Infect Immun, 1992 May, 60(5), 2133 - 5 A specific sequence of stimulation is required to induce synthesis of the antimicrobial molecule nitric oxide by mouse macrophages; Lorsbach RB et al.; Nitric oxide production by macrophages required either simultaneous or sequential exposure to gamma interferon and lipopolysaccharide; exposure to lipopolysaccharide followed by exposure to gamma interferon gave little response . The apparently evanescent nature of the lipopolysaccharide signal, necessitating persistent stimulation, could be essential to down-regulating nitric oxide production after bacteria are cleared in vivo. Dig Dis Sci, 1992 May, 37(5), 689 - 96 Defense system in the biliary tract against bacterial infection; Sung JY et al.; Bacteria can invade the biliary tract by ascending from the duodenum and via the hematogenous route from the hepatic portal venous blood . The sphincter of Oddi, situated at the junction of the biliary tract and the upper gastrointestinal tract, forms an effective mechanical barrier to duodenal reflex and ascending bacterial infection . Conversely, Kupffer cells and the tight junctions between hepatocytes help prevent bacteria and toxic metabolites from entering the hepatobiliary system from the portal circulation . The continuous flushing action of bile and the bacteriostatic effects of bile salts keeps the biliary tract sterile under normal conditions . Secretory immunoglobulin A (sIgA), the predominant immunoglobulin in the bile, and mucus excreted by the biliary epithelium probably function as antiadherence factors, preventing microbial colonization . When barrier mechanisms break down, as in surgical or endoscopic sphincterotomy and with insertion of biliary stents, pathogenic bacteria enter the biliary system at high concentrations and take up residence on any foreign bodies . Intrabiliary pressure is a key factor in the development of cholangitis . Chronic biliary obstruction raises the intrabiliary pressure . This adversely influences the defensive mechanisms such as the tight junctions, Kupffer cell functions, bile flow, and sIgA production in the system, resulting in a higher incidence of septicemia and endotoxemia in these patients . Knowledge of biliary defense against infection is still quite primitive . Unclear are the roles of sIgA in the bile, mechanism of bacterial adhesion to the biliary epithelium, Kupffer cell function in biliary obstruction, and the antimicrobial activity of bile salts. Calcif Tissue Int, 1992 May, 50(5), 411 - 9 Tetracycline administration increases collagen synthesis in osteoblasts of streptozotocin-induced diabetic rats: a quantitative autoradiographic study; Sasaki T et al.; Streptozotocin-induced, insulin-deficient diabetic rats were administrated either minocycline (MC) or a chemically modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week period; untreated diabetic and nondiabetic rats served as controls . On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection . The parietal bones of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by osteoblasts . At 20 minutes after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of the osteoblasts in the periosteal surface of the control rats . At the 4-hour time period, most of the label was present over the collagen fibers of the osteoid . In contrast, the flattened bone-lining cells in the untreated diabetic rats showed minimal uptake (20 minutes) and secretion (4 hours) of labeled proline . In both MC and CMT-treated diabetic rats, the radioprecursor was localized in the osteoblasts and osteoid matrix in a pattern similar to that seen in the control rats at both 20 minutes and 4 hours after isotope injection . Labeling of the osteoid by the radioprecursor was greater as a result of CMT treatment than during minocycline treatment . These results suggest that the diabetes-induced suppression of synthesis and secretion of protein (presumably collagen and its precursor) by osteoblasts can be restored to near-normal levels by administration of tetracycline(s) and that this effect is mediated by a non-antimicrobial property of these antibiotics. J Prosthet Dent, 1992 May, 67(5), 628 - 31 Sodium hypochlorite disinfection of irreversible hydrocolloid impression material; Rueggeberg FA et al.; Alginate impression material is one of the most frequently used in dentistry . However, this material is susceptible to dimensional distortion during disinfection because of its hydrophilic nature . This study examined the effects of alginate disinfection using a sodium hypochlorite spray or impression immersion . Spray disinfection of an alginate impression did not cause dimensional differences of the poured stone casts when compared with casts from water-rinsed controls . Immersion disinfection created dimensional distortion of the anterior, posterior, and interarch model segments . Both the spray and immersion treatments equally decreased the surface detail reproducibility . The antimicrobial effects of the spray treatment were similar to those of the immersion treatment, while mere water rinsing resulted in inadequate disinfection. J Nat Prod, 1992 May, 55(5), 620 - 5 Antimicrobial agents from Licaria puchuri-major and their synergistic effect with polygodial; Himejima M et al.; The resistance of the seeds of Licaria puchuri-major (Lauraceae) to decomposition in nature seems to be due largely to chemical defense, since its n-hexane extract contains antimicrobial principles in quantity, with a broad antimicrobial spectrum . In order to identify the active principles, the n-hexane extract was steam-distilled to yield a distillate and a residue . Subsequent bioassay indicated that the distillate retained the original broad antimicrobial activity, while the residue exhibited almost no activity . Gc-ms analysis showed that the distillate contained four phenolic compounds, seven monoterpenes, and one sesquiterpene . In contrast, the residue contained, almost exclusively, lauric acid . In the detailed antimicrobial assay with the pure compounds identified, most of them showed broad, but moderate, antimicrobial activity . Some of the components identified in the distillate were combined with polygodial {1} in order to enhance their antifungal activity . Unexpectedly, while polygodial did not synergize the antifungal activity of any of the compounds tested, the antifungal activity of polygodial was significantly increased when combined with aromatic substances such as anethole, safrole, or methyleugenol. J Clin Periodontol, 1992 May, 19(5), 322 - 5 Effect of 4 days of mouth rinsing with delmopinol or chlorhexidine on the vitality of plaque bacteria; Rundegren J et al.; Delmopinol is a new surface active anti-plaque agent that has demonstrated a low antimicrobial effect in vitro . By use of a vitality staining technique, the antimicrobial effect on bacteria in plaque samples was tested after rinsing with delmopinol or chlorhexidine . 6 healthy male subjects volunteered to rinse for 4 days using a double-blind cross-over study design with a wash-out period between the rinsing regimens . No oral hygiene measures were allowed during the test periods and each test period started with a professional tooth cleaning procedure 2 days before the start of rinsing to allow for plaque formation . Rinsing was performed with 0.2% delmopinol hydrochloride or 0.2% chlorhexidine digluconate 2 x a day . Small samples of plaque were collected from the buccal surfaces of premolars and 1st molars before the first rinse on day 1 and then before and 1, 2, 4, 7, and 24 h after the last rinse on the 4th day . The plaque samples were immediately stained with propidium iodide and fluorescein diacetate to visualize dead and vital microorganisms respectively . The vitality of the microflora was evaluated using a fluorescence microscope . The baseline vitality values were 91% for chlorhexidine and 86% for delmopinol . At day 4, the plaque vitality for chlorhexidine was approximately 40% up to 4 h and 50% at 7 h and 60% at 24 h after the last rinse . Corresponding values for plaque vitality after delmopinol rinsing were between 70 and 80% on all sampling occasions.(ABSTRACT TRUNCATED AT 250 WORDS) Jpn J Antibiot, 1992 May, 45(5), 548 - 56 {Laboratory and clinical studies on levofloxacin}; Tanaka K et al.; A newly developed broad-spectrum fluoroquinolone, levofloxacin (LVFX, DR-3355), was evaluated in vitro and in vivo in comparison with ciprofloxacin (CPFX), ofloxacin (OFLX) and norfloxacin (NFLX) . The results were as follows . 1 . Antimicrobial activity Minimal inhibitory concentrations (MICs) against 480 clinical isolates including 16 different species were determined using the microbroth dilution method . LVFX showed excellent antimicrobial activities against Gram-positive and -negative bacteria . The MIC values of LVFX for Gram-positive bacteria were superior to those of the other quinolones tested . The MIC values of LVFX for Gram-negative bacteria were comparable to those of CPFX and superior to those of OFLX and NFLX . 2 . LVFX concentrations in serum and sputum LVFX was orally administered in a single dose of 200 mg to 2 patients with chronic lower respiratory tract infections, and its concentrations in serum and sputum were measured at intervals using bioassay . The peak concentrations of LVFX in serum were 1.52 and 1.24 micrograms/ml, and 84-95% of serum level were detected in sputum . From these data, it appeared that LVFX penetrate well into the lung . 3 . Clinical efficacy and adverse reactions Fifteen patients with respiratory tract infections were treated with LVFX, and the overall efficacy rate was 78.6% (excellent in 3 cases, good in 8, fair in 3, poor in 0) . As adverse reactions, anorexia was observed in 2 cases, diarrhea in 1 case and tremor of finger in 1 case . Although an elevation of total bilirubin in serum was observed in a case as an abnormal laboratory finding, it was mild, transient and improved rapidly after the completion of LVFX treatment. Jpn J Antibiot, 1992 May, 45(5), 478 - 88 {Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms . IV . Synergistic action with dibekacin}; Deguchi K et al.; Antimicrobial activities of cefodizime (CDZM) in combination with dibekacin (DKB) were studied in vitro against clinically isolated Gram-negative rods . The results obtained are summarized as follows . 1 . Similarly to combinations of CDZM+sisomicin (SISO) and CDZM+gentamicin (GM), combined activities of CDZM and DKB were dependent on antimicrobial activities of DKB, and the combined activities were more strongly dependent on DKB concentrations than on CDZM concentrations . The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when DKB concentrations in blood are at or somewhat lower than 1 MIC, and that clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+GM combination . 2 . As we have suggested previously, it seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams. Jpn J Antibiot, 1992 May, 45(5), 468 - 77 {Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms . III . Synergistic action with gentamicin}; Deguchi K et al.; An in vitro investigation was done on antimicrobial activities of cefodizime (CDZM) in combination with gentamicin (GM) against clinically isolated Gram-negative rods . The results are summarized as follows . 1 . Combined antimicrobial activities were dependent on antimicrobial activities of GM, similar to the CDZM + sisomicin (SISO) combination . The combined activities were concentration dependent, and they were more strongly dependent on GM concentrations than on CDZM concentrations . The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when GM concentrations in blood are at or somewhat lower than 1 MIC, and clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+SISO combination . 2 . It seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams. Antimicrob Agents Chemother, 1992 May, 36(5), 1133 - 5 Helicobacter pylori infection in a pediatric population: in vitro susceptibilities to omeprazole and eight antimicrobial agents; Loo VG et al.; The in vitro activities of omeprazole and eight antimicrobial agents against 18 clinical strains of Helicobacter pylori isolated from a pediatric population were determined by an agar dilution method . Ampicillin and erythromycin were the most active agents in vitro . All strains were susceptible to azithromycin, ciprofloxacin, doxycycline, metronidazole, and tinidazole . One isolate demonstrated resistance to cefixime (MIC, greater than or equal to 4 micrograms/ml) . H . pylori was inhibited by the proton pump inhibitor omeprazole. Antimicrob Agents Chemother, 1992 May, 36(5), 1040 - 8 Levels of pyrimethamine in sera and cerebrospinal and ventricular fluids from infants treated for congenital toxoplasmosis . Toxoplasmosis Study Group; McLeod R et al.; Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography . The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis . Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies . This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital . Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital . Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05) . Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday . Levels in CSF were approximately 10 to 25% of concomitant levels in serum . Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml . To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T . gondii in vitro were assessed . The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF . Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera. Nippon Rinsho, 1992 May, 50(5), 1165 - 72 {Post-antibiotic effect and clinical significance}; Kikuchi K et al.; The postantibiotic effect (PAE) is the phenomenon of suppression of bacterial growth after brief antimicrobial exposure to microorganisms . The presence of PAE may be an important consideration in designing antibiotic dosage regimens . Antimicrobials with minimal or lesser PAEs may require serum concentration above MIC or entire dosing interval . Several antimicrobial actions are affected on the PAE phase, eg . "postantibiotic sub-MIC effect" . Moreover, the PAE may contribute to the efficacy on host-parasite relationship . This phenomenon is discussed. Nippon Rinsho, 1992 May, 50(5), 1075 - 80 {MRSA respiratory tract infection}; Shishido H et al.; Sputum isolates of MRSA have been on the increase, recently . Preventive measures against MRSA nosocomial infections have become important in Japanese hospitals . Clinical study was performed on 29 patients from whom MRSA was isolated more than 10(7) cfu/ml using the quantitative sputum culture method . All had a history of admission, therefore nosocomial infections caused by MRSA could very often occur . MRSA was determined as a causative organism in 3 on the basis of symptoms, laboratory data, chest X-rays, and effect of antimicrobial agents . These three patients improved by a single or combined administration of minocycline, arbekacin and/or fosfomycin . In 15 patients, MRSA was frequently isolated, but was thought to be colonized . In 3 patients, MRSA was not isolated without administration of antimicrobial agents thereafter . It was supposed that most of MRSA isolates from sputum were not the causative organism of the respiratory tract infection. Ear Nose Throat J, 1992 May, 71(5), 238 - 42 Otogenic brain abscess: the Syracuse experience; Nalbone VP et al.; A review is presented of five cases of otogenic brain abscesses (from among 34 cases of brain abscesses of all causes) treated during a 16-year period at a major university hospital in upstate New York . Although the morbidity and mortality rates are high for patients with brain abscess, advances in the microbial isolation methods, specificity of antimicrobial agents, and earlier diagnosis by CT scans have all contributed to an improved outcome for this dreaded disease. Pathol Biol (Paris), 1992 May, 40(5), 455 - 60 {Bacteriostatic and bactericidal activities of cyclines, macrolides and fluoroquinolones against Chlamydia trachomatis}; Dailloux M et al.; The in vitro activity of minocycline, doxycycline, erythromycin, roxithromycin, spiramycin, pefloxacin, and ofloxacin against ten C . trachomatis strains recovered from human genital tract specimens was evaluated . Mac Coy cell monolayers in 24-microwell plates were used . The C . trachomatis inoculum was 10(4) IFU/well . Appropriate dilutions of antibiotic were added and inclusions were detected by immunofluorescence using monoclonal antibodies . MICs were determined after 48 hours of exposure to each antimicrobial . The MIC90 for cyclines was 0.2 mg/l . Among tested macrolides, roxithromycin had a lower MIC than erythromycin (0.2 versus 0.4 mg/l) whereas spiramycin inhibited growth only in a concentration of 2 mg/l . Ofloxacin showed better activity than pefloxacin . Bactericidal activity was evaluated by determining two parameters: MBC1 (without transfer to new cells) measured the ability of a C . trachomatis particle to persist in a latent form within cells exposed to an antibiotic and to grow again following removal of the antibiotic, whereas MBC2 (with transfer to new cells) reflected infectivity of the bacteria after 48 hours exposure to the antimicrobial . None of the tested antibiotics was bactericidal according to both parameters . The ability of C . trachomatis to remain within antibiotic-exposed cells in a latent form was clearly demonstrated by the high MBC1 values . This feature may explain why recurrences are common in clinical practice. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1992 May, 25(2), 115 - 23 {Identification and typing of Pseudomonas pickettii during an episode of nosocomial outbreak}; Pan HJ et al.; From January to April 1989, Pseudomonas pickettii was isolated from clinical specimens of 24 hospitalized patients at the National Taiwan University Hospital in Taipei . The source of the organism was the 0.9% NaCl solution prepared by the hospital pharmacy . A total of 39 isolates of P . pickettii were collected, including 28 from clinical specimens and 11 from 0.9% saline and distilled water during the outbreak . These microorganisms were studied by using four methods, namely, conventional biochemical method, Vitek Auto-Microbic System (Vitek AMS), gas-liquid chromatographic analysis of cellular fatty acids composition and determination of the minimum inhibitory concentrations of 10 different antimicrobial agents . By conventional biochemical method, 16 isolates were typed as biovar 1 and 23 strains were biovar 3 . Strains of both biovars were recovered from clinical specimens and 0.9% saline . Vitek AMS was able to identify P . pickettii correctly, but the result of biotyping was not satisfactory . Analysis of cellular fatty acids could rapidly identify P . pickettii to the species level, but could not distinguish the different biovars . By determination of the MICs, the antibiogram could be classified into 9 patterns . Of 16 isolates of P . pickettii biovar 1, 7 (44%) belonged to pattern I, and 9 (56%) pattern II . Strains of both patterns were found in cultures of clinical specimens and 0.9% saline . Of 23 isolates of P . pickettii biovar 3, 11 (48%) belonged to pattern III, 4 (17%) pattern IV and 8 (35%) pattern V to IX . Pattern III and pattern IV were seen in isolates from clinical specimens and 0.9% saline, while pattern V to IX were only seen in isolates from clinical specimens.(ABSTRACT TRUNCATED AT 250 WORDS) Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1992 May, 25(2), 108 - 14 {Modified selective medium for isolation of Helicobacter pylori}; Yang CK et al.; To improve the detection rate of Helicobacter pylori, many kinds of media were tried and other antibiotics were incorporated according to the antimicrobial susceptibility patterns of clinical isolates in our hospital . We found that brain heart infusion agar supplemented with 1% IsoVitaleX and 5% sheep blood, containing nalidixic acid 10 micrograms/ml, vancomycin 6 micrograms/ml, amphotericin B 2 micrograms/ml and polymixin B 16 micrograms/ml (BNVP) or colistin 5 micrograms/ml (BNVC) inhibited the growth of contaminants without significant influence on the growth of H . pylori . However, colonies of primary isolates of H . pylori on BNVP media were larger than those on BNVC media, and easier to detect, Both BNVP and BNVC media yielded the same isolation rate . The organism was isolated from 67 of 91 endoscopic biopsy specimens (73.6%) obtained from the area of peptic ulcers, and from 37 of 125 specimens obtained from the area without lesion . The data were much superior to those in the early day, when the organism was only isolated from 6 of the 27 specimens (22%) obtained from patients with peptic ulcer disease . Because the contaminants and their antimicrobial susceptibility patterns may be varied in different hospitals, it is mandatory to modify selective media suitable for recovering H . pylori. Clin Exp Dermatol, 1992 May, 17(3), 173 - 5 Seborrhoea--an indicator for poor clinical response in acne patients treated with antibiotics; Layton AM et al.; The relationship between sebum excretion rate (SER) and clinical improvement was investigated in 255 acne patients treated for 6 months with either oral erythromycin (1 g/day), minocycline (100 mg/day), oxytetracycline (1 g/day) or cotrimoxazole (400 mg/day); topical therapy was 5% benzoyl peroxide . In all but the cotrimoxazole treated group, there was a significant correlation between a high SER and reduced clinical response . This was particularly evident in those patients with an SER of greater than 2.5 micrograms/cm2/min . These patients showed only 17% improvement compared with 100% improvement in those subjects with an SER of 1.0 micrograms/cm2/min or less . The presence of obvious seborrhoea in a patient who has failed to respond to an adequate 6-month course of antimicrobial therapy, should indicate the earlier rather than later use of isotretinoin for their acne. Ann Acad Med Singapore, 1992 May, 21(3), 404 - 7 Severe myelodysplasia with monosomies 5 and 7 presenting with rapidly fatal Sweet's syndrome; Kueh YK et al.; A 57 year-old Chinese man with anaemia and thrombocytopenia due to monosomies 5 and 7-associated myelodysplasia developed progressive Sweet's syndrome . Recurrent episodes of cutaneous manifestations responded dramatically to corticosteroid therapy . However, progressive pulmonary infiltrates unresponsive to antimicrobial therapy resulted in respiratory failure and death. Pharmazie, 1992 May, 47(5), 336 - 9 Synthesis of condensed heterocycles from 3-aryl-2,4-dicarbethoxy-5-methylcyclohexanones and their testing for antimicrobial activity; Metwally MA et al.; Condensation of the title compounds (1) with hydroxylamine hydrochloride, hydrazines and/or aromatic amines resulted in the formation of the benzisoxazoles 2, oximes 3, indazolines 4 and beta-keto anilides 6 . The oxime derivatives and anilides underwent cyclization to compounds 2 . The interaction between 1 and thiourea gave the benzothiazines 7 and thiouracils 8 . Compounds 8 on treatment with monochloroacetic acid gave the dioxo compounds 9, while their reaction with hydrazine hydrate afforded the hydrazino derivatives 10, which upon treatment with nitrous acid gave the azido or tetrazolo derivatives 11 and 12 . Treatment of 1 with 2,3-diaminopyridine and/or 2-amino-3-hydroxy-pyridine gave the pyrimidoquinazolines 13 or 14 . Some of the synthesized compounds were screened to test their antimicrobial properties. Kansenshogaku Zasshi, 1992 May, 66(5), 606 - 11 {Antimicrobial and microbicidal activities of tea and catechins against Mycoplasma}; Chosa H et al.; We examined tea extracts, (-) epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) for their antimicrobial and microbicidal activities against Mycoplasma . Green tea and black tea showed antimicrobial activities against M . pneumoniae . At a concentration of 0.2% green tea and black tea showed microbicidal activities against M . pneumoniae and M . orale but not against M . salivarium . Extracts of pu-erh tea showed a slight microbicidal activity against M . pneumoniae and M . orale . EGCg purified from green tea and TF3 from black tea markedly showed microbicidal activities against M . pneumoniae . M . orale and M . salivarium . These results suggest that tea and catechins can be used as prophylactic agents against Mycoplasma pneumoniae infection. Diabete Metab, 1992 May-Jun, 18(3), 187 - 201 Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved . Relevance to the increased susceptibility of diabetic patients to specific infections; Moutschen MP et al.; The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear . The virtual absence of epidemiological studies of the independent risk factors involved contrasts with the multitude of in vitro models focused on the metabolism and function of immune cells from diabetic patients . This review analyzes some of these models and their clinical relevance . The different levels of diabetes pathogenesis: genetic (Type 1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for immune abnormalities demonstrated in in vitro models . The participation of genetic and autoimmune factors has been mainly characterized on T lymphocyte function . The B8 DR3 haplotype is associated with several minor immunologic abnormalities in vitro . However, the high frequency of this haplotype in healthy individuals argues against its involvement in significant defects of antimicrobial immunity . Genetic deficiency of C4, present in 25% of Type 1 diabetic patients could, on the other hand, be responsible for opsonization defects against encapsulated pathogens . Several immunological abnormalities related to the autoimmune process preceding the onset of Type 1 diabetes mellitus, such as the depletion of memory CD4+ cells and the defective natural killer activity could transiently impair host defences against viral diseases . Several in vitro functional defects of the immune system have been correlated with the metabolic control of diabetic patients . This suggests the involvement of insulinopenia in some of the abnormalities observed . Insulinopenia-induced enzymatic defects have often been proposed to inhibit energy-requiring functions of phagocytes and lymphocytes . However, the relevance of this mechanism could be confined to patients with extremely severe metabolic abnormalities . The importance of systemic consequences of insulinopenia such as hyperglycaemia and ketosis has also been addressed . Usually, the defects induced in vitro by these factors are slight and require supraphysiologic concentrations of glucose or ketone bodies . Recent studies have shown abnormalities of signal transduction mechanisms in which insulinopenia itself and other factors such as circulating immune complexes could be involved . Despite numerous controversies, many in vitro studies of the immune cells of diabetic patients have demonstrated significant defects which bear quantitative similarities with abnormalities described in other immunodeficiency syndromes . Furthermore, several mechanisms have been proposed to link the different defects observed with the specific infections encountered in diabetic patients. Chem Pharm Bull (Tokyo), 1992 May, 40(5), 1315 - 7 Purines . LII . Synthesis and biological evaluation of 8-methylguanine 7-oxide and its 9-arylmethyl derivatives; Ogawa K et al.; The synthesis of 8-methylguanine 7-oxide (3) was accomplished via a "phenacylamine route", which started from condensation of alpha-(4-methoxybenzylamino)propiophenone (6), prepared by coupling of alpha-bromopropiophenone (4) and 4-methoxybenzylamine (5), with 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone (7) and proceeded through cyclization of the resulting phenacylaminopyrimidinone (8) and removal of the 4-methoxybenzyl group . The N-oxide 3 and its 9-arylmethyl derivatives 9 and 11 showed only very weak antileukemic activity and no antimicrobial activity. Chem Pharm Bull (Tokyo), 1992 May, 40(5), 1170 - 6 Synthesis and antibacterial activity of some imidazo{1,2-a}pyrimidine derivatives; Rival Y et al.; A series of 75 imidazo{1,2-a}pyrimidine derivatives were synthesized . The "in vitro" antibacterial activity of these compounds and their corresponding alpha-bromoketones against a variety of gram (+), gram (-) bacteria and Mycobacterium species is reported . Some of the prepared derivatives exhibited potent antimicrobial activity. Farmaco, 1992 May, 47(5), 643 - 7 Antibacterial and antiproliferative activities of vulpinic acids in vitro; Nadir MT et al.; The antimicrobial and antiproliferative activities of vulpinic acids (1 a, b, c) have been assayed in vitro . Activity was demonstrated by vulpinic acids on Gram-positive bacteria only . The MIC values of these compounds were found to be ranging from 3.8-31.5 micrograms/ml . The significance of these results is discussed. Farmaco, 1992 May, 47(5), 631 - 42 Synthesis and antimicrobial activity of some thiazolinyl tetrahydrobenzo{b}thiophenes and thiazolinyl tetrahydrobenzothieno{2,3-d}pyrimidin-4-ones; Aboulwafa OM et al.; Two series of novel 3-carbethoxy-2-(3',4'-disubstituted-2',3'- dihydrothiazol-2'-ylidenamino)-4,5,6,7-tetrahydrobenzo{b} thiophenes (3a-o) and 2-methyl-3-(3',4'-disubstituted-2',3'-dihydrothiazol-2'-ylidena mino-5,6,7,8- tetrahydrobenzothieno{2,3-d}pyrimidin-4(3H) ones (8a-o) have been synthesized and tested for antimicrobial activity . All members of the series have been found to exhibit in vitro antibacterial and/or antifungal activities . Activity was optimized by cyclization to the thienopyrimidin-4-ones . In particular, compounds 8e and 8fd were the most active against the 3 tested microorganisms . Their antifungal activity was higher than that exhibited by nystatin while their MIC was found to be nearly equal to that of nystatin. Antimicrob Agents Chemother, 1992 May, 36(5), 1163 - 5 Comparison of the intracellular activities of clarithromycin and erythromycin against Mycobacterium avium complex strains in J774 cells and in alveolar macrophages from human immunodeficiency virus type 1-infected individuals; Yajko DM et al.; The intracellular activities of clarithromycin and erythromycin, alone and in combination with other antimicrobial agents, were tested against Mycobacterium avium complex (MAC) strains inside mouse J774 cells and inside alveolar macrophages obtained from human immunodeficiency type 1-infected individuals . Clarithromycin alone had greater intracellular activity than erythromycin alone, and drug combinations that included clarithromycin were usually more active than combinations that included erythromycin. Antimicrob Agents Chemother, 1992 May, 36(5), 1147 - 50 Absolute bioavailability of clarithromycin after oral administration in humans; Chu SY et al.; The absolute bioavailability of clarithromycin, a new macrolide antimicrobial agent, was assessed in a three-way, randomized, single-dose, crossover study conducted with 22 healthy volunteers, 19 of whom provided analyzable study data . The bioavailability parameters of two 250-mg oral tablet formulations were calculated with reference to an identical dose administered by intravenous infusion of the lactobionate salt . After adjustment for formulation potency, the mean absolute bioavailabilities of the two oral formulations were 52 and 55%, on the basis of the appearance of parent compound in the systemic circulation . Metabolite peak concentration and area under the plasma concentration-time curve data after oral dosing were generally greater than those after intravenous infusion, suggesting that marked first-pass metabolism of clarithromycin occurs after oral administration . Pharmacokinetic analysis of the parent drug and the active 14-hydroxy metabolite data suggests complete (or nearly complete) absorption of the drug after oral administration. Biotech Histochem, 1992 May, 67(3), 140 - 8 Improved intracellular morphology of Pneumocystis carinii from rat lung by postfixation with a mixture of potassium ferrocyanide and osmium tetroxide; Goheen MP et al.; Pneumocystis carinii infected rat lungs were postfixed with a mixture of OsO4 and K4Fe(CN)6 . A marked improvement in staining of cell membranes, endoplasmic reticulum, nuclear membranes and glycogen was observed . These improvements were seen in both the trophic and cystic forms of the organisms . The addition of K4Fe(CN)6 did not improve the staining of cell walls, microtubules or ribosomes . Trophozoites were seen attached to both type 1 and type 2 pneumocytes by filopodia and/or intercalation of the cell body of P . carinii with the host lung cells . It is expected that the improvement in ultrastructural detail will allow better understanding of the ultrastructure of P . carinii and provide insights into the modes of action of various antimicrobial compounds on this organism. J Anim Sci, 1992 May, 70(5), 1424 - 31 Effect of dietary copper on intestinal mucosa enzyme activity, morphology, and turnover rates in weanling pigs; Radecki SV et al.; Twenty-four pigs from four litters weaned at 21 d of age (6.6 kg of BW) were used to evaluate the influence of 250 ppm of dietary Cu on intestinal mucosa glucose-6-phosphatase (GP), alkaline phosphatase (AP), and adenosine triphosphatase (ATPase) activity; mucosal morphology; and the turnover rate of the intestinal mucosa throughout the gastrointestinal tract . Pigs were allotted into four pens of six pigs each based on sex, litter, and weight . Pens were then assigned to one of two treatments: 1) corn-soybean meal-whey diet with no antimicrobials (CO), or 2) CO + 250 ppm of Cu . Pigs were fed twice daily an amount approximately equal to ad libitum intake for 14 d . On d 14, pigs were injected i.p . with {3H}thymidine (50 microCi/kg of BW) 10 h after the morning meal . One pig from each pen was euthanatized at 1, 6, 12, 20, 32, and 44 h postinjection, and intestinal tissue was collected from the duodenum, two jejunum sites (upper and lower), ileum, cecum, and colon . The activity of GP and AP in the lower jejunum tended to decrease in pigs fed Cu (P less than .11, P less than .08, respectively) . The ATPase activity was not affected by treatment (P greater than .10) . Crypt death, villus height, or epithelial cell size (P greater than .10) were not affected by feeding Cu . Migration rate of epithelial cells up the villus was also not affected by treatment (P greater than .10).(ABSTRACT TRUNCATED AT 250 WORDS) J Antimicrob Chemother, 1992 May, 29(5), 529 - 38 Postantibiotic effect of CI-960, enoxacin and ciprofloxacin on Escherichia coli: effect on morphology and haemolysin activity; Guan L et al.; The postantibiotic effect (PAE) has been classically defined as the suppression of bacterial growth that persists after limited exposure of organisms to antimicrobial agents . Morphology and haemolysin activity during the PAE of three quinolones on Escherichia coli were examined in this study . A one hour exposure to the quinolones, CI-960, enoxacin and ciprofloxacin, produced a PAE of 0.5-2.0 h . When determinated by Coulter counter, at 0.5 x MIC of enoxacin or CI-960 after 1 h exposure, 58% or 42% cells, respectively, of the treated cells were filamentous (cell length greater than 12 microns) . After drug removal, the population of the filamentous cells decreased, however, after even 4 h, 12% and 2% of the cells were still filamentous after exposure to enoxacin or CI-960 . Further morphological studies during the PAE showed that the first division of the filamentous cell was asymmetrical, and both bacterial cell division and septation were delayed after exposure to 0.5 MIC of CI-960 . Following quinolone removal, the treated E . coli did not exhibit normal activity of haemolysin for at least 2 h . Internal haemolysin activity was adversely affected for 1 h . The results of this study suggest that any consideration of postantibiotic effects should include the residual antibiotic effects on bacterial morphology and virulence factors, in addition to the defined suppression of bacterial regrowth. Clin Infect Dis, 1992 May, 14(5), 1015 - 22 Outbreak of pseudoinfection with Tsukamurella paurometabolum traced to laboratory contamination: efficacy of joint epidemiological and laboratory investigation; Auerbach SB et al.; From January 1988 to May 1989, one hospital in South Carolina reported 12 isolates of Tsukamurella paurometabolum from 10 patients . There were no common risk factors among the patients . Case-control studies revealed that the positive specimens were significantly more likely to have been processed in the TB/fungal room, to have been tissue samples, and to have been handled by one technician . Typing on the basis of biochemical, antimicrobial resistance, Southern blot, and ribotype profiles showed that the isolates from the outbreak were essentially identical and that they were distinguishable from each of two isolates obtained after the outbreak and from two type strains . These findings support the hypothesis of a common-source outbreak of pseudoinfection . There are reasons to believe that T . paurometabolum is present both in the environment and as a culture contaminant more often than has been recognized and that it is very rarely the true cause of infection in humans . Typing results show differences between one type strain and all of the other isolates studied in terms of colonial morphology, biochemistry, antimicrobial susceptibility, and ribotyping; these differences suggest that the nomenclature of T . paurometabolum may require further clarification. Infect Immun, 1992 May, 60(5), 1984 - 93 Interleukin-3 induces antimicrobial activity against Leishmania amazonensis and Trypanosoma cruzi and tumoricidal activity in human peripheral blood-derived macrophages; Ho JL et al.; The ability of interleukin-3 (IL-3) to induce antimicrobial and tumoricidal activity was evaluated . Macrophages infected with two intracellular protozoa, Leishmania amazonensis or Trypanosoma cruzi, were treated with cytokines . IL-3 induced a dose-dependent enhancement of microbistasis against leishmanias, and the activity of IL-3 (100 ng/ml) was comparable to that of gamma interferon (IFN-gamma) (1,000 U/ml) . In addition, IL-3 in combination with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage CSF (M-CSF) or with IFN-gamma reduced infection and lowered the required dose . IL-3 similarly activated macrophages to inhibit intracellular replication of T . cruzi . Furthermore, IL-3 induced antibody-independent tumoricidal activity against melanoma cells that was dose dependent and comparable to that of lipopolysaccharide and GM-CSF . The mechanisms by which IL-3 induced antimicrobial activity may involve at least the augmentation of oxidative capacity . IL-3, at concentrations of 0.5 ng/ml or greater, led to a significantly increased oxidative burst which paralleled the inhibition of protozoan replication . The enhancement of oxidative capacity by IL-3 (5 ng/ml or higher) was comparable to that of IFN-gamma . The induction of tumoricidal activity was associated with the production of tumor necrosis factor alpha (TNF-alpha), which in this system may feed back to enhance the macrophage inhibition of leishmanias, as demonstrated by neutralization of IL-3 activation by anti-TNF-alpha antibody . Thus, peripheral blood macrophages remain responsive to IL-3, as demonstrated by enhanced antimicrobial and tumoricidal activity . IL-3 may have potential clinical applications because of these properties and its effect on myelopoiesis. Zhonghua Wai Ke Za Zhi, 1992 May, 30(5), 272 - 3, 316 {In vitro measurement of antibacterial activities of topical antibacterial creams}; Zhang MQ; A new method of in vitro measurement of antibacterial activity of different antimicrobial creams is introduced in this paper . The tested cream in known quantity is uniformed suspended in a solid medium, and bacteria of known quantity are inoculated . The result is expressed in MIC . In this observation, four creams were tested against 3 bacteria . It is the authors impression that the new method is better than the traditional disc method, as it reflects better the actual antibacterial activity of the drug in a cream base . It is helpful in selecting an effective drug or to evaluate the effectiveness of certain drugs in clinical practice. J Antibiot (Tokyo), 1992 Apr, 45(4), 433 - 43 A83016F, a new member of the aurodox family; Smitka TA et al.; A new member of the aurodox family of antibiotics, A83016F, has been isolated from an unidentified actionmycete designated A83016 . The structure and relative stereochemistry of A83016F were elucidated by NMR examination of the parent compound and its diacetate derivative . A83016F exhibits only weak antimicrobial activity. Orthop Clin North Am, 1992 Apr, 23(2), 259 - 64 Total hip arthroplasty sepsis . Prevention and diagnosis; Fitzgerald RH Jr; Postoperative deep wound infection following total hip arthroplasty remains a serious and all too frequent complication . Although diagnostic capabilities have improved with the evolution of new imaging and immunologic techniques, the devastating consequences for patients with an early diagnosis cannot yet be aborted . Thus, further emphasis must be placed on prevention of this complication . Although major referral centers have managed to achieve exceptionally low incidences of postoperative sepsis with the prophylactic administration of antimicrobial agents and discipline within the operating room, these advances have not translated into a similar reduction of the national experience . Thus, further investigation and the development of additional techniques must be sought. Lancet, 1992 Apr 11, 339(8798), 893 - 5 Diagnostic value of decreasing IgG, IgA, and IgM antibody titres after eradication of Helicobacter pylori; Kosunen TU et al.; Titres of antibody to Helicobacter pylori are known to fall with eradication of bacteria . To find out what degree of fall would reliably indicate eradication, 144 patients with Helicobacter pylori infection were given antimicrobial therapy for 2 weeks and then followed up at 6 weeks, 6 months, and 12 months with serological tests, bacterial cultures, and histological studies of gastric specimens . 6 weeks after treatment IgG titres had fallen by 20-30% irrespective of the success of bacterial eradication . In the 121 bacteria-negative patients the decrease continued . 6 and 12 months after treatment the titre was 50% or less of pretreatment value in 97% of these patients . In the 23 patients who remained infected, the initial drop of IgG titres, if any, was followed by unchanged or slightly rising titres . IgA and IgM titres, initially raised in 64% and 4% of the patients, respectively, showed similar trends . The high sensitivity (97%) of the IgG antibody tests and a consistent fall within 6 months after eradication of H pylori infection made IgG the most useful immunoglobulin class for follow-up of antimicrobial therapy in individual patients . IgA antibodies were valuable in the 2% patients who had raised titres in this immunoglobulin class only . The few patients (5.5%) who had raised IgM titres also had high IgG titres . Serological tests thus are a cheap and reliable means of monitoring success of eradication of H pylori. Neurosurg Clin N Am, 1992 Apr, 3(2), 323 - 42 Use of antimicrobial agents to treat central nervous system infection; Klein O et al.; When dealing with infections of the central nervous system (CNS), the clinician is often faced with a daunting diagnostic and therapeutic challenge . The clinical presentation can vary from an insidious course that allows time for a full diagnostic examination to fulminant catastrophic events that require immediate therapeutic intervention . Fortunately, a thorough clinical evaluation combined with current laboratory and imaging techniques often allows for a prompt provisional diagnosis of infection . Clinical experience and scientific investigation have laid the basis for rational empiric antimicrobial therapy of CNS infection . The role of antibiotics in the treatment of CNS infections is reviewed and updated, emphasizing current rationale for empiric therapy as well as the proper use of specific antibiotics for specific pathogens. Neurosurg Clin N Am, 1992 Apr, 3(2), 279 - 90 Laboratory diagnostic methods for central nervous system infections; Fasola E et al.; Infections of the CNS have a high mortality, and rapid laboratory diagnosis and adequate antimicrobial therapy are critically important for their management . New techniques assist the clinical microbiology laboratory to isolate and identify micro-organisms more rapidly and accurately than with the use of classic procedures . Microbial identification using immunologic and DNA hybridization techniques has importantly reduced the time needed for the diagnosis of infectious diseases . Culture, however, is still the standard method to confirm the identity of an organism isolated from CSF or CNS sites . With the increase in the number of antimicrobial agents and the recognition of resistance in many isolates, antimicrobial susceptibility testing has become extremely important in the selection of optimal antimicrobial therapy . Communication between the physician and the clinical microbiology laboratory is essential for optimum patient care. Ther Umsch, 1992 Apr, 49(4), 227 - 33 {Acute and chronic bronchitis}; Speich R; Acute bronchitis and exacerbations of chronic bronchitis are important problems in clinical practice . Acute bronchitis is frequently caused by viruses, and rarely by Mycoplasma or Chlamydia pneumoniae . Antimicrobial therapy is generally not indicated . The causes of exacerbations in patients with chronic bronchitis are often not clear . Beside environmental irritants and hypersensitivity with acute bronchospasm, viral infections are important . The role of bacterial infections is not established . Nevertheless, early antibiotic treatment seems to be beneficial, particularly in reducing the incidence of respiratory deterioration, and therefore decreasing cost and morbidity. Zentralbl Bakteriol, 1992 Apr, 276(4), 512 - 20 Activity of antimicrobial agents against Mycobacterium avium-intracellulare complex (MAC) strains isolated in Italy from AIDS-patients; Fattorini L et al.; Twenty-five strains of Mycobacterium avium-intracellulare (MAC) isolated from acquired immunodeficiency syndrome (AIDS) patients in three medical centres in Italy have been studied . Serotyping performed on eighteen strains showed various serovars within either M . avium or M . intracellulare serotypes and with serovars 1 and 21 being the most prevalent (four strains for each serovar) . Among fourteen drugs used for testing the antibiotic sensitivity, rifapentine, rifabutin and clofazimine showed to have the best in vitro activity . In an ex vivo model of infection using peritoneal resting macrophages from the C57BL/6 mouse, the intracellular viability of a strain of M . avium (strain 489, serovar 3) was reduced by clofazimine, amikacin, ciprofloxacin, rifabutin and clarithromycin (99, 98, 93, 89 and 69%, respectively), thus indicating for clofazimine a good correlation between in vitro and ex vivo activity. J Ethnopharmacol, 1992 Apr, 36(2), 155 - 61 Antimicrobial constituents of Gomphrena martiana and Gomphrena boliviana; Pomilio AB et al.; The antimicrobial activity of extracts and constituents of Gomphrena martiana and Gomphrena boliviana (Amaranthaceae) were determined in order to identify the compounds responsible for the folk-medicinal use of these plants . Each extract was evaluated against 20 microorganisms, including Gram-positive and Gram-negative bacteria, spore-forming Gram-positive bacteria, an acid-fast bacterium, a fungus and two yeasts . Fractionation of each petroleum ether (PE) extract yielded five 5,6,7-trisubstituted flavones that were separately tested showing high activity against M . phlei (minimum inhibitory concentration (MIC) 15, 20 and 75 micrograms/ml) approaching that of commercial bactericides . Other natural and synthetic flavonoids with diverse structures were also tested to define structure-activity relationships . Each EtOH extract was subsequently fractionated and monitored by bioassays leading to isorhamnetin 3-O-beta-robinobioside (MIC 50 micrograms/ml) in both instances . This glycoside is reported here for the first time in G . boliviana. Clin Pharmacokinet, 1992 Apr, 22(4), 284 - 97 Cefotaxime dosage in infants and children . Pharmacokinetic and clinical rationale for an extended dosage interval; Kearns GL et al.; Cefotaxime is a third generation cephalosporin antimicrobial agent which has received wide acceptance as a first-line antibiotic for many infections in neonates, infants and children . With an average elimination half-life of about 1 h, cefotaxime is not considered to be a 'long half-life cephalosporin' like ceftriaxone . For this reason, currently accepted dosage regimens for cefotaxime in infants and children employ a dosage of 50 mg/kg every 6 h . Re-examination of the paediatric pharmacokinetic data for cefotaxime and use of simple multiple-dose pharmacokinetic simulation of alternative dosage regimens was performed . From this analysis, regimens administering 75 mg/kg of the drug every 8 h or every 12 h were projected to produce serum cefotaxime concentrations adequate to effectively kill many of the common pathogens against which the drug is currently indicated for use in children . The clinical utility of these alternative dosage regimens was supported by a review of the medical literature and examination of the clinical results from studies in neonates, infants and children where cefotaxime was administered in 2 to 3 divided doses daily . It would appear, therefore, that increasing the cefotaxime dosage to 75 mg/kg administered at 8 h intervals would result in less frequent drug administration which would not be expected to compromise safety and efficacy . Alternative dosage regimens for cefotaxime merit further consideration and clinical evaluation before they become commonly used in paediatric therapeutics. J Antimicrob Chemother, 1992 Apr, 29 Suppl A, 71 - 3 Toxicity of cefpirome: an overview; Donaubauer HH et al.; Cefpirome is a new cephalosporin antibiotic with a broad antimicrobial spectrum in vitro . This includes strains which are frequently resistant to other cephalosporins (Seibert et al., 1983) . This report gives a summary of the toxicological investigations on cefpirome. Am J Infect Control, 1992 Apr, 20(2), 65 - 72 Handwashing practices and resistance and density of bacterial hand flora on two pediatric units in Lima, Peru; Larson EL et al.; The handwashing practices and bacterial hand flora of 62 pediatric staff members of a teaching hospital in Lima, Peru, were studied . Handwashing followed patient contact 29.3% of the time (204/697 contacts) . Mean duration was 14.5 seconds, and significant differences in practices were found by unit (rehydration or neonatal intensive care), type of staff member (nurses or physicians), and type and duration of patient contact . Mean count of colony-forming units was log10 5.87 +/- 0.41, with significant differences in density of flora found between patient care and kitchen staffs . There was no significant effect of handwashing on counts of colony-forming units . Significant differences were also found by unit and by staff position with regard to species isolated and antimicrobial resistance of isolates . A more efficacious and cost-effective form of hand hygiene and a more prudent use of antimicrobial agents are indicated. Clin Nephrol, 1992 Apr, 37(4), 209 - 13 Netilmycin and vancomycin in the treatment of peritonitis in CAPD patients; Were AJ et al.; This study was undertaken to evaluate: 1 . The efficacy of netilmycin and vancomycin as combined first line antimicrobial regime, compared to cefuroxime, in the treatment of peritonitis . 2 . To measure the levels of netilmycin and vancomycin in the serum and dialysate . 3 . To report on the use of this combination over a one year period and compare it with that of cefuroxime used during the previous one year. J Neurosci Res, 1992 Apr, 31(4), 616 - 21 An immortalized cell line expresses properties of activated microglial cells; Bocchini V et al.; Murine cultured microglial cells were immortalized after infection with a v-raf/v-myc recombinant retrovirus . This immortalized cell line (BV-2) shares properties with body macrophages with respect to the antigen profile, their phagocytic capacity and antimicrobial activity . BV-2 cells are not constitutively able to kill tumor cells in vitro, but acquire antitumor activity following an increase in {Ca++}i . BV-2 cells, like microglial cells, are however, distinct from peripheral macrophages by their expression of inwardly rectifying K+ channels in concert with a lack in outwardly rectifying K+ channels and the formation of spineous processes . The BV-2 cell line thus represents a suitable model for in vitro studies of activated microglial cells. J Am Vet Med Assoc, 1992 Apr 1, 200(7), 964 - 8 Ankylosis of the distal interphalangeal joint in a horse after septic arthritis and septic navicular bursitis; Honnas CM et al.; A 6-month-old 300-kg Quarter Horse filly was treated for septic arthritis of the distal interphalangeal joint and septic navicular bursitis that developed as a result of a deep puncture to the foot . Initial treatment consisted of establishing ventral drainage for the navicular bursa, lavage of the distal interphalangeal joint, and administration of broad-spectrum antimicrobial drugs and non-steroidal anti-inflammatory drugs . Because of continuing sepsis in the distal interphalangeal joint, subsequent treatment included packing the defect in the bottom of the foot with cancellous bone in an attempt to prevent ascending contamination of the joint, placing the limb in a short limb cast, and inserting a Penrose drain into the joint for passive drainage of septic exudate . The goal of treatment was to encourage ankylosis of the distal interphalangeal joint . Because of the filly's persistent lameness and laxity of the lateral collateral ligament in the contralateral carpus, the palmar nerves of the affected foot were injected with a long-acting local anesthetic at the level of the proximal sesamoid bones to encourage weight-bearing . Ankylosis of the distal interphalangeal joint was complete 9 months after the puncture, but a grade-2 lameness remained and the horse had a varus deformity resulting from ligamentous laxity of the lateral collateral ligament in the contralateral carpus. J Periodontol, 1992 Apr, 63(4 Suppl), 332 - 7 Microbiological testing in the diagnosis of periodontal disease; Listgarten MA; The oral microbiota plays a primary role in the initiation and progression of the most common forms of periodontal disease . Because of the multiplicity of factors that control the establishment and long-term evolution of the oral microbiota, a great deal of heterogeneity exists in the composition of the periodontal microbiota among individual subjects . Despite these individual differences and the complex interactions between bacteria and the host and among bacteria, an association has been demonstrated between certain species and various forms of periodontal disease . However, the predictive value of either positive or negative tests for selected bacterial species has not proved to be high enough for routine use in clinical practice . Nevertheless, bacteriological tests have been of value in the management of patients with juvenile periodontitis and refractory forms of periodontal disease . The increasing availability of diagnostic laboratory services and diagnostic kits for office use will make it easier for the practitioner to select appropriate antimicrobial treatments and monitor patients undergoing antimicrobial therapy. J Clin Microbiol, 1992 Apr, 30(4), 1036 - 8 Isolation of Mycobacterium thermoresistibile following augmentation mammaplasty; Wolfe JM et al.; This is the first case report of a Mycobacterium thermoresistibile infection following augmentation mammaplasty and is the fourth human case report of M . thermoresistibile infection . Antimicrobial susceptibility results determined by a modified proportion method using a 3-day incubation were the same as those determined by the standard 3-week assay. J Clin Microbiol, 1992 Apr, 30(4), 1008 - 10 Nonmycetomic Actinomadura madurae infection in a patient with AIDS; McNeil MM et al.; Actinomadura madurae is an aerobic actinomycete which is best known worldwide as the cause of actinomycotic mycetomas . It has not previously been reported to have caused invasive pulmonary or disseminated infection in humans . We describe an AIDS patient with opportunistic A . madurae-induced pneumonia and bacteremia . The isolate from the patient's blood was subjected to dilutional antimicrobial susceptibility tests with 12 antimicrobial agents and was found to have a wide spectrum of susceptibility . This unusual microorganism may be a cause of infections in severely immunosuppressed patients. Dent Clin North Am, 1992 Apr, 36(2), 343 - 56 Medications and temporaries in endodontic treatment; Madison S et al.; We have attempted to present in this article an overview of the medications used as intracanal dressings during root canal treatment and the materials used to seal endodontic access preparations . Because all the medications reviewed have an antimicrobial effect (with the exception of steroids), they seemingly would be useful in root canal treatment . However, the potentially harmful side effects of the chemical agents, which include cytotoxicity and antigenicity, may make the treatment worse than the cure . With an improved understanding of the principles of root canal cleaning, strong medications placed into canals may be unnecessary . At best, intracanal dressings should be used only in situations that might benefit from such therapy . Temporary restoration of endodontically treated teeth is an essential part of root canal therapy . Commonly used materials and techniques for their uses have been presented . With proper temporization and timely final restoration, the potential for coronal microleakage will be minimized. Pediatr Infect Dis J, 1992 Apr, 11(4), 278 - 86 Efficacy of antimicrobial prophylaxis and of tympanostomy tube insertion for prevention of recurrent acute otitis media: results of a randomized clinical trial; Casselbrant ML et al.; To determine the efficacy of amoxicillin prophylaxis and of tympanostomy tube insertion in preventing recurrences of acute otitis media, we randomized 264 children 7 to 35 months of age who had a history of recurrent otitis media but were free of middle ear effusion to receive either amoxicillin prophylaxis, bilateral tympanostomy tube insertion or placebo . The average rate of new episodes per child year of either acute otitis media or otorrhea was 0.60 in the amoxicillin group, 1.08 in the placebo group and 1.02 in the tympanostomy tube group (amoxicillin vs . placebo, P less than 0.001; tubes vs . placebo, P = 0.25) . The average proportion of time with otitis media of any type was 10.0% in the amoxicillin group, 15.0% in the placebo group and 6.6% in the tympanostomy tube group (amoxicillin vs . placebo, P = 0.03; tubes vs . placebo, P less than 0.001) . At the 2-year end point, the rate of attrition was 42.2% in the amoxicillin group, 45.5% in the placebo group and 26.7% in the tympanostomy tube group . Adverse drug reactions occurred in 7.0% of the amoxicillin group and persistent tympanic membrane perforations developed in 3.9% of the tympanostomy tube group . The observed degree of efficacy of amoxicillin prophylaxis and of tympanostomy tube insertion must be viewed in light of the fact that study subjects proved not to have been at as high risk for acute otitis media as had been anticipated and in view of the differential attrition rates.(ABSTRACT TRUNCATED AT 250 WORDS) J Leukoc Biol, 1992 Apr, 51(4), 343 - 9 Modulation of natural killer and lymphokine-activated killer cell cytotoxicity by lactoferrin; Shau H et al.; Natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxic functions can be strongly augmented by the iron-carrier protein lactoferrin (LF) . LF significantly enhances NK and LAK activities when added at the beginning of NK or LAK cytotoxicity assays . LF is effective in augmenting cytotoxic activities at concentrations as low as 0.75 microgram/ml, and higher concentrations of LF induce greater augmentation of NK and LAK . Iron does not appear to be essential for LF to increase NK and LAK, as depleting iron from LF with the chelator deferoxamine does not affect the capacity of LF to increase cytotoxicity . LF is known to have RNase enzymatic activity, and LF enhancement of NK and LAK can be blocked by RNA . However, LFs from two different sources with over 100-fold difference in RNase activity are equally effective in enhancing NK and LAK . Furthermore, purified non-LF RNase does not modulate NK or LAK activity and DNA is as effective as RNA in blocking LF augmentation of NK or LAK cytotoxicity . Therefore, the RNase activity is unlikely to be responsible for LF enhancement of the cytotoxicities . Newborn infants are known to have low NK activity and NK and LAK cells have been implicated in host defense against microbial infections . Thus, maternal milk-derived LF may have a role in boosting antimicrobial immunity in the early stages of life . In adults, LF released from neutrophils may enhance NK and LAK functions in the inflammatory process induced by microbial infections. J Clin Invest, 1992 Apr, 89(4), 1282 - 7 Ultraviolet-irradiated monocytes efficiently inhibit the intracellular replication of Mycobacterium avium intracellulare; Mirando WS et al.; The purpose of this study was to evaluate the effect of ultraviolet (UV) radiation on the antimicrobial activities of monocytes for the intracellular pathogen Mycobacterium avium intracellulare (MAI) . UV radiation augmented monocyte antimicrobial activity for MAI in a dose-dependent fashion . UVB doses of greater than or equal to 25 J/m2 resulted in a 50-100-fold reduction in MAI growth 7 d after initiation of culture . The increased monocyte antibacterial effect could be blocked by a plate glass filter, indicating that wavelengths within the UVB were responsible for the effect . UV radiation did not stimulate monocyte phagocytosis, and enhanced inhibition of MAI growth was observed in populations of adherent mononuclear cells that were devoid of T cells . This suggested that UV radiation acted directly to augment intrinsic monocyte antimicrobial activities . The administration of 8-methoxypsoralen plus UVA radiation to monocytes also augmented their antimicrobial activities against MAI . UV radiation thus may serve as a unique agent by which to evaluate the mechanisms by which mononuclear phagocytes control the growth of MAI. Chest, 1992 Apr, 101(4), 1028 - 32 Penetration of netilmicin in the lower respiratory tract after once-daily dosing; Valcke YJ et al.; A major criticism of the use of aminoglycosides for the treatment of pneumonia is the poor penetration in infected airways . Once-daily dosing of aminoglycosides results in higher peak plasma concentrations without increasing toxic reactions and with optimization of pharmacodynamic properties . To predict intrapulmonary antimicrobial activity after once-daily dosing of aminoglycosides, it is necessary to determine the respective bronchial and alveolar disposition . We prospectively conducted a pharmacokinetic study of netilmicin following the first intravenous administration of a once-daily dosing schedule in 20 ventilated patients with pneumonia . A bronchoscopic sampling of bronchial secretions and a subsegmental bronchoalveolar lavage (BAL) were performed 60, 90, 120, and 180 min (five patients at each time point) on the first treatment day after intravenous administration over 30 min of 450 mg of netilmicin . The netilmicin concentrations in the alveolar lining fluid (ALF) were calculated using urea as an endogenous marker of dilution . In bronchial secretions, a peak concentration of 2.00 (SEM: 0.26) mg/L or 6 percent of the 30-min plasma concentration was reached at 120 min . In ALF, much higher levels were found . At 120 min, a peak ALF concentration of 14.7 (SEM: 2.22) mg/L or 41 percent of the 30-min plasma concentration was reached . Spearman's rank correlation testing failed to show a correlation between bronchial and ALF concentrations . Higher plasma concentrations of netilmicin after once-daily dosing give rise to ALF concentrations exceeding the minimum inhibitory concentration of susceptible respiratory pathogens involved in nosocomial pneumonia, while bronchial concentrations remain low . Aminoglycoside concentrations in bronchial secretions cannot be used to predict alveolar concentrations . Low diffusibility can no longer be considered as a disadvantage of aminoglycosides for treating pneumonias. J Infect Dis, 1992 Apr, 165(4), 744 - 9 Drug resistance and adherence to human intestines of enteroaggregative Escherichia coli; Yamamoto T et al.; Clinical isolates of enteroaggregative Escherichia coli (EAggEC) were tested for their in vitro susceptibilities to 27 antimicrobial agents . Marked drug resistance was observed with sulfamethoxazole, ampicillin, and chloramphenicol in contrast to such antimicrobial agents as cefixime, sparfloxacin, and ciprofloxacin . One of the EAggEC strains carried a plasmid that conferred on its host resistance to ampicillin, tetracycline, sulfamethoxazole, streptomycin, and spectinomycin and an ability to adhere to child ileal villi or HeLa cells in the characteristic aggregative pattern . This plasmid also mediated D-mannose-resistant hemagglutinin production and bacterial clump formation (autoagglutination) . The data demonstrate appearance of marked drug resistance and an intestine-adherence and drug-resistance plasmid in the newest category of diarrheagenic E . coli. Hinyokika Kiyo, 1992 Apr, 38(4), 501 - 6 {Clinical studies on tosufloxacin (TFLX) in urology}; Fukushima S et al.; We clinically evaluated the usefulness of a new oral antimicrobial agent, TFLX, in the field of urology . The dose administered was 150 mg t.i.d and the duration of administration was 3 days . The clinical effect was evaluated according to the criteria of the Japanese UTI committee . The clinical response obtained on 164 female patients with acute simple cystitis was excellent in 118, moderate in 44 and poor in 2 patients . The efficacy rate was 98.78% . The clinical response obtained on 4 male patients with acute simple cystitis was excellent in 2 and moderate in 2 patients . The efficacy rate was 100% . The clinical response obtained on 3 female patients with simple pyelonephritis was excellent in 2 and moderate in 1 patient . The efficacy rate was 100% . The clinical response obtained on one patient with non-gonococcal urethritis was excellent by doctor's evaluation . The clinical response obtained on 7 patients with complicated UTI was excellent in 3 and moderate in 4 patients . The efficacy rate was 100% . Three patients complained of stomach distress or malaise and 2 patients developed rash . No abnormal laboratory data were observed . Thus, TFLX appears to be safe and suitable for use in the field of urology. Behring Inst Mitt, 1992 Apr, (91), 126 - 37 The calcium binding proteins MRP8 and MRP14 in acute and chronic inflammation; Sorg C; Two novel calcium-binding proteins which belong to the S100 protein family were isolated and sequenced . Using monospecific antisera their expression by myeloic/monocytic cells was shown . The two proteins may form complexes particularly a heterodimer which may also be expressed on the surface of infiltrating monocytes in acute inflammations . In vitro, its surface expression is induced by agents affecting the calcium household of cells . In contrast, formation of the heterodimer is conspicuously absent in chronic inflammatory lesions . In the latter situation monocytes either express MRP8 or MRP14 and not both as in acute inflammation . In all inflammation models tested so far the cells arriving first at the lesion were MRP8- and MRP14-positive . MRP8/14 which is identical with the cystic fibrosis antigen is also found in body fluids in inflammatory conditions and thus may be considered as a very sensitive inflammation marker . Soluble MRP8/14 complexes may exert different functions, e.g . inhibition of casein kinases, binding to cytoskeletal proteins, antimicrobial effects . MRP8 and MRP14 thus represent two novel molecular parameters of the early events of inflammatory reactions which reveal interesting aspects for the pathomechanism of chronic inflammatory reactions. Pharmazie, 1992 Apr, 47(4), 261 - 3 Synthesis and antimicrobial activity of new 5-aryl-2-hydroxy-3(2H)-pyrrolinone derivatives; Kozminykh VO et al.; The synthesis of some 1-substituted 5-aryl-2-hydroxy-2-methoxycarbonylmethyl-3(2H)-pyrrolinones is described . The results of microbiological screening are given . They indicate that 2-methylene-3(2H)-furanone and 2-hydroxy-3(2H)-pyrrolinone derivatives exhibit a rather low antimicrobiological activity. Jpn J Antibiot, 1992 Apr, 45(4), 359 - 63 {Antimicrobial activity of cefetamet against fresh clinical isolates of Branhamella catarrhalis}; Deguchi K et al.; Against strains of Branhamella catarrhalis which were separated from various RTIs (respiratory tract infections) in 1991 antimicrobial activities (MICs) of cefetamet (CFMT) were determined, and the following conclusions were obtained . 1 . The MIC80 of CFMT against B . catarrhalis was 0.39 microgram/ml, which was higher than that of cefixime (CFIX) by one dilution or twofold, but was lower than that of cefpodoxime (CPDX) by two dilutions or fourfold and that of cefotiam (CTM) by three dilutions or eightfold . 2 . The fact that all of the 50 strains tested were beta-lactamase producers appeared to indicate that CFMT was stable against BRO-1 and BRO-2 beta-lactamases produced by B . catarrhalis . 3 . Blood concentrations of the test drug, CFMT, and control drugs upon normal single doses were calculated using pharmacokinetic parameters . Lengths of time periods during which drug concentrations stayed above their MICs against B . catarrhalis obtained in this study were determined for CFMT, CFIX, CPDX and CTM . They were, respectively, 12 hours, 12 hours, 6 hours, and 2 hours, thus CFMT appeared to remain above MIC for sufficiently long time for the treatment of RTIs which are affected by B . catarrhalis directly or indirectly. J Prosthet Dent, 1992 Apr, 67(4), 535 - 40 Microbial contamination in two antimicrobial and four control brands of alginate impression material; Rice CD et al.; Previous investigations have revealed commercial alginate impression material to be contaminated with viable microorganisms . Some manufacturers are now producing alginate materials that contain antimicrobial agents . The purpose of this study was to test and compare two antimicrobial and four control brands without antimicrobial agents of commercial dental alginate impression material for the presence of viable microorganisms . Forty-eight or 96 measured samples of each brand were taken from previously unopened containers using a sterile technique . The samples were placed on chocolate agar plates and in thioglycolate broth tubes and were incubated along with appropriate parallel controls . After incubation, colonies were enumerated, gram-stained, and identified using standard microbiologic methods . The two antimicrobial brands contained viable organisms in 12.5% of the samples incubated on agar media and also contained such organisms from 0% to 16.7% of the samples incubated in thioglycolate media . The four control brands contained viable organisms in from 29.2% to 100% of the samples incubated on agar media and also contained these organisms in from 25% to 79.2% of the samples incubated in thioglycolate media . There was a statistically significant difference (p less than 0.05) in contamination frequencies among some brands . Contamination frequencies of the top and middle portions of the containers did not differ significantly . The concentration of organisms in contaminated samples was 2.8 colony-formed units (CFUs) per gram for the antimicrobial alginates, and from 9 to 161.1 CFUs per gram for the control brands.(ABSTRACT TRUNCATED AT 250 WORDS) J Pharm Sci, 1992 Apr, 81(4), 365 - 6 Synthesis and antimicrobial and anti-inflammatory activities of substituted 2-mercapto-3-(N-aryl)pyrimido{5,4-c}cinnolin-4-(3H)-ones; Nargund LV et al.; Ten new substituted 2-mercapto-3-(N-aryl)pyrimido{5,4-c}cinnolin-4- (3H)-ones (4) were prepared by refluxing substituted 4-aminocinnolin-3-carboxylic acid (3) with substituted arylisothiocyanate in anhydrous pyridine . These derivatives were evaluated for their antimicrobial and anti-inflammatory activities . Some of the title compounds possess potent antimicrobial activity. Zhonghua Wai Ke Za Zhi, 1992 Apr, 30(4), 237 - 40, 256 {Clinical study of prophylactic use of gentamicin and metronidazole in the surgery of colorectal carcinoma}; Cai CJ; From Oct . 1989 to Apr . 1990, 16 patients with colorectal carcinoma undergoing elective radical resection were randomly divided into two groups to receive oral and combined (oral + i.v.) antimicrobials respectively . Patients in the oral group received preoperative oral gentamicin and metronidazole for two days, in the combined group oral medication was followed by the same antimicrobials intravenously during perioperative period . Quantitative bacterial cultures were performed before and after the regimen . Results showed that the preoperative prophylaxis with oral antimicrobial resulted in a significant reduction in the bacterial counts of the rectum contents in all the patients (P < 0.001) . The NICs of gentamicin and metronidazole for E . coli and B . fragilis were found to be 2.31 micrograms/ml and 0.66 micrograms/ml respectively . The perioperative blood samples and the intraoperative tissue specimens were taken for gentamicin and metronidazole determination . In the oral group, effective concentration of metronidazole were found in serum and tissues but gentamicin was undetected . In the combined group, effective concentrations of both gentamicin and metronidazole were detected . According to our results, the short-term preoperative oral medications combined with perioperative intravenous gentamicin and metronidazole prophylaxis appears to rational. Ir J Med Sci, 1992 Apr, 161(4), 101 - 4 Emergency appendicectomy: a one year audit; Gibney EJ et al.; A retrospective study of emergency appendicectomy over a one-year period at Beaumont Hospital was carried out . The overall normal appendicectomy rate was 22.8%, and was twice as high in women (31%) as in men (15%) . Gangrenous or perforated appendicitis was present in 20% of cases . The overall mean assessment-surgery interval was 16.7 hours . Considerable variation in the use of antimicrobial agents was noted in the study, and many haematological and radiological investigations performed did not appear to improve diagnostic accuracy . Among patients with clinical features typical of appendicitis, 16% proved to have a normal appendix . These results point to a number of aspects of the diagnosis and management of appendicitis where there appears to be room for future improvement. J Med Assoc Thai, 1992 Apr, 75(4), 223 - 30 The failure of a preprinted order form to alter physicians' antimicrobial prescribing pattern; Aswapokee N et al.; Use of antimicrobial agents is highly effective in reduction of morbidity and mortality due to infectious disease . There is, however, evidence that the use of such agents is frequently inappropriate worldwide . Several methods were tried to rationalize the use, and, among these, the preprinted order form (P.O.F.) offered the simplest and most efficient way . We studied the use of the P.O.F . in Siriraj Hospital, Bangkok Thailand, where there was overuse of antimicrobial agents using a historical-controlled intervention study . In period I (no P.O.F.), the antimicrobial overuse was 35 per cent, and this was not reduced by using the P.O.F . in period II (32%), which was one year apart . There was no difference in overuse after adjustment for differences in base-line characteristics which were thought to affect antimicrobial prescriptions i.e . physicians' workload, physicians' knowledge and the method of diagnosis of infectious disease . Reasons for failure of the P.O.F . in unclear . Misdiagnosis was unlikely since the correct diagnosis as revised by attending physicians and specialists was as high as 83 per cent . The fear of malpractice suits was also not the reason because defensive medicine is not a problem in Thailand . The nature of the diseases, which lower the threshold to treat, the clinical immaturity and other unknown factors were thought to play a part in deviation from responsibility to perform according to written-justification. Farmaco, 1992 Apr, 47(4), 489 - 96 Benzimidazole condensed ring systems . 8 (1) . Synthesis of some substituted 1-oxo-1H,5H-pyrido{1,2-a} benzimidazole-4-carbonitriles with anticipated antimicrobial activity; Badawey EA et al.; As a part of research project on the syntheses of a number of pyrido{1,2-a}benzimidazole derivatives with possible antimicrobial activity, some 3-(chloro or morpholino)-acetyloxy (2,3), 3-(N,N-dimethylcarbamoyloxy) (4,5) and 3-tosyloxy-1-oxo-1H,5H-pyrido{1,2a}benzimidazole-4-carbonitrile s (6) were prepared and evaluated for such activity . Many compounds exhibited in vitro antimicrobial activity and structure-activity relationship is discussed. Infect Agents Dis, 1992 Apr, 1(2), 114 - 8 Traveler's diarrhea: new perspectives; Barry M; Despite pre-travel advice about food and water, traveler's diarrhea is the most common infectious disease problem for travelers to developing countries . New concepts of antimicrobial prophylaxis, combination treatment with antimicrobial and antimotility agents and even a new potential vaccine are reviewed. J Hosp Infect, 1992 Apr, 20(4), 301 - 4 Assessment of risk of microbial contamination by use of multidose containers of injectable products; Christensen EA et al.; At a vaccination centre 200 emptied multidose vials were tested for sterility . All vials had contained 10 doses of a vaccine without added preservative . None of the 200 vials was culture-positive . The vaccine did not comply with the pharmacological test for effectiveness of antimicrobial preservatives. J Leukoc Biol, 1992 Apr, 51(4), 400 - 8 Monocyte adherence to fibronectin: role of CD11/CD18 integrins and relationship to other monocyte functions; Owen CA et al.; Adherence of monocytes to extracellular matrix components is critical for their accumulation at sites of infection . To gain insight into the factors that regulate monocyte recruitment, we have studied monocyte adherence with regard to the regulatory effects of bacterial lipopolysaccharide (LPS) and the mechanisms involved; moreover, we have contrasted the phenotypes of adherent and nonadherent cells . Our results show that only a minor subpopulation of monocytes (20-25%) adhere spontaneously to fibronectin and that LPS stimulated a threefold increase in the proportion of adherent cells . Basal adherence and LPS-stimulated adherence of monocytes to fibronectin were substantially mediated by CD11/CD18 integrins . Further studies revealed that spontaneously adherent monocytes were 14-fold more actively phagocytic, released 1.6-fold more superoxide anion, and contained 20-fold more peroxidase activity than nonadherent cells, whereas LPS-adherent cells had an intermediate phenotype . These results indicate that LPS may enhance the accumulation of monocytes with an antimicrobial phenotype and thereby promote resolution of tissue infection. Oral Microbiol Immunol, 1992 Apr, 7(2), 121 - 3 Tetracycline inhibition identifies the cellular origin of interstitial collagenases in human periodontal diseases in vivo; Suomalainen K et al.; Mammalian interstitial collagenases (E.C.3.4.24.7) are considered as key initiators of collagen degradation in periodontal diseases . However, the cellular sources of collagenases present in gingival crevicular fluid have not been completely clarified . Resident fibroblasts and epithelial cells as well as infiltrating neutrophils and monocyte/macrophages are potential sources of the enzymes . We have recently found significant differences in tetracycline inhibition between human neutrophil and fibroblast interstitial collagenases . To address the cellular source of collagenase present in gingival crevicular fluid in 2 distinct periodontal diseases, we studied the tetracycline inhibition of collagenase in gingival crevicular fluid of patients with localized juvenile periodontitis and adult periodontitis . Gingival crevicular fluid samples were collected from deep (greater than 5 mm) periodontal pockets and assayed for collagenase in the presence of 0-1000 microM doxycycline as well as a chemically modified tetracycline devoid of antimicrobial activity (4-de-dimethylaminotetracycline) . The drug concentration required to inhibit 50% of collagenase activity (IC50) in localized juvenile periodontitis gingival crevicular fluid was 280 microM for doxycycline and 470 microM for 4-de-dimethylaminotetracycline . Significantly lower values, 10-20 microM, were obtained for collagenase in gingival crevicular fluid of patients with adult periodontitis . We propose that systemic tetracycline levels are efficient inhibitors of collagenase in gingival crevicular fluid in affected sites of patients with adult periodontitis but not of patients with localized juvenile periodontitis and that the fibroblast type interstitial collagenase is the predominant collagenase type in gingival crevicular fluid in affected sites of patients with localized juvenile periodontitis and the neutrophil collagenase in adult periodontitis gingival crevicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Podiatr Med Surg, 1992 Apr, 9(2), 385 - 407 Penicillins, cephalosporins, quinolones; Corey SV et al.; This article details the mechanisms of action, antimicrobial spectrum, pharmacokinetics, and adverse reactions of these three antibiotics. Eur Respir J, 1992 Apr, 5(4), 471 - 6 The distribution of temafloxacin in bronchial epithelial lining fluid, alveolar macrophages and bronchial mucosa; Baldwin DR et al.; The concentrations of temafloxacin, a new fluoroquinolone antimicrobial, in the potential sites of pulmonary infection were assessed by fibreoptic bronchoscopy with bronchoalveolar lavage . Fourteen patients received a course of temafloxacin, 600 mg twice daily, for three days prior to sampling . The mean serum concentration was 9.6 (SEM 1.2) mg.l-1, compared with 14.9(SEM 1.8) mg.kg-1 for bronchial mucosa, 26.5 (SEM 3.6) mg.l-1 for epithelial lining fluid and 83.0 (SEM 11.5) mg.l-1 for alveolar macrophage . In the ten patients who completed the protocol, site concentrations correlated well with serum concentrations . Temafloxacin was concentrated in each of the potential sites of infection examined and is, therefore, a promising new agent for the treatment of respiratory tract infection. Vestn Khir Im I I Grek, 1992 Apr, 148(4), 39 - 43 {The current problems of relaparotomy}; Gushcha AL et al.; Relaparotomy was performed in 252 of 23,232 (1.08%) patients operated upon . The most frequent cause of relaparotomy is purulent complications . These patients have immunodeficient states due to different causes (duration of the disease, old age, diabetes mellitus, toxemia, anemia, extension of the injuries, irrational administration of antibiotics) . Due to it, anaerobic neclostridial infection is widely used . Its participation in the purulent process in the abdominal cavity achieves 80-90% . For prevention and treatment of purulent complications of great importance is the modern and adequate struggle against intoxication and hypoxia, correction of immunodepression, purposeful antimicrobial therapy . Problems in determination of indications for relaparotomy are emphasized and the necessity to perform it in earlier terms. Biochemistry, 1992 Mar 24, 31(11), 2998 - 3004 Binding of tachyplesin I to DNA revealed by footprinting analysis: significant contribution of secondary structure to DNA binding and implication for biological action; Yonezawa A et al.; In view of the cationic amphipathic structure of tachyplesin I and antiparallel beta-sheet as a general DNA binding motif, DNA binding of the antimicrobial peptide has been examined . Several footprinting-like techniques using DNase I protection, dimethyl sulfate protection, and bleomycin- (BLM-) induced DNA cleavage were applied in this study . Some distinct footprints with DNase I are detected, and also the sequence-specific cleavage mode of the BLM-Fe(II) complex clearly is altered in the presence of tachyplesin I . In addition, methylation of the N-7 residue of guanine situated in the DNA major groove is not entirely inhibited (or activated) by tachyplesin I . The results suggest that tachyplesin I interacts with the minor groove of DNA duplex . Disappearance of the footprints by dithiothreitol-treated tachyplesin I and Ala-tachyplesin strongly suggests a significant contribution of secondary structure containing an antiparallel beta-sheet to the DNA binding of tachyplesin I . This is the first report on DNA interaction with a small peptide which contains a unique antiparallel beta-sheet structure . The mechanism for antimicrobial action of tachyplesin I has also been inferred. Blood, 1992 Mar 15, 79(6), 1532 - 7 Characterization of defensin precursors in mature human neutrophils; Harwig SS et al.; Human defensins HNP-1 and -3 are broad spectrum antimicrobial peptides that are synthesized by human neutrophils as 94 amino acid (aa) precursors that require proteolytic removal of 64 amino-terminal residues to produce the mature defensins . Recent studies have shown that the early proteolytic processing events include two sequential cleavages, each removing 19 amino-terminal aa residues, that yield 75 aa and 56 aa prodefensins, respectively . The subsequent processing steps that convert these 56 aa prodefensins to mature (30 aa) HNP-1 and HNP-3 are not yet known . We identified four new defensin precursors in mature normal neutrophils . The most abundant of these were two 39 aa forms that resulted from the monobasic endoproteolytic cleavage of proHNP-1 and proHNP-3 . The presence of two proline residues in the vicinity of this newly defined scission site suggested that this cleavage might be "proline-directed." Smaller amounts of the 34 aa and 32 aa prodefensin forms were also found . It remains to be established if these 39, 34, and 32 aa prodefensins are obligate intermediates in the prodefensin processing pathway, or arise from side reactions . In either event, because these prodefensin intermediates accounted for only 0.25% of the total defensin content, proteolytic conversion of 56 aa prodefensins to mature defensins appears to be a highly efficient process. J Immunol, 1992 Mar 15, 148(6), 1858 - 63 Acquired resistance and granuloma formation in experimental visceral leishmaniasis . Differential T cell and lymphokine roles in initial versus established immunity; Murray HW et al.; In naive BALB/c mice, acquisition of resistance to Leishmania donovani and formation of antileishmanial tissue granulomas are linked expressions that require both L3T4+ and Lyt 2+ cells as well as both IL-2 and IFN-gamma . To determine the mechanisms of established resistance to L . donovani, rechallenged immune BALB/c mice were treated with T cell- and lymphokine-depleting mAb or cyclosporin A . In the liver, resistance to rechallenge was inhibited by treatment with anti-Lyt 2 but not anti-L3T4 mAb . Resistance was also impaired by anti-IL-2 treatment but not by anti-IFN-gamma mAb . The hepatic granulomatous response to rechallenge, however, was not impaired by either anti-Lyt 2 or anti-IL-2 mAb nor by anti-L3T4 or anti-IFN-gamma treatment . In contrast, cyclosporin A suppressed granuloma formation but not antileishmanial activity . These results indicate a particularly important antileishmanial host defense role for Lyt 2+ cells and IL-2 in sensitized animals, and when compared to prior observations in L . donovani-infected naive mice, suggest that 1) discrete T cell- and lymphokine-dependent mechanisms are involved in initial acquisition of resistance vs established immunity, 2) more than one mechanism can mediate the development of tissue granulomas, and 3) granuloma formation by itself may not be required nor necessarily sufficient to confer antimicrobial activity. J Immunol, 1992 Mar 15, 148(6), 1829 - 34 Growth inhibition of Francisella tularensis live vaccine strain by IFN-gamma-activated macrophages is mediated by reactive nitrogen intermediates derived from L-arginine metabolism; Anthony LS et al.; We have examined the abilities of the recombinant murine lymphokines IFN-gamma, granulocyte-macrophage (GM)-CSF, and IL-4 to stimulate the in vitro antimicrobial activity of macrophages against the live vaccine strain (LVS) of Francisella tularensis . Resident peritoneal macrophages from C57BL/6 strain mice were cultured overnight with IFN-gamma, GM-CSF, or IL-4, and then infected with LVS . In macrophages treated with IFN-gamma, the growth of LVS was suppressed by a factor of 100- to 1000-fold in comparison with untreated cells . This effect was dose-dependent and was enhanced by the addition of LPS . In contrast, macrophages treated with either GM-CSF or IL-4 exhibited no such enhanced antitularemic activity, even in the presence of LPS . Because reactive nitrogen intermediates derived from L-arginine metabolism have been implicated in the killing of various infectious organisms, we evaluated the possibility that such a mechanism might contribute to the antitularemic activity of IFN-gamma-stimulated macrophages . Macrophages were treated with NG-monomethyl-L-arginine (NMMA), an inhibitor of L-arginine metabolism in mammalian cells, during the activation procedure and throughout the course of infection . NMMA had no effect on the growth of LVS in unstimulated macrophages . In macrophages activated with IFN-gamma, however, NMMA suppressed their capacity to inhibit LVS growth . This effect was proportional to the dose of NMMA added and reversible by supplementing the medium with additional L-arginine, and there was a direct correlation between the production of nitrite by activated macrophages and their ability to inhibit LVS growth . Furthermore, the growth of LVS was inhibited by nitrogen metabolites in a cellfree system . The results of this study indicate that the mechanism of action of IFN-gamma on the resistance of macrophages to LVS growth is related, at least in part, to the production of reactive nitrogen metabolites. Clin Pharm, 1992 Mar, 11(3), 246 - 54 Systemic absorption of intraperitoneal antimicrobials in continuous ambulatory peritoneal dialysis; O'Brien MA et al.; The factors that influence drug movement across the peritoneum are presented, and the feasibility of administering antimicrobials intraperitoneally to treat systemic infections in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is explored . Antimicrobials are often administered intraperitoneally to treat peritonitis in patients undergoing CAPD . It would be advantageous to administer antimicrobials by the same route to treat systemic infections as well . Factors that determine the propensity of a drug to cross the peritoneal membrane include molecular weight, protein binding, volume of distribution, ionic charge, water or lipid solubility, the permeability and surface area of the peritoneum, blood flow rate, dialysate dwell time, and the concentration of dextrose in the dialysate . The bioavailability of i.p . drugs has been determined (1) by measuring the area under the plasma concentration-time curve (AUC) of an i.p . dose and comparing it with the AUC of the same dose given i.v . and (2) by estimating the residual drug content in the dialysate after a specified dwell period . Pharmacokinetic studies show that the bioavailabilities of antimicrobials given intraperitoneally in patients undergoing CAPD range from 50% to 92% . Vancomycin has been the agent most widely studied . Serum antimicrobial concentrations achieved by this route of administration are in many cases similar to those accomplished by the i.v . route and within the therapeutic range . Dosage regimens based on the pharmacokinetic data have been suggested; however, their efficacy has not been formally documented . The intraperitoneal route may have a role in the treatment of systemic infections in peritoneal dialysis patients, but specific recommendations cannot be made until clinical studies have been performed. Clin Pharm, 1992 Mar, 11(3), 223 - 35 Gram-negative sepsis, the sepsis syndrome, and the role of antiendotoxin monoclonal antibodies; Barriere SL et al.; The incidence and mortality, pathogenesis, clinical manifestations, and management of sepsis and the sepsis syndrome are reviewed, and the use of antiendotoxin monoclonal antibodies to treat patients with sepsis is discussed . The sepsis syndrome and septic shock are induced by the presence of endotoxin, a lipopolysaccharide found in the outer membrane of gram-negative bacteria . Proper management of gram-negative sepsis includes appropriate antimicrobial therapy, fluids and electrolytes, nutritional support, administration of vasopressors, and mechanical ventilation if necessary . To date, two antiendotoxin monoclonal antibodies have been produced and subjected to extensive clinical testing . HA-1A, a human cell line-derived monoclonal immunoglobulin M (IgM) antibody that contains only a small fragment of murine protein, was tested in one trial . HA-1A significantly reduced mortality in patients with sepsis and gram-negative bacteremia and produced better resolution of major morbidities than placebo in those patients . E5, an IgM antibody produced entirely via murine monoclonal antibody technology, was evaluated in two trials . Results from the first trial showed that E5 significantly reduced mortality in patients with gram-negative infection who were not in refractory shock . In contrast, results from the second trial did not show any significant reduction in mortality among patients with gram-negative infection who received E5 . However, resolution of major morbidities occurred more frequently among E5 recipients in both trials . HA-1A and E5 were both well tolerated in the trials . The cost of therapy is expected to be $3000-$4000 per treatment course . The antiendotoxin monoclonal antibodies represent the next step along the path toward important reductions in morbidity and mortality from gram-negative infection . However, the financial implications of the use of HA-1A and E5 are enormous, and stringent patient selection criteria for administration of these products will have to be developed. Chem Pharm Bull (Tokyo), 1992 Mar, 40(3), 612 - 6 Purines . LI . Synthesis and biological activity of hypoxanthine 7-N-oxide and related compounds; Ogawa K et al.; A detailed account is given of the first chemical synthesis of hypoxanthine 7-N-oxide (5), which started from coupling of 6-chloro-5-nitro-4(3H)-pyrimidinone (7) with N-(4-methoxybenzyl)phenacylamine, generated in situ from the hydrochloride (8), and proceeded through cyclization of the resulting phenacylaminopyrimidinone (9) and removal of the 4-methoxybenzyl group . The results of catalytic hydrogenolysis, methylation followed by catalytic hydrogenolysis, and rearrangement under acidic conditions of 5 supported the correctness of the assigned structure . An ultraviolet spectroscopic approach suggested that the neutral species of 5 exists in H2O mainly as the N(7)-OH tautomer (21) . In the in vitro bioassay of antileukemic activity against murine L5178Y cells, 5 was weakly cytotoxic, with IC50 of 100 micrograms/ml . It did not show any antimicrobial activity even at 1000 micrograms/ml . None of the 9-(4-methoxybenzyl) (11) and O-methyl (12, 13, and 14) derivatives was found to be antileukemic or antimicrobial. Ginecol Obstet Mex, 1992 Mar, 60, 61 - 6 {Glucose determination as prognosis index of intra-amniotic infection}; Bustos Lopez HH et al.; Intraamniotic infection is a frequent problem in Obstetrics, and is related with an important maternal and fetal impact, being important pre-term delivery and premature rupture of membranes . The "golden" test for this entity is bacteriological culture . Its use is limited in function of time (more than two days) and disponibility . The rapid diagnosis of infection in vital to start antimicrobial management and evaluation of uterine evacuation . Low concentrations of glucose (G) have been used as prognostic of infection in different biological compartments . The objective of this study is to evaluate the usefulness of G as prognostic index of intraamniotic infection (PIIAI) as compared with Gram tincture (GT) and bacteriological culture . Sixty four patients were included . Group I (n = 33) with infection, and group II (n = 31) without infection . Average of G for group I was 19.96 +/- 07.61 ES and 114.46 +/- 20.09 ES for the group II, with p less than 0.001 . The sensitivity (S), specificity (Sp), positive predictive value (+PV) and negative (-PV) for a concentration of G in amniotic fluid less than 15 mg/dl was 72, 77, 77 and 72% respectively . The S, Sp +PV and -PV for G minor than 10 mg/dl was 69, 87, 85 and 73% . Gram tinction had a S, Sp +PV and -PV of 57, 83, 79, 65% . If both determinations are put together (G and GT), one sees and S of 88%, Sp 77% +PV 80% and -PV 85%.(ABSTRACT TRUNCATED AT 250 WORDS) Baillieres Clin Gastroenterol, 1992 Mar, 6(1), 1 - 26 Medical management of severe inflammatory disease of the rectum and distal colon: non-nutritional aspects; Polson RJ et al.; Rectal bleeding is the cardinal symptom in patients with inflammation of the rectum, and initial management must be directed at establishing an underlying diagnosis . In many patients in the Western World this will be idiopathic inflammatory bowel disease, although in all cases other causes such as infection must be excluded . Idiopathic proctitis is usually due to either ulcerative colitis or Crohn's disease, and in both conditions corticosteroids, either systemic or topical, provide the mainstay of treatment . The 5-aminosalicylic acid drugs are helpful in both acute and maintenance treatment, again given either systemically or topically, while metronidazole is of value in patients with Crohn's disease . In those with refractory proctitis alternative agents such as azathioprine, immunomodulating drugs and barrier agents may be useful . Severe inflammation of the rectum secondary to pelvic irradiation will also usually respond to topical steroid therapy, although sucralfate enemas may be equally successful; in resistant cases other treatments may be needed . Infective proctitis, when diagnosed, may require treatment with specific antimicrobial agents. Ann Pediatr (Paris), 1992 Mar, 39(3), 195 - 201 {A national survey on the criteria of prescription antibiotic therapy in nasopharyngitis in pediatric practice}; Cohen R; Although nasopharyngitis usually results from a viral infection, it is the leading cause of use of antimicrobials in pediatric patients . A study of the criteria used by pediatricians to prescribe antimicrobials in uncomplicated nasopharyngitis was undertaken . Each of 700 pediatricians enrolled ten consecutive patients with uncomplicated nasopharyngitis . Use of antimicrobials was left to the discretion of the physician . Antimicrobials were used in 59% of pediatric patients evaluated for nasopharyngitis . Criteria considered as the most important for deciding to use antimicrobials induced purulent secretions (87.2%), congestion of both tympanic membranes (82.8%), cough (79.2%), fever greater than 39 degrees C (77.2%), and a history of otitis media (69.8%) . Data on the outcome was available for 69% of patients . Acute otitis media was the main complication, with a rate of 7.7%; this rate was lower in the treated group (5.4%) than in the untreated group (10.9%) . A positive history for otitis media and the appearance of the eardrums at evaluation were the best predictors of otitis media. J Appl Bacteriol, 1992 Mar, 72(3), 258 - 61 Kinetic evaluation of claimed synergistic paraben combinations using a factorial design; Gilliland D et al.; The antimicrobial effects of methyl and propyl parabens are investigated, with Escherichia coli as test organism, with a view to determining whether the parabens act synergistically . At appropriate concentrations, the parabens killed E . coli cells according to first order kinetics and the bactericidal effects were quantified by the first order kill rate constants . Combinations of methyl or propyl parabens, at concentrations which slow down or inhibit bacterial growth when used singly, produced definite kill . In this sense, the parabens are therefore synergistic since in combination they produce an effect which is not observed when they are used singly . This effect is not true synergism as shown by the results of our experiments with a factorial design . Analysis of variance indicated no significant interaction between the two parabens. Pediatr Infect Dis J, 1992 Mar, 11(3), 189 - 93 Comparison of erythromycin estolate and erythromycin ethylsuccinate for treatment of pertussis . The Erythromycin Study Group; Hoppe JE; In an open randomized multicenter study 190 culture-positive pediatric ambulatory pertussis patients were treated for 14 days with either erythromycin estolate (EST) (n = 93; 40 mg/kg/day divided in 2 doses) or erythromycin ethylsuccinate (ETH) (n = 97; 60 mg/kg/day divided in 3 doses) . On day 14 Bordetella pertussis was recovered from cultures of 2 patients (2.2%) treated with EST and 1 patient (1.0%) treated with ETH . Despite the fact that 151 patients (79.4%) had reached the early paroxysmal stage at initiation of antimicrobial therapy, clinical improvement was seen in the majority (reduced frequency and severity of coughing: EST, 77.4 and 67.7%; ETH, 74.2 and 63.9%, respectively) . Drug-related side effects were noted in 11 patients (11.8%) treated with EST and 16 patients (16.5%) treated with ETH (P greater than 0.05) and consisted mainly of minor gastrointestinal complaints . Erythromycin estolate in a lower dose administered only twice a day was equivalent to erythromycin ethylsuccinate in all aspects and proved to be adequate antimicrobial treatment for pertussis patients. Clin Infect Dis, 1992 Mar, 14 Suppl 1, S130 - 3 Laboratory evaluation of antifungal agents: a brief overview; Rinaldi MG; The increasing incidence and significance of human mycotic diseases has prompted concurrent interest in the development and evaluation of antifungal drugs . There has never been a period in medicine when the number of antimycotic agents, either commercially available or undergoing clinical investigation, is as great as at present . An integral part of new antimicrobial development is the laboratory evaluation, both in vivo and in vitro, of such agents . Each of these aspects of laboratory testing offers distinct limitations and advantages; however, such evaluation is critical for continued success in the quest for nontoxic, inexpensive, and efficacious antifungal agents. Clin Infect Dis, 1992 Mar, 14(3), 720 - 40 Oxygen tensions and infections: modulation of microbial growth, activity of antimicrobial agents, and immunologic responses; Park MK et al.; Oxygen tensions play an important role in the outcome of infections . Oxygen is cidal or static for microorganisms that lack defenses against oxidants . Hyperoxia and hyperbaric oxygen exert antimicrobial effects by increasing the intracellular flux of reactive oxygen species . In bacteria, such species cause DNA strand breaks, degradation of RNA, inhibition of amino acid biosynthesis, and inactivation of membrane transport proteins . Oxygen tensions also affect the activity of antimicrobial agents . In general, hyperoxia potentiates while anaerobiosis decreases the activity of many antimicrobial drugs . With regard to host defenses, hyperoxia elevates oxygen tensions in infected tissues to levels that facilitate oxygen-dependent killing by leukocytes . Prolonged hyperoxia inhibits DNA synthesis in lymphocytes and impairs chemotactic activity, adherence, phagocytic capacity, and generation of the oxidative burst in polymorphonuclear leukocytes and macrophages. Vet Clin North Am Food Anim Pract, 1992 Mar, 8(1), 29 - 56 Pharmacologic considerations in the management of peripartum conditions in the cow; Gilbert RO et al.; As is true with the use of drugs in veterinary medicine in general, there are many controversial issues in the management of peripartum conditions in the cow . For example, the use of PG versus antibacterial drugs in the management of postpartum uterine infections has advocates for the use of either approach . Intrauterine versus systemic administration of antibacterial drugs for the prophylaxis or treatment of postpartum metritis is another area of debate . Clearly, more research is needed in this area . Equally clearly, however, the research results that are available are being disregarded on a daily basis . In considering this discussion of the use of drugs in the peripartum period, one is struck by the frequency that optimum drug therapy of a condition relies on the extralabel use of nonapproved preparations . What guidelines are available to the practitioner in this regard? One example is lack of availability of appropriate dosage regimens or withdrawal times for food derived from treated animals . Unfortunately, pharmacokinetic and residue studies that would aid in establishing guidelines generally are not available and, in most instances, are not forthcoming . Extrapolation of data from other species to the ruminant or extrapolation of information from one drug to a related compound (such as prediction of residue and withdrawal data from an approved aminoglycoside, dihydrostreptomycin, to another unapproved drug, gentamicin) is fraught with difficulties . The need for research in this area is obvious, and lack of such information is one of the major dilemmas in trying to establish rational drug therapy in the food-producing animal . Recent developments in drug therapy have led to innovative approaches for the management of peripartum and other diseases in cattle . The use of PG in the treatment of reproductive disorders, so commonplace and widely accepted in contemporary veterinary practice, is a relatively recent approach that continues to be refined with the development of new, more potent, more specific PG analogs . What will be the role of ceftiofur, a potent, third-generation cephalosporin that currently is approved only for the treatment of respiratory infections in cattle, in the management of reproductive tract infections? The fluoroquinolones, which represent a novel approach to the control of infectious diseases, are being increasingly used in veterinary and human medicine, and one may predict that these powerful