extrachromosomal elements of DNA that can transfer resistance between bacteria . Common plasmid-encoded beta-lactamases are the TEM- and SHV-type enzymes, which include the newer extended-spectrum beta-lactamases . Infections caused by resistant bacteria frequently result in longer hospital stays, higher mortality, and increased cost of treatment . When bacteria develop resistance during antimicrobial therapy, therapeutic failure ensues in approximately 50% of patients . Clinical studies demonstrate that resistance mediated by beta-lactamases is a critical issue . Strategies for overcoming it include use of beta-lactam-beta-lactamase inhibitor combinations, development of new antimicrobial compounds, and use of regimens that optimize in vivo exposure to drug. Pharmacotherapy, 1995 Jan-Feb, 15(1 Pt 2), 22S - 26S Rationale and experience in treating suspected hospital-based mixed infections; Billeter M; Ochsner Foundation Hospital of the Ochsner Medical Institutions (OMI), a 532-bed tertiary care facility in New Orleans, uses a formulary review process common to many institutions . Considered in the selection of antimicrobial therapy are efficacy, safety, and cost . At OMI, ticarcillin-clavulanate plus gentamicin are the standard broad-spectrum antimicrobial agents for initial treatment of suspected mixed infections . The pharmacy department provides an aminoglycoside-monitoring program and convenient dosing guidelines . The regimen has resulted in good therapeutic outcomes and few adverse effects . Bacterial resistance has not been detected . Future plans include a large-scale concurrent review of patient outcomes, resistance patterns, and rates of fungal overgrowth associated with these agents. Minerva Med, 1995 Jan-Feb, 86(1-2), 21 - 32 {Antimicrobial and sporicidal efficacy of various disinfectant solutions}; Gismondo MR et al.; The often indiscriminate use of antimicrobial agents has led to increased bacterial resistance over the past years . This phenomenon is above all evident in nosocomial environments but also at a community level . It is therefore important that, in addition to the rational use of antibiotics, an accurate prophylaxis is performed which includes the correct use of disinfectants . This study examines the antimicrobial activity of various commercially available disinfectant solutions consisting of one or more active ingredients . An analysis of the results reveals that products consisting of an association of individual components (quaternary ammonium chloride with o-phenylphenol and/or isopropyl alcohol; chlorhexidine with benzalkonium chloride or with diazolidinylurea and isopropanol) demonstrate a greater efficacy in terms of microbicidal concentration and contact times. Kansenshogaku Zasshi, 1995 Jan, 69(1), 45 - 53 {Long-term monitoring of female acute uncomplicated cystitis cases after lomefloxacin single-dose therapy}; Hirose T et al.; Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy, but this is also a disease which shows a high frequency of recurrence . However, there have been no published reports regarding long-term monitoring of the course of this disease after therapy has been administered . Accordingly, using primarily a questionnaire, the authors carried out long-term monitoring (for a mean of 242 days) of the natural course of cases of female acute uncomplicated cystitis after single-dose therapy with lomefloxacin (LFLX), a new quinolone antimicrobial agent . The subjects of this study were female patients diagnosed as having acute uncomplicated cystitis with pain upon urination, pyuria (> or = 10 WBCs/hpf) and bacteriuria (> or = 10(4) cfu/ml) . LFLX was orally administered as a single dose of 100 mg or 300 mg, and the therapeutic efficacy was evaluated on the 3rd and 7th days thereafter . In principle, the evaluation of cure was performed on the 7th day after LFLX administration, and monitoring was conducted to detect early recurrence during the next 7 days (i.e., through the 14th day after treatment) . Then the subjects were monitored for late recurrence during a mean follow-up period of 242 days by means of a questionnaire . Confirmation of recurrence was carried out to the greatest extent possible . It was possible to carry out long-term monitoring of the natural course of 101 cases of female acute uncomplicated cystitis in which the clinical efficacy on the 3rd day after LFLX treatment had been evaluated as good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS) Kansenshogaku Zasshi, 1995 Jan, 69(1), 1 - 6 {Epidemiological study for comparative biological profiles on MRSA strains isolated in 1992 vs . 1993}; Ishikawa K et al.; The trend of epidemiological study against MRSA strains which were isolated in 1992 and in 1993 was investigated . Number of stains tested yearly consisted of 30 isolates that were considered to play pathogenic roles for inpatients in clinical departments at our institute . In comparing with biological studies on MRSA strains and the epidemiological surveillance of the background of the isolation, the data summarizes as followings; 1) No . of MRSA strains which were producible for TSST increased from 24/30, 80% up to 30/30, 100% . 2) No . of enterotoxin type harbouring biotype of B/C increased 0/30, 0% up to 12/30, 40% . 3) No . of type of plasmid DNA profile increased in varying from 3 types (A, B, C) to 8 types (A-H) . 4) The in vitro activity of antimicrobials, as such MINO, GM, IPM, CMZ was less potent than that of the prior year, and even for VCM, ABK, the activity proved less potent in 1-2 tubes in MIC90 . 5) No . significant hospital acquired infection was detected between the inpatients, with MRSA infection and isolates from plasmid DNA profiles . 6) Since the ratio of the coincidence of plasmid DNA profiles of MRSA was only in 4 patients out of 27, 14.9 &, nosocomial infections with MRSA brought to patients have not only been considered by medical, paramedical staff, but that the infection may be caused by broad contamination at the institute. J Ethnopharmacol, 1995 Jan, 45(1), 71 - 4 Comparative antimicrobial study of the resinous exudates of some Chilean Haplopappus (Asteraceae); Urzua A et al.; The antimicrobiol properties and preliminary chemical information of the resinous exudates from twigs and leaves of nine Haplopappus species from Chile: H . diplopappus; H . anthylloides; H . schumannii; H . cuneifolius; H . velutinus; H . uncinatus; H . multifolius, H . illinitus and H . foliosus are presented . The results show that those species of genus Haplopappus share similar antimicrobial activities although they differ dramatically in the chemical composition. Am J Nephrol, 1995, 15(2), 152 - 6 Penectomy in diabetic patients undergoing maintenance dialysis; Bali I et al.; Penectomy was performed to sustain life in 2 patients with insulin-dependent and non-insulin-dependent diabetes mellitus, respectively, who were undergoing maintenance hemodialysis . Both patients previously had manifested a series of serious macro- and microvascular diabetic complications . The histopathologic findings in both cases included gangrenous necrosis of penile tissue, while case 2 also evinced calcification of penile arteries . Penectomy has been reported as the result of penile malignancy, anticoagulant toxicity, self-inflicted injury, and criminal assault . Other reports document penectomies attributed to perineal infection (Fournier's syndrome) in diabetic patients with uremia . In five previously reported cases of penectomy in diabetic patients undergoing dialysis, systemwide arteriopathy was present in all . There is an association between uremia in diabetics and predisposition to an ischemic-infectious lesion of the penis that fails to respond to antimicrobial therapy. Urol Nefrol (Mosk), 1995 Jan-Feb, (1), 16 - 8 {The phagocytic test in the assessment of antimicrobial protection in inflammatory urologic diseases}; Kuznetsov VF et al.; As shown in in vitro original modelling of red cell action on phagocytic process in the whole blood of patients with urological inflammation, these patients have increased count of neutrophils involved in phagocytosis, but low specific absorption of these neutrophils due to red cells . In chronic renal insufficiency characterized by a l