Chemioterapia, 1987 Feb, 6(1), 3 - 7 In-vitro evaluation of antifungal agents in the treatment of yeast peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD); Edwards R et al.; This study compared the static and kinetic activities of six antifungal agents, in broth and used dialysate, against six yeast strains known to have caused peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) . Minimum inhibitory concentrations (MIC) and IC50 results show a trend towards greater activity by amphotericin B, 5-fluorocytosine, tioconazole and itraconazole in comparison to miconazole and ketoconazole although there was some strain variability . Minimum fungicidal concentrations (MFCs) of amphotericin B were less than or equal to 1mg/l, while 5-fluorocytosine and the azoles showed large discrepancies between MIC and MFC values . In kinetic studies amphotericin B was the most potent fungicidal agent . 5-fluorocytosine showed modest activity and failed to achieve total killing . The azoles demonstrated variable degrees of inhibition of C . glabrata and showed minimal activity with C . albicans . Itraconazole showed good activity against C . parapsilosis in broth . All agents, with the exception of 5-fluorocytosine, showed reduced activity in used dialysate in comparison to broth. J Pharm Sci, 1987 Feb, 76(2), 153 - 6 Determination of binding parameters of macrolides, lincosamides, and streptogramins to Legionella pneumophila; Fournet MP et al.; Parameters of {3H}erythromycin binding to Legionella pneumophila were determined in vitro using both an equilibrium and a kinetic method . Different L . pneumophila serogroups, 1-3, and a virulent strain serogroup, 1, were tested . All strains of bacteria exhibited the same binding pattern, with a dissociation constant of 0.15 microM . Other macrolides, streptogramin B-types, and lincosamides competitively displaced bound erythromycin suggesting that these compounds share common binding sites on the bacteria . Minimum inhibitory concentration (MIC) values for macrolides, streptogramin B-types, and lincosamides were determined with buffered charcoal yeast extract (BCYE) medium . A good correlation (r = 0.994) was found between the corresponding inhibition constants of these antibiotics and their MIC . It was also noted that for lincosamides the microbiological inactivity was associated with a very low bacterium affinity . Thus, it is concluded that binding parameters of these antibiotics reflect their efficacy against L . pneumophila in vitro and may serve as a useful adjunct in developing new compounds. Br J Dermatol, 1987 Feb, 116(2), 233 - 5 Sensitivities of Pityrosporum sp . to selected commercial shampoos; Butterfield W et al.; Sensitivity of 25 strains of Pityrosporum sp . to four commercial shampoos was tested using a gel diffusion method and determination of minimum inhibitory concentrations (MICs) . All the shampoos when undiluted gave inhibition zones in the gel diffusion test with 13 of the 15 strains tested . Two strains were resistant to 'Polytar' . 'Polytar' was fungistatic, 'Selsun' 'Cetavlon P.C.' and 'Genisol' were fungicidal . MIC results showed the yeast to be most sensitive to 'Cetavlon' and 'Selsun'. J Med Chem, 1987 Feb, 30(2), 383 - 8 Structure-activity studies of 5-{{4-(4,5-dihydro-2-oxazolyl) phenoxy}alkyl}-3-methylisoxazoles: inhibitors of picornavirus uncoating; Diana GD et al.; A series of substituted phenyl analogues of 5-{{4-(4,5-dihydro-2-oxazolyl) phenoxy}alkyl}-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes . Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound . Many of these compounds exhibited mean MICs (MIC) against five serotypes as low as 0.40 microM . The mean MIC correlated well (r = 0.83) with the MIC80 (the concentration that inhibited 80% of the serotypes tested) . A quantitative structure-activity relationship study indicated a strong dependency of MIC on lipophilicity (log P) in combination with inductive effects (sigma m) and bulk factors (MW). Int J Radiat Oncol Biol Phys, 1987 Feb, 13(2), 243 - 9 Regional lymph node and pulmonary metastases after local hyperthermia of melanomas in C57BL/6 mice; Nathanson SD et al.; The effects of local tumor hyperthermia on regional lymph node metastases are inconclusive . We studied the effects of hyperthermia on the incidence of popliteal, femoral, and abdominal lymph node metastases in C57BL/6 mice with primary B16 melanomas (F10 variant) growing subcutaneously in the left foot . Tumors were heated to 42.3, 43.5, and 44.2 degrees C for 90 minutes either 7 days after inoculation of 5 X 10(4) viable cells (microscopic tumor = mic) or when the tumors were approximately 3 mm in diameter (macroscopic tumor = mac) . Femoral lymph node metastases occurred in 0/21 control animals and in 8/22 (36%), 11/19 (58%), and 11/17 (65%) animals whose primary tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively . For all three treatments, the increase in metastases as compared to controls was statistically significant (p less than 0.004, Fisher's exact test) . The incidence of abdominal lymph node metastasis was slightly higher in the treated groups than controls . Twenty of 21 (95%) control mice developed popliteal lymph node metastases and hyperthermia-induced increases could not be demonstrated . Fifteen of 21 control mice killed 3 weeks after amputation of tumor-containing leg had pulmonary metastases with an average of 6 +/- 4 (standard deviation) lesions per affected mouse . Pulmonary metastases occurred in 22/22 (100%), 17/19 (89%), and 13/17 (76%) of mice whose tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively . The numbers of metastases for affected mice were significantly increased compared to controls for tumors heated to 43.5 and 44.2 degrees C (28 +/- 43, 43 +/- 52, 119 +/- 121, p greater than 0.02, p less than 0.006, p less than 0.002, for two sample T-test) . While 0/8 mic tumors were cured 5/9 mac tumors heated to 44.2 degrees C disappeared (p less than 0.03, Fisher's exact test) and there was a growth delay in the remaining mice . Mic tumors, heated to 43.5 degrees C, had an accelerated onset of growth while mac tumors heated to this temperature had a slight growth delay . Growth of both mic and mac primary tumors heated to 42.3 degrees C was similar to controls . These results show that therapeutic and subtherapeutic local hyperthermia increases metastases to regional lymph nodes and to lungs even when primary tumor growth rate is partially or totally controlled. Clin Pharm, 1987 Jan, 6(1), 59 - 68 Comparison of antibiotic dosage regimens using pharmacokinetic and microbiologic factors; Schumacher GE; A pharmacokinetic meta-analysis was performed for 33 antibiotics used in treating infections caused by microorganisms for which the antibiotics are considered to be agents of first choice or primary alternatives . The pharmacokinetic indices assessed were the following components of the steady-state blood concentration-time profile: the magnitude of the peak antibiotic serum concentration at steady state compared with the minimum inhibitory concentration (CSSmax/MIC) and the intensity index, a dimensionless term that reflects the contribution of the peak serum antibiotic concentration and the duration that this concentration is above the MIC . Substantial differences in CSSmax/MIC and intensity-index values were observed among antibiotics within an antibiotic class for individual microorganisms and for groups of microorganisms . Piperacillin, amikacin, and tetracycline showed the best mean performances of the ureido penicillins, aminoglycosides, and tetracyclines, respectively . For the cephalosporins, cefadroxil displayed the highest mean values of the first-generation cephalosporins; cefuroxime and cefotetan showed the greatest measures for the second-generation agents; and all third-generation cephalosporins demonstrated very high mean performance indices . Meta-analysis of pharmacokinetic performance factors is a useful technique for making intergroup and intragroup comparisons of antibiotics. Environ Mutagen, 1987, 9(1), 37 - 58 Methyl isocyanate: an evaluation of in vivo cytogenetic activity; Tice RR et al.; The ability of inhaled methyl isocyanate (MIC) to induce genotoxic and cytotoxic damage in vivo was evaluated by assessing the induction of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in bone marrow metaphase cells, the induction of micronuclei in polychromatic erythrocytes (MN-PCEs), and the inhibition of bone marrow cellular proliferation and erythropoiesis . B6C3F1 mice were exposed to MIC by two exposure regiments: in two experiments, male mice only were exposed to 3, 10, and 30 ppm for 2 hr; in four experiments, male and female mice were exposed to 1 and 3 ppm (in one experiment, to 6 ppm, also), 6 hr per day for 4 consecutive days . The various cytogenetic endpoints were analyzed in bone marrow and peripheral blood (4-day exposure regimen only) samples taken from bromodeoxyuridine tablet-implanted animals killed 11 to 22 hr after cessation of the exposure to MIC . Exposure to MIC for 2 hr induced a significant delay in cellular proliferation but did not induce a significant increase in CAs, SCEs (evaluated at 3 and 10 ppm, only) or in bone marrow MN-PCEs . Also, this exposure regimen did not inhibit the rate of erythropoiesis . Following exposure to MIC for 4 days, a weak but significant increase in CAs and SCEs was observed in male (in one experiment) and in female (in two experiments) mice . The induction was especially apparent in the single experiment in which mice were exposed to 6 ppm MIC . At this concentration, a significant increase in MN-PCEs in peripheral blood was observed in male but not female mice . Delay in bone marrow cell proliferation was observed in male mice beginning at 3 ppm and in female mice at 6 ppm . The 4-day exposure regimen resulted also in a depressed rate of erythropoiesis, with male mice appearing to exhibit greater depression than female mice . The results demonstrate that exposure to MIC by inhalation results in bone marrow damage, indicating the systemic genotoxic/cytotoxic activity of MIC and/or reactive metabolites. Environ Mutagen, 1987, 9(1), 29 - 36 Sister chromatid exchange analysis in lung and peripheral blood lymphocytes of mice exposed to methyl isocyanate by inhalation; Kligerman AD et al.; Mice were exposed to 1, 3, or 6 ppm methyl isocyanate (MIC) for 6 hr/day for four consecutive days . Lung cells and peripheral blood lymphocytes (PBLs) were removed and cultured for analysis of sister chromatid exchange (SCE) and cell cycle kinetics . MIC caused a small but significant increase in SCE frequency of cultured lung cells from mice exposed to 1, 3, or 6 ppm MIC . MIC did not significantly increase SCE levels in PBLs of mice exposed to concentrations as high as 6 ppm . In cultured PBLs, MIC had a stimulatory effect on cell cycling rates as measured by the replicative index, and it caused a significant reduction in mononuclear leucocyte counts and the mitotic indices. Am Rev Respir Dis, 1987 Jan, 135(1), 10 - 6 Sulfonamide-containing regimens for disease caused by rifampin-resistant Mycobacterium kansasii; Ahn CH et al.; Fourteen wild strains and 14 relapse or treatment failure isolates of Mycobacterium kansasii were tested and found to be highly susceptible to sulfamethoxazole (SMX), with 26 of 28 isolates having minimal inhibitory concentrations (MIC) of less than or equal to 4 micrograms/ml), using a broth microdilution method . Treatment failure isolates frequently exhibited resistance to rifampin (RMP) (greater than 2 micrograms/ml), isoniazid (INH) (greater than 4 micrograms/ml), and ethambutol (EMB) (greater than 4 micrograms/ml) not seen among the wild strain isolates . Eight patients with cavitary disease caused by RMP-resistant M . kansasii were treated with SMX-containing regimens that also included high dose INH (900 mg), EMB (25 mg/kg), and an aminoglycoside (either streptomycin or amikacin) . Patients were treated initially in the hospital for 4 to 10 wk . In 7 of the 8 patients, sputum cultures became negative in a mean of 10 wk (range, 7 to 14 wk) . Acquired drug resistance to INH, RMP, and EMB can be demonstrated in M . kansasii, and SMX in combination with other agents chosen on the basis of MIC determinations are effective in the treatment of disease caused by RMP-resistant M . kansasii. Chemotherapy, 1987, 33(5), 328 - 30 Ciprofloxacin concentrations in human aqueous humor following intravenous administration; Behrens-Baumann W et al.; 16 patients received an intravenous infusion of 200 mg ciprofloxacin 1, 2, 3 and 6 h, respectively, before cataract extraction . This dosage produced mean aqueous humor levels of 0.165 +/- 0.09 and 0.126 +/- 0.028 microgram/ml after 1 and 3 h, respectively . The mean serum levels were 1.760 +/- 0.873 and 0.854 +/- 0.283 microgram/ml after 1 and 3 h, respectively . These levels are above the minimum inhibitory concentration of ciprofloxacin for sensitive organisms. Trans R Soc Trop Med Hyg, 1987, 81(2), 345 - 7 A radiometric assay for antigiardial drugs; Inge PM et al.; Susceptibility of Giardia lamblia trophozoites to 3 antigiardial drugs was determined morphologically by 24h parasite counts and radiometrically by uptake of {3H}thymidine and by rapid 4h microassays of motility and viability . Growth of Giardia trophozoites in liquid culture correlated well with uptake of {3H}thymidine during a 72h period (r = 0.91, P less than 0.01) . ED50 and MIC for metronidazole, mepacrine and sodium fusidate were similar in both morphological and radiometric growth assays and, except for mepacrine, results were similar to previously reported drug efficacies obtained with more labour intensive methods . Motility and viability 4h microassays were insensitive and time-consuming and cannot be recommended for routine screening of antigiardial drugs . The radiometric growth assay is therefore a simple, objective measure of antigiardial drug activity which could be used to determine drug sensitivity profiles of clinical isolates or for screening new antigiardial drugs. Int Arch Allergy Appl Immunol, 1987, 83(4), 432 - 5 IgA class and subclass thyroid auto-antibodies in Graves' disease and Hashimoto's thyroiditis; Weetman AP; The reported prevalence of IgA class thyroid antibodies in Hashimoto's thyroiditis is variable and the IgA subclass distribution in unknown, despite recent reports of IgG subclass restriction in the thyroid auto-antibody response . Using an ELISA, IgA class antibodies were found against thyroglobulin (Tg) and microsomes (Mic) in 40-52% of patients with Graves' disease and Hashimoto's thyroiditis, and, against thyroglobulin, they were detected in the absence of IgG antibodies in 10% of the cases . Both IgA1 and IgA2 subclasses were detected in all patients with IgA class antibodies, although a significantly higher proportion of IgA2 relative to IgA1 was found in microsomal compared with thyroglobulin antibodies . In view of the high turnover rate and unique complement-fixing properties of IgA2 antibodies, this class of thyroid auto-antibody may play an important role in determining the response in thyroid auto-immunity. Chemotherapy, 1987, 33(4), 255 - 8 In vitro susceptibility of Mycobacterium avium to a new macrolide (RU-28965); Casal M et al.; The in vitro susceptibility of Mycobacterium avium to RU-28965 alone and in combination with rifampin, isoniazid, and sulfametoxipiridazine was studied by the agar dilution method . The synergistic effect of the RU-28965 with rifampin has been demonstrated . At a concentration of 16 micrograms/ml or lower of RU-28965, 100% of M . avium strains were inhibited . If 2 micrograms/ml of rifampin is added the MIC of RU-28965 is lowered to 0.25 microgram/ml. J Toxicol Environ Health, 1987, 21(3), 265 - 75 Reproductive toxicity of methyl isocyanate in mice; Varma DR et al.; The effects of methyl isocyanate (MIC) vapor on pregnancy and fertility were studied in mice in view of the reported increase in reproductive complications in Bhopal following the December 3, 1984, accident . The whole-body exposure of mice to 9 and 15 ppm MIC for 3 h on d 8 of gestation led to resorption of greater than 80% of implants . In more than 75% of MIC-exposed animals, all implants were lost . At these concentrations, MIC did not cause external malformations . However, there was evidence of an increase in visceral abnormalities and a decrease in fetal and placental weights and in fetal skeleton sizes . MIC disturbed the estrus cycle and decreased the mating and pregnancy rate of female mice . The mating performance of MIC-exposed male mice was also decreased . Exposure to MIC increased serum corticosterone levels of male and nonpregnant female mice . MIC exerted no significant effects on serum corticosterone and progesterone levels of pregnant mice if the pregnancy was retained but caused a significant decrease in the serum levels of these two hormones in animals that lost all the implants . These studies show that the effects of MIC in mice mimic many of the reproductive complications in Bhopal . The mechanism of the reproductive toxicity of MIC remains to be identified. J Infect Dis, 1987 Jan, 155(1), 93 - 9 Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration; Moore RD et al.; In an examination of the relationships among plasma aminoglycoside concentrations, the minimal inhibitory concentration (MIC) for the infecting organism, and therapeutic outcome, data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin, tobramycin, and amikacin . Clinical response to therapy occurred in 188 (80%) patients . Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response (P less than .00001 and P less than .0001, respectively) . A graded dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response . By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response . These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy. J Antimicrob Chemother, 1987 Jan, 19(1), 39 - 43 Susceptibility of Branhamella catarrhalis to sulphamethoxazole and trimethoprim; Riley TV et al.; Fifty strains of Branhamella catarrhalis were examined for susceptibility to sulphamethoxazole, trimethoprim and a combination of the two by determinating minimum inhibitory concentrations (MICs) and fractional inhibitory concentrations (FICs) . All strains were susceptible to sulphamethoxazole and resistant to trimethoprim . On the basis of the MIC results it was predicted that greater synergy between sulphamethoxazole and trimethoprim would be observed with approximately equal proportions of each component . The lowest FIC values were obtained with a ratio of 1:1 and the greatest synergy was observed at this ratio with 39 strains (78%) . Only seven strains were most synergistically inhibited at the ratio of 20:1 (sulphamethoxazole: trimethoprim) although this ratio was still synergic for most strains . Overall the 1:20 ratio was not synergic. Drugs, 1987, 34 Suppl 1, 14 - 9 Interpretive criteria for the agar diffusion susceptibility test with ofloxacin; Grimm H; Regression analyses to determine the correlation of minimal inhibitory concentrations (MICs) and inhibition zones produced by ofloxacin discs were carried out with 300 freshly isolated cultures of infective organisms (20 strains from each of 15 species) . After pilot studies, 5 micrograms loaded discs were chosen . Studies were performed simultaneously by using ICS/DIN and Kirby-Bauer/NCCLS methods on Mueller-Hinton agar . It was found that the correlation becomes poorer with increasing disc loads and when the Kirby-Bauer method is used . Based on preliminary MIC breakpoints of greater than or equal to 2 mg/L and greater than or equal to 8 mg/L and by calculations from regression equations, the following zone interpretations using the NCCLS method are recommended: resistant up to 12mm, intermediate 13 to 15mm, susceptible 16mm or more . The values for the DIN method are: resistant up to 13mm, intermediate 14 to 17mm, susceptible 18mm or more . No major errors were found in zone interpretations . Minor errors were observed in 0.7% when the NCCLS method was used, and in 1.3% with the DIN method. Acta Endocrinol Suppl (Copenh), 1987, 281, 125 - 32 The thyroid microenvironment in autoimmune thyroid disease: effects of TSH and lymphokines on thyroid lymphocytes and thyroid cells; McLachlan SM et al.; Thyroid lymphocytes synthesize thyroid autoantibodies in close proximity to thyroid cells and consequently soluble mediators such as TSH and interleukins (IL) 1 and 2 may have unforeseen effects on lymphocytes and thyrocytes, respectively . Investigations of thyroid autoantibody synthesis by thyroid lymphocytes in vitro showed that TSH did not affect microsomal (Mic) antibody production, but thyroglobulin (Tg) antibody synthesis was decreased, probably as a result of complexing between Tg antibody and Tg secreted by small numbers of thyrocytes in the cell suspension . IL-1 and IL-2 partially mimicked the inhibitory effects on spontaneous autoantibody synthesis induced by Pokeweed mitogen (PWM) in cultures of thyroid lymphocytes . This inhibition may require a number of soluble mediators released by T cells in response to the mitogen; however, depletion studies indicated that the cell type responsible for PWM inhibition is unlikely to be a suppressor T cell and may be an NK cell . IL-1 and IL-2 had little effect on the viability of thyrocyte monolayers in an 18 h assay, but antibody dependent cells cytotoxicity (ADCC) using blood lymphocytes and thyroid autoantibody positive sera was demonstrated; further, the cytotoxicity appeared to be due to Mic antibodies . It is possible that IL-1 and/or IL-2 (as well as other cytokines) may affect thyroid cells after longer periods of exposure, either by altering them functionally or by direct damage . However, assuming that NK cells are present in sufficient numbers in the gland, ADCC could play a major role in the development of hypothyroidism in Hashimoto's disease. Arch Immunol Ther Exp (Warsz), 1987, 35(2), 109 - 15 Microbial transformation of azacarbazoles . IV . Conversion of chloro-substituted alpha-carbolines by Kitasatosporia setae strain; Peczynska-Czoch W et al.; Biotransformation of alpha-carboline derivatives substituted at positions C-5, C-6, C-7 and C-8 with chlorine, carried out with Kitasatosporia setae strain yielded corresponding 1-methyl-alpha-iso-carbolines . The formation of products is dependent on the position of chlorine in substrate molecule . When chlorine is introduced at C-6, the yield of N-1 methylation is low, about 5% . Derivatives of alpha-carboline substituted with chlorine at C-7 and C-8 form corresponding alpha-iso-carbolines with yield up to 20% and 30%, respectively, whereas 5-chloro-alpha-carboline is converted into 5-chloro-1-methyl-alpha-iso-carboline with 60% yield . Apparently, additional pathway of microbial transformation of 2-chloro-alpha-carboline has been found . Primarily formed 2-chloro-1-methyl-alpha-iso-carboline subjected to complex enzymic conversion yields quantitatively 2-methoxy-1-methyl-alpha-iso-carboline-9-N-oxide . It has been found that 2-chloro-1-methyl-alpha-iso-carboline exhibit strong cytotoxic activity, against KB cells tissue culture, ID50 = 0.01 microM/ml and inhibits growth of Kitasatosporia setae strain, MIC = 0.5 microM/ml . Toxicity of formed 2-methoxy-1-methyl-alpha-iso-carboline-N-9-oxide is markedly lower, ID50 = 0.3 microM/ml and MIC = 3.5 microM/ml . The remaining C-5, C-6, C-7 and C-8 chloroderivatives of alpha-iso-carboline occur to be less active than 2-chloro-1-methyl-alpha-iso-carboline. Drugs Exp Clin Res, 1987, 13(9), 529 - 38 Determination of MICs of conventional and experimental drugs in liquid medium by the radiometric method against Mycobacterium avium complex; Heifets LB et al.; The aim of this study was to search for new drugs active against the Mycobacterium avium complex and to re-examine the activity of some conventional antituberculosis drugs against these species . This progress report describes the protocol and phases of in vitro experiments in a search which included 57 different compounds tested against numerous strains of M . avium clinical isolates . The preliminary screening and MIC determination of these drugs were conducted in 7H12 broth by the radiometric method (BACTEC system) . Of the total of 57 drugs, 23 were discarded after preliminary screening and 17 after MIC determination . The remaining 17 drugs were considered sufficiently promising for more detailed in vitro studies . These, now in progress, include MIC determination by two additional methods (in broth by sampling and plating and in 7H11 agar plates), MBC determination and drug combination studies . The following drugs are currently undergoing these detailed studies: isoniazid, rifampin, rifabutine (ansamycin LM427), amikacin, streptomycin, ethambutol, ethionamide, cycloserine, clofazimine (CF), CF derivative B746, CF derivative B1865, ofloxacin, ciprofloxacin, cephalosporin BMY 28142, trimethoprim-sulfamethoxazole, spectinomycin derivative U6633F(B), and dihydromycoplanecin. Scand J Infect Dis Suppl, 1987, 52, 20 - 5 Efficacy and safety of imipenem/cilastatin in the empirical treatment of septicemia; Del Valle J et al.; The clinical efficacy and safety of imipenem/cilastatin in the empirical treatment of adult non-immunocompromised patients with severe bacterial septicemia was studied in a prospective and open trial . The dosage of imipenem/cilastatin was 500 mg q 6 h . Of 58 patients included, 41 were evaluable for efficacy . In those patients, 35 had chronic underlying diseases and the foci of bacteremia were identified in 37; the most common ones being cardiovascular, urologic or intraabdominal infections . All isolated organisms were sensitive to imipenem with an MIC for 90% of the strains of 1 mg/l . Imipenem/cilastatin treatment resulted in rapid control of the infections in 39 of the 41 evaluable patients (95.5%) . In the remaining two patients treatment had to be prematurely discontinued due to adverse effects . The causative bacterial strains were eradicated from blood in all patients who received more than one day of imipenem/cilastatin treatment but persisted sensitive to imipenem in peripheral foci in five patients (17%) . Clinical and laboratory adverse reactions were noted in seven patients . In conclusion, imipenem/cilastatin was a well tolerated and effective empirical drug for treatment of septicemia. Microbiol Immunol, 1987, 31(7), 615 - 23 Two groups of Mycobacterium avium complex strains determined according to the susceptibility to rifampicin and ansamycin; Tsukamura M; Mycobacterium avium complex strains previously not exposed to any antituberculosis agents could be divided into two groups according to their susceptibility to rifampicin and ansamycin; one group susceptible to 80 micrograms/ml rifampicin and to 1.25 micrograms/ml ansamycin, and another resistant to these concentrations . In each group, the ratio of the minimal inhibitory concentration of ansamycin against that of rifampicin was greatly different depending on the strain . This naturally occurring resistance to rifampicin and ansamycin was frequently correlated to naturally occurring resistance to ethambutol, kanamycin, enviomycin, kitasamycin, and minocycline, but not correlated to that to isoniazid and sulfadimethoxine . Ansamycin was more active than rifampicin against M . bovis, M . kansasii, M . marinum, M . xenopi, and M . haemophilum. Acta Microbiol Hung, 1987, 34(2), 121 - 4 Diffusion of metronidazole through the dentinal tubules of extracted teeth; Csukas Z et al.; Passing of metronidazole from the root canal of extracted gangrenous teeth through the dentinal tubules was proved by agar diffusion and minimum inhibitory concentration assay . The findings explain the excellent clinical experience with metronidazole in root treatment. Chemotherapy, 1987, 33(4), 250 - 4 Susceptibility of Bordetella pertussis and Bordetella parapertussis to 24 antibiotics; Hoppe JE et al.; The susceptibility of Bordetella pertussis (28 strains) and Bordetella parapertussis (6 strains) to 24 antibiotics (penicillin and cephalosporin derivatives, erythromycin, josamycin, cotrimoxazole, imipenem, aztreonam and fosfomycin) was studied by means of the agar dilution method using charcoal horse blood agar . Piperacillin and mezlocillin showed the highest activity (MIC 0.0039-0.00781 micrograms/ml) against B . pertussis while B . parapertussis was most susceptible to piperacillin (0.03125-0.0625 microgram/ml), mezlocillin and latamoxef (0.125-0.25 microgram/ml). Eur J Clin Microbiol, 1986 Dec, 5(6), 629 - 33 Pharmacokinetics of intravenous antibiotics in acutely ill elderly patients; Jonsson M et al.; In a study of 20 acutely ill elderly patients treated with cefotaxime (1 g, 2 X daily) the pharmacokinetics in serum and tissue fluid were examined . Patients with impaired renal function showed increased values for the area under the curve and half-life in both serum and tissue fluid . Patients with pathological peripheral circulation manifested delayed peak concentrations in tissue fluid . Although the passage of cefotaxime into tissue fluid was slow in the elderly, its concentration was higher than the minimal inhibitory concentration for most bacterial species of clinical importance and lasted for 5.5-7h in tissue fluid and for more than 10h in serum . Thus, this study clearly illustrates that the twice-daily dosage regimen used was quite adequate in elderly patients. J Am Diet Assoc, 1986 Dec, 86(12), 1679 - 83 Prenatal weight gains related to the birth of healthy-sized infants to low-income women; Brown JE et al.; Prepregnancy weight status and weight gain during pregnancy are major independent variables associated with infant birth weight . This study quantitated the influence of weight gain on birth weight and identified rates and total amounts of weight gain related to the birth of healthy-sized infants to healthy low-income women who entered pregnancy underweight, at normal weight, overweight, or obese . Data used in the study were obtained from randomly sampled prenatal health records from Maternal and Infant Care (MIC) projects in Cleveland and Minneapolis . Subsamples of healthy mothers who delivered healthy-sized infants were identified from each sample, and rates and total amounts of weight gain by prepregnancy weight status group were calculated . There were 384 healthy mother and healthy-sized infant pairs in the Cleveland subsample and 75 such pairs in the Minneapolis sample . Multiple regression analysis revealed that the influence of prenatal weight gain and birth weight varied depending on prepregnancy weight status . Prenatal weight gains related to the birth of healthy-sized infants (newborns with birth weights of 3,000 to 4,500 gm) to healthy mothers in the Cleveland MIC sample averaged 33 lb for underweight, 32 lb for normal weight, 29 lb for overweight, and 19 lb for obese women . Except for obese women, rates and total amount of weight gain associated with the birth of healthy-sized infants were equivalent for the two samples. Arch Pathol Lab Med, 1986 Dec, 110(12), 1183 - 5 Granulomatous encephalitis caused by Bipolaris hawaiiensis; Morton SJ et al.; We describe a case of granulomatous encephalitis caused by Bipolaris (Drechslera) hawaiiensis in an immunocompetent patient . An 18-year-old man with a seven-month history of seizures and right leg weakness was found by computed tomographic scan to have a left frontoparietal enhancing lesion . Biopsy of the lesion revealed granulomatous inflammation and numerous septate hyphae . Culture of the biopsy specimen yielded a pure culture of B hawaiiensis in four days . Susceptibility studies revealed the organism to be sensitive to amphotericin B (minimal inhibitory concentration {MIC} equals 0.25 mg/L) and miconazole lactate (MIC equals 0.064 mg/L), but resistant to flucytosine (MIC greater than 100 mg/L) . No synergy was demonstrated with amphotericin B and flucytosine in vitro . The patient was successfully treated with surgery and systemic and intrathecal amphotericin B therapy, and a negative culture was obtained from a repeated brain biopsy six weeks later. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Dec, 263(1-2), 112 - 8 European Borrelia burgdorferi isolated from humans and ticks culture conditions and antibiotic susceptibility; Preac-Mursic V et al.; Growth of Borrelia burgdorferi in a modified Kelly-medium is described . Borrelia strains were isolated from patients (n = 11) and ticks I . ricinus (n = 19) . The modified medium which contained Co-trimoxazole is a very effective medium for isolating and culturing of Borrelia sp . The susceptibility of 7 strains of B . burgdorferi to antibiotics was studied by the macrodilution and microdilution test . After preliminary testing for optimal conditions, we determined MICs in modified Kelly medium . The MIC concentration of each antibiotic was determined as the lowest concentration which completely inhibited growth of the tested organism . The B . burgdorferi was most susceptible to Erythromycin with MIC of less than or equal to 0.15 microgram/ml . Of the Penicillins tested, Ampicillin and Mezlocillin were more active than Penicillin G . The use of Tetracycline-HCl is recommended because of its low MIC in vitro its extra- and intracellular efficiency. Antimicrob Agents Chemother, 1986 Dec, 30(6), 906 - 12 Involvement of penicillin-binding protein 2 with other penicillin-binding proteins in lysis of Escherichia coli by some beta-lactam antibiotics alone and in synergistic lytic effect of amdinocillin (mecillinam); Gutmann L et al.; Compared with cefotaxime, ceftazidime, moxalactam, and aztreonam, ceftriaxone produced the best lytic and bactericidal effects when each was added at about 10 times the MIC to Escherichia coli W7 . When each of these antibiotics was added at its MIC, only bacteriostasis occurred, but the simultaneous addition of amdinocillin (mecillinam) was synergistic in causing rapid lysis and bactericidal effects . Induction of lysis of two E . coli mutants containing either a thermosensitive penicillin-binding protein (PBP) 2 or 3 by relatively PBP 3-specific (aztreonam) and PBP 2-specific (amdinocillin) antibiotics indicated that inhibition of only PBPs 2 and 3 can cause lysis . Examination of the interactions of cefotaxime, aztreonam, and cefsulodin, with or without amdinocillin, with their targets suggested that other combinations of PBPs could be involved in the onset of lysis . However, inhibition of both PBPs 2 and 3 may explain the better lysis-inducing activity of ceftriaxone (which binds well to both of these PBPs), as well as the synergistic effect of amdinocillin when added together with low concentrations of other beta-lactam antibiotics that interact with PBP 3. Am Rev Respir Dis, 1986 Dec, 134(6), 1276 - 82 Characterization of beta-lactamases in Mycobacterium fortuitum including a role in beta-lactam resistance and evidence of partial inducibility; Nash DR et al.; The beta-lactamases from the 3 biovariants of M . fortuitum were compared on the basis of substrate profiles, susceptibility to enzyme inhibitors, and inducibility in the presence of selected beta-lactams . Despite differences in the distribution of beta-lactamase bands observed when enzymes from different isolates were subjected to isoelectric focusing, substrate profiles for the 3 biovariants were similar . All demonstrated a comparable broad spectrum hydrolytic activity for both cephalosporins and penicillins . The MIC for amoxicillin were reduced 4- to 16-fold when combined with the beta-lactamase inhibitor clavulanic acid, but not to a clinically susceptible range . The degree of reduction in MIC for amoxicillin correlated well with the susceptibility of enzyme to inhibition by clavulanic acid as determined in an in vitro assay . Although all M . fortuitum strains produce beta-lactamase under routine growth conditions, 90% of strains demonstrated an increase in the amount of this enzyme when cultured in the presence of selected beta-lactams as potential inducers . Quantitative assays and isoelectric focusing further indicated that this apparent induction of beta-lactamase is a simple enhancement of the same enzyme(s) produced in the absence of a known inducer . This is the first demonstration of any inducibility among mycobacterial beta-lactamases and suggests that synthesis of these enzymes in M . fortuitum is under some form of regulatory control . These results indicate that the beta-lactamases have a role in resistance of M . fortuitum to the beta-lactams . Other factors, such as permeability and penicillin-binding proteins, were not evaluated. Antimicrob Agents Chemother, 1986 Dec, 30(6), 927 - 32 Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis; Heifets LB et al.; We determined the MICs of ethambutol for both Mycobacterium avium and Mycobacterium tuberculosis strains by using broth dilution (7H12 broth, radiometric method) and agar dilution (7H11 agar) methods . We found the MICs to be much lower in liquid than in solid medium . The broth-determined MICs for susceptible M . tuberculosis and most of the M . avium strains were comparable to the levels in blood of patients, being lower than the peak levels . We propose that the MICs, determined radiometrically in in 7H12 broth, be considered as tentative criteria for susceptibility testing of M . avium isolates in future clinical trials . The use of these values instead of critical concentrations should also be considered as an alternative to the conventional susceptibility testing method in chemotherapy of tuberculosis . Ethambutol produced bactericidal effects against both M . tuberculosis and M . avium, and the MIC/MBC ratios were in the same range for both species when MICs and MBCs were tested in 7H12 broth by conventional sampling and plating. J Dent Res, 1986 Dec, 65(12), 1420 - 3 Metronidazole concentrations in human plasma, saliva, and gingival crevice fluid after a single dose; Van Oosten MA et al.; Metronidazole concentrations were estimated in four human volunteers after a single dose of 750 mg taken orally . Samples of blood, saliva, and gingival crevice fluid were collected before intake and during the following 24 hours . The concentrations of metronidazole in plasma and saliva were measured by high-performance liquid chromatography (HPLC) . The concentrations in gingival fluid were estimated by a capillary agar-diffusion assay . The results of the metronidazole measurements as obtained by both methods were significantly correlated . The peak concentrations of metronidazole in plasma and saliva were in the same range, 8.7-13.8 micrograms/mL, and similar concentrations were found in the gingival fluid samples . It is concluded that metronidazole taken orally has similar pharmacokinetics in both saliva and plasma, and that a single oral dose of 750 mg metronidazole leads to a concentration of the drug in the gingival crevice fluid that exceeds the minimal inhibitory concentration for most anaerobic oral micro-organisms. J Clin Microbiol, 1986 Dec, 24(6), 976 - 81 Susceptibility testing of slowly growing mycobacteria by a microdilution MIC method with 7H9 broth; Wallace RJ Jr et al.; Based on previous success with rapidly growing mycobacteria, a microdilution MIC system was devised for slowly growing mycobacterial species using 7H9 broth . Test drugs included isoniazid, rifampin, ethambutol, streptomycin, clofazamine, and sulfamethoxazole . Sixty isolates of four mycobacterial species, including Mycobacterium tuberculosis, from patients who had never received drug therapy were evaluated in the system, as well as 25 drug-resistant isolates and 11 control strains . MICs were read when good macroscopic control growth was evident, a period which varied with each species . Most species exhibited a narrow range of MICs with easily discernible growth endpoints . The aminoglycosides, ethambutol, clofazamine, and sulfamethoxazole were the only drugs with activity against all species at clinically achievable levels in serum . Correlation between susceptibilities by the proportion method in agar with single drug concentrations and the broth method were excellent for M . tuberculosis, M . kansasii, and M . marinum for isoniazid, rifampin, and ethambutol . Isolates of the M . avium complex were much more susceptible in broth than in agar for rifampin, ethambutol, and streptomycin . Given the successful transition of most microbiology laboratories to MIC plates for other bacterial species, this method would allow for testing of multiple drugs at multiple concentrations and has good potential for evaluation of drug combinations and drug-resistant isolates. Southeast Asian J Trop Med Public Health, 1986 Dec, 17(4), 591 - 4 In vitro studies on the sensitivity of local Entamoeba histolytica to anti-amoebic drugs; Chintana T et al.; The in vitro activity of drugs, namely dehydroemetine, ornidazole, metronidazole and tinidazole were determined against the locally isolated strains of E . histolytica in Thailand . The test was performed in liquid monophasic medium, i.e . liver marmite serum medium . In all, locally isolated strains from thirty hosts studied, the minimal inhibitory concentration (MIC) for dehydroemetine ranged from 0.125 to 1 microgram/ml, ornidazole ranged from 0.0625 to 0.25 microgram/ml, metronidazole ranged from 0.0625 to 0.125 microgram/ml, and tinidazole ranged from 0.0625 microgram/ml to 0.25 microgram/ml . The MIC of dehydroemetine was significantly different from ornidazole, metronidazole and tinidazole . Metronidazole was superior to that of dehydroemetine but was not significantly different among ornidazole, metronidazole and tinidazole. Hinyokika Kiyo, 1986 Nov, 32(11), 1747 - 61 {Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of norfloxacin}; Sakai S et al.; We studied the basic and clinical effects of norfloxacin (NFLX) in 120 patients with gonococcal infections (110 men with urethritis and 10 women with cervicitis)--all residents at Sapporo City; and epidemiologically analyzed the sources of their infections . The male patients were between 16 and 67 years old and the female patients were between 20 and 61 years old, with a peak in the early 20s both for sexes . 70.6% of the male patients in their 10s were infected from their girl friends or so-called pick-up friends and 50% of the female patients from their husbands . The other half of the female were workers serving at so-called special massage parlors . The minimum inhibitory concentration (MIC) of NFLX against N . gonorrhoeae distributed was 0.0125 approximately 3.13 micrograms/ml, with a peak at 0.025 micrograms/ml . NFLX inhibited 93.3% of the clinical strains of this species at less than 0.1 microgram/ml and 96.2% at less than 1 microgram/ml, where the inoculation was 10(6) CFU/ml . Twenty one (20.2%) of the 104 N . gonorrhoeae strains were penicillinase-producing one (PPNG) . NFLX inhibited 18 of these PPNG (85.7%) at less than 0.1 microgram/ml and the other 3 strains at 1.56 approximately 3.13 micrograms/ml . Oral administration of 200 mg NFLX showed the average peak serum level of 0.72 micrograms/microliter in 2 hours and the average peak level in the urethral secretions of 0.5 micrograms/ml in one hour . These two concentrations of NFLX covered 95.2% of the MIC distribution against N . gonorrhoeae . The clinical efficacy of 600 mg NFLX (peros) was 97.4 and 93.1% for a 3-and 7-day treatment for male urethritis; and 100% for both 3-and 7-day treatment for female cervicitis . Complicated urethritis with C . trachomatis was noticed in 32.7% of the male urethritis and in 20% of the female cervicitis cases . Urethral secretions among about half of these patients were observed even after treatment with NFLX . As a subsequent treatment, another effective chemotherapeutic is required against C . trachomatis . No adverse reactions were detected with NFLX . All the above results demonstrate that NFLX is a highly effective and safe chemotherapeutic agent for treatment of gonorrhoea. Antimicrob Agents Chemother, 1986 Nov, 30(5), 675 - 8 Comparative pharmacokinetics of two multiple-dose mezlocillin regimens in normal volunteers; Colaizzi PA et al.; Mezlocillin was previously reported to exhibit dose-dependent pharmacokinetics . These reports suggest that it may be possible to administer a relatively large dose at a longer interval than is usual and still achieve therapeutic concentrations in serum . In a randomized, crossover study, we compared concentrations of mezlocillin in serum after a single dose and at steady state in 12 healthy volunteers who received 4 g every 6 h and 5 g every 8 h . A slight, but statistically significant, dose-dependent effect was observed upon the area under the concentration-time curve and total body clearance . No accumulation was observed with either schedule . Although concentrations in serum were higher after the 5-g dose, the more frequent administration of the 4-g dose schedule produced serum concentrations above the MIC for susceptible bacteria for a greater portion of the day . In the absence of clear guidelines from human studies which relate serum concentrations to clinical response, the available data indicate that the more frequent dosage schedule is appropriate for severe infections. Am J Vet Res, 1986 Nov, 47(11), 2325 - 8 3-Acetyl-4''-isovaleryl tylosin for prevention of swine dysentery; Jacks TM et al.; The 21 field isolates of Treponema hyodysenteriae which were tested were sensitive to 3-acetyl-4''-isovaleryl tylosin (AIV); the minimal inhibitory concentration was 0.25 to 16 micrograms/ml . 3-Acetyl-4''-isovaleryl tylosin administered prophylactically to pigs at concentrations of 5 to 100 mg/kg of feed and tylosin at 110 mg/kg of feed for 28 or 31 days prevented swine dysentery induced by tylosin-sensitive T hyodysenteriae strain SQ2; 15 nonmedicated, inoculated control pigs had bloody diarrhea, and 9 pigs died . In 2 additional trials, AIV administered prophylactically for 28 days at 55 or 110 mg/kg of feed prevented swine dysentery induced by tylosin-insensitive T hyodysenteriae strain B204 . All of the inoculated principal pigs medicated with AIV at 55 or 110 mg/kg of feed or carbadox at 55 mg/kg of feed and the noninoculated sentinel pigs for each group had solid feces throughout the 56-day trial . In the nonmedicated, inoculated control groups, bloody diarrhea began at 4 to 5 days after inoculation was done, and 9 of 10 principal pigs and 6 of 9 sentinel pigs had dysentery; 2 pigs died . In the groups medicated with AIV at 27.5 or 5.5 mg/kg of feed, all 5 principal pigs and 3 or 4 sentinel pigs in each group had dysentery; 3 or 4 pigs in each group died . In the group medicated with tylosin at 110 mg/kg of feed, 7 of 10 principal pigs and all 9 sentinel pigs had dysentery; 1 pig died.(ABSTRACT TRUNCATED AT 250 WORDS) J Antimicrob Chemother, 1986 Nov, 18 Suppl D, 31 - 41 Morphological and biochemical changes in Escherichia coli after exposure to ciprofloxacin; Diver JM et al.; Examination of morphological and biochemical changes in Escherichia coli KL-16 after exposure to ciprofloxacin revealed distinct concentration-dependent responses . At levels close to the MIC extensive filamentation was seen, whereas at the most bactericidal concentration cells were elongated but not filamented . At higher concentrations ovoid cells were seen . Some cells showed surface vacuoles, but no significant leakage of cell contents was detected . Filamentation and vacuolation were shown to make only a minor contribution to ciprofloxacin-induced cell death, and the data indicate that there are two or more mechanisms involved in the lethal action of ciprofloxacin. J Antimicrob Chemother, 1986 Nov, 18(5), 575 - 83 Elimination of plasmids by enoxacin and ofloxacin at near inhibitory concentrations; Weisser J et al.; The abilities of the 4-quinolones enoxacin and ofloxacin, inhibitors of DNA gyrase subunit A, to eliminate plasmids from Escherichia coli have been studied in a narrow concentration range just below the MIC . These compounds cured most efficiently at the highest concentration which still allows cell growth and produced 20% to 100% plasmid-free cells, depending upon the plasmid tested . Higher concentrations were required to eliminate plasmids from a gyrANalr strain, consistent with their higher MICs, but maximal curing frequencies were similar to those obtained with the Nals strain . Kinetics of plasmid elimination indicated that plasmid loss occurred by inhibition of plasmid replication, which seems to be somewhat more sensitive to the action of 4-quinolones than chromosome replication . Low or high curing frequencies with a given curing agent seem to be a property of the plasmid tested. Cancer Genet Cytogenet, 1986 Nov, 23(3), 189 - 97 Morphologic, immunologic, and cytogenetic (MIC) working classification of acute lymphoblastic leukemias . Report of the workshop held in Leuven, Belgium, April 22-23, 1985 . First MIC Cooperative Study Group; {In vitro activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis et al.; Thomas L, Naumann P, Crea A. The in vitro activity of ciprofloxacin and ofloxacin against 33 strains of mycobacteria was investigated in a comparative study . The resulting MIC values were compared with serum levels, measured in a cross-over study . Possible therapeutic application of these substances in mycobacterial infections are being discussed . We found the antimycobacterial activity of ciprofloxacin to be insufficient for its clinical application, whereas the corresponding MIC values for ofloxacin could be achieved in vivo . Further animal and clinical studies appear justified. Antimicrob Agents Chemother, 1986 Nov, 30(5), 777 - 80 Purification and properties of DNA gyrase from a fluoroquinolone-resistant strain of Escherichia coli; Sato K et al.; Subunit A and B proteins of DNA gyrase were separately purified from fluoroquinolone-resistant Escherichia coli GN14181 (MIC of ofloxacin, 100 micrograms/ml) and susceptible strain KL-16 . The supercoiling activities of reconstituted Ar+Br (r, resistant) and Ar+Bs (s, susceptible) were 250-fold more resistant to new fluoroquinolones than those of As+Bs and As+Br. Fundam Appl Toxicol, 1986 Oct, 7(3), 502 - 22 Methyl isocyanate subchronic vapor inhalation studies with Fischer 344 rats; Dodd DE et al.; Groups of Fischer 344 rats were exposed to 3.1, 0.6, 0.15, or 0.0 (control) ppm of methyl isocyanate (MIC) vapor 6 hr per day for two 4-day sessions separated by a 2-day rest . There were no deaths during the study . The rats were killed the morning following the last exposure day . The 3.1-ppm-exposed rats had decreased body weight, food consumption, and blood oxygen saturation (males only) . Increased hemoglobin concentration (males only) and lung weights were also observed in this group of rats . Multiple histologic lesions, limited to the respiratory tract, were observed in rats of the 3.1-ppm group only . The lesions consisted of necrosis, suppurative inflammation, squamous metaplasia, and intraluminal and submucosal fibroplasia (bronchi and bronchioles only) which extended from the anterior nasal cavity to the terminal bronchioles . In a second study, rats were exposed to 3.0 ppm MIC, 6 hr per day, for either one or two 4-day sessions and sacrificed on postexposure Days 1, 15, 43, and 85 . All rats survived the 4- or 8-day exposure regimen, although significant decreases in body weight and encrustation of the eyes, nose, or mouth area were observed . During the first 15 days postexposure, male mortality was 63%; only 6% of the MIC-exposed females died . The cause of death was interpreted to be a combination of pulmonary vascular and inflammatory changes coupled with anorexia . For survivors, recovery from the necrotizing and irritating effects of MIC vapor was observed . Squamous metaplasia of respiratory epithelium, observed in rats sacrificed at the end of the exposure period, was replaced by tall pseudostratified columnar (regenerative) epithelium beginning in the bronchi and bronchioles as well as the distal trachea . Collagen maturation and condensation of the intraluminal and submucosal fibroplasia occurred during the postexposure period . The results of these investigations support the current threshold limit value for MIC of 0.02 ppm. J Clin Microbiol, 1986 Oct, 24(4), 647 - 9 Cefixime disk susceptibility test criteria; Fuchs PC et al.; A total of 583 bacterial isolates was tested for susceptibility to cefixime by broth microdilution and by disk agar diffusion with 5-, 10-, and 30-microgram disks . At MIC breakpoints of less than or equal to 1.0 and greater than or equal to 4 micrograms/ml for susceptible and resistant, respectively, the 5-microgram disk showed slightly better discrimination . The 5-microgram cefixime disk is recommended with proposed interpretive breakpoint criteria of: less than or equal to 17 mm, resistant; 18 to 20 mm, intermediate; and greater than or equal to 21 mm, susceptible. Kidney Int, 1986 Oct, 30(4), 481 - 7 Benefit from high intrarenal levels of gentamicin in the treatment of E . coli pyelonephritis; Bergeron MG et al.; The importance of high intrarenal levels of gentamicin on the outcome of experimental pyelonephritis was studied in rats receiving either a short course (three days) of gentamicin (G) alone or combined with a longer course (14 days) of ampicillin (A), cephalothin (C), or trimethoprim (T), or two weeks of therapy with ampicillin, cephalothin, trimethoprim and gentamicin given alone . While ampicillin, cephalothin and trimethoprim were undetectable in the medulla within six hours of cessation of therapy, gentamicin was still detectable in levels six folds above the MIC up to six months after treatment had ceased . Six months after the end of treatment, the percentage of sterile left kidneys in animals treated with ampicillin (50%), cephalothin (15%), trimethoprim (20%) was lower than the percentage of animals receiving 14 days of gentamicin (100%), or the combinations AG:89%, CG:67% and TG:60%, P less than 0.01 . Following three days of gentamicin, 50% of the left kidneys were sterilized . When compared to ampicillin, cephalothin or trimethoprim alone, combined therapies significantly reduced the number of CFU in the kidneys P less than 0.01 . These combinations were almost as effective as two weeks of therapy with gentamicin . Short-term therapy (three days) with an aminoglycoside which concentrates in the renal parenchyma, combined with an antibiotic which will accumulate in other parts of the nephron, may result in "pharmacological synergy" . This new approach to therapy of pyelonephritis may be promising. J Antimicrob Chemother, 1986 Oct, 18(4), 441 - 51 Inhibition of K88-mediated adhesion of Escherichia coli to mammalian receptors by antibiotics that affect bacterial protein synthesis; Chopra I et al.; The ability of ten inhibitors of bacterial protein synthesis to decrease adhesion of Escherichia coli bearing K88ac fimbriae was examined . In the presence of the antibiotics at concentrations below the MIC values neomycin was the least effective inhibitor of adhesion and minocycline the most active . The effect of minocycline on the synthesis of individual polypeptides encoded by the K88ac determinant was examined in detail . The rate of synthesis of K88ac pilus protein in the presence of minocycline 0.75 mg/l (0.5 MIC) was less than that of total cell protein synthesis, suggesting that pilus protein becomes progressively 'diluted' in the outer membrane during exposure to this antibiotic concentration . Furthermore, the synthesis of two 'helper' polypeptides (molecular weights of 27.5 K and 27 K) which are probably involved in secretion of K88ac pilus protein through the cell envelope, was particularly sensitive to minocycline . Our observations suggest that the ability of translational inhibitors to decrease K88ac mediated adhesion probably results from direct inhibition of synthesis of fimbrial protein itself, together with inhibition of 'helper' polypeptide synthesis. Hinyokika Kiyo, 1986 Oct, 32(10), 1551 - 72 {Epidemiological and therapeutic studies on gonorrheal infections--clinical efficacy of T-2588 . (Sapporo Clinical Research Group for STD)}; Kumamoto Y et al.; T-2588, a new oral cephalosporin antibiotic, for gonorrheal infections, was administered to 146 patients with gonorrheal infection cases (140 urethritis cases in males, 6 cervicitis cases in females) . Twenty three strains (20.9%) out of 110 clinically isolated gonococci were PPNG . The MICs of T-2588 for the clinically isolated gonococci strains showed a distribution peak at 0.025 microgram/ml and ranged between 0.0125 microgram/ml to 0.1 microgram/ml when an inoculum size of 10(6)/CFU/ml was used . The distribution of MICs of PPNG also showed a peak at 0.025 microgram/ml and the maximum MIC was 0.2 microgram/ml, which is one dilution tube higher than the maximum MIC of non-PPNG . The rate of complication by Chlamydia trachomatis was 20.9% in male and 33.3% in female . At the dose of 400 mg given 2 times a day, the efficacy rate for the males on the 3rd and 7th day was 90.5% (efficacy rate against PPNG, 73.3%) and 95.3% (80.0%), respectively . At the dose of 300 mg given 3 times a day, it was 93.3% and 100%, respectively, and at the dose of 600 mg given 3 times a day, it was 100% and 100%, respectively . Therefore, the administration of T-2588 3 times a day resulted in a higher efficacy rate than that given 2 times a day . This effect was extremely marked in the case of patients with PPNG . The best clinical results were obtained at a daily dose of 600 mg t.i.d . Although the female patients were few, in number and no conclusion can be drawn, the best results were obtained with a daily dose of 600 mg t.i.d . (100%) . There were three mild side effects (1.7%), which could not be attributed to the administration of T-2588 in the present study . In conclusion, T-2588 can be to be expected sufficiently clinically effective against gonorrheal infections, including PPNG, at a daily dose of 600 mg t.i.d . for 3 days. J Clin Hosp Pharm, 1986 Oct, 11(5), 335 - 42 Determination of in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations; Cottrell WN et al.; The in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations were determined by utilizing high-performance liquid chromatography techniques following a once daily irrigation . A total of 14 chlorhexidine irrigations established a mean concentration of 0.006% w/v, 2-3 h post irrigation . A total of 12 noxythiolin irrigations established a mean concentration of 0.266% w/v, 2-3 h post irrigation, which correlated to a mean formaldehyde concentration of 0.0119% w/v at 2-3 h, as estimated from N-methylthiourea . For both solutions the minimum inhibitory concentration was exceeded for up to 5 h post irrigation, which is sufficient contact time to establish a total kill, thus indicating the possibility that a once daily irrigation may be appropriate in asymptomatic bacteriuria which utilizes either chlorhexidine or noxythiolin. Gan To Kagaku Ryoho, 1986 Oct, 13(10), 3046 - 55 {Serum and tissue concentrations of UFT in patients with lung cancer}; Aota M et al.; Postoperative serum and tissue concentrations of 5-FU, FT-207 and uracil were measured in 36 patients with lung cancer who were administered UFT for seven days preoperatively . The concentration of 5-FU was high in tumor tissue and lymph nodes, but very low in serum . Such differences were not observed in the FT-207 levels . Tumor concentration of 5-FU in patients administered daily doses of 600 mg was 0.151 +/- 0.099 microgram/g which was three times higher than the minimum inhibitory concentration, and higher than that seen with other doses . The histological type and T factor were not related to the tissue concentration of 5-FU . Lymph node metastasis was not related to the concentration of 5-FU in the lymph nodes . The optimal daily dose of UFT for patients with lung cancer was considered to be 600 mg. Life Sci, 1986 Sep 15, 39(11), 993 - 1001 Effect of atriopeptin III on renin release in vitro; Henrich WL et al.; The ability of atriopeptin III (AP) to directly inhibit renal renin release has not been resolved . This issue was examined in a series of experiments performed in a system of rat renal cortical slices (dry weight 1.91 mg) in which the goal was to explore the effects of AP on renin release induced by cyclic AMP (cAMP)-coupled stimuli or by agents which are believed to decrease intracellular calcium (Cai) . Concentration response relationships were initially established for all test agents . The cAMP stimuli utilized were isoproterenol (10(-5) M), forskolin (10(-5) M), and dibutyryl cAMP (3 X 10(-4) M); each of these agents produced a significant increase in renin release in the system (with isoproterenol a 59% increase, with forskolin 37%, and with dibutyryl cAMP 52%) . The addition of AP (2.09 X 10(-8) M, a minimum inhibitory concentration derived from preliminary studies) significantly blunted these increases; in the case of the dibutyryl cAMP-stimulated renin release, the inhibition was partial as a significant 25% increase in renin occurred in the presence of AP . The addition of the calcium channel blocking agent diltiazem (10(-4) M) resulted in a significant increase in renin release (364 to 567 ng X mg-1, p less than .05) which was not blocked by the addition of AP . Similarly, TMB-8 (0.6 X 10(-4) M), another agent thought to lower Cai, also resulted in increased renin release (455 to 810 ng X mg-1), p less than .01) which was also unaffected by the addition of the AP . In summary, these results show that AP is capable of partially inhibiting renin release in vitro, particularly renin release coupled to cAMP action . In contrast, renin release induced by a decline in Cai appears to be unaffected by the addition of AP. Hum Genet, 1986 Sep, 74(1), 81 - 4 Cytogenetic effects of methyl isocyanate exposure in Bhopal; Goswami HK; Among human survivors following the methyl isocyanate (MIC) gas tragedy the major complaints have been related to deep-seated suffocation, terrible pain in breathing, and severe ocular irritations . In order to assess the possible genetic effects we have used lymphocyte cultures and screened chromosomes by two techniques; one by looking for chromosomal aberrations and the other by estimating sister-chromatid exchange (SCE) frequencies . Both these parameters are good indicators of genetic damage in chromosomal DNA . SCE frequencies in lymphocytes have been increased more than three times in MIC-exposed persons . The results were compared to two groups of controls (one group comprising persons present in the same house; the second group of persons were chosen from distant places, 20-50 km away from the incident) . Chromosomal breaks have been observed in 10 out of 14 MIC-affected people (71.4%) studied while only 6 out of 28 (21.4%) controls had chromosomal breaks . Some MIC-exposed persons had chromatin bodies in addition to the normal 46 chromosomes . These observations suggest that chromosomal DNA has been damaged. J Clin Microbiol, 1986 Sep, 24(3), 448 - 50 Tentative disk diffusion susceptibility interpretive criteria for pefloxacin; Fuchs PC et al.; Standardized broth microdilution and disk diffusion susceptibility tests for pefloxacin were performed on 585 clinical isolates . The 5-micrograms pefloxacin disk is recommended, and the following breakpoints are proposed: susceptible, greater than or equal to 19 mm (MIC, less than or equal to 2.0 micrograms/ml); resistant, less than or equal to 15 mm (MIC, greater than 4.0 micrograms/ml); and intermediate, 16 to 18 mm. Antimicrob Agents Chemother, 1986 Sep, 30(3), 468 - 74 Inhibition of DNA replication initiation by aminoglycoside antibiotics; Matsunaga K et al.; The reinitiation of DNA replication induced by a temperature shift in a dnaC(Ts) mutant of Escherichia coli was markedly inhibited by aminoglycoside antibiotics around the MIC in a short period . Protein synthesis continued for several minutes after the addition of aminoglycosides but was immediately blocked by chloramphenicol, suggesting that the inhibition of initiation of replication by aminoglycosides is not a secondary effect due to the interruption of protein synthesis . Aminoglycosides did not significantly affect RNA synthesis, suggesting that primer RNA synthesis for DNA initiation is not blocked by the agents . The lethal action of habekacin was observed simultaneously with the inhibition of DNA reinitiation . DNA elongation demonstrated with a dnaE(Ts) mutant or toluene-treated cells of a polA mutant was not significantly affected by aminoglycosides . The oriC-membrane complex formation was markedly interrupted by habekacin in the dnaC(Ts) mutant, and the in vitro reconstitution of the oriC-membrane complex was completely blocked by aminoglycosides . The present studies show that aminoglycosides block initiation of DNA replication and suggest that the inhibition is caused by the interruption of oriC-membrane attachment. Clin Exp Immunol, 1986 Aug, 65(2), 319 - 28 Subpopulations of thyroid autoantibody secreting lymphocytes in Graves' and Hashimoto thyroid glands; McLachlan SM et al.; Lymphocytes isolated from Graves' and Hashimoto thyroid tissue by enzymatic (dispase) digestion or mechanical disaggregation were markedly different in terms of their ability to synthesize thyroid autoantibodies in culture . Dispase digestion, followed by removal of thyroid follicular cells, gave a lymphocyte population with a high T:B cell ratio (6:1) . However, the ability of these cell suspensions to synthesize microsomal (Mic) and thyroglobulin (Tg) antibodies spontaneously was significantly increased compared with lymphoid suspensions isolated by mechanical means . Spontaneous synthesis of thyroid autoantibodies was not markedly enhanced in cell suspensions prepared from patients' lymph node tissue by digestion compared with mechanical disaggregation . Further, Mic and Tg antibody production by thyroid lymphocytes prepared using dispase was inhibited by pokeweed mitogen (PWM) whereas in most cases suspensions prepared from the same tissues by mechanical dispersion synthesized low or undetectable levels of autoantibodies whether PWM was present or absent . Digestion of tissue debris remaining after mechanical removal of lymphocytes gave suspensions which had an increased proportion of suppressor/cytotoxic T cells compared with suspensions produced mechanically or by digestion alone; however, in terms of spontaneous autoantibody synthesis and PWM induced inhibition, these suspensions were similar to these obtained by digestion alone . It would therefore seem that enzymatic digestion of thyroid tissue resulted in the isolation of a lymphoid population which was different from that extracted by mechanical disaggregation . The digestion process appears to permit the recovery of lymphocytes closely associated with thyroid follicular cells and our studies suggest that it is this population which makes the major contribution to autoantibody synthesis. Mutat Res, 1986 Aug, 174(4), 285 - 93 Mutagenicity of methylisocyanate and its reaction products to cultured mammalian cells; Caspary WJ et al.; Methylisocyanate (MIC) induced mutagenic responses in the absence of exogenous activation in the mouse lymphoma cell forward mutation assay at concentrations as low as 8-24 microM . MIC produced predominantly small mutant colonies, suggesting the possibility of clastogenic activity . The intermediate hydrolysis product, methylamine, was also mutagenic without exogenous activation but required several hundred-fold higher concentrations (ca . 3 mM) . N,N'-Dimethylurea, the final product in the reaction of methylisocyanate and water, was totally refractory in either the presence or absence of S9 for concentrations up to 57 mM (5 mg/ml) . The ethyl ester of N-methylcarbamic acid was also tested since it was the only available analogue to the highly reactive N-methylcarbamic acid intermediate . This compound was mutagenic only in the presence of S9 at doses exceeding 5-40 microM, which suggested the possibility that the free acid, produced by enzymatic hydrolysis, is also mutagenic . The mutagenic activity of the ester resulted solely in the production of small mutant colonies. J Immunol Methods, 1986 Jul 11, 91(1), 129 - 38 Measurement of spontaneous and stimulated anti-microsomal antibody synthesis in vitro by avidin-biotin enzyme immunoassay; Harigai M et al.; The spontaneous and stimulated anti-microsomal (anti-Mic) antibody synthesis in vitro by peripheral blood lymphocytes (PBL) from patients with Hashimoto's thyroiditis (HT) was studied by a highly sensitive and thyroid microsome-specific enzyme immunoassay using an avidin-biotin system (A-B EIA) . Since the amount of the synthesized anti-Mic antibody by PBL in vitro is very small, it is difficult to study its kinetics and response to mitogens or the specific antigen by conventional assay systems . We applied the avidin-biotin system to conventional indirect EIA and established an assay system which was about four times as sensitive as indirect EIA . PBL from patients with HT synthesized significant amount of IgG anti-Mic antibody spontaneously but those from normal individuals and patients with rheumatoid arthritis did not . IgG anti-Mic antibody synthesis with pokeweed mitogen stimulation was increased in all HT patients and that with thyroid microsome stimulation was increased in three out of five patients . These results indicate that A-B EIA is a useful system to study the mechanism of anti-Mic antibody synthesis in vitro. Br Med J (Clin Res Ed), 1986 Jul 5, 293(6538), 11 - 3 Intramuscular loading dose of quinine for falciparum malaria: pharmacokinetics and toxicity; Wattanagoon Y et al.; In a study of intramuscular injection of quinine eight adults with moderately severe falciparum malaria resistant to chloroquine were treated with quinine dihydrochloride, being given a loading dose of 20 mg salt (16.7 mg base)/kg followed by three or four eight hourly maintenance doses of 10 mg salt (8.3 mg base)/kg injected into the anterior thigh . All patients responded to treatment . Fever and parasite clearance times (mean (SD) 60 (23) h and 53 (22) h respectively) were comparable with those obtained with intravenous quinine . The mean peak plasma quinine concentration of 11.0 mg/l (34.4 mu mol/l) {corrected} was reached a median of five hours after administration of the loading dose . In all patients plasma quinine concentrations exceeded the high minimum inhibitory concentration for Plasmodium falciparum malaria prevalent in Thailand within four hours of the start of treatment but did not cause toxicity other than mild cinchonism . When intravenous infusion is not possible an intramuscular quinine loading dose is an effective means of starting treatment in patients with moderately severe falciparum malaria who cannot swallow tablets. Indian J Lepr, 1986 Jul-Sep, 58(3), 401 - 6 Blood dapsone levels in leprosy patients treated with acedapsone; George J et al.; The metabolism of the repository drug acedapsone (DADDS,4,4'-diacetyldiaminodiphenyl sulfone) was studied in 15 individuals receiving 225 mg of DADDS, intramuscularly for a period of 75 days . Plasma levels of DDS were determined on the 2nd, 7th, 15th, 30th, 60th and 75th day after administration of the drug by spectrophoto-fluorometric technique . The mean peak levels of DDS (85.36 ng/ml) were noticed on 7th day followed by a gradual decrease in DDS concentration . The mean half-life level (44.53 ng/ml) of DDS were observed around the 15th day . The mean DDS level for the entire period of observation after one dose was 41.95 ng/ml . On the 75th day, the DDS level reached the minimum value of 14.76 ng/ml which was still about 5 times more than the minimal inhibitory concentration (MIC) level of DDS against M . leprae (3 ng/ml) . The results are discussed. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 Jul, 261(4), 425 - 31 The susceptibility of a strain of Leptospira interrogans serogroup icterohaemorrhagiae to amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline; Broughton ES et al.; The failure of prophylactic penicillin to prevent a laboratory acquired case of Icterohaemorrhagiae leptospirosis prompted determination of the MIC and MBC of amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline for the infecting strain . Amoxycillin followed by erythromycin were the most effective, with MBCs of 0.5 mg/l after 7 days exposure and 0.1 mg/l after 21 days exposure respectively . Leptospires grew in the presence of high concentrations of tetracycline hydrochloride and oxytetracycline after prolonged incubation . This effect was less pronounced with minocycline, with MIC's of 0.025, 0.05 and 0.1 mg/l after 7, 14 and 21 days exposure respectively . The MIC of lincomycin was 0.25 mg/l at each time interval . These results support the high dose, long duration antibiotic regimens recommended in the literature. Antimicrob Agents Chemother, 1986 Jul, 30(1), 15 - 9 Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis; Heim KL et al.; The disposition of cefotaxime (CTX) and desacetyl cefotaxime (DAC) was studied in eight noninfected patients on continuous ambulatory peritoneal dialysis . Each patient received a single intravenous (i.v.) infusion and an intraperitoneal (i.p.) instillation of 2 g of CTX . Multiple blood and dialysate samples were collected during the 72-h period after drug administration . The half-life, steady-state volume of distribution, and total body clearance of CTX following i.v . administration were 2.2 +/- 1.0 h (mean +/- standard deviation), 0.17 +/- 0.03 liters/kg, and 81.0 +/- 31.0 ml/min, respectively . No significant differences were observed in these parameters after i.p . administration . The continuous ambulatory peritoneal dialysis clearances of CTX and DAC were 1.82 +/- 0.43 and 2.84 +/- 0.70 ml/min, respectively, after i.v . administration . The bioavailability of CTX after i.p . instillation was 74.6 +/- 21.3% . Peak peritoneal dialysate CTX and DAC concentrations of 264.3 and 25.8 mg/liter, respectively, were observed after i.p . dosing . Administration (i.v.) of 2 g every 12 h or i.p . instillation of 2 g every 24 h may be used for the treatment of i.p . infections with highly susceptible organisms (MIC less than 1.0 microgram/ml). Infection, 1986 Jul-Aug, 14(4), 186 - 9 Activity of the trometamol salt of fosfomycin in an in vitro model of the treatment of bacterial cystitis; Greenwood D; The response to trometamol fosfomycin of four strains of Escherichia coli was studied in an in vitro model in which the hydrokinetic aspects of the treatment of bacterial cystitis can be stimulated . Two strains of E . coli that were fully susceptible to fosfomycin, and a strain of intermediate susceptibility responded well to relatively low concentrations of the trometamol salt: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for at least 18 h; however, the emergence of resistance was completely suppressed only when a peak concentration of 2500 mg/l was achieved in the bladder model . A strain of E . coli that was fully resistant to fosfomycin in conventional minimum inhibitory concentration titrations responded to the highest dosage used, but this did not prevent further resistance from emerging . These results were obtained in the absence of the potentiating agent, glucose-6-phosphate, which is commonly used in susceptibility tests of fosfomycin . The implications of the results for fosfomycin dosage in bacterial cystitis and for the interpretation of susceptibility tests is discussed. Z Lebensm Unters Forsch, 1986 Jul, 183(1), 1 - 7 {In vitro toxicity tests of diethyleneglycol with cell cultures and an automated bacterial test system}; Lindl T et al.; Diethyleneglycol was tested for its general cytotoxic effects in three cell culture test systems and in a novel, automated bacterial test system . The first cytotoxic effects were detected in the cell culture test systems at DEG-concentrations of 1 g/1 and 3g/1 . The bacterial test system showed a minimal inhibitory concentration of 5 g/1 DEG (20% growth reduction) . Morphological observations showed evidence of membrane damage to the cultured cells by DEG . With the bacterial test system one could determine the amount of DEG semiquantitatively in wines to which this material had been added. Antimicrob Agents Chemother, 1986 Jul, 30(1), 127 - 31 Tellurite susceptibility and non-plasmid-mediated resistance in Escherichia coli; Tomas JM et al.; Tellurite (TeO3(2-)) is highly toxic toward Escherichia coli (MIC, approximately 1 microgram ml-1) . Mutants (Tel) that were resistant to low levels of TeO3(2-) (MIC, approximately 10 micrograms ml-1) and collaterally resistant to arsenate were isolated . These Tel mutants were unable to grow on media containing low levels of Pi, which supported growth of the parent strain . When grown at much higher Pi levels they exhibited depressed levels of the outer membrane phoE protein and the periplasmic phoS protein, as well as several other proteins indicative of Pi starvation . Tel mutants were markedly defective in 32Pi transport, and TeO3(2-) was shown to be a potent competitive inhibitor of 32Pi transport in the parent strain . The Tel phenotype could be complemented by an F' plasmid harboring the phoR, phoB, and phoA loci, and curing of the F' plasmid completely restored TeO3(2-) resistance . Of a variety of well-characterized Pi transport mutants, only phoB mutants were equally resistant to TeO3(2-), and susceptibility could also be restored in strains carrying an F' plasmid for the phoB region and lost once more after F' curing . The tel and phoB loci were equally cotransducible with lac . Tel mutants still synthesized alkaline phosphatase, the phoA gene product, after Pi starvation, suggesting that the phoB locus per se was not involved because phoB is a positive regulatory gene for phoA expression . The results indicate that TeO3(2-) is transported into E . coli by a phosphate transport system and that resistance to TeO3(2-) specifically selects for as yet uncharacterized mutants in the phoB-phoA region of the chromosome. Pathol Biol (Paris), 1986 Jun, 34(5 Pt 2), 684 - 7 {Comparative study of the fungistatic activity in vitro of omoconazole and 6 other imidazoles against yeasts}; Mosse M et al.; Omoconazole (CM 8282) is a new synthetic antifungal agent with a spectrum of activity quite similar to that of the imidazole family . Fungistatic activity of this product was compared to that of the six following reference products: clotrimazole, econazole, isoconazole, ketoconazole, miconazole, and tioconazole . MICs against 55 recent clinical yeast isolates were determined by agar dilution on pH 5.5-adjusted Sabouraud and casitone media . MIC 90% values showed that tioconazole was the most active product, followed by omoconazole and econazole, whereas ketoconazole was the least active compound under our experimental conditions. Methods Find Exp Clin Pharmacol, 1986 Jun, 8(6), 367 - 72 Activities of cefoxitin in vitro and in vivo: a study in patients with biliary tract infection undergoing percutaneous transhepatic biliary drainage; Masuda G et al.; Activities of cefoxitin and the effect on killing of bacteria in bile from six patients undergoing percutaneous transhepatic biliary drainage were analyzed in relation to in vitro activities of the drug, with particular reference to the incubation time . The bacteriostatic and bactericidal activities of cefoxitin with short term (6 hr) incubation correlated well with the duration of the effective cefoxitin concentration and the decrease of viable bacteria in bile juice from the patients . These timed in vitro activities can be used as well as the conventional MIC and MBC with the prolonged incubation of 24 hr, in the deductive analysis of bacterial response in vivo. Jpn J Antibiot, 1986 May, 39(5), 1273 - 8 {Penetration of cefotaxime into human bone marrow blood}; Endo F et al.; Concentrations of cefotaxime (CTX) in bone marrow blood and venous blood were examined with the passage of time in 21 cases which received operations of bone and joint . Concentrations of CTX in bone marrow blood at 30 minutes of a single intravenous administration 2 g each of CTX were found to be 85.2 +/- 24.5 micrograms/ml . Concentration ratio of CTX in bone marrow blood to that in venous blood was reached the peak at 120 minutes after administration . Concentrations of CTX observed were higher than the MIC of CTX against major pathogens responsible for the postoperative infections in orthopaedic field . The CTX, therefore, is expected to have an effective antibiotic in prophylaxis. Fundam Appl Toxicol, 1986 May, 6(4), 756 - 71 Acute inhalation studies with methyl isocyanate vapor . II . Respiratory tract changes in guinea pigs, rats, and mice; Fowler EH et al.; Hartley guinea pigs, Fischer-344 rats, and B6C3F1 mice of both sexes were exposed to varying concentrations of methyl isocyanate (MIC) vapor with the highest concentration being 20.4 ppm for rats and mice and 10.5 ppm for guinea pigs . A control group for each species was exposed to air only . All animals were exposed for a duration of 6 hr, and survivors were sacrificed 14 days following exposure . The respiratory tract was removed and examined microscopically from all animals . Guinea pigs were more sensitive to the MIC vapor than were rats which were in turn more sensitive than mice . Gross lesions encountered in many of the animals that died consisted of nasal discharge, often blood tinged, and discoloration of the lungs . Microscopic lesions included acute necrosis of epithelial lining throughout the respiratory tract in animals that died shortly after exposure coupled with congestion, edema, and inflammation . A microscopic lesion which appeared unique to guinea pigs was bronchiolitis obliterans where the necrosis and inflammation had completely closed the bronchioles . Additional microscopic lesions observed in some animals that died or were sacrificed at the end of the study (postexposure Day 14) consisted of squamous metaplasia of respiratory epithelium in the nasal cavity, which extended into the larynx, trachea, and, in some cases, the bronchi . In addition, epithelial regeneration throughout the tract and submucosal fibroplasia in the trachea, bronchi, and bronchioles were observed, the latter lesion being primarily confined to rodents . No animals exposed to 2.4 or 1.0 ppm of MIC vapor died following exposure . There were minimal microscopic lesions at sacrifice in the 2.4 ppm-exposed animals from all three species . Only in guinea pigs were there lesions in the 1.0-ppm group attributed to MIC vapor exposure. Fundam Appl Toxicol, 1986 May, 6(4), 747 - 55 Acute inhalation studies with methyl isocyanate vapor . I . Methodology and LC50 determinations in guinea pigs, rats, and mice; Dodd DE et al.; Groups of male and female Fischer 344 rats, B6C3F1 mice, and Hartley guinea pigs were exposed once for 6 hr to mean concentrations of 10.5, 5.4, 2.4, 1.0, or 0 (control) ppm of methyl isocyanate (MIC) vapor . Rats and mice were also exposed to 20.4 ppm of MIC . No deaths occurred in animals exposed to 2.4 or 1.0 ppm . The majority of deaths for the 20.4- and 10.5-ppm groups occurred during postexposure Days 1 through 3, while at 5.4 ppm deaths were observed throughout the 14-day postexposure period . The 6-hr LC50 values (with 95% confidence limits) were 6.1 (4.6 to 8.2) ppm for rats, 12.2 (8.4 to 17.5) ppm for mice, and 5.4 (4.4 to 6.7) ppm for guinea pigs . Notable clinical observations during and immediately following MIC exposure were lacrimation, perinasal/perioral wetness, respiratory difficulty (e.g., mouth breathing), decreased activity, ataxia, and hypothermia . The frequency of clinical signs decreased during the second postexposure week . Body weight losses were common in all species following MIC exposures of 2.4 ppm or greater . At 1.0 ppm, only female mice had body weight depression . Recovery of body weight loss was observed in the 5.4- (guinea pigs only), 2.4- and 1.0-ppm concentration groups . The lungs of all animals that died were discolored . Following microscopic examination of the respiratory tract, deaths were attributed to pulmonary edema and congestion . In a separate study, Fischer 344 rats and Hartley guinea pigs were exposed once for 4 hr to mean concentrations of 36.1, 25.6, 15.2, or 5.2 ppm of MIC vapor . In general, the results were similar to those of the single 6-hr exposure study. Pathol Biol (Paris), 1986 May, 34(5), 445 - 7 {Comparative in vitro activity of a new macrolide RU 28965 and of erythromycin against Chlamydia trachomatis}; Dutilh B et al.; Activity of a new macrolide, RU 28965, and erythromycin against 8 Chlamydia trachomatis strains isolated from the human genital tract was studied . Minimal inhibitory concentrations were determined using cycloheximide-treated McCoy cells . Giemsa and immunofluorescence staining with monoclonal antibodies were used to detect Chlamydial inclusions . Immunofluorescence proved more sensitive and easier to read . All the strains were highly susceptible to RU 28965 (MIC = 0.05 mg/l - 0.1 mg/l) and erythromycin (MIC = 0.02 mg/l - 0.2 mg/l). Jpn J Antibiot, 1986 May, 39(5), 1359 - 71 {Fundamental and clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology}; Cho N et al.; A combination of imipenem (MK-0787), a new carbapenem antibiotic, plus cilastatin sodium (MK-0791), a dehydropeptidase inhibitor (MK-0787/MK-0791 = 1:1) was studied in the field of obstetrics and gynecology and the following results were obtained . Absorption and penetration into genital organ tissues were good . Following a 0.5 g/0.5 g intravenous drip infusion, the maximum plasma concentration in uterine arterial blood was 20.8 micrograms/ml, and the maximum concentrations of the drug in tissues were 9.9 approximately 16.8 micrograms/g, and these levels of MK-0787 exceeded the MIC values against main causative organisms . Rates of elimination of the drug from the tissue and from the plasma were similar . Against gynecological and obstetrical infections, a dose of 0.5 g/0.5 g twice daily for an average duration of 6.3 days produced a clinical efficacy ratio of 94.4% (17/18) and a bacteriological effects rating of 76.9% (10/13) . As side effects, one patient showed an eruption and another had an elevated GOT and GPT . Based on the above results, MK-0787/MK-0791 appears to be effective against gynecological and obstetrical infections. Jpn J Antibiot, 1986 May, 39(5), 1259 - 72 {Concentrations of cefmenoxime and cefotiam in the bile and gallbladder tissue following intravenous administration in patients with biliary tract diseases}; Shoda Y et al.; To test the effectiveness of cefmenoxime (CMX) and cefotiam (CTM) in patients with biliary tract diseases, concentrations of either antibiotic were measured after an intravenous bolus injection of 1.0 g of CMX or CTM, or simultaneous injection of both (1.0 g each) . CMX or CTM was injected in 76 patients with biliary tract diseases (mostly cholelithiasis) prior to a cholecystectomy and concentrations of CMX or CTM were measured by the bioassay (agar well) method at 30 to 60 minutes after the injection . Average concentrations of both CMX and CTM in gallbladder bile and gallbladder tissue sufficiently exceeded the minimal inhibitory concentration (MIC) against main causative organisms of biliary tract infections . Concentrations of both antibiotics in gallbladder bile were significantly higher in patients with patent cystic ducts than with obstructed cystic ducts . Concentrations of both antibiotics in the gallbladder tissue reached at a similar high level regardless of the patency of the cystic ducts, but concentrations were lower in severely inflamed gallbladders . CMX and CTM were administered alternatively (cross-over fashion), or simultaneously (combined) to 13 patients with T-tube drainage or percutaneous transhepatic cholangio-drainage, and concentrations of both antibiotics in bile from the drainage tube were measured by high performance liquid chromatography at hourly intervals after the injection . Concentrations of both antibiotics were far greater than MICs against main attributable microorganisms in biliary tract infections . The concentration of CMX slightly exceeded that of CTM . Concentrations of both antibiotics were lower in bile of patients showing abnormally high serum GTP, A1-P, and total bilirubin levels than in bile of patients with normal values of these variables . It is speculated that the secretion of both antibiotics in the bile may decrease in cases with severe hepatic failure, but effective concentrations of both antibiotics in the gallbladder tissue should be maintained as long as the blood circulation in the gallbladder was maintained. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1986 May, 182(3), 299 - 309 On the influence of different growth conditions to the resistance of some methylotrophic bacteria to aldehydes; Heinzel M; The resistance to formaldehyde of several facultatively methylotrophic bacteria has been investigated . The MIC-values were in the range of formaldehyde concentrations used for preservation purposes . The resistance could be explained partly by the action of aldehyde dehydrogenase found in two of the strains and by the development of a penetration barrier by the cell envelopes described formerly. Antimicrob Agents Chemother, 1986 May, 29(5), 797 - 802 Evaluation of the bactericidal activity of beta-lactam antibiotics on slowly growing bacteria cultured in the chemostat; Cozens RM et al.; The bactericidal activity of 23 beta-lactam antibiotics was compared in slowly growing bacteria cultured in a chemostat . In an attempt to mimic possible in vivo conditions, slowly growing cultures were produced by limitation of iron, glucose, phosphate, or magnesium . Only select antibiotics remained effectively bactericidal against slowly growing cells . For these compounds, the rate of antibiotic-induced loss of viability was a constant when killing was expressed per generation (in contrast to absolute time) in that slowly growing bacteria were killed proportionately more slowly . Individual antibiotics differed greatly, however, in their specific bactericidal activities against slowly growing cells, i.e., in the absolute degree of killing elicited during exposure of the bacteria to MIC equivalents of the drugs . Specific bactericidal activities varied not only with drug structure but also with the bacterial strains and, to a lesser extent, with the nature of the growth-limiting nutrient . In slowly growing cultures exposure to the low drug concentrations studied here (near MIC) caused killing without detectable lysis . Antibiotics with high specific bactericidal activities were capable of rapidly killing cultures of slowly growing pathogens despite extremely long generation times approaching those reported for in vivo growth rates. Pathol Biol (Paris), 1986 May, 34(5), 360 - 3 {Sensitivity to various antibiotics of spiroplasmas isolated from mosquitoes in France}; Abalain-Colloc ML et al.; Spiroplasmas are helical mycoplasmas that play a significant role in plant diseases . They are also found in arthropods that are likely to bite humans, such as ticks and mosquitoes . These arthropods can act as vectors and therefore may be of epidemiologic significance . Furthermore, mainly on the grounds of morphologic evidence, spiroplasmas have been incriminated in the genesis of human Creutzfeld-Jacob disease . We recovered six strains of Spiroplasma sp . from 1927 female mosquitoes . In vitro susceptibility of each strain to the following antibiotics was studied: tetracycline, oxytetracycline, doxycycline, erythromycin, chloramphenicol, rifampin, kanamycin, gentamicin and pefloxacin . Minimal inhibitory concentrations (MICs) were determined by dilution in liquid SP4 medium using microtiter plates . Plates were incubated for 24 to 48 hours at 30 degrees C . The inoculum contained approximately 5 X 10(5) CFU/ml . Each of the six strains was found to be highly susceptible to tetracycline, oxytetracycline, doxycycline, erythromycin, chloramphenicol and pefloxacin (MICs less than or equal to 0.16 microgram/ml, 0.63 microgram/ml, 0.08 microgram/ml, 0.16 microgram/ml and 0.32 microgram/ml respectively) . On the opposite, the strains exhibited resistance to rifampin and variable degrees of susceptibility to kanamycin (12.5 micrograms/ml less than MIC less than 50 micrograms/ml) and gentamicin (3.12 micrograms/ml less than MIC less than 50 micrograms/ml) . From our results, spiroplasmas seem to have more or less the same susceptibility to antibiotics as mycoplasmas. J Hosp Infect, 1986 May, 7(3), 269 - 76 A comparative trial between cefotetan and cephazolin for wound sepsis prophylaxis during elective upper gastrointestinal surgery with an investigation of cefotetan penetration into the obstructed biliary tree; Leaper DJ et al.; Cefotetan is a cephamycin antibiotic theoretically suited to prophylaxis of wound infection during upper elective gastrointestinal surgery . In a prophylaxis trial 100 patients undergoing this type of surgery were randomly allocated to receive 1g cefotetan or cephazolin iv at induction of anaesthesia . Cefotetan-treated patients had significantly fewer postoperative infections overall (P less than 0.05) and there were no wound infections recorded in this group . In a separate pharmacokinetic study the penetration of cefotetan into common bile duct bile and gallbladder wall was measured in a further six patients, all of whom had been jaundiced preoperatively . At the time of maximum risk concentrations of cefotetan in bile and biliary tissue as well as blood and wound fat were in excess of the minimum inhibitory concentration for the majority of relevant pathogens . Cefotetan appears to be equally or more effective than cephazolin and is a suitable alternative prophylactic agent in elective upper gastrointestinal surgery. J Med Chem, 1986 Apr, 29(4), 494 - 9 Synthesis and antitumor and antiviral properties of 5-alkyl-2'-deoxyuridines, 3',5'-cyclic monophosphates, and neutral cyclic triesters; Beres J et al.; A series of 5-alkyl-2'-deoxyuridine 3',5'-cyclic monophosphates (5-R-cdUMP's, R = Et, i-Pr, n-Pr, n-Bu, n-Pent, n-Hex, n-Oct) was prepared and tested in culture systems as antitumor and antiviral agents in comparison to the 5-alkyl-2'-deoxyuridines (5-R-dUrd's) themselves . Only the 5-Et- and 5-n-Bu-cdUMP showed appreciable cytostatic activities against murine L1210 and human lymphoblast Raji cells (ID50 range: 28-82 micrograms/mL) . 5-Et-dUrd itself was much more active (ID50 = 1.6 and 2.9 micrograms/mL) . The 5-i-Pr-, and 5-n-Bu-dUrd's were inactive, but activity increased again for groups with chain lengths of five carbons or greater . 5-Et-cdUMP and 5-Et-dUrd had greatly reduced activities against deoxythymidine kinase deficient (TK-) L1210 and Raji cells . 5-Et-cdUMP evidently is not an efficient prodrug source of the corresponding 5'-monophosphate where the TK- cells are concerned . Of the 5-R-cdUMP's, 5-Et-cdUMP displayed reasonably good antiviral potency against herpes simplex types 1 and 2 (MIC50, mostly 7-70 micrograms/mL) and vaccinia virus (MIC, 70 micrograms/mL) . The activity was nonetheless 10- to 100-fold less than that for 5-Et-dUrd . The other 5-R-dUrd's generally showed decreasing antiviral activity with increasing 5-R chain length . Methyl and/or benzyl neutral triesters of certain 5-R-cdUMP's were inactive as antivirals and largely inactive against tumor cells in culture . In contrast to the 5'-monophosphates, the 5-R-cdUMP's failed to inhibit thymidylate synthetase from L1210 cells. Clin Pharm, 1986 Apr, 5(4), 319 - 24 Correlation of pharmacokinetic indices with therapeutic outcome in patients receiving aminoglycosides; Deziel-Evans LM et al.; The influence of five pharmacokinetic indices on therapeutic response was retrospectively studied in 45 adult patients treated with aminoglycosides for bacterial infections . Subjects were treated for a minimum of five days, had culture and sensitivity reports, and had at least one set of steady-state peak and trough serum aminoglycoside concentrations . Serum drug concentrations were determined by enzyme-multiplied immunoassay or by fluorescence polarization assay . Minimum inhibitory concentrations (MICs) for the drugs were determined by microdilution assays . Cure was determined by negative cultures or absence of clinical evidence of infection . Values for five pharmacokinetic indices were determined for each patient: ratio of steady-state peak serum concentration to MIC (Cssmax/MIC); time that the serum concentration remained above the MIC during a 72-hour period (tsupra-MIC(72)); the intensity index for a 72-hour period (II(72)), which is related but not identical to the area under the curve (AUC), reflecting the contributions of Cssmax/MIC and tsupra-MIC(72); time that the serum concentration was greater than four times the MIC during a 72-hour period (tsupra-(4 X MIC)(72)), and the intensity index related but not identical to AUC greater than four times the MIC (II4 X MIC(72)), which reflects the contribution of Cssmax/(4 X MIC) and tsupra-(4 X MIC)(72) . Statistical analysis revealed significant correlations between each of the five indices and the patients' therapeutic responses . The following index values were associated with cures: Cssmax/MIC greater than 4 (and ideally greater than 8); tsupra-MIC(72) of at least 40 hours; tsupra-(4 X MIC)(72) of at least 10 hours; (4) II(72) greater than 400; and II4 X MIC(72) greater than 50 . All five pharmacokinetic indices were good predictors of patient outcome . The ratio of maximum steady-state serum aminoglycoside concentration to minimum inhibitory concentration is the index most easily monitored and interpreted. J Clin Hosp Pharm, 1986 Apr, 11(2), 95 - 100 An investigation of the in vitro anti-bacterial activity of noxythiolin against 1,000 pathogenic bacterial isolates; Ashley KC et al.; The susceptibility of 1,000 recent bacterial isolates to noxythiolin was determined by the disc susceptibility method . No Gram-positive strains were resistant to this method but 56 (5.6%) of Gram-negative strains gave zones of inhibition of 12 mm diameter or less . The minimum inhibitory concentration (MIC) of the latter were determined by the agar incorporation method . No strains had MIC values greater than 4096 mg/litre . Since concentrations of 50,000 mg/litre can be used for topical treatment, these organisms may be considered susceptible. Presse Med, 1986 Mar 8, 15(10), 471 - 4 {Treatment of septicemia and endocarditis with pefloxacine . 15 cases}; Wolff M et al.; The therapeutic effectiveness of pefloxacin was evaluated in 15 patients admitted to an intensive care unit and suffering from septicaemia or endocarditis . Seven of these patients had a focal infection (acute anterior mediastinitis or epiduritis) . Pefloxacin was combined with an aminoglycoside in 13 cases and with rifampicin in 1 case . Blood cultures became or remained negative in all patients . The associated focus of infection was sterilized in 5 patients; a pefloxacin-resistant pathogen was subsequently isolated in 2 other patients . Three patients died some time after the infectious episode . The minimum inhibitory concentration of pefloxacin ranged from 0.25 to 2 mg/l . The bactericidal activity of the serum at peak concentration was greater than or equal to 1/8 in all cases and greater than or equal to 1/32 in 10 cases . No resistant mutants were selected during treatment . However, 8 strains of a species different from that of the initial pathogen were isolated from a site other than the primary focus . Pefloxacin can therefore be used successfully in the treatment of systemic infections, but close monitoring of bacterial ecology is required. J Clin Microbiol, 1986 Mar, 23(3), 634 - 6 Tentative disk diffusion susceptibility interpretive criteria for BMY-28142, a new cephalosporin; Fuchs PC et al.; A total of 750 bacterial isolates, including 37 different species, were tested for susceptibility to BMY-28142 by standardized broth microdilution and disk diffusion tests . The zone diameter interpretive criteria tentatively suggested for the 30-micrograms BMY-28142 disk are as follows: susceptible = greater than or equal to 18 mm (MIC less than or equal to 8.0 micrograms/ml), resistant = less than or equal to 14 mm (MIC greater than or equal to 32 micrograms/ml), and indeterminate = 15 to 17 mm. Jpn J Antibiot, 1986 Mar, 39(3), 721 - 5 {Clinical study on the tissue distribution of cefmenoxime in the field of otolaryngology}; Fujita K et al.; Concentrations of cefmenoxime (CMX) in serum and tissue were determined in surgical patients with chronic sinusitis, maxillary cyst or chronic tonsillitis . CMX was intravenously administered in a dose of 1 gram . Thirty minutes after the administration, patients were operated under local anesthesia . Concentrations of CMX in tissues were determined 1 hour after administration, and were 15.8 micrograms/g and 20.3 micrograms/g in mucous membrane of maxillary sinus and maxillary cyst . CMX was not detectable in tonsils of 8 patients out of 11 examined . An examination of MIC against various bacteria isolated from sinus pus and pharyngeal swab indicated that CMX was effective enough to produce a prophylactic effect against otolaryngo-infections. Antimicrob Agents Chemother, 1986 Mar, 29(3), 482 - 7 Antirhinovirus activity of purine nucleoside analogs; De Clercq E et al.; A wide variety of purine nucleoside (mainly tubercidin and adenosine) analogs, which had previously been shown to inhibit the replication of a broad spectrum of RNA viruses, were evaluated for their antirhinovirus activity in human diploid (WI-38) fibroblasts . Tubercidin, 5-(1-hydroxyethyl)tubercidin, 5-(2-buten-1-yl)tubercidin, toyocamycin, and sangivamycin emerged as the most potent inhibitors . These compounds inhibited the replication of rhinovirus types 1A, 1B, and 9 at an MIC well below 1 microgram/ml . However, these compounds proved cytotoxic for the uninfected host cells at concentrations which were only slightly higher (3- to 10-fold, on the average) than those required for inhibition of rhinovirus replication . The most selective inhibitor of rhinovirus replication was 3-deazaguanine, with a selectivity index of 50 . None of the carbocyclic and acyclic analogs of adenosine tested exhibited a potent or selective antirhinovirus activity. J Antimicrob Chemother, 1986 Mar, 17(3), 389 - 96 A non-comparative study of parenteral ampicillin and sulbactam in intra-thoracic and intra-abdominal infections; Mehtar S et al.; Fifty-four patients were treated with intravenous ampicillin and sulbactam in an open study of intra-thoracic and intra-abdominal infection . Thirty-one were treated with 500 mg each of the combination 6-hourly while 23 patients were given 1 g of ampicillin and 500 mg of sulbactam, 6-hourly . Thirteen of fourteen (93%) patients with severe respiratory tract infection and 22/26 (85%) patients in the intra-abdominal infection group responded clinically and bacteriologically . Seven patients with clinical sepsis (but not confirmed bacteriologically) improved on therapy . 50/55 (91%) clinical isolates from this study were eliminated . An increase in MIC was found in two cases . There were minimal side effects, pain at site of injection being the commonest complaint. Chemioterapia, 1986 Feb, 5(1), 23 - 5 Ciclopiroxolamine: clinical and microbiological considerations . Preliminary data; Oliveri S et al.; Ciclopiroxolamine's action has been evaluated in 20 cases of dermatophytosis . The minimum inhibitory concentrations (MIC) for the strains was determined in vitro before treatment (To), after the 4th day (T4), and after the 7th day (T7) of treatment, in relation with the drug's fungicide effect . No significant variation was observed among the MIC values . By comparing the MIC of T4 versus the MIC of To a 0.93 coefficient of linear correlation was obtained while in comparing T7 versus T4 the coefficient was equivalent to 1.0 . After 7 days of treatment 5 patients clinically recovered, 11 improved and 4 showed no improvement . Drug tolerance was excellent except for one case. J Clin Pharmacol, 1986 Feb, 26(2), 79 - 86 Factors associated with nephrotoxicity and clinical outcome in patients receiving amikacin; Williams PJ et al.; Data from 60 patients treated with amikacin were analyzed for factors associated with nephrotoxicity . In 42 of these patients, data were examined for factors associated with clinical outcome . Variables evaluated included patient weight, age, sex, serum creatinine level, creatinine clearance, duration of therapy, total dose, mean daily dose, organism minimum inhibitory concentration (MIC), mean peak levels, mean trough levels, mean area under the serum concentration-time curve (AUC), total AUC, mean AUC greater than MIC, total AUC greater than MIC, mean Schumacher's intensity factor (IF), total IF, In (mean maximum concentration {Cmax}/MIC) . Model-dependent pharmacokinetic parameters were calculated by computer based on a one-compartment model . When the parameters were examined individually, duration of therapy and total AUC correlated significantly (P less than .05) with nephrotoxicity . In contrast, a stepwise discriminant function analysis identified only duration of therapy (P less than .001) as an important factor . Based on this model and on Bayes' theorem, the predictive accuracy of identifying "nephrotoxic" patients increased from 0.17 to 0.39 . When examined individually, mean IF, MIC, total dose, mean daily dose, and ln (mean Cmax/MIC) correlated significantly (P less than .05) with cure . In contrast, a simultaneous multivariable analysis identified IF, MIC, and total dose according to one model and ln (mean Cmax/MIC) according to a second statistical model of parameters selected to have the greatest prospective value . Based on Bayes' theorem and the first model, the predictive accuracy of identifying patients not cured increased from 0.19 to 0.83 . For the second model, the predictive accuracy increased from 0.19 to 0.50.(ABSTRACT TRUNCATED AT 250 WORDS) Toxicol Appl Pharmacol, 1986 Feb, 82(2), 329 - 35 Sensory and pulmonary irritation with exposure to methyl isocyanate; Ferguson JS et al.; Methyl isocyanate (MIC) was tested for its potency as a sensory irritant and as a pulmonary irritant in mice . To evaluate sensory irritation, animals were exposed to MIC at concentrations between 0.5 and 7.6 ppm for a period of 90 min . A characteristic reflex decrease in respiratory rate indicating sensory irritation was observed . The concentration evoking a 50% decrease in respiratory rate (RD50) was found to be 1.3 ppm . To evaluate pulmonary irritation, animals were first anesthetized and fitted with a tracheal cannula . Following recovery from anesthesia, they were exposed to MIC at concentrations between 0.4 and 7.3 ppm for a period of 90 min . A characteristic decrease in respiratory rate indicating pulmonary irritation in tracheally cannulated (TC) mice was observed . The concentration evoking a 50% decrease in respiratory rate (RD50TC) was found to be 1.9 ppm . Thus, MIC was found to be a potent sensory and pulmonary irritant. J Antimicrob Chemother, 1986 Feb, 17(2), 165 - 71 Antigiardial activity of the bile salt-like antibiotic sodium fusidate; Farthing MJ et al.; Possible antigiardial activity of the bile salt-like antibiotic, sodium fusidate has been investigated during 24 h liquid culture of Giardia lamblia trophozoites and in 4 h microassays for parasite motility inhibition and viability . Sodium fusidate inhibited Giardia growth (ED50 0.2 mM; MIC 0.3 mM) but was considerably less potent than metronidazole (ED50 0.002 mM; MIC 0.05 mM) . Sodium fusidate and metronidazole were active inhibitors of parasite motility (ED50 0.9 and 0.3 mM respectively) but were largely without effect in the 4 h viability assay . Sodium fusidate was active at concentrations well below its critical micellar concentration (2.7 mM) suggesting that its effect was not merely related to its membranolytic detergent properties . Its taurine and glycine conjugates were markedly less potent and paradoxically stimulated growth at low concentration . The studies suggest that sodium fusidate does have antigiardial activity and in view of its relative freedom from teratogenic and other toxic effects may be useful in pregnancy when other antigiardial agents are contra-indicated or as an adjunct in combination therapy when other single agents have failed to eradicate infection. Hinyokika Kiyo, 1986 Feb, 32(2), 293 - 6 {Clinical study of cinoxacin in acute simple cystitis}; Inaba T et al.; Cinoxacin (CINX) was administered twice a day for 7 consecutive days (400 mg X 2/day) to 34 female patients suffering from acute simple cystitis . The overall clinical efficacy was excellent in 15 cases (94%) and moderate in one case (6%) according to the criteria for clinical evaluation by the UTI committee . The efficacy was not determined in 18 cases . Bacteriological examination revealed 11 cases of single infection by E . coli, 2 cases of single infection by P . cepacia and S . epidermidis and one case of single infection by S . sunguis . MIC of E . coli ranged from 3.13 to 6.25 micrograms/ml . MIC of P . cepacia was 3.13 micrograms/ml and MIC of S . epidermidis more than 100 micrograms/ml . All the strains were eradicated with the efficacy of 100% . There was no relapse of acute simple cystitis in 16 cases after 7 days treatment of CINX . No serious side effects were recognized except for slight general fatigue and heart burn in 2 cases . It was thus concluded that CINX is clinically effective and safe for acute simple cystitis caused by E . coli and P . cepacia. J Antimicrob Chemother, 1986 Feb, 17(2), 139 - 46 Behaviour of TEM-1 beta-lactamase as a resistance mechanism to ampicillin, mezlocillin and azlocillin in Escherichia coli; Livermore DM et al.; Escherichia coli isolates which synthesised the extremely common 'TEM-1' plasmid mediated beta-lactamase were more resistant to the alpha-aminopenicillins, ampicillin, mezlocillin and azlocillin, than were strains which lacked this enzyme . However, many TEM-1+ isolates remained sensitive to therapeutic concentrations of mezlocillin (less than 64 mg/l), whereas virtually none was susceptible to su