Antimicrobials

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 antimicrobial drugs will find application in bovine practice, including for the treatment of peripartum infections . Pharmacologic manipulation of immune and defense mechanisms also is an approach with some promise.(ABSTRACT TRUNCATED AT 400 WORDS)

Vet Clin North Am Food Anim Pract, 1992 Mar, 8(1), 17 - 28
Treatment of subclinical mastitis; Tyler JW et al.; Topics addressed in this article include applied pharmacology of the bovine mammary gland, principles of antibiotic sensitivity testing, mechanisms of antimicrobial resistance, causes of treatment failures, diagnostic considerations, and therapy of specific subclinical mastitis syndromes . Recent research concerning systemic therapy of subclinical mastitis is highlighted and critically reviewed . Limitations of antibiotic sensitivity testing are discussed . The lack of proven, efficacious therapy for many subclinical mastitis syndromes is emphasized.

J Histochem Cytochem, 1992 Mar, 40(3), 367 - 78
A novel peptide-producing cell in Xenopus: multinucleated gastric mucosal cell strikingly similar to the granular gland of the skin; Moore KS et al.; We have characterized a novel peptide-containing cell within the gastric mucosa of Xenopus laevis . The cell is a spherical, multinucleated syncytial structure containing a cytoplasmic space filled with dense rice-shaped granules, and is strikingly similar in morphology to the well-studied granular gland of the amphibian skin . Immunohistochemical and immunogold methods were used to demonstrate that several peptides previously isolated from the granular glands of the skin, including the antimicrobial peptides magainin and PGLa (a peptide with amino-terminal glycine and carboxy-terminal leucinamide), are also stored in granules present in these enteric cells . These data demonstrate that this enteric peptide-producing cell is strikingly similar both morphologically and biochemically to the granular gland, previously considered a highly specialized structure of the amphibian integument . This novel gastric mucosal cell, which we have designated a "granular multinucleated cell," is distinct in its morphology and its diversity of stored peptide products from other well-characterized peptide-containing cells in the vertebrate gastrointestinal tract.

Mayo Clin Proc, 1992 Mar, 67(3), 276 - 87
Antiparasitic agents; Rosenblatt JE; In recent years, introduction of new and more effective agents has improved the overall therapy for parasitic infections . This field, however, is still plagued by numerous problems, including the development of resistance to antimicrobial agents (especially with malaria), unavailability of agents in the United States or lack of approval by the Food and Drug Administration, and major toxicities or lack of experience in pregnant women and children, which limits use in these groups of patients . Widespread resistance of Plasmodium falciparum to chloroquine and other agents has complicated the treatment and prophylaxis of this type of malaria . A combination of quinine and Fansidar is usually effective oral therapy for falciparum malaria; quinidine may be administered if intravenous therapy is needed . Mefloquine, which is currently recommended for prophylaxis against chloroquine-resistant P . falciparum, is also effective for single-dose oral treatment, although this regimen has not yet been approved by the Food and Drug Administration . Metronidazole has been widely used for treatment of gastroenteritis due to Entamoeba histolytica and Giardia lamblia (not approved by the Food and Drug Administration for the latter) and is considered safe and effective . A new macrolide, azithromycin, has been reported to be effective for cryptosporidiosis in experimental animals; currently, no effective therapy is available for human infections . Combinations of sulfonamides with other antifolates, trimethoprim or pyrimethamine, are recommended therapy for Pneumocystis carinii pneumonia or toxoplasmosis, respectively . Therapies for the various types of leishmaniasis and trypanosomiasis are complex, often toxic, and often of limited efficacy . The benzimidazoles are effective for roundworm infections, although thiabendazole has severe toxic effects . The recent introduction of ivermectin has revolutionized the treatment and control of onchocerciasis . Another relatively new agent, praziquantel, is a true broad-spectrum anthelmintic agent that is effective against most trematodes, many adult cestodes, and larval cestodes as well (especially cysticerci of Taenia solium).

J Surg Res, 1992 Mar, 52(3), 276 - 85
Differential inhibition of human basal keratinocyte growth to silver sulfadiazine and mafenide acetate; McCauley RL et al.; The impact of topical antimicrobial agents on improving the survival of patients with major thermal injuries is significant . However, the effects of these agents on cells responsible for wound healing has only recently received attention . Fresh human basal keratinocytes were grown in serum-free modified MCDB 153 medium under standard tissue culture conditions . Cells were subsequently exposed to concentrations of silver sulfadiazine and mafenide acetate as low as 1/100 of that used clinically over a period of 5-7 days . Cellular responses documented with hemocytometer cells counts, cellular protein assays, phase-contrast microscopy, and transmission electron microscopy show only severe toxicity to mafenide acetate . Such data imply that inhibition of wound epithelialization is greater with the use of mafenide acetate than with the use of silver sulfadiazine.

J Infect Dis, 1992 Mar, 165(3), 513 - 7
L-arginine-dependent reactive nitrogen intermediates and the antimicrobial effect of activated human mononuclear phagocytes; Murray HW et al.; The L-arginine-dependent generation of reactive nitrogen intermediates (RNI) has been identified as a key intracellular antimicrobial mechanism of activated mouse macrophages . To determine the role of this mechanism in the activity of human mononuclear phagocytes, monocyte-derived macrophages activated in vitro by interferon (IFN)-gamma and monocytes from patients receiving IFN-gamma as therapy were treated with NG-monomethyl-L-arginine (NMA) or arginase . Neither competitive inhibition of L-arginine metabolism (NMA) nor depletion of L-arginine (arginase) altered intracellular antimicrobial activity against Toxoplasma gondii, Chlamydia psittaci, or Leishmania donovani . In contrast, NMA and arginase readily reversed the antimicrobial effect of mouse peritoneal macrophages stimulated either in vitro or in vivo by IFN-gamma, and activated mouse but not human cells could be induced to release enhanced levels of nitrite . These results suggest that the L-arginine-dependent generation of RNI is a species-restricted macrophage mechanism unlikely to participate in the intracellular antimicrobial activity of IFN-gamma-stimulated human mononuclear phagocytes.

J Neurosci, 1992 Mar, 12(3), 970 - 5
Pentamidine is an N-methyl-D-aspartate receptor antagonist and is neuroprotective in vitro; Reynolds IJ et al.; Acquired immunodeficiency syndrome (AIDS) is frequently associated with dementia . The wide spectrum of neurological abnormalities associated with this dementia may involve a neurotoxin that activates the NMDA subtype of glutamate receptor in neurons . We have found that the antimicrobial agent pentamidine, which is prescribed for AIDS patients for the prophylaxis and treatment of Pneumocystis carinii pneumonia, is an effective NMDA receptor antagonist . Pentamidine inhibited 3H-dizocilpine binding to the NMDA receptor in rat brain membranes at a site separate from glutamate, glycine, and spermidine, with an affinity near 2 microM . Similar concentrations of pentamidine block NMDA-induced increases in intracellular Ca2+ and NMDA-induced currents in cultured forebrain and cortical neurons, apparently without use dependence or voltage dependence, suggesting that pentamidine may represent a novel chemical class of NMDA receptor antagonist . Finally, pentamidine protects neurons from the lethal effects of acute NMDA exposure in vitro . AS pentamidine may accumulate in the brain at relevant concentrations following repeated high-dose parenteral administration, these findings suggest that the drug may be neuroprotective in vivo.

Curr Opin Dent, 1992 Mar, 2, 63 - 79
The potential role of controlled-release delivery systems for chemotherapeutic agents in periodontics; Fiorellini JP et al.; Following advances in periodontal disease etiology and pathogenesis, treatment strategies have evolved to eliminate specific pathogens or suppress the destructive host response . Research indicates that chemotherapeutic agents such as antimicrobials and antimetabolites can alter disease progression; consequently, three delivery systems have been investigated: systemic, topical, and controlled release . Using polymers to control drug administration, controlled-release delivery systems theoretically produce concentration profiles that are more constant and longer lasting than those of other systems . Furthermore, patient compliance can be maximized, and systemic complications avoided . During the past two decades, numerous investigations have been conducted to evaluate the potential role of controlled delivery in periodontal treatment . These investigations fall into two distinct categories: those documenting release kinetics, and those documenting clinical effects . Accordingly, pharmacologic agents can be released from drug polymers at therapeutic levels within the periodontal pocket . Many researchers have demonstrated that controlled delivery of antimicrobial agents such as tetracycline, metronidazole, and chlorhexidine can be effective in reducing the signs of periodontitis . In addition, controlled release of antimicrobial agents can alter the periodontal flora with a decrease in total bacterial mass and pathogenic species . Although the majority of these studies are proof-of-principle trials, many agents have been evaluated with undefined hypotheses, ill-suited outcome variables, unrepresentative patient populations, poor controls, and less-than-ideal therapy applications . The true test of controlled delivery will be the demonstration of its slowing disease progression . While future research will concentrate on developing more ideal polymers and introducing new agents, controlled delivery offers clinicians a potential adjunct or alternative to traditional treatment modalities.

Jpn J Antibiot, 1992 Mar, 45(3), 265 - 9
{Fundamental study on levofloxacin in the field of obstetrics and gynecology}; Soyama Y et al.; We performed a fundamental study on levofloxacin (LVFX, DR-3355), a new synthetic antimicrobial agent, in the field of obstetrics and gynecology . Concentrations in serum and intrapelvic genital organs (various regions in the uterus, ovary and oviduct) were determined following single oral administration . The transport of LVFX into genital tissues was found to be good, with the tissue levels of 0.64-2.13 micrograms/g after oral administration of 100 mg and 0.77-4.86 micrograms/g after administration of 200 mg . These tissue levels of LVFX were higher than those in serum and exceeded the MIC90 values against most causative organisms isolated from the lesions of obstetric and gynecological infections . These data indicate that LVFX should be useful in the field of obstetrics and gynecology.

Jpn J Antibiot, 1992 Mar, 45(3), 258 - 64
Efficacy of a new quinolone, levofloxacin in patients with surgical infections; Morimoto K et al.; The pharmacokinetics and clinical efficacy of levofloxacin (LVFX, DR-3355), an optically pure S(-)-enantiomer of ofloxacin, were studied in patients after surgery . In the pharmacokinetic study, 4 patients undergoing bile drainage were given 2 100-mg tablets by mouth . Peak levels of LVFX were from 2.22 to 4.02 micrograms/ml of plasma at 2-4 hours after the oral administration, and from 7.5 to 11.3 micrograms/ml of bile at 2-6 hours . Forty-three patients with surgical infections, including 16 skin and soft-tissue infections and 12 wound infections, were treated with LVFX . Twenty-eight (70%) of the 40 patients whose results could be evaluated had excellent or good results; 42 (93%) of the 45 causative organisms identified were eradicated . An episode of diarrhea with chills and fever occurred in a 38-year-old man . The results suggested that LVFX has satisfactory antimicrobial effects in surgical infections.

East Afr Med J, 1992 Mar, 69(3), 126 - 9
Layman's perception of antimicrobial agents: a challenge to health education strategy in Zimbabwe; Nyazema NZ et al.; In many developing countries there has not been any systematic analysis of societal beliefs and attitudes towards drug entities, the meaning which is attributed to drugs and their effects and how such meanings might influence drug consumption and health seeking behaviour . It is in many developing countries that a lot of antimicrobial agents are available freely over the counter or on the street . This is said to make the assessment of the therapeutic outcome during their use often very difficult . The present study has shown that continued health education while at the same time paying attention to societal beliefs and attitudes towards infectious diseases and medicines used, is required . The specific aims must be to reinforce beliefs that facilitate appropriate use of antimicrobial agents and to discourage those that impede it.

J Hepatol, 1992 Mar, 14(2-3), 249 - 52
Diuresis increases ascitic fluid opsonic activity in patients who survive spontaneous bacterial peritonitis; Runyon BA et al.; Patients with low protein ascites and deficient ascitic fluid opsonic activity have been shown to be unusually predisposed to development of spontaneous bacterial peritonitis . Survivors of spontaneous peritonitis frequently develop recurrent infection . Diuresis has been shown to increase the ascitic fluid opsonic activity of patients who have never had spontaneous bacterial peritonitis . Patients with adequate opsonic activity are protected from ascitic fluid infection . Theoretically, the subset of patients who develop spontaneous peritonitis may have such severe liver disease that (i) their ascites is refractory to diuretic therapy or (ii) their ascitic fluid opsonic activity does not increase in response to diuresis . In this study, opsonic activity and concentrations of total protein and complement components were measured in the ascitic fluid of 11 patients who were hospitalized with spontaneous bacterial peritonitis and who responded to oral diuretics . The mean values of all of these parameters were found to increase significantly comparing the end-of-diuresis samples to the specimens that were diagnostic of ascitic fluid infection . Patients who survive spontaneous bacterial peritonitis are able to increase their ascitic fluid total protein and opsonic activity in response to diuresis . This increase in endogenous antimicrobial activity may help prevent recurrence of ascitic fluid infection.

Med Lab Sci, 1992 Mar, 49(1), 8 - 11
Diagnosis of bacterial vaginosis in a routine diagnostic laboratory; Burns FM et al.; Vaginal swabs from 299 hospital and general practitioners' patients were examined for Gardnerella vaginalis by Gram film and by culture, G . vaginalis was isolated in 12% of cultures . Comparison between the 'clue' cell and culture methods suggested that the former is a rapid, acceptable routine screening method for the detection of G . vaginalis . The value of the traditional method of identifying G . vaginalis by sensitivity testing is questioned . All specimens were also examined by Gram film and culture, for the presence of Mobiluncus spp, which was detected in 8.4% of specimens by Gram film but only 0.7% by culture . From a questionnaire returned by 84% of clinicians, metronidazole was found to be the most commonly used antimicrobial agent for the treatment of G . vaginalis, and in all but one case appeared to be clinically effective.

Clin Oral Implants Res, 1992 Mar, 3(1), 42 - 8
Treatment of an early implant failure according to the principles of guided tissue regeneration (GTR); Lehmann B et al.; The present case report demonstrates the application of guided tissue regeneration (GTR) in combination with antimicrobial therapy for the treatment of an early implant failure . This treatment approach both prevented further loss of bone as well as led to the regeneration of lost bone . By means of color-converted digital subtraction images, remodelling of the tissues adjacent to the defect was documented as early as one month postsurgically . The images demonstrated "bone-fill" in the apical portion of the defect and resorptive changes at the bone crest . This case report demonstrates that combined regenerative and antimicrobial therapy may be a successful treatment approach restoring osseointegration of dental implants following loss of bone due to infection . Continuously increasing bone-fill inside the defect was documented when comparing the radiograph obtained immediately before the GTR procedure and at months 1, 2, 4, 5 and 6 of the healing period, respectively . Clinical measurement obtained at the time of the surgery and at the time of the membrane removal confirmed the radiographic evidence of bone-fill by demonstrating new tissue resistant to probing in close contact to the implant surface at the site of the previous defect . Antimicrobial therapy included an antibiotic regimen during the 1st month of healing as well as topical rinses with an antiseptic (chlorhexidine) over the entire healing period of 6 months . As a result of this treatment approach, the implant was saved and could be used as an abutment for a bridge reconstruction.

J Med Assoc Thai, 1992 Mar, 75 Suppl 2, 6 - 10
Hospital acquired Janthinobacterium lividum septicemia in Srinagarind Hospital; Patijanasoontorn B et al.; Nine patients admitted to the intensive care unit, Srinagarind Hospital, who had septicaemia by J . lividum were reported . Seven patients died, one directly of septicaemia, despite intensive antimicrobial therapy . Investigation revealed that the sources of infection were: special mouth wash solution, distilled water and normal saline used in the ward . After changing to uncontaminated solution and more meticulous care of medical equipment, there was no evidence of the micro-organism after one year follow-up.

Cesk Farm, 1992 Mar, 41(2), 40 - 6
{Antimicrobial activity of selected aqua-carboxyl-cupric complexes}; Sokolik J et al.; The activity of compounds of different structural types of aqua-complexes of the composition Cu(R-COO)2.nH2O-methoxybenzoatocupric complexes, R = 2-, 3- and 4-methoxyphenyl (n = 1, 1 and 3); aryloxyacetatocupric complexes, R = phenoxymethyl (n = 3), 2-, 3- and 4-chlorophenoxymethyl (n = 4, 2 and 2) and 1-naphthoxymethyl (n = 4), and furthermore isomeric furanecarboxylato-(R = 2- or 3-furyl, n = 3, or 1) and thiophencarboxylatocupric complexes (R = 2- or 3-thienyl, n = 1 and 1), was examined by the methods of the 1st screening on selected anthropo- and phytopathogenic microorganisms . The effects of all aqua-complexes (suspension dosage form) on the representatives of bacteria and yeasts are minimal . On the other hand, the effect of these substances on the causative agents of dermatomycoses (Trichophyton terrestre, Microsporum gypseum) in the case of methoxybenzoato- and furoatocupric complexes achieves a MIC value of 500 micrograms/cm3 and lower . The activity against phytopathogenic fungi (both in vitro and in vivo experiments) is generally relatively low at 0.05% concentration of active ingredients (dispersible powders) . At the same time the antimicrobial activity of the pertinent free carboxylic acids was investigated in relation to the cupric salts being formed . They are able to form the required pharmacoactive form prevalently as late as they are in the form of aqua-carboxylatocupric complexes.

Appl Microbiol Biotechnol, 1992 Mar, 36(6), 749 - 53
Extracellular production system of heterologous peptide driven by a secretory protease inhibitor of Streptomyces; Taguchi S et al.; The value of a heterologous peptide extracellular production system in Streptomyces using a secretory protease inhibitor, was examined . DNA was synthesized encoding apidaecin 1b (AP1), an interesting antibacterial peptide discovered in lymph fluid of the honeybee, and was joined to the Streptomyces subtilisin inhibitor (SSI) gene via a 12-bp nucleotide sequence corresponding to the amino acid sequence specific for cleavage by blood coagulation factor Xa . The fusion protein (SSI-AP1) could be expressed and excreted efficiently into the medium by culturing S . lividans 66 harbouring a plasmid vector constructed for SSI secretion, into which the synthetic DNA was introduced . Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and amino acid analysis of the purified SSI-AP1 provided reasonable results of molecular size and composition value . Interestingly, SSI-AP1 protein showed bifunctional activity: inhibitory activity of SSI and antibacterial activity of AP1 . The inhibitory activity against Escherichia coli could be also detected after the fusion protein was cleaved by factor Xa . The extracellular production system presented here should provide a useful tool for production, analysis of mode of action, and also for genetic improvement of antimicrobial peptides such as apidaecin.

J Leukoc Biol, 1992 Mar, 51(3), 296 - 9
Soluble TNF and membrane TNF expressed on CD4+ T lymphocytes differ in their ability to activate macrophage antileishmanial defense; Birkland TP et al.; In our studies of host defense against the intracellular parasite Leishmania major, we obtained evidence for a novel mechanism of macrophage activation for antimicrobial defense that involves direct cell contact between CD4+ T lymphocytes and Leishmania-infected macrophages . The mechanism is distinctive as it does not involve secretion of lymphokines but is apparently mediated by the membrane-anchored form of tumor necrosis factor (mTNF; approximately 50-60 kd) present on the surface of the effector T lymphocytes . Furthermore, it is not cytotoxic to the host cell and its expression is antigen specific and genetically restricted . We prepared a Leishmania-specific cloned T-T cell hybridoma line 1B6 (CD4+, TH1) that expresses membrane-bound TNF but does not secrete TNF or other macrophage activators . We now report that 1B6 cells can activate antileishmanial defense in inflammatory macrophages, whereas soluble recombinant murine TNF (sTNF) alone is unable to do so . On the other hand, both 1B6 cells and sTNF can act synergistically with recombinant murine interferon-gamma (IFN-gamma, a known soluble macrophage-activating factor) in activating antimicrobial defense and NO2- release . The effects of 1B6 alone and the synergistic effects of 1B6 and IFN-gamma or sTNF and IFN-gamma are arginine dependent . These results suggest that mTNF may be more efficient than sTNF in macrophage activation and that contact with effector CD4+ lymphocytes that express mTNF may be an important mechanism of host defense.

Eksp Klin Farmakol, 1992 Mar-Apr, 55(2), 11 - 3
{The neurotropic and cardiotropic properties of new amino acid derivatives of isonicotinic acid}; Samvelian VM et al.; Different derivatives of isonicotinic acid are used widely enough as antimicrobial and antituberculous agents . However, their neurotropic and cardiotropic effects have been studied little . The paper is concerned with investigations of these types of the activity of the new derivatives of isonicotinic acid: beta-phenyl-beta-alanine, l-proline, DL-valine, beta-alanine and DL-threonine synthesized for the first time at the Institute of Fine Organic Chemistry, Academy of Sciences of Armenia.

Curr Opin Dent, 1992 Mar, 2, 80 - 90
Host modulation with tetracyclines and their chemically modified analogues; Golub LM et al.; Recent studies have suggested the use of drugs to modulate host response as a new approach in periodontal therapy . In this regard, the tetracycline antibiotics have been found to inhibit host-derived collagenases and other matrix metalloproteinases by a mechanism independent of the antimicrobial activity of these drugs; this effect may suppress connective tissue breakdown during periodontal disease and during a variety of medical disorders including (but not limited to) noninfected corneal ulcers, serious (sometimes life-threatening) skin-blistering diseases, rheumatoid arthritis and osteoarthritis, systemically--as well as locally--induced bone loss, and perhaps even tumor-induced angiogenesis . Two therapeutic strategies based on the host-modulating properties of tetracyclines are currently being developed: 1) the use of low-dose doxycycline (the most potent anticollagenase of commercially available tetracyclines) formulations, which do not appear to result in tetracycline side effects such as the emergence of antibiotic-resistant microorganisms; and 2) the production of a family of chemically modified tetracyclines that have lost their antimicrobial activity, but have retained their anticollagenase activity . A description of several of these compounds and a discussion of their efficacy in inhibiting collagenases in vitro and reducing tissue destruction in several animal models of periodontal and medical diseases is presented.

Nippon Saikingaku Zasshi, 1992 Mar, 47(2), 387 - 93
{In vitro antimicrobial activities of new quinolone antibiotics against Mycoplasma pneumoniae}; Gohara Y et al.; The antimicrobial activities against Mycoplasma pneumoniae of new quinolones (temafloxacin, ofloxacin, ciprofloxacin, enoxacin, and norfloxacin) and of tetracyclines and macrolides as controls were compared . Among new quinolones, temafloxacin, ofloxacin, and ciprofloxacin were more active than enoxacin and norfloxacin against fifty strains of Mycoplasma pneumoniae, giving MIC50 and MIC90 significantly lower than those of the latter two, by the agar-dilution method . The three more active antibiotics in the above assay were then determined for MICs and MBCs by the broth-dilution method . The MICs of every antibiotic except erythromycin determined by both the methods were very similar each other . The MICs of erythromycin determined by the broth-dilution method were ten-times higher than those determined by the agar-dilution method . Temafloxacin and ofloxacin gave MBCs only about four-times higher than MICs, whereas ciprofloxacin, minocycline, erythromycin and josamycin gave MBCs as much as 15 to 1,000-times higher than MICs . From the MICs and MBCs determined by the two assay methods, it is apparent that temafloxacin and ofloxacin, and to a less extent ciprofloxacin, have more potent mycoplasmacidal activities than do macrolides and tetracyclines.

J Antibiot (Tokyo), 1992 Mar, 45(3), 363 - 73
6 alpha-hydroxypenicillanic acid-S(S)-oxide and analogues: synthesis and antimicrobial activity; Roberts JL et al.; The synthesis and in vitro antibacterial activity of a series of 6-oxygenated penicillanic acid sulfoxides is described . 6 alpha-Hydroxypenicillanic acid-S(S)-oxide (1a) exhibits weak Gram-negative antibacterial activity and appears to be similar to amdinocillin (5) in its mode of action . 6 alpha-Hydroxypenicillanic acid-S(R)-oxide (4a) has a broader spectrum of activity, but again is rather weak . The corresponding 6 beta-hydroxy series is essentially devoid of activity.

Dent Update, 1992 Mar, 19(2), 68, 70 - 2, 74
The specific plaque hypothesis and the antimicrobial treatment of periodontal disease; Loesche WJ; According to the specific plaque hypothesis a measurable amount of periodontal disease is due to the overgrowth of specific bacterial types . The author advocates the theory and discusses treatment . This includes techniques for diagnosing the predominant bacterial types, antibiotic therapy and the relevance of regular debridement.

Schweiz Med Wochenschr, 1992 Feb 22, 122(8), 266 - 8
{Role of antibiotics in surgically treated active endocarditis}; Zimmerli W et al.; In a retrospective study of 30 patients in whom a valve was replaced during active endocarditis, the role of the concomitant antimicrobial therapy was analyzed . In 75% of the patients with less than 1 week of adequate treatment before surgery, but only in 13% (p less than 0.001) with at least 1 week of therapy, could the microorganism be cultivated from the excised valve . Patients with bacteria on the valve had a 4-fold increased risk for prosthetic valve endocarditis and 2.7-fold more frequent paravalvular leakage . Therefore, in the absence of severe cardiac failure, the valve replacement should not be performed before the second week of therapy . Patients in whom microorganisms can be cultivated from the valve need a complete postoperative course of antimicrobial therapy.

Gastroenterology, 1992 Feb, 102(2), 493 - 6
Factors influencing the eradication of Helicobacter pylori with triple therapy; Graham DY et al.; Helicobacter pylori infection has been associated with gastritis, duodenal ulcer, gastric ulcer, and the epidemic form of gastric carcinoma . Eradication of H . pylori infection has proven to be difficult . Recently, combinations of antimicrobial drugs have been shown to eradicate greater than 50% of infections; however, the results have proven variable, and the factors influencing effectiveness of therapy are unclear . In the present study, the effectiveness of a triple therapy for eradication of H . pylori infection was evaluated . Triple therapy consisted of 2 g tetracycline, 750 mg metronidazole, and five or eight tablets of bismuth subsalicylate daily in 93 patients (70 with duodenal ulcer, 17 with gastric ulcer, and 6 with simple H . pylori gastritis) . Combinations of a sensitive urea breath test, serology, culture, and histology were used to confirm the presence of infection, eradication, or relapse . Eradication was defined as inability to show H . pylori greater than or equal to 1 month after ending therapy . The overall eradication rate was 87% . The factors evaluated for their effect on predicting eradication included age, gender, type of disease, duration of therapy, amount of bismuth subsalicylate {five or eight Pepto-Bismol tablets daily (Procter & Gamble, Cincinnati, OH)}, and compliance with the prescribed medications . Stepwise regression showed that compliance was the most important factor predicting success; the success rate was 96% for patients who took greater than 60% of the prescribed medications and 69% for patients who took less . For those taking greater than 60% of the prescribed therapy, the eradication rates were similar (a) for patients receiving therapy for 14 days or when tetracycline and bismuth subsalicylate were taken for an additional 14 days; (b) for patients with duodenal ulcer, gastric ulcer, and simple H . pylori gastritis; and (c) whether five or eight bismuth subsalicylate tablets were taken . It is concluded that triple therapy is effective for eradication of H . pylori and that future studies need to take compliance into account for comparisons between regimens.

J Biol Chem, 1992 Feb 5, 267(4), 2228 - 33
Isolation and characterization of a novel class of plant antimicrobial peptides form Mirabilis jalapa L . seeds; Cammue BP et al.; We have isolated from seeds of Mirabilis jalapa L . two antimicrobial peptides, designated Mj-AMP1 and Mj-AMP2, respectively . These peptides are highly basic and consist of 37 and 36 residues for Mj-AMP1 and Mj-AMP2, respectively . Both peptides contain three disulfide bridges and differ from one another only by 4 amino acids . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the reduced and unreduced peptides suggests that the peptides associate into dimers in their native form . The Mj-AMPs exhibit a broad spectrum of antifungal activity since they are active against all 13 tested plant pathogenic fungi . Concentrations required for 50% inhibition of fungal growth vary from 6 to 300 micrograms/ml for Mj-AMP1 and from 0.5 to 20 micrograms/ml for Mj-AMP2 . These peptides were also active on two tested Gram-positive bacteria but were apparently nontoxic for Gram-negative bacteria and cultured human cells . Although the Mj-AMPs show sequence similarity to mu-agatoxins, a class of insecticidal neurotoxic peptides isolated from the venom of spiders, they do not affect pulse transmission in insect nerves.

Schweiz Med Wochenschr, 1992 Feb 1, 122(5), 158 - 60
{Pericardectomy and acute infectious pericarditis}; Niederhauser U et al.; Between 1980 and 1990 12 patients (5 male, 7 female) were operated on for acute infectious pericarditis at a mean age of 42 years . The infections were 6 bacterial (purulent 4, abscess 2), 4 tuberculous, 1 viral and 1 Candida . Pericarditis resulted from contiguous spread of infection from bilateral pneumonia in 3 patients, from subphrenic abscess in 2 and followed bacteremia in 1 . Clinical signs were: tamponade/shock in 9, elevated jugular venous pressure in 11, edema in 6, hepatomegaly in 6, ascites in 1, and pericardial friction rub in 3 . A preoperative pericardiocentesis in 9 patients allowed only 4 positive microbiological diagnoses and was an insufficient drainage in all cases . The preoperative mean NYHA class was 3.3 . The pericardectomy was total in 9 patients and partial in 3 . Total mortality was 1/12 patients (8%) with one late death due to recurrent tuberculous pericarditis . No patient with purulent pericarditis died . Another recurrence occurred 6 months after acute viral pericarditis . Atrial fibrillation in one patient was the only postoperative complication . After a mean follow-up period of 48.5 months no cardiac constriction had occurred in 11 surviving patients Actuarial survival after pericardectomy is 100% after 1 month and remains 91% after 5 years . The mean NYHA class has significantly improved to 1.2 (p less than 0.05) at the end of the follow-up . We conclude that pericardectomy combined with a specific antimicrobial therapy is a safe treatment for acute infectious and especially purulent pericarditis with low mortality and excellent longterm results . Early pericardectomy allows rapid decompression of the heart, removal of intrapericardial adhesions and infected tissue and prevents late constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Otolaryngol Head Neck Surg, 1992 Feb, 106(2), 181 - 8
Characterization of the immune barrier in human olfactory mucosa; Mellert TK et al.; Immunologic defense factors in the human olfactory mucosa were localized immunohistochemically . Olfactory epithelium was identified with an antiserum to olfactory marker protein, specific for olfactory receptor neurons . Constituents of the secretory immune system, including IgA, IgM, secretory component, and J chain, were localized in the acinar and duct cells of Bowman's glands and in the mucociliary complex . In addition, B lymphocytes in the lamina propria near Bowman's glands displayed immunoreactivity for IgA, IgM, and J chain . Immunostaining also localized other humoral factors . Immunoreactivity for IgG was present throughout the stroma and in B lymphocytes in the lamina propria . Antibody to IgD stained numerous B lymphocytes clustered below the basement membrane . Antibody to IgE stained similarly distributed cells; toluidine blue staining demonstrated that many were mast cells . In addition, antibodies to IgD and IgE stained occasional intraepithelial B lymphocytes or mast cells . Two antimicrobial proteins, lactoferrin and lysozyme, were localized in Bowman's glands and the mucociliary complex . Thus, the human olfactory mucosa, which provides a direct neural route for pathogens to the brain, is a site for synthesis and secretion of immune and other defense factors.

Diagn Microbiol Infect Dis, 1992 Feb, 15(2 Suppl), 43S - 47S
A review of traditional resistance surveillance methodologies and infection control; Koontz FP; The hospital affords an excellent environment for the proliferation of pathogenic bacteria and for the selection of antimicrobial-resistant strains . This article traces the evolution of microbiologic surveillance techniques and highlights some of the more effective means of infection control . Traditional surveillance methods relied on nationwide antimicrobial susceptibility data for practical information regarding the nature of infectious disease trends in order to guide the selection of appropriate empiric antibiotic therapy . The application of nationwide antibiograms to the local hospital setting may mask the local emergence of rapidly developing resistances, such as chromosomally mediated type-I beta-lactamase resistance, which has been associated with increased use of certain cephalosporins . "Focused surveillance" techniques yield improved detection of emerging localized resistances within specific hospital units . In addition to unit-specific surveillance, many hospitals are now observing the advantages of an infection site-specific monitoring program . Judicious use of newer antimicrobials and implementation of detailed hospitalwide surveillance procedures will help to minimize the spread of epidemic and resistant infections . It remains the responsibility of the infection control and antibiotic utilization or advisory committees to make appropriate recommendations concerning the selection, restriction, and proper use of the newer extended-spectrum antibiotics . The clinical microbiology laboratory as a source of information remains a key participant in a quality program.

Obstet Gynecol, 1992 Feb, 79(2), 179 - 84
Why patients fail antibiotic prophylaxis at cesarean delivery: histologic evidence for incipient infection; Gonik B et al.; A prospective, blinded study was conducted to test the hypothesis that antimicrobial prophylaxis failure after cesarean delivery is associated with incipient infection of the uterus, as determined by histologic evaluation of bacterial invasion and acute inflammatory cell response . One hundred nineteen patients undergoing cesarean delivery and receiving antibiotic prophylaxis were included in this study . At the time of the operation, a hysterotomy biopsy was obtained for hematoxylin and eosin staining . Marked histologic differences were noted in decidual inflammation, myometrial inflammation, and myometrial polymorphonuclear cell invasion in those patients who subsequently developed endometritis (N = 7) compared with subjects without postpartum endometritis . Using two techniques for in situ identification of bacteria within myometrial tissue (acridine orange and fluorescein DNA probe to bacterial ribosomal RNA), all clinically infected parturients demonstrated large numbers of organisms in the myometrial layer of the biopsy specimen, compared with few organisms seen in a matched subset of noninfected controls . These data support the concept that incipient infection at the time of cesarean delivery may limit the effectiveness of antimicrobial prophylaxis . Use of rapid-diagnosis methodologies may allow timely identification of these at-risk patients so that therapeutic antibiotics can be initiated.

Arzneimittelforschung, 1992 Feb, 42(2), 152 - 5
Synthesis and structure-antimicrobial activity relationships of quaternary ammonium derivatives of perhydropyrrolo-{3,4-c}pyridine; Altomare C et al.; A large homologous series of quaternary ammonium derivatives of perhydropyrrolo{3,4-c}pyridine 5 was synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria . Compounds 5 proved to be always more potent than benzalkonium chloride, taken as reference . Antibacterial activity, expressed as log 1/MIC, was found linearly related to lipophilicity up to C13-C14 homologs, where a break in the linear relationship was observed.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 401 - 7
Use of norfloxacin to study colonization ability of Escherichia coli in in vivo and in vitro models of the porcine gut; Nielsen EM et al.; The colonization resistance conveyed by the intestinal microbiota can prevent colonization of the intestinal system by new strains . In this study, this resistance was partly circumvented by use of the antimicrobial drug norfloxacin . The colonization abilities of two closely related Escherichia coli strains, which were resistant to nalidixic acid and rifampin, respectively, were investigated in minipigs and a two-stage continuous-flow in vitro gut model . Whereas both strains were unable to colonize the intact enteric system in vivo and in vitro, a 3-day norfloxacin treatment modified both systems to allow colonization by the nalidixic acid-resistant strain but not the rifampin-resistant strain . The results indicate the usefulness of norfloxacin to circumvent the normal colonization resistance while keeping a fairly normal microbiota in the gut . The results also indicate that it could be possible to construct in vitro gut models which could distinguish between strains with different gut colonization abilities . Both of these possibilities could come to be used in the study of the colonization and effects in the gut of new bacterial strains, i.e., genetically modified microorganisms.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 387 - 93
Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice; Tomioka H et al.; Newly synthesized benzoxazinorifamycin, KRM-1648, was studied for its in vivo anti-Mycobacterium avium complex (MAC) activities . When the MICs were determined by the agar dilution method with Middlebrook 7H11 agar medium, KRM-1648 exhibited similarly potent in vitro antimicrobial activities against the MAC isolated from AIDS and non-AIDS patients, indicating possible usefulness of KRM-1648 against AIDS-associated MAC infections . KRM-1648 exhibited potent therapeutic activity against experimental murine infections induced by M . intracellulare N-260 (virulent strain) and N-478, which has much weaker virulence . Similarly, KRM-1648 exhibited an excellent therapeutic efficacy against M . intracellulare infection induced in NK-cell-deficient beige mice (as a plausible model for AIDS-associated MAC infection), in which a much more progressed state of gross lesions and bacterial loads at the sites of infection were observed . When the infected beige mice were killed at weeks 4 and 8, obvious therapeutic efficacy was seen on the basis of reduction in the incidence and degree of lung lesions and bacterial loads in the lungs and spleen with infections due to M . intracellulare N-241, N-256, and N-260 . In this case, the efficacy was the highest in N-260 infection, followed by strain N-241 . When mice were observed until infection-induced death, survival time of the infected beige mice was found to be prolonged by KRM treatment . However, KRM-1648 was not efficacious in suppressing the progression of pulmonary lesions and the increase in bacterial loads at the sites of infection, including lungs and spleen, at the late phase of infection . This may imply some difficulty with chemotherapy for AIDS-associated MAC infection, even with KRM-1648 treatment, which has excellent in vitro and in vivo anti-MAC activities, as shown in present study.

Indian J Biochem Biophys, 1992 Feb, 29(1), 77 - 81
Role of rusticyanin in the electron transport process in Thiobacillus ferrooxidans; Hazra TK et al.; Effect of diethyl dithiocarbamate (DEDC), an antimicrobial agent, on growth of Thiobacillus ferrooxidans, possibly by inhibiting rusticyanin present in the periplasmic space of the microorganism, has been studied to gain more insight into the electron transport chain in the bioleaching process . DEDC is found to form a stable complex with rusticyanin in solution and also in polyacrylamide gel . The spectrum of the complex is identical to that of Cu-DEDC complex, suggesting binding of DEDC with copper moiety of rusticyanin and resulting in inhibition of growth . In vitro reduction of purified rusticyanin by Fe(II) in absence of acid-stable cytochrome c is very slow, indicating the importance of cytochrome c in electron transport . Thus, in the iron oxidation process, acid-stable cytochrome c is the primary acceptor of electron, transferring the electron to rusticyanin at pH 2.0, which, in turn, affects electron transfer to iron-cytochrome c reductase around pH 5.5.

Ann Pediatr (Paris), 1992 Feb, 39(2), 142 - 8
{Efficacy and tolerance of a new formulation of amoxicillin 100 mg--clavulanic acid 12.5 mg in acute otitis in infants}; Astruc J; A multicenter study of the new pediatric formulation of Augmentin (containing 100 mg amoxicillin and 12.5 mg clavulanic acid per ml) in acute otitis media (AOM) in patients aged three months to three years was carried out by hospital-based pediatricians . Study patients seen at the hospital outpatient clinics were given the drug in a daily dosage of 80 mg in three (83% of cases) or four (15%) divided doses for 6 to 10 days; 28% of patients were also given an antiinflammatory agent . A total of 83 patients with a mean age of 13.5 months were included (89% of patients were less than two years of age); one-third of these patients were included after failure of another antimicrobial agent (macrolide 46%, cephalosporin 23%) . The AOM was bilateral in most patients (69.5%) and 46% of patients had a history of previous AOM . Temperature was elevated in 85% of cases and more than half the patients had gastrointestinal symptoms (vomiting, diarrhea) prior to initiation of the study drug . At the interim evaluation on the fourth treatment day, tympanic membranes were normal in 43.5% of cases and improved in 22% of cases . Over 92% of patients achieved resolution of their AOM by the end of the treatment period, regardless of whether or not myringostomy had been performed on Do . Among the 27 patients given the study drug as rescue therapy after failure of another antimicrobial, 24 (89%) recovered fully.(ABSTRACT TRUNCATED AT 250 WORDS)

Ital J Gastroenterol, 1992 Feb, 24(2), 79 - 84
Helicobacter pylori and gastric ulcer therapy: reflections and uncertainties; Dobrilla G et al.; The relationship between Helicobacter pylori (HP) and gastric ulcer therapy is examined by analyzing both the data that suggest that eradication of HP renders the gastric mucosa less susceptible to development of gastric ulcer as well as the substantial body of evidence that does not support this contention . The results reported in clinical trials with colloidal bismuth citrate, antimicrobial agents (furazolidone), and combinations of anti-ulcer and antimicrobial agents (H2-antagonist+cefixime, H2-antagonist+metronidazole) are reviewed . Also analyzed is the relationship between HP eradication and ulcer recurrence . Only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing . The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of HP facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.

Rheum Dis Clin North Am, 1992 Feb, 18(1), 23 - 35
Gut and spondyloarthropathies; Leirisalo-Repo M et al.; There is a link between gut and spondyloarthropathies, which extends from the acute ReA triggered by enteritis due to gram-negative bacteria to ankylosing spondylitis and peripheral arthritis in association with Crohn's disease and ulcerative colitis . In addition, in studies using ileocolonoscopy, an unexpectedly high proportion of patients with prolonged or chronic seronegative oligoarthritis or sacroiliitis have inflammatory changes in the terminal ileum or colon or both . These changes have either features of acute gut inflammation or infection, but about one quarter of the patients have chronic lesions, probably early Crohn's disease . The conventional treatment of spondyloarthropathies consists of liberal use of NSAIDs, local corticosteroid injections if indicated, and physiotherapy . In patients with acute ReA, the conventional antimicrobial therapy to eradicate the triggering infection is necessary if there is evidence of chlamydial or gonococcal etiology . This therapy does not, however, influence the course of the subsequent arthritis . Patients with chlamydia arthritis probably host living bacteria for prolonged periods, and they seem to benefit from a prolonged antimicrobial therapy with tetracyclines . In the face of frequent gut involvement in patients with prolonged or chronic spondyloarthropathies, the use of sulfasalazine is the logical alternative, as short-term studies on patients with ankylosing spondylitis indicate.

Burns, 1992 Feb, 18(1), 39 - 44
Evaluation of the penetration strength, bactericidal efficacy and spectrum of action of several antimicrobial creams against isolated microorganisms in a burn centre; Herruzo-Cabrera R et al.; The antibacterial activity of eight antiseptic creams: 1 per cent silver sulphadiazine; 0.2 per cent nitrofurazone; 0.1, 0.5 and 1 per cent chlorhexidine; 2.2 per cent cerium nitrate; 10 per cent povidone iodine; and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were evaluated in vitro . The evaluation included the minimum inhibitory concentration (MIC) against 100 microorganisms isolated from burn patients, the chronology of the bacterial activity against Ps . aeruginosa and Staph . aureus and the penetration strength of the creams through a novel in vitro model contaminated with 17 microorganisms of different species isolated from burn patients . The results revealed that 0.5 per cent or 1 per cent chlorhexidine, 2.2 per cent cerium nitrate, and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were the creams which were effective at the highest dilutions . 0.5 per cent chlorhexidine and 10 per cent povidone iodine had the greater bactericidal activity . Finally, 0.2 per cent nitrofurazone showed greater penetration strength within the eschar model in comparison with the weaker penetration of 0.5 per cent and 1 per cent chlorhexidine and the absence of penetration by the rest of the antibacterial creams.

Burns, 1992 Feb, 18(1), 35 - 8
A new in vitro model to test the effectiveness of topical antimicrobial agents . Use of an artificial eschar; Herruzo-Cabrera R et al.; An in vitro method using a burn eschar 'equivalent' is described to compare the efficacy of several antimicrobial creams . Fragments of lyophilized pigskin were used as 'germ carriers' and after 24 h of treatment the effectiveness of the antimicrobial creams was tested through the evaluation of bacterial recovery both from the surface and from within the 'germ carriers' . The results showed a striking full skin thickness effectiveness of 0.5 per cent chlorhexidine, 10 per cent providone iodine and 2 per cent cerium nitrate in comparison with the weak activity demonstrated by 1 per cent silver sulphadiazine cream.

J Antibiot (Tokyo), 1992 Feb, 45(2), 235 - 9
Four diastereoisomers of cyclo(-Asp-Val-): inconsistency of their properties with the proposed structure of cairomycin A; Ueda T et al.; The four diastereoisomers of cyclo(-Asp-Val-) were synthesized to compare with a proposed structure of cairomycin A . Their antimicrobial activities were determined against both Gram-positive and Gram-negative bacteria . The physico-chemical properties of the isomers were characterized by mp, 1H NMR, IR, FAB-MS, and solubility in solvents, which were different from those reported for cairomycin A.

Clin Infect Dis, 1992 Feb, 14(2), 501 - 5
Mitral valve endocarditis caused by a serum-resistant strain of Escherichia coli; Watanakunakorn C et al.; Endocarditis due to Escherichia coli is rare . The case of a 79-year-old woman with E . coli bacteremia and multiple hemorrhagic cerebral infarcts is reported . A two-dimensional echocardiogram showed no evidence of a vegetation . While she was receiving antimicrobial therapy, bacteremia, hematuria, conjunctival petechiae, and a mitral regurgitant murmur occurred . The patient died, and at autopsy a large (2.2 x 2.0 x 0.7 cm) necrotic vegetation on the anterior leaflet of the mitral valve and several hemorrhagic infarcts of the brain were noted . An in vitro study with use of pooled human serum was performed and demonstrated that the patient's infecting strain of E . coli was serum resistant, in contrast to a serum-sensitive control strain of E . coli that was isolated from the cultures of blood from a patient with pyelonephritis . Including our case, 19 well-described cases of E . coli endocarditis from 1945 to 1990 have been reported . E . coli can cause endocarditis of both sides of the heart . More cases of endocarditis of host valves than of prosthetic valves have been documented.

Clin Pharmacokinet, 1992 Feb, 22(2), 116 - 31
Fleroxacin clinical pharmacokinetics; Stuck AE et al.; Fleroxacin is a new member of the class of fluoroquinolones . The drug has good activity (i.e . minimum inhibitory concentrations at less than 2 mg/L against 90% of strains) against a wide range of Gram-positive and Gram-negative bacteria . High performance liquid chromatography is used to determine concentrations of fleroxacin and its metabolites in biological fluids . Absorption of orally ingested drug is rapid as the peak plasma concentration of approximately 5 mg/L is reached in 1 to 2h after a single dose of 400mg . The systemic availability is close to 100% . Fleroxacin is poorly bound to plasma proteins (23%) and exhibits excellent tissue distribution . Renal clearance accounts for 60 to 70% of elimination . The drug is metabolised to form antimicrobially active N-demethyl-fleroxacin and inactive N-oxide-fleroxacin . In multiple dose studies the accumulation ratio of a once-daily dosage regimen is about 1.3, as predicted from the elimination half-life of 10 to 12h . Compared with ciprofloxacin, fleroxacin has a greater systemic availability and a longer half-life . Fleroxacin concentrations are higher in elderly patients, but further studies are needed to establish whether a dosage reduction should be recommended for this age group . In patients with renal disease dosage adjustment is recommended since a decreased renal clearance of fleroxacin leads to a significant prolongation of the elimination half-life . Fleroxacin is only poorly eliminated by peritoneal dialysis or haemodialysis . The most important drug-drug interaction is a decrease in systemic availability of fleroxacin after ingestion of aluminium- or magnesium-containing antacids . There is no evidence of a significant interaction between fleroxacin and theophylline . Only limited data are available on adverse reactions of fleroxacin . The most important adverse effects appear to be photosensitivity and a dose-dependent incidence of central nervous system reactions including sleep disorders.

J Clin Pharm Ther, 1992 Feb, 17(1), 51 - 4
The antimicrobial action of zinc ion/antioxidant combinations; McCarthy TJ et al.; The potentiation of action of antimicrobial preservatives/antiseptics by, respectively, antioxidants and metal ions has been established . In this investigation the antimicrobial effect of two antioxidants (Butylated hydroxyanisole and Propyl Gallate) and zinc ions, both separately and combined, was determined against three organisms at 37 degrees C . With the exception of Escherichia coli at low zinc concentrations, definite potentiation occurred, as reflected by a decrease in killing times.

Ther Drug Monit, 1992 Feb, 14(1), 81 - 4
Effect of education on the appropriateness of serum drug concentration determination; Carroll DJ et al.; The purpose of this study was to document the effect of education on the appropriateness of serum drug concentration (SDC) collection . This study included a period of education for hospital personnel involved in the acquisition of drug levels . These included nursing staff, lab personnel, house-staff (residents/interns), ward clerks, and pharmacists . This study included patients receiving aminoglycoside and/or vancomycin while on the general medicine service during the specified study periods . Patients receiving less than 72 h of antimicrobial therapy and patients transferred to or from the surgery service were excluded from the study . A retrospective pre- and posteducation comparison using Chi-square analysis was made to determine whether the percentage of appropriate and useful SDCs was improved through education . There was a significant difference (p less than 0.005) between the percentage of appropriate SDCs in the pre- and posteducation period . As a result of the study, a change in procedure for ordering SDCs was initiated, using an educational program, in order to continue the trend of appropriate SDCs at the Veterans Administration.

J Prosthet Dent, 1992 Feb, 67(2), 275 - 7
Control of microbial contamination with commercially available cleaning solutions; Assery M et al.; The elimination of cross-contamination from operatory to laboratory is required for effective infection control . This study determined whether microbial cross-contamination occurs during cleaning of dental prostheses with an ultrasonicator and examined ways to reduce or eliminate the contamination that might occur . The antimicrobial activities of a temporary cement remover and tartar and stain remover were compared with deionized water and a known strong antimicrobial agent . All solutions were assessed without and with ultrasonication . The microbicidal strains were cultured in brain-heart infusion broth, with and without acrylic resin slabs, and the organisms were killed either without or with sonication and without or with acrylic resin slabs . Further testing with natural plaque-contaminated denture materials is warranted.

Oral Surg Oral Med Oral Pathol, 1992 Feb, 73(2), 145 - 50
Periodontal disease associated with HIV infection; Winkler JR et al.; Patients with severe immunosuppression as a consequence of infection by human immunodeficiency virus (HIV) are at risk for a number of severe periodontal diseases . HIV-associated gingivitis and HIV-associated periodontitis (HIV-P) are seen exclusively in HIV-infected persons . In some cases HIV-P may extend into adjacent soft tissue and bone, resulting in necrotizing stomatitis of periodontal origin . In addition, acute necrotizing ulcerative gingivitis has also been reported to have an increased prevalence in HIV-infected patients . The clinical and microbiologic features of HIV-associated gingivitis and HIV-P suggest that these diseases are early and later stages of the same lesion, that results in severe gingival erythema, extensive soft tissue necrosis, and destruction of alveolar bone . Although acute necrotizing gingivitis and the initial stages of HIV-P share a number of clinical signs current evidence indicates that they are distinct pathologic processes . Treatment of these lesions requires debridement, local antimicrobial therapy, immediate follow-up care, and long-term maintenance . In addition, patients with systemic involvement or extensive and rapidly progressing lesions may require systemic antibiotics appropriate to the organisms that dominate the lesion.

J Neurosci Nurs, 1992 Feb, 24(1), 34 - 9
Brain abscess: an update; Twomey CR; Brain abscess has been a known complication of head trauma, dental and rhinogenic infections and congenital heart defects, but is rapidly becoming a new diagnosis in the ever-growing population of the immunocompromised patient . Organ transplantation has become commonplace . But, with the advent of more sophisticated agents to prevent organ rejection, comes the threat of brain abscess . In addition to the transplanted patient, the acquired immunodeficiency syndrome patient population is also at risk for development of brain abscess, making brain abscess an important diagnosis . A combination of surgical excision and antimicrobial therapy is usually indicated . Nursing care of these patients involves current knowledge of the antimicrobial agents used and their adverse effects, as well as availability of home health services and need for follow-up care.

Oral Microbiol Immunol, 1992 Feb, 7(1), 1 - 6
Peptostreptococcus micros in human periodontitis; Rams TE et al.; Peptostreptococcus micros is a recognized pathogen in medical infections, and its association with progressive periodontitis was examined in this study . P . micros was isolated from paper-point subgingival samples on anaerobic enriched blood agar plates and identified on the basis of cellular and colonial morphology and selected biochemical tests . In a cross-sectional study involving 907 people with advanced adult periodontitis, 127 with early-onset periodontitis, and 12 with localized juvenile periodontitis, P . micros in these patient groups occurred with a prevalence of 58-63% . In culture-positive patients, P . micros averaged 12-15% of total viable counts . P . micros demonstrated similar occurrence and proportional recovery in all age groups . In a longitudinal study of 91 adult periodontitis patients on maintenance therapy, P . micros demonstrated a significantly higher prevalence in disease-active than in disease-inactive patients (47% vs 14%) . Mechanical subgingival debridement and 0.12% chlorhexidine pocket irrigation was unable to eradicate subgingival P . micros from 18 of 22 adult periodontitis patients . In vitro antimicrobial susceptibility testing showed P . micros to be sensitive to therapeutic levels of penicillin, clindamycin and metronidazole . Our findings indicate that P . micros is a potential pathogen in adult periodontitis . The methods for its eradication from subgingival sites remain to be determined.

Indian J Exp Biol, 1992 Feb, 30(2), 152 - 4
Effect of antimicrobials on cholesterol synthesis and content in liver and small intestines; Pugalendhi KV et al.; The antimicrobials tetracycline, ampicillin and bactrim (cotrimoxazole) decreased HMG CoA reductase activity in liver and small intestines of albino rats . Diminished incorporation of 1, 2, 14C acetate into cholesterol of small intestines in bactrim group was noted . There was a significant fall in cholesterol content of liver, duodenum, jejunum and ileum of the bactrim group and jejunum only in tetracycline group.

Indian J Exp Biol, 1992 Feb, 30(2), 140 - 1
Antimicrobial activities of mycotoxin MT81 and its structural derivatives; Choudhury S et al.; Antimicrobial activities of mycotoxin MT81 and its acetylated, benzoylated and acetic acid derivatives were determined by zone inhibition method . MT81, acetylated MT81 and acetic acid MT81 exhibited sensitivity (31.25, 62.50, 62.50 micrograms/ml respectively) to all the test bacteria . Benzoylated-MT81 did not exhibit any activity even up to 1000 mcg/ml . MT81, its acetylated and acetic acid derivatives exhibited antifungal activity up to 62.5 micrograms/ml and 125.0 micrograms/ml respectively against test yeasts and other fungi . Benzoylated MT81 also exhibited antifungal activity but the degree was comparatively less.

Farmaco, 1992 Feb, 47(2), 229 - 38
1-Acylaminoimidazoles synthesis and antimicrobial activity; Cocco MT et al.; Several new 1-acylamino-2-alkyl-4-arylimidazoles were synthesized . The compounds were obtained by reaction of N1-acylacetamidrazones and alpha-bromoketones . The antimicrobial activity of the prepared compounds was tested.

J Ethnopharmacol, 1992 Feb, 36(1), 39 - 41
Antimicrobial activity of benzylisoquinoline alkaloids from Annona salzmanii D.C; Paulo Mde Q et al.; Bark of Annona salzmanii D.C . (Annonaceae), used in Brazilian folk medicine, was found to contain four benzylisoquinoline alkaloids, namely reticuline, anonaine, laurelliptine and isoboldine . Only anonaine possesses some antibacterial property while all four alkaloids show some antifungal activity.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 291 - 4
In vitro evaluation of activities of azithromycin, erythromycin, and tetracycline against Chlamydia trachomatis and Chlamydia pneumoniae; Welsh LE et al.; The in vitro activities of azithromycin (CP-62,993; Pfizer), erythromycin, and tetracycline were evaluated by inhibiting Chlamydia trachomatis and Chlamydia pneumoniae, formerly TWAR, propagation in vitro in McCoy cells, HeLa cells, and HL cells . Eleven clinical isolates of C . trachomatis (serovars D, E, F, J, K, and L2) and four strains of C . pneumoniae were tested with an inoculum of 10(3) inclusion-forming units in a 96-well microtiter plate . The MIC ranges of these antimicrobial agents against C . trachomatis were as follows: azithromycin, 0.125 to 0.5 microgram/ml; erythromycin, 0.25 to 0.1 microgram/ml; and tetracycline, 0.0625 to 1.0 microgram/ml . The MBC ranges, calculated from passage into antibiotic-free medium, were as follows: azithromycin, 0.125 to 4.0 micrograms/ml; erythromycin, 0.5 to 8.0 micrograms/ml; and tetracycline, 0.0625 to 4.0 micrograms/ml . The MIC ranges for C . pneumoniae in both HeLa and HL cells were as follows: azithromycin, 0.125 to 1.0 micrograms/ml; erythromycin, 0.0625 to 1.0 microgram/ml; and tetracycline, 0.125 to 1.0 microgram/ml . The MBC ranges were as follows: azithromycin, 0.25 to 1.0 microgram/ml; erythromycin, 0.25 to 1.0 microgram/ml; and tetracycline, 0.125 to 4.0 micrograms/ml . From the results of this in vitro study, azithromycin appears to be an effective antibiotic comparable to tetracycline and erythromycin for use in the treatment of both C . trachomatis and C . pneumoniae infections.

Biochem Med Metab Biol, 1992 Feb, 47(1), 10 - 20
HPLC determination of a chemically modified nonantimicrobial tetracycline: biological implications; Yu Z et al.; Chemically modified tetracycline (4-de-dimethylamino tetracycline), like commercially available tetracyclines, is known to inhibit experimentally induced pathologic collagen breakdown . A method for measurement of chemically modified tetracycline in small volumes (50 microliters) of rat serum was developed using reversed-phase HPLC; this was necessary because this tetracycline analog lacks antimicrobial activity and, therefore, cannot be measured with standard bioassays . This method uses the same solution for extraction and elution thus providing a simple and rapid assay for both drugs . Using this technique, the concentration of chemically modified tetracycline and tetracycline were determined in rat serum at different times after oral administration . The serum concentration of chemically modified tetracycline was much higher than that for tetracycline, and its serum half-life was greater . The IC50 of chemically modified tetracycline and tetracycline, as inhibitors of collagenase from rat polymorphonuclear leukocytes, was determined and found to be 4.1 x 10(-8) M (0.02 micrograms/ml) and 2.4 x 10(-4) M (120 micrograms/ml), respectively . Based on the serum levels of these drugs after oral administration, and their IC50 values, chemically modified tetracycline is potentially a far more potent inhibitor of excess collagenase activity than tetracycline, during pathologic conditions, and may have the added advantage of not producing some of the typical complications of long-term antibiotic therapy.

Oral Surg Oral Med Oral Pathol, 1992 Feb, 73(2), 215 - 25
Management of oral health in persons with HIV infection; Scully C et al.; Prevention and treatment of oral disease is required to maintain quality of life and to improve prognosis of patients infected with the human immunodeficiency virus (HIV) . Management requires a team approach, and close collaboration with the appropriate responsible physicians and other health care workers is necessary . Oral infection is frequent and usually opportunistic, and management is based on certain principles . Infections may disseminate and can be persistent and severe; multiple concurrent or consecutive infections with different microorganisms are frequent; fungal, viral, and parasitic infections are rarely curable; and long-term antimicrobial therapy may be required . This article reviews the management of oral candidiasis, hairy leukoplakia, and infections with herpes simplex virus, varicella-zoster virus, and cytomegalovirus . The management of Kaposi's sarcoma, lymphomas, aphthous ulceration, gangrenous stomatitis, bleeding, xerostomia, and adverse drug reactions is also described . Treatment should avoid further immunosuppression and inducement of xerostomia or caries, and should be designed to avoid adverse drug reactions and possible drug interactions.

Arthritis Rheum, 1992 Feb, 35(2), 195 - 8
The anticollagenolytic potential of lymecycline in the long-term treatment of reactive arthritis; Lauhio A et al.; OBJECTIVE . We sought to determine the antiinflammatory properties of lymecycline in the long-term treatment of reactive arthritis (ReA) . METHODS . Quantitative assay of collagenase activity by densitometry after sodium dodecyl sulfate-polyacrylamide gel electrophoresis . RESULTS . Therapeutic levels of lymecycline do not directly inhibit the activity of human neutrophil interstitial collagenase, but can prevent the oxidative activation of latent human neutrophil collagenase . CONCLUSION . This non-antimicrobial, anticollagenolytic property of lymecycline may contribute to its therapeutic efficacy in the treatment of patients with ReA.

J Infect Dis, 1992 Feb, 165(2), 344 - 51
Interleukin-4 inhibits human macrophage activation by tumor necrosis factor, granulocyte-monocyte colony-stimulating factor, and interleukin-3 for antileishmanial activity and oxidative burst capacity; Ho JL et al.; Interleukin (IL)-4 has been implicated in the pathogenesis of leishmaniasis in a murine model . Experiments were done to examine the effect of IL-4 on cytokine activation of macrophages . Interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and IL-3 activate macrophages to inhibit replication of leishmaniae . IL-4 abrogated in a dose- and time-dependent manner the induction of antileishmanial activity by these cytokines . The depression of oxidative burst capacity is one mechanism by which IL-4 inhibits macrophage activation . IL-4 diminished in a dose- and time-dependent manner the TNF alpha enhancement of oxidative capacity . Pretreatment with IL-4 for 48, 24, or 0 h, respectively, inhibited the generation of superoxide induced by TNF alpha by 90%, 60%, and 40% . Furthermore, IL-4 abrogated the enhancement of oxidative capacity by IFN-gamma, GM-CSF, and IL-3 . These data suggest that IL-4 is a potent deactivator of macrophage antimicrobial functions and may contribute to the pathogenesis of visceral leishmaniasis.

Tidsskr Nor Laegeforen, 1992 Jan 30, 112(3), 368 - 70
{Hospital infections . Extended hospital queues and unnecessary costs of the health services}; Andersen BM; In Norway the prevalence of nosocomial infections is 5-20%; more than 50,000 patients per year . The consequences may be serious for the individual patient and his family, a serious problem for the hospital department concerned and a burden on the Norwegian health services . Nosocomial infections can be treated by antimicrobial drugs which generate selective pressure towards more resistant organisms . Infections caused by resistant strains may result in longer hospitalization, more difficult treatment, and more severe illness . In future, efforts must be directed at preventing nosocomial infections by means of education, surveillance and control.

Tidsskr Nor Laegeforen, 1992 Jan 20, 112(2), 199 - 201
{Spontaneous bacterial peritonitis}; Jacobsen MB et al.; We describe five patients with spontaneous bacterial peritonitis . The condition is reported more frequently than before and survival has improved . Important clinical features are increasing ascites and unexpected derangement of liver function . Possible predisposing factors, as well as diagnostic and therapeutic measures, are discussed . We emphasize the significance of ascitic polymorph nuclear cell count and bedside inoculation of ascites on blood culture medium, and stress the importance of prompt antibiotic therapy . The choice of empiric antimicrobial treatment is based on the reported frequency of causative agent and toxicity to drugs . Our experience so far indicates that cefotaxime administered as monotherapy is safe and efficient in these patients . Aminoglycosides should be avoided because of increased nephrotoxicity in patients with liver failure.

Lancet, 1992 Jan 18, 339(8786), 148 - 9
Ciprofloxacin for treatment of malakoplakia; van Furth R et al.; The tumour-like lesions of the rare disease malakoplakia, which consist of macrophages containing undigested coliform bacteria, are often misdiagnosed as a carcinoma . Although an infectious aetiology is likely, no antimicrobial therapy has been successful in the long-term . Since ciprofloxacin penetrates well into macrophages, this drug was given to two patients with advanced malakoplakia (500 mg twice daily) . After long-term treatment all granulomatous lesions disappeared . Thus, malakoplakia can be cured by antibiotic treatment.

JAMA, 1992 Jan 15, 267(3), 400 - 2
Chronic Chlamydia trachomatis infections in infants; Bell TA et al.; OBJECTIVE.--To study the natural history of Chlamydia trachomatis infections in infants . DESIGN.--Bacteriologic and serologic study of an inception cohort . SETTING.--University of Washington Medical Center, Seattle . PARTICIPANTS.--Twenty-two infants with C trachomatis infections either not treated early in life or recurring after antimicrobial treatment . MAIN OUTCOME MEASURES.--Persistence of infection in various anatomic sites, antibody responses to specific serovars (serologic variants) of C trachomatis, and serovars of isolates from mothers and infants . RESULTS.--The cumulative proportion of infants still infected at the age of 1 year was 35% . Infection persisted in the conjunctiva, nasopharynx, and oropharynx in one child for as long as 866 days (28.5 months), when she was cured by treatment . In none of the infants did serologic tests suggest acquisition of infection other than at birth . Isolates of C trachomatis from mothers and their respective infants were always of the same serovar . CONCLUSIONS.--Many infants infected with C trachomatis at birth remain infected for months or years in the absence of specific antimicrobial therapy . Such infections may be confused with those acquired by sexual abuse.

Pharmacoeconomics, 1992 Feb, 1(2), 116 - 23
A comparison of the safety, timing and cost-effectiveness of administering antibiotics by intravenous bolus (push) versus intravenous piggyback (slow infusion) in surgical prophylaxis; Garrelts JC et al.; This study was carried out to evaluate the safety, timing and cost-effectiveness of administering perioperative antimicrobial prophylaxis with cefmetazole via intravenous (IV) bolus, or 'push', compared with the more common method of IV 'piggyback' administration . A total of 60 patients were studied, 30 in each group . No major adverse reactions were noted in either group . Phlebitis did not occur with either method of administration . Loss of patency was noted in 2 patients in the IV bolus group at the time of catheter removal . While no overall difference in timing of antibiotic administration in relation to the surgical procedure was noted, 2 patients in the IV piggyback group did not receive their preoperative dose until after surgery had started . Both pharmacy preparation time and nursing administration time were shorter with the IV push method, resulting in a cost avoidance of $US0.60 per dose . Material cost avoidance, primarily due to elimination of the minibag and IV tubing with bolus administration, was $US3.25 per dose . Extrapolated cost avoidance for our institution, for both prophylaxis and treatment, is $US184 000 per year . Administration of selected antibiotics by IV push is safe, allows optimal timing of administration, minimises preparation and administration time, and is cost-effective . Hospitals and outpatient care facilities should consider this alternative method of antibiotic administration.

G Batteriol Virol Immunol, 1992 Jan-1993 Dec, 85(1-12), 35 - 46
{Antimicrobial activity of NK cells}; Cavallo R; NK Lymphocytes were first identified by their cytotoxic and cytolytic activity against tumor cells . However there is now increasing evidence that these cells are also mediators of natural resistance against viruses, fungi, protozoa and bacteria . The purpose of this review is to summarize the data on the antimicrobial activity of NK cells and to discuss the influence of corticoids and of other molecules interfering with innate resistance against pathogenic micro-organisms.

Otolaryngol Head Neck Surg, 1992 Jan, 106(1), 75 - 80
Absence of sensorineural hearing loss in treated infants and children with congenital toxoplasmosis; McGee T et al.; Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis . As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenitally infected infants and children were evaluated for auditory function . Serial testing, beginning within 2 months of birth, was performed . Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible . Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media . No infant or child had sensorineural hearing loss . The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy . Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings.

Neurology, 1992 Jan, 42(1), 32 - 42
PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients; Keller TL et al.; We used the polymerase chain reaction (PCR), a method useful in the detection of Borrelia burgdorferi in vitro, to evaluate CSF in patients thought to have neuroborreliosis . Nested pairs of oligonucleotide primers were designed to recognize the C-terminal region of B burgdorferi OspA . CSF samples were obtained from (1) patients with immunologic evidence of systemic B burgdorferi infection and clinical manifestations suggestive of CNS dysfunction, (2) seronegative patients with clinical disorders consistent with Lyme borreliosis, and (3) patient and contamination controls; all were analyzed in a blinded fashion . PCR detected B burgdorferi OspA DNA in CSF of (1) 10 of 11 patients with Lyme encephalopathy, (2) 28 of 37 patients with inflammatory CNS disease, (3) seven of seven seronegative patients with Lyme-compatible disorders, and (4) zero of 23 patient controls . Zero of 83 additional contamination controls were PCR-positive . In eight patients from whom we obtained CSF before and after parenteral antimicrobial therapy, PCR results invariably predicted clinical outcome accurately.

Diagn Microbiol Infect Dis, 1992 Jan, 15(1), 89 - 97
Comparison of the efficacy and adverse effect profile of cefotaxime and ceftriaxone in ICU patients with susceptible infections; Thomas P et al.; In a prospective randomized double-blind trial, the efficacy and safety of cefotaxime and ceftriaxone were compared in intensive care unit (ICU) patients with serious infections requiring systemic antimicrobial therapy . Patients were randomly assigned to receive either cefotaxime 1 g i.v . t.i.d . or ceftriaxone 2 g every 24 hr . Clinical and bacteriologic assessments were made before treatment, at 48 hr and 5 days during treatment, and 48 hr after treatment . At the time of reporting, a total of 34 patients had been entered into the trial, 27 of whom were evaluable; 23 patients (85%) completed a minimum of 5 days antibiotic treatment . At the end of treatment, using current statistics 67% of cefotaxime and ceftriaxone patients demonstrated clinical cure or improvement . Bacteriologic responses appeared greater in the cefotaxime group (55% vs 42%) . The incidence of adverse effects, which were usually minor, was similar in each group . From these preliminary results, it would appear that at the doses used in this study, cefotaxime and ceftriaxone are equally effective in the treatment of infections in the ICU.

Ann Otol Rhinol Laryngol Suppl, 1992 Jan, 155, 58 - 64
Current indications for tonsillectomy and adenoidectomy; Bluestone CD; Tonsillectomy and adenoidectomy are currently the most common pediatric surgical procedures performed in the United States . Tonsillectomy may be effective in recurrent acute throat infection (acute tonsillitis), chronic tonsillitis, tonsillar hypertrophy, and peritonsillar abscess . Antimicrobial therapy may also be beneficial . Clinical trials evaluating children with obstructive adenoids are currently being evaluated; anecdotal evidence points to improvement in development and quality of life after surgery . The efficacy of adenoidectomy in paranasal sinusitis has not been evaluated in clinical trials; antimicrobial therapy or the possibility of upper respiratory tract allergy should be considered in such cases . For acute otitis media, recommendations range from no treatment in cases that will abate with time, to anti-microbial prophylaxis, to myringotomy with tympanostomy tube insertion, adenoidectomy with or without tonsillectomy, or a combination of adenoidectomy with myringotomy and/or tympanostomy tubes . The decision for or against otic and/or pharyngeal surgery should be individualized on the basis of severity, duration, and frequency of illness; previous treatment; and risk.

Ann Otol Rhinol Laryngol Suppl, 1992 Jan, 155, 5 - 8
Antimicrobial use in otolaryngeal infections: general considerations; Medoff G; With the development of numerous new antimicrobials and the improved efficacy of existing agents, more infections are being treated successfully, but the benefits of one agent over another have become an issue of subtle distinctions . Some clinical studies of new drugs have inherent drawbacks in their design and may not yield a comprehensive picture of antimicrobial characteristics in a wide range of patient types and diseases . Studies should therefore be carefully evaluated to determine whether a real advantage exists for a new agent . At Barnes Hospital (St Louis, Missouri), antimicrobials are chosen for the formulary on the basis of efficacy, toxicity, and cost . One or two agents are selected from a group of "therapeutic equivalents." Nonformulary agents or uses must be approved by the infectious disease staff . Evaluation and discussion of therapy with formulary and nonformulary drugs educates house staff, who can then use approved agents with greater knowledge and skill.

Ann Otol Rhinol Laryngol Suppl, 1992 Jan, 155, 33 - 6
Antimicrobial prophylaxis for recurrent acute otitis media; Paradise JL; Antimicrobial prophylaxis for recurrent otitis media was first reported in 1960 in an uncontrolled study using a long-acting sulfonamide in Native American children younger than 11 years of age . In subsequent controlled studies using various antimicrobial drugs (primarily aminopenicillins or sulfonamides) subjects receiving prophylaxis continued to have episodes of acute otitis media, but at rates substantially lower than those of controls . More recently, prophylaxis has appeared effective in reducing the number of acute recurrences, but not the cumulative proportion of time with middle ear effusion that was present independent of such recurrences . Although questions remain about choice of drug, optimal dosage schedules, risk of untoward drug reactions, duration of use, and the risk of encouraging the emergence of resistant strains of pathogenic bacteria, antimicrobial prophylaxis currently appears to be the most logical first approach in the management of the child with recurrent otitis media.

Ann Otol Rhinol Laryngol Suppl, 1992 Jan, 155, 21 - 3
Otitis media update: pathogenesis and treatment; Giebink GS; Otitis media primarily affects children, but can also lead to lifelong sequelae . Middle ear histopathologic changes and clinical manifestations can represent any part of a disease continuum, from acute to recurrent to chronic otitis media . Acute otitis media is most often caused by an acute respiratory viral infection and secondary replication of bacteria in the middle ear space and tissues, leading to symptoms and signs of infection (ie, fever, pain, tympanic membrane erythema) . Antimicrobial therapy is the mainstay of management, and clinical response to different antimicrobial drugs appears to be similar . The bacteriologic efficacy of these drugs, however, is quite variable . Clearly, antimicrobial treatment of acute otitis media, which currently is largely empiric, must be fine-tuned on the basis of patient and disease variation.

Ann Otol Rhinol Laryngol Suppl, 1992 Jan, 155, 16 - 20
Antibiotic prophylaxis in clean-contaminated head and neck oncologic surgery; Weber RS et al.; The use of antibiotic prophylaxis in head and neck oncologic surgery has greatly reduced the risk of postoperative wound infection and the corresponding increase in morbidity and health care costs . Conversely, inappropriate perioperative use of antibiotics increases costs and risk to patients . Antibiotic prophylaxis is beneficial only in clean-contaminated head and neck surgery; targets are the bacterial flora that commonly inhabit the skin and upper aerodigestive tract, with antibiotics effective against gram-positive aerobic organisms and anaerobic organisms providing the best coverage . Maximum efficacy is achieved with immediate preoperative and short-term (less than 48 hours) postoperative antimicrobial administration in adequate doses . Optimum benefit from prophylaxis in head and neck oncologic surgery depends on appropriate selection and administration of antibiotics in combination with sound, established surgical principles.

Intensive Care Med, 1992, 18 Suppl 1, S10 - 7
Procedures for the diagnosis of pneumonia in ICU patients; Chastre J et al.; The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation . An important advance has been the development of the protected specimen brush technique . Secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia . However, this procedure has important limitations in that results are not available immediately, and in that a few false negative of false positive results may occur . Bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, because the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture . Microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for the early and rapid diagnosis of pneumonia in this setting . The lavage technique can also be conveniently incorporated into a protocol along with quantitative culture of samples obtained using the protected specimen brush . This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in most patients with pneumonia.

Br J Neurosurg, 1992, 6(3), 249 - 53
Solitary brainstem abscess successfully treated by microsurgical aspiration; Jamjoom ZA; A case of pyogenic pontine abscess detected by computerized tomography scan in a 10-year-old boy is presented . While on broad-spectrum antimicrobial treatment, he deteriorated and developed new symptoms of respiratory distress . Microsurgical exposure of the abscess and aspiration of pus resulted in rapid improvement in his neurological state and radiological resolution of the lesion . The aim of this article is to emphasize the importance of prompt diagnosis and the role of surgical drainage of pus in the management of brainstem abscesses.

J Emerg Med, 1992 Jan-Feb, 10(1), 7 - 11
Effective hand degerming in the presence of blood; Larson E et al.; This study evaluated the effect of blood on the antimicrobial activity of several agents used for handwashing . Seventy-one healthy adult volunteers used 1 of 6 products (70% isopropyl alcohol {IPA}; liquid hand rinse containing 70% ethyl alcohol and 0.5% chlorhexidine gluconate {EA}; detergent containing 7.5% povidone-iodine {PI}; detergent containing 4% chlorhexidine gluconate {CHG}; a nonantimicrobial soap; and a control group that used no product) in two tests: with and without 1.2 mL of dried sterile sheeps' blood on the hands . In the presence of blood, the two alcohol products (IPA and EA) resulted in significantly greater reductions in numbers of colony-forming units than other products (P less than 0.001) . When no blood was present, IPA was associated with significantly greater reductions, whereas soap and control groups had significantly lower reductions (P = 0.008) . We conclude that hands are effectively degermed with a variety of products in the presence of blood, and that alcohols give greater initial reductions in colonizing flora . This is of particular relevance in emergency situations during which contamination with blood is likely and handwashing facilities are inaccessible.

Aust Clin Rev, 1992, 12(2), 53 - 6
The effect of an educational intervention on the use of peri-operative antimicrobial agents; Johnston J et al.; The objective of this study was to evaluate the effect of an educational intervention on the prescribing behaviour of doctors who order antimicrobial therapy for patients undergoing abdominal surgery . Two confidential criterion audits were separated by the intervention which involved completion of a 10-item questionnaire followed by a fully referenced answer sheet . The results showed a significant improvement in the prescribing habits of the junior surgical staff after the educational intervention . The overall error rate decreased from 50% to 20% (P = 0.003).

J Pharm Sci, 1992 Jan, 81(1), 45 - 8
Possible effect of pigment on the pharmacokinetics of ofloxacin and its excretion in hair; Uematsu T et al.; The mechanism of excretion of the antimicrobial ofloxacin in human scalp hair was investigated . When black and white hairs were taken from a patient with grizzled hair, who had been treated with ofloxacin, a much larger quantity of the drug was detected in the black hair . To study this difference and to elucidate the cause, ofloxacin (6, 20, and 60 mg/kg/day, b.i.d.) was administered ip for 5 weeks to albino and pigmented rats, whose backs had been depilated beforehand . In the last week of administration, the time-plasma concentration profile of ofloxacin was determined . One week after the last dosing, the newly grown hair on the depilated area was collected, and the drug concentration in hair was measured . The concentration in hair of the pigmented rats correlated significantly with the daily dose, area under the plasma concentration curve (AUC), and maximum plasma concentration (Cmax) at steady state, whereas that in the albino rats correlated with the dose and Cmax only, because AUC did not increase linearly with the dose in the albino rats . Moreover, the drug concentration in the hair of the pigmented rats was always much larger than that in the hair of the albino ones, although AUC and Cmax did not differ greatly between both rat groups . The findings suggest that ofloxacin is excreted in the hair in relation to the dose administered, and that the mechanism of the excretion is closely linked with the presence of melanin.

Farmaco, 1992 Jan, 47(1), 99 - 110
Macrocyclic polyesters . I . A novel class of 1,3-butandiol derivatives as potential antimicrobial agents; Fadda AM et al.; This paper reports the synthesis of a novel class of macrocyclic tetraesters containing 1,3-butandiol sub-units by reacting the stannolan derivative of the diol with diacyl chloride . The structure of the possible isomers was assigned by spectroscopic data and comparison with samples otherwise prepared . Preliminary screening revealed that these compounds have low antimicrobial activity, although it is higher than that of the starting diol.

Intensive Care Med, 1992, 18(2), 127 - 8
Mediastinitis due to Nocardia asteroides after cardiac transplantation; Thaler F et al.; Nocardia infection classically occurs in immuno-compromized patients . Only a few cases of mediastinal infection due to this pathogen have been described in the literature . We report a patient who developed mediastinitis due to Nocardia asteroides after cardiac transplantation . The treatment was surgical debridement, dressing, sugaring and antibiotic therapy . The emergence of a severe acute renal failure possibly induced by drug interaction between Cyclosporin, cyclines and aminoglycosides, led us to modify the antimicrobial treatment . The intravenous use of Imipenem 2 g per day and Ciprofloxacin 400 mg per day for four weeks and then oral Ciprofloxacin 1.5 g per day for 1 year, was effective and allowed a good outcome, without any drug interaction with Cyclosporin, adverse effect, graft rejection episode or infection relapse.

Photochem Photobiol, 1992 Jan, 55(1), 35 - 8
Phototoxic and photochemical properties of sanguinarine; Arnason JT et al.; Sanguinarine, a commercial drug exhibiting antimicrobial and antitumor properties, was studied with respect to its basic photochemical characteristics and also with regard to its phototoxicity to mosquito larvae (Aedes atropalpus) . Sanguinarine proved to be clearly phototoxic to larvae, with an LD50 of 0.096 mg/mL with near UV exposure as compared with 23.3 mg/mL without . Flash photolysis experiments enabled the study of the triplet state of sanguinarine to be undertaken . Quenching by oxygen occurs with a rate constant of 6 x 10(9) M-1s-1 and time-resolved emission studies indicate that sanguinarine produces a significant amount of singlet oxygen (phi delta = 0.16) as does the isoquinoline alkaloid, berberine (phi delta = 0.25) . These values represent the first direct quantitative measurements of photosensitization parameters of these compounds . Additionally, sanguinarine exhibits efficient electron donation properties, undergoing reaction with methyl viologen with a rate constant greater than 10(10) M-1s-1, but is a poor electron acceptor . Phototoxicity of sanguinarine can thus be explained in terms of its photosensitization properties.

Free Radic Res Commun, 1992, 16(3), 137 - 57
Microbial strategies to prevent oxygen-dependent killing by phagocytes; Haas A et al.; Microorganisms which are taken up by professional phagocytic cells of a host organism (e.g., by macrophages and polymorphonuclear leukocytes) encounter a series of antimicrobial events including confrontation with toxic oxygen species, derived mainly from the superoxide radical produced by phagocytic NADPH oxidase after uptake of the microorganism . Many microbes are susceptible to the oxygen-dependent phagocytic stress and are efficiently killed . The strategies of some microorganisms to bypass an encounter with the phagocytes' reactive oxygen species, and biochemical systems contributing to the microbes' resistance to killing by reactive oxygen species are outlined.

Arch Oral Biol, 1992 Jan, 37(1), 7 - 13
The use of capillary electrophoresis to identify cationic proteins in human parotid saliva; Lal K et al.; Eight proteins, HRPs 1, 2, 3, 4, 5 and 6, lysozyme and histatin 6, are the major cationic components of the parotid salivas of normal healthy individuals . Histatins 2 and 4 appear to be further degradation products of the HRPs . Capillary electrophoresis separates all of these eight components, thus allowing future studies to correlate protein concentration with antimicrobial activity in health and disease.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 32 - 8
Fleroxacin pharmacokinetics in aqueous and vitreous humors determined by using complete concentration-time data from individual rabbits; Miller MH et al.; Although composite data from separate subjects can be used to generate single-subject estimates, intersubject variation precludes rigorous ocular pharmacokinetic analysis . Therefore, a rabbit model in which sequential aqueous and vitreous humor samples were obtained following the administration of the quinolone fleroxacin was developed . Mean data from individual animals were used for pharmacokinetic analysis . Following direct intravitreal or systemic drug administration, sequential paracenteses did not alter pharmacokinetic constants or ocular penetration and were not associated with an increase in ocular protein; contamination of vitreous humor with blood was minimal (less than 0.1%) . Following direct injection or intravenous administration, vitreous humor concentration-time data were best described by one- and two-compartment models, respectively . The maximum concentration and the penetration into the aqueous and vitreous humors were 1.54 and 0.5 micrograms/ml and 27 and 10%, respectively . Elimination rates from aqueous and vitreous humors and serum were similar following parenteral drug administration . Drug elimination following direct injection was rapid, and the elimination rate from the vitreous humor was not prolonged by the coadministration of probenecid . Our animal model provides a new approach to the rigorous examination of the ocular pharmacokinetics of quinolone antimicrobial agents in the eye.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 185 - 7
Bactericidal activity of antimicrobial agents against slowly growing Helicobacter pylori; Millar MR et al.; The doubling times of bacteria at sites of colonization or infection are considerably longer than those in laboratory culture media, and slow growth reduces the susceptibility of bacteria to antimicrobial agents . Helicobacter pylori is susceptible to a wide range of antimicrobial agents in vitro; however, tests for inhibitory activity do not adequately predict which antimicrobial agents will eradicate slowly growing H . pylori from the stomachs of patients . The chemostat can be used to compare the bactericidal activities of antimicrobial substances against slowly growing bacteria . In this study we compared the bactericidal activities of antimicrobial agents against slowly growing H . pylori . The bactericidal activities of erythromycin, minocycline, ampicillin, amoxicillin, cefixime, metronidazole, and bismuth subcitrate against slowly growing H . pylori NCTC 11,637 in a chemostat were compared . Antimicrobial agents were added to the system at four to eight times the MIC . Exposure of H . pylori to metronidazole was associated with the rapid development of metronidazole resistance, preventing assessment of the bactericidal activity of metronidazole . Resistance to the other antimicrobial agents tested did not develop . The poor bactericidal activities of the antimicrobial agents against slowly growing H . pylori may be a contributory factor in limiting their clinical efficacies . Of the agents tested, only amoxicillin and bismuth subcitrate showed bactericidal activity against slowly growing H . pylori . The chemostat allows comparison of the bactericidal activities of antimicrobial agents against slowly growing H . pylori and may therefore provide results which more accurately identify those agents or combinations of agents that will eradicate H . pylori from patients.

ORL J Otorhinolaryngol Relat Spec, 1992, 54(1), 5 - 9
Ciprofloxacin and the inner ear--a morphological and round window membrane permeability study; Bagger-Sjoback D et al.; This study was conducted in order to evaluate ototoxic potential and passage through the round window membrane of ciprofloxacin, a newly developed antimicrobial drug with an antibacterial spectrum well suited for the treatment of suppurative otitis media . Ciprofloxacin was injected intraperitoneally in 40 guinea pigs in doses ranging from 25 to 150 mg/kg body weight for 14 consecutive days . Sixteen inner ears of chinchillas were exposed to ciprofloxacin at a concentration of 0.1 mg/ml applied directly to the intact round window membrane . Despite severe deterioration of the animals injected with the highest doses, no behavioral or definite morphological evidence of inner ear or vestibular damage could be seen . Ciprofloxacin concentrations in the perilymph were determined with high-performance liquid chromatography . Direct passage of ciprofloxacin, presumably via the round window membrane, was demonstrated . After 1 h and 15 min, an arithmetic mean concentration of 0.165 micrograms/ml (95% confidence interval +/- 0.053) could be demonstrated in the perilymph . It can be concluded that ciprofloxacin has no ototoxic effect when administered systemically . Furthermore, when locally applied into the middle ear, it has the capacity to pass into the inner ear.

Infect Control Hosp Epidemiol, 1992 Jan, 13(1), 21 - 32
Intervention to discontinue parenteral antimicrobial therapy in patients hospitalized with pulmonary infections: effect on shortening patient stay; Ehrenkranz NJ et al.; OBJECTIVES: Current efforts to contain anti-microbial costs in hospitals are based on restricting drugs . We explored the effects of unsolicited case-specific recommendations to physicians to discontinue parenteral antimicrobial therapy in medically stable patients with pneumonia, in order to shorten hospital length of stay . METHODS: A nurse-interventionist, working as an emissary of an appropriate committee in 3 nonteaching community hospitals, presented randomly assigned physicians with nonconfrontational suggestions to substitute comparable oral antimicrobials for parenteral antimicrobials . Blinded observers evaluated in-hospital and 30-day postdischarge courses of patients of physicians who had been contacted by the nurse (cases) and those who had not (controls) . RESULTS: Eighty-two patient episodes (47 physicians) met study criteria . There were 53 cases and 29 controls . In 42 of 53 (79%) case episodes, physicians discontinued parenteral antimicrobials; patients' mean length of stay was 2.4 days less than for 29 control episodes (estimated cost savings was $884/patient) . In 11 (21%) episodes, case physicians continued parenteral therapy; patients' mean length of stay was 1.9 days longer than for controls (estimated cost excess was $704/patient) . Education, training and practice characteristics were comparable in physician groups . Severity of illness indicators and postdischarge outcomes were comparable in patient groups . CONCLUSIONS: The major cost-saving potential for shifting from parenteral to oral antimicrobial therapy is shortened length of stay . Timely information about alternative drug therapies, offered on a patient-specific basis, appears to modify the treating behavior of physicians . The program as currently conducted is cost-effective, with an estimated net savings of $50,000 per 100 interventions.

Annu Rev Med, 1992, 43, 465 - 86
Quinolone antimicrobial agents; Neu HC; This chapter reviews the chemistry, microbiology, pharmacology, and clinical use of the fluoroquinolone antimicrobial agents . The molecular and clinical problems of bacterial resistance are reviewed . The clinical areas in which fluoroquinolones have been investigated are detailed, with particular attention to areas of appropriate and inappropriate use.

Respiration, 1992, 59 Suppl 1, 28 - 32
Role of surfactant in chronic obstructive pulmonary disease: therapeutic implications; Lusuardi M et al.; A potential role of surfactant in COPD pathogenesis is not yet clearly demonstrated . Cigarette smoke is an important risk factor for COPD and it is known to adversely affect surfactant . In a series of 20 smoker, non-asthmatic COPD patients compared with 5 nonsmoker healthy controls we found a marked decrease (about 6-7 times) of total phospholipids in bronchoalveolar lavage fluids . We were not able to find differences in % composition, with the exception of phosphatidylglycerol-cardiolipin, which appeared significantly increased in smoker COPD patients (p less than 0.02) . An alteration of mucociliary clearance and an impairment of antimicrobial defence might be important surfactant related factors in COPD, but no definitive data are available . We do not know at present if a therapy increasing surfactant would be of any value in COPD treatment . Surfactant replacement therapy is at present advisable only for those conditions in which a surfactant impairment plays (IRDS) or seems to play (ARDS) a crucial role . Pharmacologic stimulation of type 2 pneumocytes could have several advantages over replacement therapy . Ambroxol is probably one of the most promising surfactant stimulating agents, but preliminary data show that in smoker COPD patients drug dosages higher than those usually employed to affect bronchial mucus are necessary to obtain a significant increase of surfactant phospholipids.

J Assoc Acad Minor Phys, 1992, 3(2), 46 - 9
The role of Helicobacter pylori in the pathogenesis of acid-peptic disease; Smoot DT et al.; Helicobacter pylori (H pylori) is likely the most common cause of chronic active gastritis in humans . Also, H pylori has been found in up to 100% of patients with peptic ulcer disease . Recent studies have shown that long-term infection by H pylori is associated with an increased risk of developing gastric carcinoma . The mechanism(s), however, by which H pylori causes gastritis or leads to the development of peptic ulcers and gastric cancer is not well understood . The prevalence of H pylori gradually increases with age and is much higher in underdeveloped countries . In the United States, H pylori is present in 50% to 60% of people 60 years of age and older . The prevalence of H pylori in African Americans in the United States is approximately 38% higher than that in whites in all age groups . The route of transmission of this organism is unknown, but it is most likely from person to person . H pylori infection has been rather difficult to eradicate . At present, the most effective antimicrobial therapy includes bismuth salts and two antibiotics plus an H2-receptor antagonist.

Mikrobiyol Bul, 1992 Jan, 26(1), 90 - 6
{Immune system evolution . (From cells to humans)}; Belek AS; The great variety of cells and molecules observed in the mammalian immune system can be explained by stepwise acquisition of them during phylogeny . Self/nonself discrimination and cell-mediated immunity have been present since the early stages of evolution . Although some inducible antimicrobial molecules have been demonstrated in invertebrates, immunoglobulins appear in vertebrates . T and B cell diversity, development of the lymphoid organs, MHC molecules, complement and cytokines are the characteristics that appear through the evolution of vertebrates . Further knowledge that will be obtained from phylogenetic studies will improve our understanding of the immune system of human.

Clin Infect Dis, 1992 Jan, 14(1), 15 - 22
Renal ultrasonographic correlates of acute pyelonephritis; Johnson JR et al.; To determine the frequency and clinical significance of ultrasonographically detectable alterations in renal volume and anatomy that are associated with acute pyelonephritis, 25 women underwent renal ultrasonography during the acute phase of their illness, and 21 of these patients underwent the procedure after receiving antimicrobial therapy . One patient had a predisposing anatomic abnormality (4%; 95% confidence interval, 0-12%), and one patient each (8%; 95% confidence interval, 0-19%) experienced focal complications (an intrarenal mass and perinephric fluid collection) . The kidneys of the 21 evaluable patients were acutely swollen (mean, 20%; P = .0001); one or both kidneys were enlarged by greater than or equal to 15% in 17 (81%) . Acute renal enlargement was associated with protracted pretherapy symptoms (P less than .01), leukocytosis (P less than .01), focal infectious complications (P less than .01), and prolonged hospitalization (P less than .05) . Thus, ultrasonographically demonstrable renal swelling characteristically occurs in women with acute pyelonephritis but is usually apparent only in retrospect . The degree of swelling correlates with selected clinical parameters, and the frequency of underlying anatomic abnormalities and focal infectious complications is low.

Am J Hosp Pharm, 1992 Jan, 49(1), 109 - 15
Multidisciplinary protocol for determining aminoglycoside dosage; Lynch TJ et al.; A protocol for determining optimal dosages of aminoglycosides early in therapy is described, and the effectiveness of the protocol is evaluated . The protocol was developed jointly by physicians and pharmacists at a 550-bed hospital to ensure that surgical patients prescribed aminoglycosides were quickly and consistently put on a safe and effective course of therapy . Physicians select an aminoglycoside and calculate a loading dose and initial maintenance dosage by using a nomogram printed on an antimicrobial order form . Nurses are trained to administer and document aminoglycoside doses accurately and to draw blood samples at the correct times . Pharmacists order serum aminoglycoside concentration assays, analyze the results, and recommend changes in dosage when necessary . To evaluate the effectiveness of the dosing protocol, the records of surgical patients treated before and after the protocol was in place were reviewed . Compared with the control group, a higher percentage of patients treated under the protocol were receiving therapeutic, nontoxic dosages of aminoglycosides within 48 hours of the start of therapy . In addition, fewer serum drug concentration tests were ordered per patient under the protocol, and the percentage of concentration determinations useful for analysis was higher . The mean duration of aminoglycoside therapy was identical before and after the protocol was instituted, and nephrotoxic reactions tended to be less common among the protocol patients . An aminoglycoside dosing protocol requiring the cooperation of pharmacists, nurses, and physicians provides a consistent, safe, and effective means of managing aminoglycoside therapy for the hospitalized patient.

Infection, 1992 Jan-Feb, 20(1), 25 - 9
Effect of subinhibitory concentrations of antibiotics on extracellular Shiga-like toxin I; Walterspiel JN et al.; Patients with diarrhea due to strains of enterohemorrhagic Escherichia coli (EHEC) (e . g . O157:H7) might be at a higher risk of developing hemolytic uremic syndrome when treated with antimicrobial agents . It has been suggested that this might be due to an increase of release or production of vero or shiga-like toxin from such organisms, possibly as a stress response to antimicrobial agents . The aim of this study was to detect such increases in extracellular toxin in vitro with a newly developed method that exposed EHEC to high sublethal concentrations followed by a recovery phase at progressively lower concentrations . Five strains of EHEC were exposed to continuously changing concentrations of ciprofloxacin, co-trimoxazole, cefixime and tetracycline . The amount of free shiga-like toxin I (SLT-I) released was compared to the amount released from inocula that were not exposed to antibiotics . There were significant differences between the five EHEC strains in the amount of toxin detected after exposure to antimicrobial agents (p less than 0.001) . Equally important was the type of antibiotic (p less than 0.001), with ciprofloxacin inducing the largest increase ranging from 169 to 436%, followed by co-trimoxazole, cefixime and tetracycline . In addition, the increases in free toxin correlated with the concentration of the antibiotics (p less than 0.001) . The association between antibiotic-induced increases in SLT-I produced by strains of EHEC and certain classes of antibiotics might influence the analysis of future epidemiological studies on risk factors for HUS.

Zentralbl Bakteriol, 1992 Jan, 276(2), 280 - 7
Influence of 12 antibiotics on antitumor immunity in BALB/c-mice; Roszkowski K et al.; The effects of 7 days' chemotherapy with penicillin G, piperacillin, mezlocillin, cephalothin, cefamandole, cefotaxime, gentamicin, amikacin, streptomycin, rifampicin, doxycycline, and clindamycin on local tumor growth and metastatic lung colonization were studied in an experimental tumor model (BALB/c-mouse-sarcoma L-1) . The antibiotic dosages administered to mice were calculated on a body weight basis from doses recommended for human therapy . Except for mezlocillin, piperacillin, rifampicin and doxycycline, antibiotic treatment did not significantly influence local tumor growth, lung colonization and immune functions . Whereas mezlocillin exerted positive (tumor suppressive) or negative (tumor promoting) effects depending on the chemotherapy schedule, tumor growth and spread were significantly increased independent of the timing scheme after rifampicin or doxycycline treatment . Since certain immune functions (delayed type hypersensitivity; proliferation of spleen lymphocytes) were significantly suppressed after administration of mezlocillin, rifampicin and doxycycline, a correlation between antimicrobial chemotherapy and tumor progression may be possible.

Adv Intern Med, 1992, 37, 173 - 95
Hemorrhagic colitis associated with Escherichia coli O157:H7; Cohen MB et al.; E . coli O157:H7, the predominant serotype of EHEC, is a cause of both outbreaks and sporadic cases of hemorrhagic colitis . In sporadic cases, and especially in outbreaks, there is an association with the consumption of improperly cooked ground beef . Both young children and geriatric patients have an increased attack rate for EHEC infection as well as an increased incidence of the two sequelae of intestinal infection with EHEC, hemolyticuremic syndrome, and thrombotic thrombocytopenic purpura . The hallmark of hemorrhagic colitis due to EHEC is the development of bloody diarrhea several days after the onset of nonbloody diarrhea and abdominal pain . Fever is usually absent or low-grade . The pathogenesis of EHEC infection is probably related to at least two bacterial virulence factors: adherence of bacteria to intestinal mucosa and production of one or more cytotoxins . These cytotoxins are closely related to Shiga toxin and therefore are often referred to as Shiga-like toxins . Treatment for hemorrhagic colitis is supportive care; most illnesses are self-limited . At present, there is no evidence that antimicrobial therapy shortens the course of illness or prevents the development of sequelae.

Br Vet J, 1992 Jan-Feb, 148(1), 54 - 62
Clinical, bacteriological and therapeutic aspects of bovine mastitis caused by aerobic and anaerobic pathogens; Pyorala S et al.; Twenty cows and three heifers with summer mastitis-like signs were included in the study . Forty aerobic and 38 anaerobic bacterial isolates representing 23 different species were isolated from udder secretions, the mean number of species being 3.4/sample . Pathogens most often were recovered in quantities exceeding 10(5) CFU/ml . Growth of pathogenic bacteria in the blood was found in only one case . Most cases occurred in housed animals and had often been preceded by teat injury . No anaerobic growth was found in milk samples of a control group consisting of 29 cows with ordinary acute mastitis . Values of indicators of inflammation in milk (NAGase and plasmin activity) were high, mean values being 914.1 and 1.3 units . The animals with aerobic/anaerobic mastitis were treated using various antimicrobial agents . All but three quarters were lost to milk production . Two animals with complete recovery were given a combination of penicillin G and tinidazole.

Kekkaku, 1992 Jan, 67(1), 1 - 8
{Relationship between virulence to mice and macrophage chemiluminescence-triggering activity of the Mycobacterium avium complex belonging to various serovars}; Tomioka H et al.; Macrophage chemiluminescence (M phi CL)-triggering activities of Mycobacterium avium complex (MAC) strains belonging to various serovars were examined . When SmT colonial variant (smooth, transparent, irregularly shaped) of M . intracellulare N-260 strain was compared with its SmD variant (smooth, opaque, dome-shaped) for M phi CL-triggering function and resistance to antimicrobial activity of murine resident peritoneal M phi s, the SmT variant showed much lower M phi CL-triggering activity accompanied by its high resistance to M phi microbicidal functions . Thus, difference in the virulence of the two MAC colonial variants seems to be originated from their different activities in M phi-triggering to be stimulated state in terms of O2-dependent antimicrobial functions . When disease-associated MAC strains belonging to serovars 1, 14, 16 (major serovars seen in Japan), 8 (intermediate serovar) and 9 (minor serovar) were challenged to mice, their virulence, in terms of mortality of host animals and growth of the organisms in the lungs, was nearly in the order of serovar 16, 14, 8, 1 and 9 . However, there was found no obvious serovar-dependent difference in M phi CL-triggering activity of these MAC strains . Thus, no significant correlation was found between virulence of the MAC strains of various serovars and their triggering activities for M phi active oxygen production, which is important for the O2-dependent microbicidal mechanisms of host M phi s.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Emerg Med, 1992 Jan, 21(1), 72 - 80
Controversial issues in clinical management of the simple wound; Berk WA et al.; The primary goals of the practitioner managing a simple wound are to encourage primary healing and avoid infection . We conclude from this analysis that the four basic aspects of wound management we have reviewed, the timing of wound repair, the preparation of the wound, local anesthetic management, and antimicrobial therapy, will continue to be fertile topics for investigation and debate.

J Clin Pharmacol, 1992 Jan, 32(1), 32 - 6
Drug-food interaction potential of clarithromycin, a new macrolide antimicrobial; Chu S et al.; To evaluate the effect of food on bioavailability, clarithromycin and 14-hydroxyclarithromycin (active metabolite) pharmacokinetics were assessed in 26 healthy adult volunteers after ingestion of a single oral 500-mg dose of clarithromycin in a fasting state (2 hours before breakfast after an overnight fast) and a nonfasting state (0.5 hours after the start of breakfast) . Clarithromycin and 14-hydroxy metabolite plasma concentrations were measured using a high-performance liquid chromatographic technique . Food intake immediately before dosing increased the extent of absorption from the 500-mg tablet formulation by approximately 25% . The mean increase in metabolite area under the plasma concentration-time curve was approximately 9% . These results suggest that clarithromycin can be taken without regard to timing in relation to meals.

J Basic Microbiol, 1992, 32(1), 43 - 7
Potassium leakage from Escherichia coli cells treated by organic ammonium salts; Mlynarcik D et al.; The effect of the homologous series of 1,1-dialkylpiperidinium bromides on the potassium leakage from Escherichia coli cells has been studied . The minimum concentration for each compound which is able to release maximum of cellular potassium has been determined and correlated with the inhibitory activities of the compounds . The relationship between the structure and the activity enables to consider the K+ leakage as the marker of inhibitory activity of the membrane active antimicrobials.

Infection, 1992, 20 Suppl 1, S45 - 7
Immunological evaluation of cefodizime: a unique molecule among cephalosporins; Labro MT; The immunomodulatory properties of cefodizime, a new aminothiazolyl cephalosporin, are reviewed . Cefodizime displays in vitro and ex vivo stimulatory effects on phagocyte bactericidal function . It also increases certain lymphocyte responses, including delayed type hypersensitivity and antibody production . In addition, it restores various immune functions in immunocompromised animals and humans . The immunomodulating activity of this drug is further supported by its in vivo efficacy in experimental models of infections using cefodizime-sensitive or -resistant pathogens . Cefodizime appears to be a promising molecule, exhibiting potent antimicrobial activity and exerting potentially beneficial effects on the immune system.

Eur J Cancer, 1992, 28A(4-5), 873 - 8
Selective oral antimicrobial prophylaxis for the prevention of infection in acute leukaemia-ciprofloxacin versus co-trimoxazole plus colistin . The EORTC-Gnotobiotic Project Group; Donnelly JP et al.; 230 leukaemic patients were entered into a randomised, prospective, multicentre trial of either ciprofloxacin (1 g/day) or co-trimoxazole (1920 mg/day) plus colistin (800 mg/day) for the prevention of infection during granulocytopenia . Bacteraemia due to resistant gram-negative rods occurred only in the co-trimoxazole-colistin group though both regimens were effective for selective gastrointestinal tract decontamination . However, there were fewer patients without any infective complications (31% vs . 18%: P = 0.02), fewer febrile days {mean (S.D.) 5.9 (1.1) vs . 8.2 (1.4): P = 0.0242}, a lower proportion of infective events (0.9 (0.16) vs . 1.2 (0.18): P = 0.005) and fever occurred later (median 19 vs . 14 days: 0.025 less than P less than 0.05) in the co-trimoxazole-colistin group . The choice of prophylactic regimen therefore appears to depend upon whether or not protection against gram-negative infection is required or better systemic prophylaxis overall.

Chemotherapy, 1992, 38 Suppl 2, 25 - 8
Cefetamet pivoxil in pediatric otitis media; Pukander JS et al.; Cefetamet, an oral 3rd-generation cephalosporin, was investigated in 40 children with acute otitis media in a comparative randomized trial . The efficacy of 20 mg/kg cefetamet syrup in 20 patients was compared with that of 20 mg/kg cefaclor in another 20, both drugs being given orally twice daily for 7 days . Tympanocentesis was performed for every child before the initiation of antimicrobial treatment . After 7 days treatment with cefetamet pivoxil, clinical cure was obtained in 12 patients, 3 were failures and 5 could not be assessed . In the cefaclor group, 10 patients were cured, 1 improved and 9 were failures . No severe adverse events were observed with either drug.

Adv Enzyme Regul, 1992, 32, 117 - 29
Antimicrobial peptides of frog skin; Spencer JH; A mechanism of action for frog skin antimicrobial peptides has been proposed, based on the amphipathic nature of the peptides when they contact bacterial surfaces . This results in anion channel formation and penetration of the membrane which allows efflux of OH- and uncoupling of respiration in the bacteria . The question of occurrence of human antimicrobial peptides analogous to those in frogs has not been answered but early studies indicate that Erspamer's prediction is correct.

Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl, 1992, 35(3), 243 - 52
{Antimicrobial activity of composite filling materials}; Komarek S et al.; Antimicrobial effects of several composite fillers are monitored in response to a mixed aerobic and anaerobic microbial flora of the oral cavity . None of observed both self-polymerizing and photopolymerizing composites showed antimicrobial effects.

Pharmacotherapy, 1992, 12(6), 435 - 9
Potential warfarin-ciprofloxacin interaction in patients receiving long-term anticoagulation; Bianco TM et al.; This study prospectively evaluated the potential interaction between the oral anticoagulant warfarin and the quinolone antimicrobial agent ciprofloxacin . After a 10-day placebo lead-in phase, 16 patients stabilized with long-term warfarin therapy were randomized to receive ciprofloxacin 500 mg or a matching placebo twice/day for 10 days . International normalized ratios (INRs) measured by both standard laboratory analysis and by Coumatrak (finger-stick) methods were evaluated at 3- to 5-day intervals . No patient experienced a significant increase in INR . No patient experienced a bleeding event . These data support the fact that a warfarin-ciprofloxacin interaction does not routinely occur at this dosage and duration of ciprofloxacin therapy.

Infection, 1992, 20 Suppl 3, S138 - 42
Diagnostics and categories of patients; Schaeffer AJ; Care in identifying and categorizing patients is a critical first step in proper drug evaluation . The appropriate diagnostic tests include culture and urinalysis . They are essential for the firm establishment of a diagnosis and should be sensitive and specific enough to meet the appropriate clinical requirements . The clinical categories outlined are encountered in clinical practice with a frequency that is sufficient to provide enough patients for an assessment of the response to antimicrobial therapy and to give information that will have practical value for clinicians.

Vasa, 1992, 21(4), 355 - 9
The effect of antimicrobial impregnation on vascular graft healing . An experimental porcine study; Parsson H et al.; This study evaluates the impregnation of a phenol derivative (Y105) to polymerized Dacron grafts . Y-105 has broad spectrum anti-microbial characteristics . The grafts were inserted end to side in the iliac artery of pigs . Reexploration and graft removal was performed after 7, 14 and 30 days . After pressure fixation with glutaraldehyde the grafts were evaluated for gross morphology and by scanning electron microscopy . A gradual development of pseudo-intima was observed without sign of graft occlusion . The addition of the antimicrobial impregnation did not interfere with healing.

Retina, 1992, 12(4), 331 - 5
Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid; Whitcup SM et al.; It has been hypothesized that coinfection with mycobacteria occurs in patients with Pneumocystis carinii choroiditis, but cases demonstrating ocular infection by both organisms have not been reported . This study reports the case of a patient with P . carinii choroiditis who was treated with intravenous trimethoprim and sulfamethoxazole, followed by intravenous trimethoprim and dapsone . The choroidal lesions failed to resolve despite 6 weeks of treatment, and the patient died from massive pulmonary infection caused by P . carinii, Mycobacterium avium-intracellulare, and cytomegalovirus infections . Ocular histologic and electron microscopic examinations revealed choroidal infection by both P . carinii and M . avium-intracellulare . Serum levels of sulfamethoxazole were below the recommended therapeutic range for treating P . carinii infection during the first week of therapy, but adequate drug levels were subsequently obtained . Failure of choroidal lesions of P . carinii to resolve in some cases may suggest insufficient antimicrobial levels in the blood or raise the possibility of coexistent M . avium-intracellulare or other opportunistic infection.

Arch Orthop Trauma Surg, 1992, 112(1), 33 - 5
Ciprofloxacin-impregnated poly-L-lactic acid drug carrier . New aspects of a resorbable drug delivery system in local antimicrobial treatment of bone infections; Teupe C et al.; Resorbable poly-L-lactic acid (PLLA) cylinders (3.5 mm diameter, 5 mm in length) carrying 6% of weight ciprofloxacin (Ciprobay, Bayer AG, Leverkusen, FRG) were investigated in vitro to explore their properties as a slow-release antibiotic deposit . Forty bioactive cylinders stored in test tubes were covered with phosphate buffer (pH 7.4 at 37 degrees C) and 40 with fresh human blood plasma and tested under various conditions . For comparison a gentamicin-polymethylmethacrylate (PMMA) chain (Septopal, E . Merck, Darmstadt, FRG) was exposed to similar test conditions . The quantities of ciprofloxacin and gentamicin released were analysed by a microbiological method (bioassay) . The concentrations of ciprofloxacin released were analysed by a microbiological method (bioassay) . The concentrations of ciprofloxacin released from 40 cylinder were initially very high (up to 180 mg/l) but they decreased rapidly within the first 5 days (4.2-22.5 mg/l) . Early release of gentamicin reached up to 227.5 mg/l but dropped to of 22 mg/l on the 14th day . Complete degradation of the PLLA-cylinders was not seen in the observed period of 92 days . The mean loss of mass was 8.4% . The recovery of incorporated ciprofloxacin was 6.5% on average.

Arkh Patol, 1992, 54(8), 40 - 5
{A hypothesis about resorptive cellular resistance as a special form of antimicrobial host protection}; Pigarevskii VE; The ability of macrophages to phagocyte granulocyte debris ("cleaning" reaction) is evolutionary developed and represents the mechanism of cellular resistance preceding immunity . Activation of the mononuclear phagocyte system and acquisition by the macrophages of the capacity to the intracellular chlamydia destruction as well as other infectious agents parasitizing in the intact cells occurs in the process of the granulocyte debris phagocytosis . This phenomenon termed by the author as a resorptive cellular resistance is one of host barrier mechanisms.

Pharmacotherapy, 1992, 12(6 Pt 2), 64S - 70S
Pharmacodynamic factors of antibiotic efficacy; Rotschafer JC et al.; The primary focus of the pharmaceutical industry in past years has been on developing more potent antibiotics rather than on establishing optimum therapy with currently available agents . Concepts that can be used to tailor patient- and pathogen-specific antimicrobial regimens include concentration-dependent killing, concentration-independent killing, and postantibiotic effect . It is possible to administer single daily doses (SDD) of aminoglycosides; however, a fixed SDD regimen cannot meet the goals for therapy in all patients . Instead, it is necessary to consider both pharmacodynamic concepts and pharmacokinetic principles . Even with tailored, patient-specific regimens, however, limitations exist with antibiotic therapy alone . Immunotherapy, used as an adjunct to antimicrobial therapy, may play a role in improving patient outcomes.

J Med, 1992, 23(3-4), 253 - 64
Synthetic trehalose dicorynomycolate and antimicrobials increase survival from sepsis in mice immunocompromised by radiation and trauma; Ledney GD et al.; When mammalian antimicrobial defenses are compromised by radiation, death from sepsis may occur . Tissue trauma in irradiated hosts significantly increases mortality from bacterial infections and makes antimicrobial treatments more difficult than when individuals are subjected to trauma or radiation alone . We determined that postirradiation therapy with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) and antimicrobials increases survival in mice after lethal irradiation and tissue trauma . Single agent therapy with systemic oxacillin, gentamicin, ofloxacin, and S-TDCM did not increase survival . Topical treatment of the injury with gentamicin cream in addition to systemic therapy with oxacillin or S-TDCM was necessary to enhance survival . Therapy with gentamicin and S-TDCM had a synergistic effect on survival . Therapies combining augmentation of non-specific host defense mechanisms with antimicrobials may be valuable in treating irradiated patients also sustaining tissue trauma.

Nord Med, 1992, 107(11), 272 - 3
{Prevention and treatment of traveler's diarrhea}; Svenungsson B et al.; Travelers' diarrhea (TD) affects 20-50 per cent of individuals going to developing countries in Asia, Africa, or Latin America . The etiology varies but is dominated by enterotoxigenic E . coli, found in 30-50 per cent . TD is usually a mild disease, self-limiting in 3-4 days, but 10 per cent of those afflicted have symptoms for one week or more . Prophylaxis of TD involves dietary restrictions and, in selected medical risk groups, antimicrobial drugs . The most important treatment of TD is oral rehydration and loperamide in mild to moderate, non-invasive illness . Antibiotics for self-treatment shall be restricted for medical risk groups and individuals travelling far from medical service.

Adv Pediatr, 1992, 39, 283 - 306
Helicobacter pylori, gastritis, and ulcers in pediatrics; Judd RH; Hp now appears to be more than a simple commensal organism in patients with gastritis or peptic ulcer disease . Microbiologic, serologic, and epidemiologic studies all confirm that Hp has an important role in children with abdominal pain . Hp is found in the gastric mucosa of children with histologically proven gastritis or peptic ulcer . The organism can be transmitted from human to human with evidence of colonization, appearance of gastritis, and serum antibody response . Antimicrobial therapy directed at Hp eradicates colonization and resolves symptoms . Hp antibodies appear more frequently in familial clusters and the frequency of antibody positivity increases with age . Children are more likely to have symptomatic disease associated with elevated antibody titers . Recurrence of disease is associated with reappearance of the organism . At the present time, colonization can be detected only by gastric biopsy; however, it may be possible eventually to diagnose or follow infections by obtaining serum antibody titers or urea breath-testing . The natural history of Hp infection is unclear . Although it can cause an acute gastritis, it generally is found in association with chronic gastritis . The increase in seropositivity with age may mean that slow changes evolve over decades or that age cohorts have been infected differentially . How does antral colonization with Hp cause duodenal ulceration? The organism is not found in the duodenum and most patients with gastritis do not develop ulcers . This may be related to changes in acid production and mucosal protection associated with Hp colonization, but few studies have been done . What factors initiate Hp infection? Both volunteers who became colonized first suppressed acid secretion with H2-antagonists . Hypochlorhydria also seems to follow Hp infection in these same studies . The role of diet and drugs, or other environmental and genetic factors, in initiating infection is largely unexplored . An effective means of therapy needs to be developed . Although Hp appears sensitive in vitro to many compounds, it is difficult to eradicate in vivo, especially with monotherapy . Single-drug therapy suppresses the organism, but recurrence rates are high . It is difficult to deliver effective doses of drugs to the mucous niche the organism has selected and concerns about long-term therapy and its side effects persist . Current data suggest no ready solution to the initial case presentation . A child with primary gastritis or duodenal ulcer should be treated first with standard antacid and H2-receptor antagonist therapy . If endoscopy is performed, biopsies of normal-appearing areas of gastric antrum should be stained for Hp and a biopsy urease test should be performed.(ABSTRACT TRUNCATED AT 400 WORDS)

Yao Xue Xue Bao, 1992, 27(6), 462 - 6
{Determination of ofloxacin in human plasma and studies of its pharmacokinetics using HPLC method}; Xu DK et al.; Ofloxacin is a new broad-spectrum oral bactericidal antimicrobial agent . Its primary effect is the inhibition of bacterial DNA gyrase . This paper describes the development of a simple method for its determination using HPLC with UV detection . We used a Waters liquid chromatograph equipped with a Model 490 E multi-wavelength detector, a Model 510 pump and a U6K injector . The separation was performed on a Spherisorb C18 column (200 mm x 4.6 mm ID, 5 microns) with a mobile phase of methanol-0.01 mol/L phosphate buffer-0.5 mol/L tetrabutylammonium bromide (35:65:4, pH 2.50) . The flow-rate was 1.0 ml/min and detection was at 294 nm . A specimen (0.2 ml) was spiked with the internal standard (norfloxacin) and deproteinized by adding 1.0 ml methanol . The precipitated mixture was shaken and then centrifuged at 3000 x g for 10 min, the supernatant was evaporated at 75 degrees C under a nitrogen stream . The residue was taken up with 0.4 ml of the mobile phase and 50 microliters aliquots were injected into the system . The minimal detectable concentration in plasma is 20 ng/ml . There is a linear relationship between the peak area ratio over the range of 0.5-4.0 micrograms/ml with r = 0.9999 . The method has been applied to assay ofloxacin concentration in human plasma . The pharmacokinetic characteristics were studied.

Stomatologiia (Mosk), 1992 Jan-Feb, (1), 25 - 6
{A comparative study of the efficacy of the action of a number of local antimicrobial preparations on the species and quantitative composition of the microbial flora in periodontal pockets}; Grudianov AI et al.; The effects of a number of antibiotics were studied with the use of phase contrast microscopy . The time course of the qualitative and quantitative changes of the periodontal pouch microflora evidences that a mixture of trichopol with chlorohexidine is the most effective therapy for periodontal pouch sanitization.

Pharmacotherapy, 1992, 12(5), 397 - 402
Bacterial resistance to beta-lactams, and its prevention with combination antimicrobial therapy; Barriere SL; The clinical and economic impacts of bacterial resistance are substantial . The development of bacterial resistance during a course of therapy often leads to clinical failure, prolonged hospitalization, increased morbidity, mortality, and increased health care costs . Resistance has been reported to occur most frequently with aminoglycosides, quinolones, and beta-lactam antimicrobials, and often occurs during the course of treatment of gram-negative bacillary infection . Resistance is most commonly due to enzymatic inactivation, permeability changes, or receptor mutation . Strategies for the prevention of resistance include appropriate infection-control practices, judicious use of antimicrobials, enhancement of host defenses, and the use of antimicrobial combinations . Despite success in vitro and in experimental animal models of infection, clinical trials in humans of antimicrobial combinations for the prevention of resistance have yielded mixed results . Use of the most potent agents available, preferably in bactericidal synergistic combinations, may be effective in preventing in vivo emergence of bacterial resistance.

Drugs Exp Clin Res, 1992, 18(3), 99 - 104
Tetracycline inhibition identifies the cellular sources of collagenase in gingival crevicular fluid in different forms of periodontal diseases; Suomalainen K et al.; Tetracyclines have recently been shown to inhibit the activity of mammalian matrix metalloproteinases, i.e . type I collagenase (MMP-1) and type IV collagenase/gelatinase (MMP-2) . The specificity of this effect, however, has not been examined in detail . In the present study, doxycycline (a clinically widely used commercial tetracycline) and 4-de-dimethylaminotetracycline (CMT-1, a chemically modified non-antimicrobial tetracycline) were tested, at a wide range of concentrations, for their ability to inhibit human neutrophil and fibroblast interstitial collagenases, which are distinct gene products, as well as collagenase in human gingival crevicular fluid (an inflammatory exudate in periodontal lesions) obtained from adult, juvenile and diabetic adult periodontitis patients . The concentrations of these two tetracyclines, required to inhibit 50% of the collagenase activity (IC50), were found to be 15-30 microM for purified human neutrophil collagenase as well as collagenase in gingival crevicular fluid of adult periodontitis patients and diabetic adult periodontitis patients, thus approximating in vivo therapeutic tetracycline levels . In contrast, the fibroblast collagenase and collagenase in gingival crevicular fluid of patients with juvenile periodontitis were relatively resistant to tetracycline inhibition: the IC50 for doxycycline and CMT-1 were 280 and 500 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Dtsch Zahn Mund Kieferheilkd Zentralbl, 1992, 80(3), 165 - 70
{Microbiological studies of self-disinfecting alginate impression materials}; Oehring H et al.; Using microbiologically experimental methods and observations corresponding to praxis the efficiency of the addition of antiseptics to alginate is evaluated . The addition of chlorhexidine to the alginate leads to a considerable reduction of the amounts of germs, but an one hundred percent disinfection of the alginates is not always performed . An influence of the alginate materials and the water quality on the antimicrobial efficacy of chlorhexidine has been proved . The always occurring contamination of the impression tray rules out a complete stopping of infection between the patient and the laboratory staff.

Acta Otorhinolaryngol Belg, 1992, 46(3), 293 - 301
{Orbital involvement of sinusitis}; De Vos G et al.; Sinusitis can spread to the orbital tissues . 'Preseptal' soft-tissue bacterial infections are relatively common during childhood and with appropriate antimicrobial therapy they usually resolve quickly . 'Orbital' soft-tissue infections, in contrast, are relatively rare and frequently cause serious morbidity . Four cases are presented . Symptomatology and pathogenesis are reviewed . Diagnostic procedures, especially CT-scan, are discussed and recommendations are given for medical and surgical management.

Rev Med Chir Soc Med Nat Iasi, 1992 Jan-Jun, 96(1-2), 69 - 72
{Phthalazinilides . The action of ethyl bromopyruvate on phthalazine}; Caprosu M et al.; Our investigation for obtaining carbon-nitrogen stable ilides continued by the synthesis of new phthalazinic derivatives by the action of ethyl brompyruvate . The structure of the obtained products was confirmed by chemical and spectral analyses . The results regarding their antimicrobial action are also presented.

Rev Med Chir Soc Med Nat Iasi, 1992 Jan-Jun, 96(1-2), 65 - 8
{The quality assessment of a product with adhesive properties for complete dental prostheses}; Verbuta A et al.; A formula of dental adhesive using as an agent responsible for this activity an indigenous product, C.M.C.Na 1080, gelified with preservative solution with added astringent agents was elaborated . The possible interaction between the constituents during preservation and the product qualities by determining the pH, extensibility index, sliding limit tension, antimicrobial activity and certain clinical aspects were evaluated.

Rev Med Chir Soc Med Nat Iasi, 1992 Jan-Jun, 96(1-2), 57 - 64
{The physicochemical characterization and therapeutic evaluation of Cicatrol}; Popovici I et al.; Cicatrol ointment with the formula: argentic sulphamethoxydiasine 1 g, bentonite hydrogel 12.5% for 100 g is manufactured at the Microproduction Laboratory of the Faculty of Pharmacy of Iasi . The one-year physicochemical determinations of the aspect, colour, homogeneity, pH, rheological behaviour and relative viscosity, content in argentic sulphamethoxydiasine as well as "in vitro" antimicrobial activity of Cicatrol showed a good stability and gel properties enabling an uniform and long-term contact with the wound . The clinical investigations carried out until now in patients with burns, varicose ulcers, trophic shank ulcers, superficial phlebitis with atonic ulcerations or wounds with multiple sites revealed its remarkable therapeutic value . As compared to other similar products, Cicatrol by its aseptic properties favours the scarring of any type of wound, a normal skin, without keloid scars being obtained, it also being well tolerated.

Rev Environ Contam Toxicol, 1992, 129, 51 - 66
Acute pesticide morbidity and mortality: California; Mehler LN et al.; The California Pesticide Illness Surveillance Program collects, investigates, abstracts, and records reports received from physicians . A minority of the reports are received through the county health officers who are notified by physicians under a state requirement for reporting pesticide-caused conditions . Most of the cases are identified by review of workers' compensation records . All the cases identified are investigated by the agricultural commissioners of the counties where exposure occurred . The investigation reports are reviewed and abstracted by staff of the Worker Health and Safety Branch of the California Department of Pesticide Regulation, California Environmental Protection Agency (Cal/EPA) . The crucial determination is assessment of the degree of relationship between the exposure and subsequent disease: definite, probable, possible, unlikely, or unrelated . In most years, the number of cases investigated has been between 2,500 and 3,000 . Excluding antimicrobials, the number of cases found after investigation to have a definite, probable, or possible relationship with pesticide exposure has ranged from 970 (in 1989) to 1,372 (in 1988) . Cases involving antimicrobials rarely were reported prior to 1987 . In that year, surveillance staff began reviewing workers' compensation records personally, with the specific goal of identifying antimicrobial cases . Since then, antimicrobials have been found to account for 746-813 cases annually, primarily involving splashes and squirts to the eye and inhalation of fumes or vapors . Numbers of case reports from agricultural situations have varied irregularly, driven by small numbers of episodes concerning multiple individuals . Variability in numbers of cases involving the skin has depended almost entirely on variation in numbers of field worker dermatitis . The most common situation for field worker dermatitis has been summer work in table grapes grown in the southern San Joaquin valley . In the two years since reentry intervals for the acaricide propargite were lengthened, there have been no more major clusters of field worker dermatitis . Although the cases collected by the surveillance program are predominantly occupational, because of dependence on workers' compensation for case identification, most recorded deaths are nonoccupational . Nonoccupational fatalities include suicides, mistaken ingestion of pesticides (especially if stored in food containers), and entry into structures being fumigated . Occupational deaths are less common and more varied . The circumstances of each reported occupational death are summarized above.

Pediatriia, 1992, (4-6), 38 - 42
{Use of oral antibacterial drugs in the treatment of acute pneumonia in children}; Fedorov AM et al.; The efficacy of oral antimicrobial agents was studied under conditions of monitored clinical trials . Overall 279 children with different clinical forms of acute pneumonia were entered into the study . It has been shown that the treatment of uncomplicated acute pneumonias may be started since the day of admission to the hospital . The total efficacy of oral drugs was 75% . This does not differ essentially from the efficacy of antibiotics administered parenterally (89%) . It has been established that early change (on days 1-3 since the effective treatment) from parenteral to oral administration of antibiotics does not reduce the treatment efficacy but noticeably lowers the injection load of the patients . The side effects (dyspeptic disorders) that occur very frequently during erythromycin treatment suggest that this antibiotic should not be administered to infants.

J Clin Lab Anal, 1992, 6(4), 219 - 24
Comparison of serum amyloid A and C-reactive protein as indicators of lung inflammation in corticosteroid treated and non-corticosteroid treated cystic fibrosis patients; Smith JW et al.; Serum amyloid A (SAA) and C-reactive protein (CRP) levels were compared in 830 serum samples from 155 cystic fibrosis (CF) patients . Correlation coefficients were calculated for all samples (r = 0.73), for samples from non-corticosteroid treated (CFNS) patients (n = 698, r = 0.80), and for samples from corticosteroid treated (CFS) patients (n = 132, r = 0.35) . SAA was the more sensitive indicator of pulmonary inflammation when SAA and CRP were compared to pulmonary function tests of 49 hospitalized patients at admission and discharge . CRP levels were significantly (p less than .05) lower at admission in CFS patients than in CFNS patients, whereas SAA levels were not significantly different between the two groups . All nine CFS patients hospitalized had elevated SAA levels (average 22 times above normal limits) at admission, while only six had elevated CRP levels (average 3.7 times above normal limits) at admission . In the 40 CFNS patients both SAA and CRP levels were significantly elevated at admission . In each case SAA and CRP levels declined as pulmonary functions improved with effective antimicrobial therapy . In three instances SAA levels increased during hospitalization while CRP levels did not . In each case, rising SAA levels indicated clinical deterioration associated with evolving resistance of P . aeruginosa which required a change in antibiotic therapy.

Rhinol Suppl, 1992, 14, 269 - 73
Fireside conference 19 . Wegener's granulomatosis and lethal midline granuloma; Teicoplanin--its role as systemic therapy of burn infections and as prophylaxis for orthopaedic surgery . Italian Study Groups for Antimicrobial Prophylaxis in Orthopaedic Surgery and Burns; Dipartimento di Farmacologia, Universita degli Studi, Firenze, ItaliaTwo randomized studies have been initiated to establish the role of teicoplanin as systemic therapy for infections in burns patients and as short-term prophylaxis for orthopaedic implant surgery . Opportunistic micro-organisms causing infections in burn patients are often acquired in hospital . These infections commonly involve Gram-positive organisms which may be resistant to several antibiotics . Teicoplanin, alone and in combination with additional antibacterial drugs, is effective in the treatment of Gram-positive infections of various types . In addition, teicoplanin has proved useful as prophylaxis against infection in orthopaedic surgery . Deep prosthetic infections are very difficult to cure without removing the infected device; the outcome can be devastating, such as total loss of joint function, amputation, and, occasionally, death . Preliminary results from the two studies are encouraging and show that teicoplanin has a role to play both in treatment of infection and as prophylaxis against hospital-acquired infection.

Eur J Surg Suppl, 1992, (567), 19 - 21
Teicoplanin vs cephamandole for antimicrobial prophylaxis in prosthetic joint implant surgery: (preliminary results); Mollan RA et al.; Infection following prosthetic joint implant jeopardizes the prosthesis and may lead to long-term locomotor disability . Interoperative antimicrobial prophylaxis can reduce the incidence of infectious complications . The comparative safety and efficacy of single-dose teicoplanin and four doses of cephamandole over a 24-hour period is currently being assessed in a single-blind, randomized concurrent study of patients who undergo first time hip or knee arthroplasty . Of 660 evaluated patients, 352 have received cephamandole and 308 teicoplanin . Two patients in each group had a surgical wound infection at 1 week after surgery . Reassessment 30 days postoperatively showed resolution of the infection in both of the teicoplanin patients and in one of the cephamandole patients . Proven or suspected infection involving other body systems occurred in 30 teicoplanin and 38 cephamandole patients at 1 week postoperatively and in 5 teicoplanin and 3 cephamandole patients 1 month after surgery . Adverse events occurred in 20 (5.1%) teicoplanin patients and 29 (7.1%) cephamandole patients . These preliminary results suggest that single-dose teicoplanin is a safe and effective prophylactic agent in prosthetic joint implant surgery.

Acta Chir Plast, 1992, 34(1), 10 - 9
Experimental substantiation of allogenic tendon tissue transplantation; Plotnikova VA et al.; Substantiation of transplantation of tendon allografts treated with a new solution showing both sterilizing and preservatory effects was provided in experiments on 84 dogs . The solution prepared on the basis of 0.1% formaldehyde with the addition of dimethyl sulphoxide, monomycin and prednisolone (FDMP) shows a high antimicrobial activity, preserves the structure of the tendons and their elasticity . In their duration, the processes of reconstruction of allografts preserved in FDMP are very similar to autotransplants . Clinical application of preserved tendons on repairing defects in 418 patients proved the method to be highly effective.

J Antibiot (Tokyo), 1992 Jan, 45(1), 29 - 37
Antibiotics from basidiomycetes . XLI . Clavicoronic acid, a novel inhibitor of reverse transcriptases from Clavicorona pyxidata (Pers . ex Fr.) Doty; Erkel G et al.; A novel inhibitor of RNA-directed DNA-polymerases was isolated from fermentations of Clavicorona pyxidata . Its structure was elucidated by spectroscopic methods . Clavicoronic acid (1) is a noncompetitive inhibitor of avian myeloblastosis virus (Ki 130 microM) and Moloney murine leukemia virus (Ki 68 microM) reverse transcriptases . In permeabilized cells and isolated nucleic DNA- and RNA-synthesis are not affected . Clavicoronic acid markedly inhibits the multiplication of vesicular stomatitis virus in baby hamster kidney cells by interfering with this virus's RNA-directed RNA-polymerase . 1 exhibits no cytotoxic and very weak antimicrobial activities.

J Chem Technol Biotechnol, 1992, 55(4), 355 - 60
s-triazole systems . Part IV: Novel substituted thio-s-triazole derivatives; Awad IM et al.; Interaction of (3-aryloxymethyl-4-phenyl-s-triazol-5-yl)thioacethydrazid e (1a-c) with phenyl isocyanate and/or with methyl/phenyl isothiocyanate gave semicarbazides (2a-c) and thiosemicarbazides (3a-f) respectively . Cyclization of (3a-f) yielded s-triazoles (4a-f) . Compounds 4b,d,f were easily alkylated giving S-substituted thio-s-triazoles (5a-e) . Furthermore, compounds 4b,d,f underwent a Mannich reaction to give the expected Mannich bases (6a-f) . All compounds were fully confirmed by elemental and spectral analyses and have been screened in vitro for antimicrobial activity.

J Chem Technol Biotechnol, 1992, 55(3), 217 - 25
Spiroheterocyclic system . Part IV: Novel azo dye sulpha drugs of spiroheterocyclic naphthenes; Awad IM et al.; Novel azo-dyes have been synthesized by diazotization of 4-amino benzene-4'-(substituted heterocyclo) sulphonamide derivatives and coupling with 1-oxa-4-thia-spiro{4,4}nonan-2-one (I) and/or with 1-oxa-4-thia- spiro{4,5}decan-2-one (I') in acid medium to give the corresponding 3-azo-(4'-substituted benzenesulphonamido)-1-oxa-4-thia-spiro{4,4}nonan-2-one (II-IX) and/or 1-oxa-4-thia-spiro{4,5}decan-2-one (II'-IX'} as spiro-ligands . Treatment of these ligands with metal salts of iron (Fe3+), copper (Cu2+) and mercury (Hg2+) as chlorides in ethanolic solution furnished the corresponding metal chelates (IIa-c-IXa-c) and/or (II'a-c-IX'a-c) . The compounds were tested in vitro for antimicrobial activity to study the structure-activity relationship.

J Chem Technol Biotechnol, 1992, 55(3), 209 - 15
Synthesis of some new 3-(2'-heterocyclicethyl)-2-methyl-3,4- dihydroquinazolin-4-one derivatives as antimicrobial agents; el-Zohry MF et al.; 3-(2'-Chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one was reacted with acetylacetone, ethyl acetoacetate and diethylmalonate in the presence of sodium ethoxide to afford the alkylation products IV, V and VI . Compounds IV, V and VI were reacted with hydrazine hydrate, phenylhydrazine, hydroxylamine hydrochloride, urea and thiourea to yield 3-(2'-heterocyclicethyl)-2-methyl-3,4-dihydroquinazolin-4-on e derivatives VII-XV . The structures of the synthesized compounds were elucidated by elemental analyses and spectroscopic (IR and 1H-NMR) analyses . The prepared compounds were tested for their antimicrobial activities in comparison with tetracycline as a reference compound.

J Chem Technol Biotechnol, 1992, 53(4), 329 - 36
Synthesis and antibacterial activity of certain quinoline and quinazoline derivatives containing sulfide and sulfone moieties; el-Zohry MF et al.; Some aryl and/or heterocyclic mercaptans were allowed to react with 8-quinolyl chloroacetate (II), 8-quinolinoxyacetyl chloride (IV) and 3-(2'-chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one (X) in dry benzene and/or sodium hydroxide in absolute ethanol to give corresponding 8-quinolyl-alpha-mercaptoacetate (V), 8-quinolinoxythioacetate (VI) and 3-(2'-arylmercaptoethyl)-2-methyl-4-(3H)quinazolin-4-ones or 3-(2'-heterocyclicmercaptoethyl)-2-methyl-4(3H)-quinazolin-4 -ones (XIa-h) . The mercaptans V and XI were subjected to oxidation with hydrogen peroxide/acetic acid mixture (1:2) to afford the corresponding sulfones VII and XII . The structures of the synthesized compounds were elucidated by spectroscopic (IR and 1H-NMR) and elemental analyses . Some of these compounds were tested for their antimicrobial activities in comparison with tetracycline as a reference compound.

Caries Res, 1992, 26(4), 310 - 4
Long-term effects of syrup medications for recurrent otitis media on the dental health of 6- to 8-year-old children; Karjalainen S et al.; The dental response to repeated antimicrobial and antihistamine medications was studied by comparing the dental health of 64 adenoidectomized children 5 years after surgery to that of 212 untreated controls . Annual dental recordings starting from the age of 3 years were obtained from health care centers . As expected, the proportion of children who had several (> or = 11) syrup medications was significantly higher (p < 0.001) in the adenoidectomized than in the control group . Sucrose-containing syrup medications were prescribed twice as often for the children of the adenoidectomized as for the control group (p < 0.001) . However, the average amount of antimicrobial syrup medications prescribed was 19.2 +/- (SD) 13.0 per child for the adenoidectomized as compared to 8.5 +/- 8.3 for the control children (p < 0.001) . The dmf value of the adenoidectomized children at the age of 3 years (mean +/- SEM: 0.5 +/- 0.1) was significantly (p < 0.005) lower than that of the controls (1.1 +/- 0.2) . The difference was still significant (p < 0.01) at the age of 4 years, but disappeared thereafter . In conclusion, the antibacterial syrup medication seemed to be associated with a significant decline in dental caries at first . The simultaneous use of antihistamines was, however, thought to delay normal tooth maturation, so that after discontinuation of the antimicrobial medication, accelerated formation of new carious lesions took place.

Nippon Rinsho, 1992 Jan, 50(1), 53 - 9
{Proton pump inhibitors: their merits and demerits, and perspectives for future investigation}; Kamada T et al.; Proton pump inhibitors have a potent antisecretory activity and are under development in many pharmaceutical companies . In this paper, the merits and demerits of the drugs, which have been revealed by experimental studies in humans and animals, are reviewed . Issues of the drugs which remain to be examined in the future are also discussed in reletion to their application in peptic ulcer patients . The issues include 1) genotoxicity of the drugs with long-term treatment; 2) their possible contribution to defensive factors of gastro-intestinal mucosa; 3) their antimicrobial activity against Helicobacter pylori; 4) interaction with the other drugs; etc.

Rev Cubana Med Trop, 1992, 44(1), 17 - 20
{Mycobacterium fortuitum: the determination of its susceptibility by the disk diffusion technic}; Ferra Salazar C et al.; A study was carried out on 40 Mycobacterium fortuitum strains isolated from 39 symptomatic respiratory patients and 1 from a chronic skin ulcer, the susceptibility of whom to different antimicrobial agents was determined by the disk diffusion method . The strain showed sensitivity to aminoglucosides such as amikacin, gentamicin and kanamycin, and in all cases resistance to the penicillins ans cephalosporins used.

Acta Microbiol Hung, 1992, 39(3-4), 317 - 22
Diazald, a newly recognized antimicrobial agent and its spectrophotometric determination; Uri JV et al.; Diazald, a chemical intermediate for the synthesis of biologically active compounds, was found to be a potent in vitro antimicrobial agent against yeasts, yeast-like and filamentous fungi as well as Gram-positive and Gram-negative bacterial strains . Its activity is not inhibited by either para-aminobenzoic acid (PABA) or the nitroso group-specific 2-aminothiazole-methoxyimino acetic acid (ATMAA) . This suggests that the molecule as such is responsible for the antimicrobial activity . For its quick measurement a sensitive spectrophotometric method has been developed.

Folia Med Cracov, 1992, 33(1-4), 103 - 16
{Biological role of metabolic pathways from L-arginine to nitric oxide}; Zembowicz A; This paper reviews recent developments in the biochemistry, pharmacology and physiology of the L-arginine/nitric oxide pathway . Nitric oxide accounts for the biological activity of endothelium-derived relaxing factor (EDRF) and its continuous release plays a crucial role in the regulation of vascular tone and platelet activity . In the nervous system nitric oxide is a neurotransmitter . In the peripheral nervous system, nitroxergic nerves form a part of the non-adrenergic, non-cholinergic innervation of the visceral organs . In the immune system, nitric oxide generated by activated macrophages has tumoricidal and antimicrobial activities . Growing evidence suggests that the alterations in the formation of NO in various tissues contribute to the pathogenesis of various diseases, including hypertension, atherosclerosis, diabetes, subarachnoid hemorrhage and septic shock . Therefore, the improvements in our understanding of the regulation of L-arginine/nitric oxide pathway on the molecular level may lead to the development of new drugs.

Biol Res, 1992, 25(1), 21 - 5
Bacterial chemistry . VI . Biological activities and cytotoxicity of 1,3-dihydro-2H-indol-2-one derivatives; Haun M et al.; The biosynthetic pigment from Chromobacterium violaceum BB-78, 1,3-dihydro-2H-indol-2-one and its derivatives exhibit biological activities such as antimicrobial action, low hemolytic effects on red blood cells and in vitro trypanocide activity . A relatively high cytotoxicity on V-79 hamster fibroblast cells of the biosynthetic pigment was found, although with the methylol derivative the toxicity was almost eliminated . The methylol derivative exhibited similar toxicity as Nifurtimox, a known, commercial trypanocide compound.

Swed Dent J, 1992, 16(5), 183 - 9
Antimicrobial effect of a dental varnish, in vitro; Petersson LG et al.; The effects of a polymer based antimicrobial releasing varnish Cervitec were investigated against different gram-positive and gram-negative bacterial strains as well as a yeast using the agar diffusion inhibitory test (ADT-test in vitro) . As positive controls a 1% chlorhexidine gel and 1% aqueous solution of thymol and a placebo polymer varnish without active agents were employed . The test experimental varnish containing 1% chlorhexidine and 1% thymol showed antimicrobial activity against all gram-positive and gram-negative microorganisms tested including one Candida strain . The positive controls were similar in effect compared to the test varnish . No antimicrobial effect was observed with the placebo varnish without active ingredients . Toothpicks and dental floss treated with the test varnish showed an antimicrobial effect against S . mutans even after storing in room temperature up to 12 months . The results from this study support earlier laboratory studies that chlorhexidine and thymol diffuse out of the experimental varnish and that the varnish is active against various of oral pathogens . The possibility to use toothpicks or dental floss impregnated with the varnish with the aim to become chemotherapeutically active against periodontal diseases as well as against dental caries, is promising and should be tested in vivo.

Ann Pharmacother, 1992 Jan, 26(1), 46 - 55
The new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin; Bahal N et al.; OBJECTIVE: To review the chemistry, antimicrobial spectrum, pharmacokinetics, clinical trials, adverse effects, and drug interactions of four new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin . DATA SOURCES: Information was obtained from comparative clinical trials, abstracts, conference proceedings, and review articles . Indexing terms included azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, and macrolide antibiotics . STUDY SELECTION: Emphasis was placed on comparative clinical trials involving the new macrolide antibiotics . DATA EXTRACTION: Data from human studies published in the English language were evaluated . Trials were assessed by sample size, macrolide dosage regimen, and therapeutic response . DATA SYNTHESIS: The erythromycins have gained widespread use in treating a variety of infections . Although they are effective, limitations include the need to administer four times a day and the intolerable adverse gastrointestinal effects . Four of the more extensively studied agents, azithromycin, clarithromycin, dirithromycin, and roxithromycin, are currently being studied in patients . Based on the studies to date, the newer macrolides may offer several advantages over erythromycin, including: (1) greater antimicrobial activity against certain organisms; (2) longer elimination half-life, thus allowing less frequent administration; and (3) lower incidence of adverse gastrointestinal effects . CONCLUSIONS: The new macrolide antibiotics appear to offer an improvement over erythromycin . Definitive conclusions about the role of these drugs should await completion of ongoing clinical studies.

Br J Pharmacol, 1992 Jan, 105(1), 13 - 8
Non-competitive inhibition of GABAA responses by a new class of quinolones and non-steroidal anti-inflammatories in dissociated frog sensory neurones; Yakushiji T et al.; 1 . The interaction of a new class of quinolone antimicrobials (new quinolones) and non-steroidal anti-inflammatory agents (NSAIDs) with the GABAA receptor-Cl- channel complex was investigated in frog sensory neurones by use of the internal perfusion and 'concentration clamp' techniques . 2 . The new quinolones and the NSAIDs (both 10(-6)-10(-5) M) had little effect on the GABA-induced chloride current (ICI) when applied separately . At a concentration of 10(-4) M the new quinolones, and to a lesser degree the NSAIDs, produced some suppression of the GABA response . 3 . The co-administration of new quinolones and some NSAIDs (10(-6)-10(-14) M) resulted in a marked suppression of the GABA response . The size of this inhibition was dependent on the concentration of either the new quinolone or the NSAID tested . The inhibitory potency of new quinolones in combination with 4-biphenylacetic acid (BPAA) was in rank order norfloxacin (NFLX) much greater than enoxacin (ENX) greater than ciprofloxancin (CPFX) much greater than ofloxacin (OFLX), and that of NSAIDs in combination with ENX was BPAA much greater than indomethacin = ketoprofen greater than naproxen greater than ibuprofen greater than pranoprofen . Diclofenac, piroxicam and acetaminophen did not affect GABA responses in the presence of ENX . 4 . In the presence of ENX or BPAA, there was a small shift to the right of the concentration-response curve for GABA without any effect on the maximum response . However, the co-administration of these drugs suppressed the maximum of the GABA concentration-response curve, indicating a non-competitive inhibition, for which no voltage-dependency was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Nippon Yakurigaku Zasshi, 1992 Jan, 99(1), 13 - 8
{Central stimulating effect of the combination of the new quinolone group of antimicrobials and nonsteroidal anti-inflammatory drugs in mice}; Murayama S et al.; Six new quinolones: enoxacin, norfloxacin, ofloxacin, ciproflosacin, lomefloxacin, and tosufloxacin and eight nonsteroidal anti-inflammatory drugs: fenbufen, flurbiprofen, ketoprofen, pranoprofen, ibuprofen, indomethacin, mefenamic acid and aspirin were tested for their ability to produce a central stimulating effect in mice . At 5 min after the oral administration of one of the nonsteroidal anti-inflammatory drugs, a new quinolone was administered orally . The combination of drugs induced convulsions in a dose-dependent manner, and some mice died as a result of the convulsions . The survival time was used as an index to measure the intensity of convulsions induced by the drug combination . The new quinolones in combination with fenbufen at 100 mg/kg produced convulsions in the following order of potencies: enoxacin greater than lomefloxacin greater than norfloxacin . In contrast, administration of fenbufen together with ofloxacin, ciprofloxacin, or tosufloxacin up to a dose of 1000 mg/kg caused no convulsions . Four nonsteroidal anti-inflammatory drugs combined with enoxacin at 100 mg/kg also caused convulsion dose-dependently . The order of potency in producing convulsion was as follows: fenbufen greater than flurbiprofen greater than ketoprofen = pranoprofen . However, no convulsions were produced by treatment of ibuprofen, indomethacin, mefenamic acid or aspirin together with enoxacin . From these results, the important chemical structures of the new quinolones particularly concerned with the appearance of convulsion were discussed.

Hinyokika Kiyo, 1992 Jan, 38(1), 121 - 8
{Clinical and bacteriological study of sparfloxacin on bacterial prostatitis}; Suzuki K et al.; Sparfloxacin (SPFX), a new oral quinolone antimicrobial, was studied for the bacterial response, pharmacokinetics and clinical efficacy in the treatment of bacterial prostatitis . The minimum inhibitory concentration (MIC) values for 48 strains isolated from expressed prostatic secretion were measured . The values for 8 out of 12 strains of S . epidermidis were below 0.05 microgram/ml and those for all 6 strains of E . coli were below 0.025 microgram/ml . The SPFX concentrations in prostatic fluid (PF) were 0.33 to 0.49 microgram/ml at 1 to 3 hours after oral administration of 200 mg, the PF/serum ratio being 1.15 to 1.47 . SPFX was administered at a dose of 200 to 400 mg daily for an average of 14.1 days to 14 patients with prostatitis (5, acute: 9, chronic) . The clinical efficacy judged by physician in charge was effective in 12 cases with an efficacy rate of 85.7% . The bacterial eradication rate was 93.3% (14/15 strains), and eradication was complete in all 7 cases infected with gram-negative rods . SPFX-related abnormal laboratory values were observed in one case with transient increase of glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and alkaliphosphatase activities, and decrease of platelet . As side effects, one case with gastrointestinal symptoms and the other case with photosensitivity skin rash accompanied by sensory abnormality of palms were observed . The abnormal values or side effects in these patients recovered to normal or disappeared after completion of the treatment without any treatments . In view of the higher concentrations in PF than the MIC values with long remaining in the tissues, SPFX is considered to be effective in the treatment of bacterial prostatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha Omegan, 1992, 85(4), 49 - 53
Monitoring the periodontal microbiota as an adjunct to periodontal therapy: rationale, interpretation of test results and application to patient management; Listgarten MA; Recent developments in our understanding of the relationship of the oral microbiota to periodontal diseases have led to improved approaches to controlling the pathogenic influence of certain bacterial species . In addition to non-specific control of bacterial accumulations in the sulcus region, antibiotics may be useful in suppressing persistent species with pathogenic potential . This approach is indicated in cases that do not respond adequately to mechanical plaque control measures or certain categories of periodontal diseases likely to be caused by a specific infection . Monitoring the composition of the microbiota before, during and after antimicrobial therapy is helpful in the selection of appropriate antimicrobial agents, monitoring the effectiveness of the therapy and detecting the return of undesirable microorganisms.

Ciba Found Symp, 1992, 171, 276 - 90; discussion 290-3
Defensins: endogenous antibiotic peptides from human leukocytes; Lehrer RI et al.; A variety of endogenous antimicrobial peptides equip mammals, amphibians, insects and plants to defend themselves against microbial pathogens . Defensins are small peptides of mammalian cells that contain 29-35 amino acid residues, including six invariant cysteines that form three intramolecular disulphide bonds . They are produced by the sequential proteolysis of precursors that contain approximately 95 amino acids and are synthesized by several types of cells, especially the bone marrow precursors of blood neutrophils . Defensins constitute 5-7% of the total protein in human neutrophils and are present in high concentration in the azurophil granules and phagocytic vacuoles . The production of defensins by human neutrophils amounts to approximately 10 mg/kg body weight per day . In certain mammalian species lung macrophages and specialized epithelial (Paneth) cells in the small intestine also produce defensins . Defensins are complexly folded, amphipathic, rich in antiparallel beta-sheet but devoid of alpha-helical domains . Their unusually broad antimicrobial spectrum encompasses Gram-positive and Gram-negative bacteria, many fungi, mycobacteria, spirochetes and several enveloped viruses . The antimicrobial properties of defensins result from their insertion into target cell membranes and the formation of voltage-sensitive channels . Given their abundance and broad spectrum of antimicrobial activity, defensins may contribute substantially to innate resistance to infection.

Ciba Found Symp, 1992, 171, 236 - 49; discussion 249-54
Secondary metabolites from marine organisms; Rinehart KL; Marine macroorganisms and microorganisms, like terrestrial species, produce a dizzying array of secondary metabolites, including terpenes, steroids, polyketides, peptides, alkaloids and porphyrins . Most of the marine metabolites are found in terrestrial species as such or have close counterparts in land-based species, but some are sufficiently unusual to constitute a separate class (e.g . marine sterols) . Although in many cases the functions of these secondary metabolites in the marine species themselves are unclear, other compounds play well-defined roles-for example as trail markers, sexual attractants, antifouling substances or antifeedants . What is clear is that many of the most interesting marine secondary metabolites have potent activities largely unrelated to their in situ roles . Examples abound of antitumour, antiviral, immunosuppressive and antimicrobial agents, as well as neurotoxins, hepatotoxins and cardiac stimulants . Relatively few biosynthetic studies of marine secondary metabolites have been done because of the logistical problems of working under water and the primitive state of techniques for growing marine invertebrates in culture . However, recent studies indicate that many compounds isolated from marine macrospecies (e.g . sponges) may instead be produced by microorganisms (e.g . bacteria or phytoplankton) . Studies of these symbionts may facilitate efforts to understand the biosyntheses of these metabolites.

Klin Khir, 1992, (11), 40 - 1
{Use of absorbable antimicrobial suture material at the gastroenteric anastomosis in patients with gastric and duodenal disease}; Chkhikvadze TF et al.; The authors in creation of the internal layer of sutures of gastroenteric anastomoses in 80 patients have used the synthetic antimicrobial absorbable material . No complications related to use of the suture material were revealed . The results obtained permit to recommend the new suture material for more wide use in the gastrointestinal surgery.

Drugs Exp Clin Res, 1992, 18(7), 299 - 302
Penetration of fleroxacin into human lung, muscle, and fat tissue; Cakmakci M et al.; Fleroxacin is a new fluoroquinolone with established potent antimicrobial and pharmacokinetic properties, and the aim of this study was to determine its rate of penetration into human lung, muscle, and fat tissues . In a total of eight patients undergoing lung surgery, plasma and tissue concentrations of unmetabolized fleroxacin were determined . This was done in subgroups of two patients each, receiving either 6, 8, 12 or 24 hours prior to surgery one single oral dose of 400 mg fleroxacin . It was found that fleroxacin penetrates well into muscle and lung tissues, but not into fat tissue . The levels in muscle and lung were 1.1 to 4.7 times higher than the according plasma concentrations.

APMIS Suppl, 1992, 30, 7 - 14
The antimicrobial activity of non-antibiotics . Report from a congress on the antimicrobial effect of drugs other than antibiotics on bacteria, viruses, protozoa, and other organisms; Kristiansen JE; In May 1990 the 1st International Conference on Antimicrobial Activity of Non-Antibiotics was held in Copenhagen, Denmark . More than 200 scientists were drawn from 34 countries and from all five continents . Papers were presented dealing with the antimicrobial activity of different synthetic and natural compounds, and interactions between antibiotics and non-antibiotics . The conference pointed to the unusual properties of non-antibiotic drugs . These effects might create unexpected therapeutic possibilities and lead to new basic insights.

Immunopharmacol Immunotoxicol, 1992, 14(4), 769 - 82
Antimicrobial agents induce monocytes to release IL-1 alpha, IL-6, and TNF, and induce lymphocytes to release IL-4 and TNF tau; Tufano MA et al.; Evaluation was carried out on the action of different antibiotics on the release of cytokines . Experiments were done in vitro on monocytes and on human lymphocytes . Results show that the majority of the antibiotics tested are able to induce the release of one or more cytokines from their respective producing cells . Among the beta-lactams the most active were the cephalosporins (cephalexin, cefamandol, ceftazidin, and a sulbactam-ampicillin combination) in inducing the release of TNF, IL-1 alpha, and IL-6 from monocytes, and releasing IL-4 and IFN-tau from lymphocytes . The sulbactam-ampicillin combination and cefamandole were extremely active in the production of IFN-tau . Among the lincosamides, clindamycine notably stimulated the release of TNF and IL-6, while lincomycine induced a notable increment of IL-4 from monocytes . Teicoplanin is a very strong inducer of TNF, IL-1 alpha and IL-6.

J Fr Ophtalmol, 1992, 15(6-7), 389 - 94
{Evaluation of the efficacy of antimicrobial drugs in ophthalmic solutions}; Economou-Stamatelopoulou C et al.; The antimicrobial efficacy of preservatives in ophthalmic solutions was tested . Five strains were used as challenge organisms . They represented bacteria, yeasts and molds . Sixty per cent of the ophthalmic solutions showed a good preservation against S . aureus ATCC 6538, according to the standards and in 40% of cases, the bacteria disappeared on the second week . Against E . coli ATCC 8739, 90% of the samples were well preserved and in 10% the bacteria disappeared by the second week . Against Ps . aeruginosa ATCC 9027, C . Albicans ATCC 10231 and Asp . niger ATCC 16404, the ophthalmic solutions showed a 100% preservation . The majority of the products showed a satisfactory preservation . They contained declared preservatives and sometimes combinations of two antimicrobial agents.

Nucleic Acids Symp Ser, 1992, (27), 161 - 2
Tachyplesin I as a model peptide for antiparallel beta-sheet DNA binding motif; Yonezawa A et al.; In this study, we present a model compound for antiparallel beta-sheet-DNA interaction . Tachyplesin I, cationic antimicrobial peptide, interacts through contacts with the minor groove . Secondary structure of tachyplesin I, antiparallel beta-sheet constrained by two disulfide bridges and connected by beta-turn, contributes significantly to its DNA binding . The present results give valuable information for design of sequence-specific DNA binding peptide based on antiparallel beta-sheet.

Chemotherapy, 1992, 38(6), 410 - 9
Chlorpromazine: a drug potentially useful for treating mycobacterial infections; Crowle AJ et al.; Chlorpromazine (CPZ) is one of several phenothiazines known to have antimicrobial properties . It can inhibit mycobacteria, and was reported in the early literature to improve tuberculosis clinically . CPZ was tested here for its ability to inhibit the replication of Mycobacterium tuberculosis and Mycobacterium avium in cultured normal human macrophages, as determined by counts of viable bacteria at 0, 4, and 7 days after bacterial infection of the macrophages . CPZ inhibited the intracellular bacteria at a concentration range of 0.23-3.6 micrograms/ml, and was more effective intracellularly than extracellularly . It was further tested for its ability to cooperate with isoniazid, streptomycin, pyrazinamide, rifampin, rifabutin, penicillin and ethambutol (EMB) against intramacrophage M . tuberculosis and M . avium . CPZ enhanced the effectiveness of most of the drugs tested against intracellular mycobacteria . However, the combination of CPZ and EMB did not result in augmented antimycobacterial activity.

Adv Exp Med Biol, 1992, 316, 293 - 8
Improvement of pulmonary gas exchange after surfactant replacement in rats with Pneumocystis carinii pneumonia; Eijking EP et al.; The effect of intratracheal surfactant instillation on pulmonary function in rats with pneumocystis carinii pneumonia (PCP) was investigated . In these animals which developed PCP with severe respiratory failure after s.c . administration of cortisone acetate over 8-12 weeks, pulmonary function could be improved by surfactant instillation, as measured by an increase in PaO2 . Histological examination showed that alveoli of rats with PCP which received no surfactant treatment are filled with foamy edema, whereas after surfactant treatment alveoli are stabilized and well-aerated . These results indicate that surfactant therapy could be used in patients with severe PCP to overcome an acute stage of respiratory distress while at the same time surfactant could serve as a carrier substance for antimicrobial drugs to attain high intra-alveolar and low systemic antimicrobial drug concentrations.

Postgrad Med J, 1992, 68 Suppl 3, S68 - 72
Broad- versus narrow-spectrum antibiotic use: the role of in vitro testing and its correlation with clinical efficacy; Mouton Y et al.; The spectrum of activity of any antibiotic varies with time, the geographical locale and the site of isolation of the bacteria . This variability is related to the changing heterogeneity (specifically, the degree of resistance) of the bacterial population . In order to choose the most appropriate antimicrobial agent, it is necessary to know the infection site, the degree of diffusion of antibiotics at this site, and the pathogen responsible, and then to determine the sensitivity of the pathogen . If the pathogen is unknown, an assessment of the patient's clinical status should be made; generally, the weaker the patient, the broader the spectrum of antibiotics that should be used . If the pathogen and its in vitro susceptibility pattern are known, narrow-spectrum antibiotics are preferable . The carefully standardized conditions of in vitro testing do not correlate with the in vivo situation, in which the effectiveness of antibiotics is altered by diffusion and immune response . The in vitro tests available do not always correlate with the clinical situation; some bacteria showing resistance in the laboratory are actually susceptible in practice in some infection sites, and vice versa . In vitro tests are also affected by technical limitations . An in vitro test can aid the assessment of efficacy but cannot guarantee it.

Postgrad Med J, 1992, 68 Suppl 3, S38 - 41; discussion S42
Possible mechanisms of action of antimicrobial agent-associated gastrointestinal symptoms; Borriello SP; Gastrointestinal symptoms, particularly diarrhoea, are a relatively common side effect of antibiotic usage . In the vast majority of cases the mechanisms involved in these side effects are not understood . Proposed mechanisms include the direct action of antibiotics on intestinal function, inducing predisposition to infection with an enteric pathogen, and factors secondary to disturbance of the normal intestinal flora that do not involve infection with a known pathogen . There is some evidence for all three potential scenarios.

Chemotherapy, 1992, 38(5), 319 - 23
Antibacterial properties of investigational, new, and commonly used antibiotics against isolates of Pseudomonas cepacia in Michigan; Bhakta DR et al.; Microdilution antimicrobial susceptibility testing was performed with 73 isolates of Pseudomonas cepacia collected from the sputum of patients throughout Michigan with cystic fibrosis . Susceptibility testing was done using new and investigational antibiotics (loracarbef, cefixime, cefpirome, desacetyl-cefotaxime, cefpodoxime, cefmetazole, cefepime, cefprozil, and fleroxacin) and commonly used antibiotics (ceftazidime, mezlocillin, piperacillin, ciprofloxacin, tobramycin, and amikacin) . Ceftazidime was the most active antibiotic, and 91.8% of isolates were susceptible to it with MIC50 and MIC90 values of < or = 4 and 16 micrograms/ml, respectively . For mezlocillin, piperacillin, and ciprofloxacin 84.9, 89 and 39.7% of the isolates, respectively, were mostly moderately susceptible . Loracarbef, cefixime, cefprozil, cefmetazole, cefepime, fleroxacin, cefpodoxime, tobramycin, and amikacin did not show activity against P . cepacia . For cefpirome and desacetylcefotaxime 24.7 and 60.3% of the isolates, respectively, were moderately susceptible . Both MIC50 and MIC90 were > 32 micrograms/ml for cefpirome and 32 and > 64 micrograms/ml for desacetylcefotaxime.

Am J Med, 1991 Dec 30, 91(6A), 81S - 86S
Drug interactions with fluoroquinolones; Stein GE; The fluoroquinolones are a new class of antimicrobial agents that are now widely prescribed for a number of bacterial infections . Because of their complex pharmacokinetics, there is a potential for several types of drug interactions . Currently, only two drug interactions have been well studied . These involve a decrease in absorption when fluoroquinolones are given in combination with multivalent metal cations and an inhibition in the metabolism of methylxanthines by fluoroquinolones such as ciprofloxacin, enoxacin, and norfloxacin . These drug interactions can be easily avoided . Significant decreases in the absorption of fluoroquinolones by metal cations can be prevented by staggering the doses of these drugs . To avoid alterations in methylxanthine metabolism, newer fluoroquinolones, such as lomefloxacin, ofloxacin, and temafloxacin, should be utilized; alternatively, theophylline serum levels can be carefully monitored . Several other potentially serious drug interactions involving cyclosporine, warfarin, and nonsteroidal anti-inflammatory drugs have been reported, but additional investigations are required before their overall clinical significance can be fully determined . Since the use of fluoroquinolones will continue to escalate over the next decade, continued patient surveillance is necessary so that potential drug interactions can be recognized, described, and prevented.

Am J Med, 1991 Dec 30, 91(6A), 153S - 161S
Overview of fluoroquinolone safety; Wolfson JS et al.; The safety of the fluoroquinolone antimicrobial agents is reviewed, discussing documented and potential clinical and laboratory adverse effects and drug-drug interactions . In prospective, randomized, double-blind clinical trials comparing fluoroquinolones to nonquinolone drugs or placebo, the fluoroquinolones were not significantly different (22 studies) or were superior (5 studies) to comparison agents but were only rarely more toxic (2 studies) . Adverse effects included mild gastrointestinal toxicities and less common but more problematic central nervous system toxicities . Clinically important interactions occurred with coadministration of antacids and all fluoroquinolones and with theophylline and enoxacin and to a lesser extent ciprofloxacin and pefloxacin but not other fluoroquinolones . Potential adverse effects such as cartilage damage, DNA damage, teratogenicity, and crystalluria, while of concern, have not as yet been shown to be of clinical importance . Therapy of bacterial infections in children and adolescents is relatively contraindicated, but growing clinical experience with treatment of these patients has not so far revealed serious bone or cartilage toxicity . The fluoroquinolones thus far have exhibited a favorable safety profile, but our clinical experience is still limited, and monitoring for as yet unappreciated toxicities is warrantedPublication Types:

	Clinical Trial
	Randomized Controlled Trial
	Review

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