Chin Med Sci J, 1991 Sep, 6(3), 166 - 8 A clinical and laboratory study of ciclopirox olamine (8% Batrafen) in the treatment of onychomycosis; Yu B et al.; Ciclopirox olamine, a new synthetic substituted pyridone derivative, is an antimycotic agent with activity against a broad spectrum of pathogenic and nonpathogenic fungi . The clinical efficacy and safety of 8% ciclopirox olamine nail liquor were evaluated in 100 cases with finger (or great toe) onychomycosis . After 16 weeks and 24 weeks of treatment for finger and great toe onychomycosis, respectively, the overall therapeutic results were excellent in 36 cases, good in 17, fair in 24, and poor in 23 . The period of treatment was extended in 31 cases; among them, 10 cases showed further improvement . As for in vitro inhibitory activity, the MIC of ciclopirox olamine against T . rubrum and C . albicans was 1 to 4 mg/L and 1 to 16 mg/L, respectively . This study indicates that 8% ciclopirox olamine nail liquor, with its satisfactory efficacy and lack of side effects, is a good remedy for onychomycosis. Mycoses, 1991 Sep-Oct, 34(9-10), 411 - 4 Susceptibility of Trichophyton rubrum to griseofulvin; Scholz R et al.; Two hundred and seventy isolates of Trichophyton rubrum from 182 patients were subjected to susceptibility testing with griseofulvin according to Granade & Artis . A slight modification of the method concerning homogenization procedures gave better growth of controls in our investigation . In 245 cases an MIC could be determined . Among these isolates, seven strains from six patients presented MICs between 2 and 3 micrograms griseofulvin per ml, a value which, according to Artis et al., is to be considered as relatively resistant . The other isolates proved to be more susceptible to griseofulvin . Three of the patients showed no indication of therapeutic failure of griseofulvin treatment . The other three patients had onychomycoses of long standing and had been treated with griseofulvin previously with little or limited success . It is our conclusion that griseofulvin susceptibility testing is not a reliable instrument in explaining failure of griseofulvin therapy in Trichophyton rubrum mycoses. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1991 Sep-Oct, 32(5), 319 - 24 {Penicillin-resistant pneumococcal meningitis: report of two cases}; Huang FY et al.; Cases of penicillin-resistant pneumococcal meningitis have been reported in other countries since 1977, but never before reported in Taiwan . In 1990, two cases of the disease were diagnosed here . Case one was a two-year-old boy who had had fever and vomiting for several days prior to admission . Under the impression of meningitis, a spinal tap was done . The CSF yielded pneumococcus, which was misinterpreted as sensitive to penicillin . Penicillin (400,000 units/kg/day) was given parenterally without effect . On the 12th day after admission, another spinal tap still yielded pneumococcus . This time the sensitivity test was reread with great care, and then reported to be penicillin-resistant pneumococcus . Minimal inhibitory concentration (MIC) of penicillin was performed simultaneously and it revealed 0.1 microgram/ml . Vancomycin (60 mg/kg/day) was substituted for penicillin . The patient became afebrile two days later, and was discharged ten days later without sequelae . Case two, a five-month-old girl, was diagnosed to have meningitis because of fever, vomiting, tense fontanel and seizure on admission . After a spinal tap was done, she was put on ampicillin and cefotaxime . The fever subsided two days later . At that time, the CSF was reported to grow pneumococcus, again misread as sensitive to penicillin . The antibiotics was switched to penicillin, but fever recurred . The second spinal tap still yielded pneumococcus which was sensitive to penicillin but resitstant to oxacillin . Based on experience with the first case, penicillin was changed to vancomycin, and performed MIC immediately . The MIC was 1.0 microgram/ml . The patient became afebrile two days later, and was discharged in good condition after ten days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) Semin Respir Infect, 1991 Sep, 6(3), 168 - 82 Antibiotic pharmacokinetic considerations in pulmonary infections; Cunha BA; The factors affecting the penetration of antibiotics into the respiratory tract and their clinical relevance in treating pulmonary infections are discussed in this article . The importance and interpretation of sputum, bronchial fluid, pleural fluid, and lung tissue levels are emphasized, including a tabular summary of published data on antibiotic levels in the respiratory tract . The relative predictive efficacy of antibiotics against pulmonary pathogens is best expressed by comparing tissue levels with the mean minimum inhibitory concentration of the infecting organism, ie, the "kill ratio." The kill ratio is the best way to compare dissimilar antibiotics in terms of their likely efficacy in treating pulmonary infections, ie, those with high kill ratios (greater than or equal to 2) are more likely to be associated with a favorable clinical outcome than those with lower kill ratios . The difficulties with interpreting pharmacokinetic data from various parts of the respiratory tract in terms of specimen timing, handling, processing, and interpretation are also discussed in this article. J Vet Pharmacol Ther, 1991 Sep, 14(3), 257 - 62 Pharmacokinetics of tinidazole in dogs and cats; Sarkiala E et al.; Pharmacokinetics of tinidazole in dogs and cats after single intravenous (15 mg/kg) and oral doses (15 mg/kg or 30 mg/kg) were studied in a randomized crossover study . Tinidazole was completely absorbed at both oral dose levels in cats and dogs . Peak tinidazole concentration in plasma was 17.8 micrograms/ml in dogs and 22.5 micrograms/ml in cats after 15 mg/kg p.o . The oral dose of 30 mg/kg resulted in peak levels of 37.9 micrograms/ml in dogs and 33.6 micrograms/ml in cats . The apparent total plasma clearance of the drug was about twofold higher in dogs than in cats, resulting in an elimination half-life that was twice as long in cats (8.4 h) as in dogs (4.4 h) . The apparent volume of distribution was 663 ml/kg in dogs and 536 ml/kg in cats . Therapeutic plasma drug concentrations higher than the MIC values of most tinidazole-sensitive bacteria were achieved for 24 h in cats and for 12 h in dogs after a single oral dose of 15 mg/kg . From the pharmacokinetic standpoint tinidazole seems to be well-suited to clinical use in small animal practice. J Antimicrob Chemother, 1991 Sep, 28(3), 347 - 55 The use of RNA/DNA ratio measurements to assess rifampicin-induced growth inhibition of Escherichia coli; Ellard GA; Growth rates and cellular levels of RNA, DNA and protein were studied in Escherichia coli during and following exposure to rifampicin, and in the transition from stationary to exponential phase growth in drug-free medium . At rifampicin concentrations of up to twice the MIC, significant changes in growth rates were only apparent after several generations . At higher rifampicin concentrations growth was terminated much more rapidly . In every case changes in growth rates were closely paralleled by corresponding changes in RNA/DNA ratios . These findings suggest the possibility of using RNA/DNA ratio measurements to monitor the drug-induced growth inhibition of other bacteria. Mol Biochem Parasitol, 1991 Aug, 47(2), 223 - 33 Characterization of microneme proteins of Toxoplasma gondii; Achbarou A et al.; Three microneme proteins of Toxoplasma gondii have been characterized using 3 monoclonal antibodies and a recombinant protein specific antiserum . In all cases, apical labeling of tachyzoites and bradyzoites was observed by indirect immunofluorescence assay . Immunogold localization on ultrathin sections of bradyzoites or tachyzoites showed a specific labeling of micronemes . The following proteins were characterized using 2-dimensional gel electrophoresis and Western immunoblotting: Mic 1 (60 kDa, Pi 6.5), Mic 2 (120 kDa, Pi 5) and Mic 3 (90 kDa, Pi 6.75) . The 90-kDa protein (Mic 3) is a heterodimer of two 38-kDa polypeptides (Pi 6.7 and 6.75 respectively) linked by disulfide bridges . Metabolic labeling and immunoprecipitation assays showed that at least one of the 38-kDa polypeptides was processed from a 40-kDa precursor . No processing was observed during the biosynthesis of the 120- and 60-kDa polypeptides. Br J Clin Pharmacol, 1991 Aug, 32(2), 255 - 7 Pharmacokinetics of trospectomycin sulphate in healthy subjects after single intravenous and intramuscular doses; Nichols DJ et al.; The pharmacokinetics of trospectomycin (75-1000 mg free base equivalents) were studied in 128 healthy males (eight per dose group), after a 20 min intravenous (i.v.) infusion and intramuscular (i.m.) injection of trospectomycin sulphate . The concentrations of trospectomycin in serum were described by bi- or tri-exponential disposition functions indicating an initial half-life of 1.1-1.4 h for the i.v . dose and 1.6-2.1 h for the i.m . dose and terminal half-lives of over 15 h . Most of the drug was eliminated rapidly (mean residence time 5-12 h) . The distribution volume was 59-112% of body weight and clearance was 112-152 ml min-1 . The absorption into blood after i.m . dosing was rapid . The area under the concentration-time curve and maximum concentration values were linearly related to dose . Serum drug concentrations fell below the minimum inhibitory concentration values for a variety of organisms by 8-12 h, which indicates that two or three times daily dosing would be appropriate . However, the long terminal half-life suggests that significant accumulation is likely in some tissues with an 8 h dose interval and this may prolong the action of trospectomycin. Antimicrob Agents Chemother, 1991 Jul, 35(7), 1381 - 5 Lytic effect of two fluoroquinolones, ofloxacin and pefloxacin, on Escherichia coli W7 and its consequences on peptidoglycan composition; Vincent S et al.; Examination of biochemical changes in Escherichia coli W7 after exposure to ofloxacin or pefloxacin revealed distinct concentration-dependent responses . At levels close to the MIC, extensive filamentation was followed by a lytic event, which involved an active protein synthesis . This lysis was correlated with changes in the peptidoglycan composition, particularly a decrease in the average glycan chain length, involving the action of the autolysines . At higher concentrations, no lysis occurred and the growth was totally inhibited as well as the protein synthesis . The peptidoglycan composition exhibited an increase in the average glycan chain length, suggesting an apparent reduced activity of the lytic transglycosylase . These results show that exposure to low concentrations of quinolones leads to the induction of lysis and peptidoglycan modifications which might contribute to the bactericidal effects of quinolones. Antimicrob Agents Chemother, 1991 Jul, 35(7), 1360 - 4 Cefonicid versus clindamycin prophylaxis for head and neck surgery in a randomized, double-blind trial, with pharmacokinetic implications; Swanson D et al.; Perioperative single-dose antibiotic prophylaxis of cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing oncologic head and neck surgery . Antibiotics were administered intravenously beginning 1 to 2 h preoperatively . Cefonicid, 1 g, was given as a single dose . Clindamycin, 600 mg, was administered every 8 h for a total of four doses . Blood and wound drainage samples were collected for 24 h following the dose of cefonicid and assayed for total and free cefonicid concentrations, using reverse-phase high-performance liquid chromatography . Although total concentrations of cefonicid in both serum and wound drainage exceeded the MIC for 90% of the isolates of common bacterial pathogens for 24 h, free concentrations in serum and wound drainage (11.0 and 14.9% of total concentrations) were subinhibitory within 6 h following administration . Free concentrations of cefonicid in the postoperative wound drainage were subinhibitory for the entire study period, both perioperatively and postoperatively . Postoperative wound infection occurred significantly (P less than 0.05) more frequently in patients receiving cefonicid (24%) as compared with those receiving clindamycin (8.2%) . The relatively low free levels of cefonicid achieved in serum and wound drainage were attributed to the high degree of protein binding (89% in serum) and may be related to the poor clinical outcome. Chem Res Toxicol, 1991 Jul-Aug, 4(4), 436 - 44 Carbamoylation of peptides and proteins in vitro by S-(N-methylcarbamoyl)glutathione and S-(N-methylcarbamoyl)cysteine, two electrophilic S-linked conjugates of methyl isocyanate; Pearson PG et al.; The reactivity toward peptides and proteins of S-(N-methylcarbamoyl)glutathione (SMG), the glutathione conjugate of methyl isocyanate, and the corresponding cysteine adduct, S-(N-methylcarbamoyl)cysteine (SMC), was investigated with the aid of in vitro model systems . Incubation of SMC or a trideuteriomethyl analogue of SMC with either the reduced or oxidized forms of oxytocin afforded similar mixtures of mono-, bis- and tris-N-methylcarbamoylated peptides . Structure elucidation of the mono and bis adducts by fast atom bombardment tandem mass spectrometry indicated that carbamoylation of oxytocin occurred preferentially at Cys-6 and that Cys-1 and/or Tyr-2 were secondary sites of modification . Upon incubation of S-{N-({14C}methyl)carbamoyl}glutathione (14C-SMG) with native bovine serum albumin (BSA), radioactivity became bound covalently to the protein in a time- and concentration-dependent fashion . "Blocking" of the lone Cys-34 thiol group of BSA in the form of a disulfide prior to exposure of the protein to 14C-SMG failed to decrease significantly the extent or time course of this covalent binding . It is concluded that carbamate thioester conjugates of MIC are reactive, carbamoylating entities which can donate the elements of MIC to nucleophilic functionalities on peptides and proteins . Free thiols appear to be preferred sites for such carbamoylation processes, a phenomenon that may have important toxicological consequences in the pathology of tissue lesions induced by MIC and related isocyanates. Arch Surg, 1991 Jul, 126(7), 890 - 3 Pharmacokinetics of cefazolin applied topically to the surgical wound; Matushek KJ et al.; Topical application of antibiotics is used in the prophylaxis of postoperative surgical infections . However, whether topically applied antibiotics remain primarily in the surgical wound fluid or are systemically absorbed is uncertain . The pharmacokinetics of topically applied cefazolin were studied in a canine model that allowed simultaneous determination of serum and wound fluid antibiotic concentrations . Topical administration of cefazolin resulted in high antibiotic concentrations in the wound fluid for prolonged periods and rapid systemic absorption . Bioavailability after topical administration was 95% . Within 1 hour, the serum concentrations after topical administration equaled the serum concentrations after intravenous administration, and the concentration time curves declined in parallel . In wound fluid, the mean time above the susceptibility break point minimum inhibitory concentration after topical administration of cefazolin was 5.76 hours compared with the estimated time above the minimum inhibitory concentration of 2.55 hours after intravenous administration. Br J Ind Med, 1990 Sep, 47(9), 596 - 601 Effects of methyl isocyanate on rat brain cells in culture; Anderson D et al.; Since the disaster in Bhopal, India, people exposed to methyl isocyanate (MIC) have complained of various disorders including neuromuscular dysfunction . In an attempt to get information about such dysfunction we have previously shown that MIC can affect muscle cells in culture . The present communication reports investigations into the effect of MIC on brain cells in culture . MIC was toxic to brain cells and the response was dose related . The observations were supported by light and electron microscopy. Am Rev Respir Dis, 1990 Sep, 142(3), 512 - 5 Pulmonary aspergillosis in mice: treatment with a new triazole SCH39304; Defaveri J et al.; The triazole SCH39304 was compared with amphotericin B and fluconazole for the treatment of pulmonary aspergillosis in corticoid-immunosuppressed mice intranasally challenged with 5 x 10(6) conidia of Aspergillus fumigatus . In vitro, the minimum inhibitory concentration (MIC) for fluconazole was greater than 80 micrograms/ml, for SCH39304 40 micrograms/ml, and for amphotericin B 0.29 micrograms/ml . Beginning 1 day after challenge, groups of 10 mice were treated orally, twice daily, for 15 days with Noble agar (control), SCH39304, fluconazole, or amphotericin B at various doses . For lung tissue counts of A . fumigatus, mice were similarly challenged and treated only for 5 days with SCH39304, fluconazole, or amphotericin B . Only SCH39304 significantly reduced the number of A . fumigatus in the lung . SCH39304 at doses of 5 mg/kg or higher significantly prolonged the survival of mice, as did amphotericin B at 3 mg/kg . Fluconazole did not significantly prolong survival at doses of 15 or 30 mg/kg . SCH39304 appears to be as effective as amphotericin B in murine pulmonary aspergillosis and warrants further evaluation for aspergillosis in humans. Hiroshima J Med Sci, 1990 Sep, 39(3), 65 - 9 Beta-lactamase in gram-negative rods: the relationship between penicillinase and R plasmids in gram-negative rods; Takesue Y et al.; Concomitant with the extensive use of antibiotics, the number of multiple antibiotic-resistant strains has been increasing . Since resistance is mainly mediated by R plasmids, we undertook to investigate the characteristics of R plasmid-determined beta-lactamase in 6 Gram-negative rods . The beta-lactamase produced by each organism was classified by its substrate: type P which attacks penicillins, type C which attacks cephalosporins, and type C/P which attacks both penicillins and cephalosporins . Though the chromosomally mediated beta-lactamase of almost all Gram-negative rods is classified as type C, R plasmid-mediated beta-lactamase is almost equally active against both penicillins and cephalosporins . Therefore, we suggest that type C/P beta-lactamase was mediated by R plasmids in Gram-negative rods which already produced chromosomally mediated type C beta-lactamase . The strains which produced type C/P beta-lactamase tended to be more resistant to antibiotics than the other beta-lactamase producing strains . Among type C/P strains, the sensitivity to cephalosporins varied with the bacterial species, whereas all these strains were highly resistant to penicillins . Even for piperacillin, which is stable to cephalosporinase, the MIC at which the cumulative percentage of strains inhibited was 50% (MIC50) was over 50 micrograms/ml in all strains tested. Biochim Biophys Acta, 1990 Aug 27, 1050(1-3), 27 - 33 Effects of mutagenesis of C912 in the streptomycin binding region of Escherichia coli 16S ribosomal RNA; Frattali AL et al.; Four different mutations were produced at position 912 of Escherichia coli 16S rRNA in the multicopy plasmid pKK3535 . Cells transformed with the mutant plasmids were assayed for growth in steptomycin . The U912 mutant conferred low level streptomycin resistance as reported originally by Montandon and co-workers (EMBO J 1986; 5:3705-3708) . The G912 mutant also gave low level resistance but, unlike U912, caused significant retardation in growth rate and tended to select for fast-growing revertants . The A912 mutant was without effect on growth rate or streptomycin sensitivity, while deletion of C912 was lethal . Cells with U912 were selected for increased streptomycin resistance (MIC up to 160 micrograms/ml) and then cured of the plasmid . The cured cells retained a higher level of streptomycin resistance (MIC: 80 micrograms/ml) than the original wild type strain (MIC: 10 micrograms/ml), but sequencing by reverse transcriptase showed no evidence of U912 in the cellular 16S rRNA . Thus, recombination of the plasmid-coded U912 mutation into host rrn operons was not the mechanism by which increased streptomycin resistance occurred . The plasmid with U912 was transformed into three different streptomycin-dependent strains to determine whether the rRNA mutation, which presumably alters streptomycin binding, was compatible with S12 mutations which require bound streptomycin in order to function properly . In one strain, no transformants could be isolated, indicating that the plasmid was lethal . The two other streptomycin-dependent strains were transformed, but ribosomes containing the mutant rRNA were non-functional. Bull Soc Ophtalmol Fr, 1990 Aug-Sep, 90(8-9), 805 - 6, 809-11 {Ciprofloxacin: intraocular absorption in man}; Bron A et al.; The intraocular penetration of Ciprofloxacin in man: authors have studied the penetration of Ciprofloxacin in the aqueous humor of 30 patients (30 eyes) . The concentration in the anterior chamber was on average 0.73 mg/l which is 33% of serum level, from 1.30 hours after a single oral dose of 1000 mg till the 4th hour after this dose . The samples were assessed by a microbiological method . These results are over the minimal inhibitory concentration for many bacterial agents found in endophthalmitis . So this antibiotic may be proposed in the treatment of endophthalmitis . Anyway further investigation is mandatory to assess the safety on efficacy of these antibiotics. Antimicrob Agents Chemother, 1990 Aug, 34(8), 1602 - 4 Comparison of ofloxacin, gentamicin, and tobramycin concentrations in tears and in vitro MICs for 90% of test organisms; Richman J et al.; Concentrations of three anti-infective agents in tear film were monitored after one topical application in rabbits . Ofloxacin concentrations exceeded the MIC for 90% of the organisms tested (MIC90) (gram-negative and gram-positive organisms) for 240 min . Tobramycin concentrations exceeded the MIC90 for 10 min . Gentamicin concentrations exceeded the MIC90 for 20 min for gram-positive organisms and 120 min for gram-negative organisms. Antimicrob Agents Chemother, 1990 Aug, 34(8), 1593 - 6 In vitro susceptibility of Ehrlichia sennetsu to antibiotics; Brouqui P et al.; Antibiotic efficacies were evaluated by Diff-Quik (Dade, Dudingen, Federal Republic of Germany) staining of Ehrlichia sennetsu in P388D1 murine macrophages grown in 96-well microtiter plates . Sennetsu disease is generally cured with tetracyclines . In vivo, E . sennetsu is susceptible to doxycycline and is resistant to erythromycin, penicillin, and chloramphenicol . Our study confirmed, in vitro, the efficacy of doxycycline, which had an MIC of 0.125 micrograms/ml . E . sennetsu was found to be resistant to erythromycin, chloramphenicol, penicillin, gentamicin, and co-trimoxazole, while it was very susceptible to ciprofloxacin (MIC, 0.125 micrograms/ml) and rifampin (MIC, 0.5 micrograms/ml). Acta Ophthalmol (Copenh), 1990 Aug, 68(4), 455 - 65 Intraocular levels of cefuroxime in uninflamed rabbit eyes; Koul S et al.; Intraocular levels of cefuroxime following subconjunctival, intravitreal and combined intravitreal and intravenous administration were determined in uninflamed rabbit eyes . Intraocular levels of the antibiotic were assayed by a biological method . Penetration of cefuroxime into the vitreous following subconjunctival administration was poor . Subconjunctival administration produced higher levels of cefuroxime in the aqueous when compared to parenteral administration alone . Higher levels of cefuroxime were achieved both in the aqueous and in the vitreous after an intravitreal injection . Intravitreal injection of 100 and 1000 micrograms cefuroxime produced intravitreal levels close to the minimum inhibitory concentration (MIC) for most ocular pathogens up to 24 h after drug administration . Intravenous supplementation did neither enhance the intraocular levels nor did it delay the clearance of the intravitreally injected antibiotic . Mild histopathological changes were seen with equal frequency both in the control and the test eyes and are attributed to the sampling techniques . Electroretinography (ERG) showed no definite changes suggestive of retinal toxicity up to 55 days after intravitreal administration. Hindustan Antibiot Bull, 1990 Aug-Nov, 32(3-4), 91 - 3 Fungitoxic properties of Prunus persica oil; Mishra AK et al.; During screening of leaves of 15 higher plant species, the leaves of Prunus persica exhibited absolute inhibition of mycelial growth of Aspergillus flavus . The active fraction was isolated in form of an essential oil which exhibited fungistatic nature at its minimum inhibitory concentration of 0.1% and showed a broad antifungal range . The oil was found non-phytotoxic to the seedling growth and seed germination of wheat. Zhonghua Nei Ke Za Zhi, 1990 Aug, 29(8), 482 - 4, 511 {Effect of fluoroquinolones made in China in the treatment of acute bacillary dysentery . A report of 212 cases}; Wang XF et al.; 212 cases of acute bacillary dysentery were treated with enoxacin and norfloxacin, another 15 cases were treated by chujunsheng . The cure rate in enoxacin group was 99.1%, in norfloxacin group 98.04% and in chujunsheng group 63.64% . The isolated pathogens were tested for susceptibility with disk diffusion and MIC determination . The results showed that both enoxacin and norfloxacin are better than gentamycin, ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole . Side effects of enoxacin group and norfloxacin were noted in are 2.7% and 3.0% of the patients respectively . This study suggests that enoxacin and norfloxacin are highly effective, quite convenient for use and have few adverse reactions . They are considered to be drugs of choice for the treatment of acute bacillary dysentery. Gene, 1990 Jul 2, 91(1), 35 - 41 Cloning of Saccharomyces cerevisiae promoters using a probe vector based on phleomycin resistance; Gatignol A et al.; Vectors that confer high levels of phleomycin (Ph) resistance to Saccharomyces cerevisiae have been constructed with the TEF1 and ENO1 promoters, the Tn5 ble gene and the CYC1 terminator . They are able to transform yeast cells grown on rich glucose medium containing a moderate level of Ph (10 micrograms/ml, corresponding to 100-fold the minimal inhibitory concentration) . Frequencies of transformation are identical to those obtained with the URA3 marker on a defined medium . A promoter probe vector, based on the same ble marker, enabled us to isolate sequences from chromosomal yeast DNA that had promoter activities . These DNA fragments have been sequenced and those which promote the highest levels of Ph resistance have been found to be either A + T-rich or have a potentially new and more efficient translation start site. Antimicrob Agents Chemother, 1990 Jul, 34(7), 1442 - 3 In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to six new oral cephalosporins; Hoppe JE et al.; Of six new oral cephalosporins, cefixime and cefpodoxime were the most active (MIC for 90% of isolates tested {MIC90}, 16 micrograms/ml) against Bordetella pertussis, followed by cefetamet, cefprozil, and loracarbef (LY163892) (MIC90, 64 micrograms/ml) and ceftibuten (MIC90, 128 micrograms/ml) . Against Bordetella parapertussis, loracarbef was more active (MIC90, 32 micrograms/ml) than the other compounds tested (MIC90s, 64 to greater than 128 micrograms/ml) . The new oral cephalosporins are unlikely to play a role in pertussis treatment. J Clin Microbiol, 1990 Jul, 28(7), 1616 - 22 Trichosporon beigelii, an emerging pathogen resistant to amphotericin B; Walsh TJ et al.; Trichosporon beigelii caused fatal disseminated infections that were resistant to amphotericin B in two granulocytopenic patients . In vitro susceptibility studies demonstrated that both index strains of T . beigelii were inhibited but not killed by amphotericin B at achievable concentrations in serum . The minimum lethal concentration for both isolates was greater than or equal to 18 micrograms/ml . Five of seven other isolates were found to have a similar pattern of amphotericin B resistance . The fact that the minimum lethal concentration of T . beigelii was many times greater than its MIC was consistent with a resistance pattern of tolerance . We concluded that T . beigelii may be resistant in vitro to amphotericin B and that this in vitro resistance was correlated with refractory, disseminated trichosporonosis in granulocytopenic patients . T . beigelii should be included in the expanding list of amphotericin B-resistant fungi. Eur J Obstet Gynecol Reprod Biol, 1990 Jul-Aug, 36(1-2), 137 - 45 Single-dose prophylaxis with broad-spectrum penicillins (piperacillin and mezlocillin) in gynecologic oncological surgery, with observation on serum and tissue concentrations; van Lindert AC et al.; Serum, fat and pelvic tissue levels of piperacillin or mezlocillin (patients randomly selected to receive one of both) were measured during surgery of 48 patients (mean age 55 years) with gynecologic cancer and related to the minimal inhibitory concentrations (MIC) . Only during the first 3 hours the fat and pelvic tissue levels of these antibiotics were above the MIC levels (3 to 5 mg/l), while the serum reached marginal levels after 4 to 5 hours . Excessive blood loss (more than 1.500 ml) decreases the serum and fat levels; however, during the first 3 hours not below the MIC values . Single-dose prophylaxis with both antibiotics appeared fully effective in debulking surgery, total abdominal hysterectomy and radical hysterectomy . However, out of a group of 12 patients who underwent radical vulvectomy, 8 patients had postoperative infections. Am J Clin Nutr, 1990 Jul, 52(1), 87 - 92 Changes in eating behavior after horizontal gastroplasty and Roux-en-Y gastric bypass; Kenler HA et al.; Postoperative changes in eight dietary variables were compared at 6-mo intervals over 24 mo in 53 horizontal-gastroplasty (HGP) and 51 Roux-en-Y gastric-bypass (RYGB) patients; the variables included 1) calorie intake; percent intake of 2) protein, 3) carbohydrate, and 4) fat; 5) sweets and high-calorie beverages (SWS) and 6) milk and ice cream (MIC) as percent of calories; and 7) high-calorie liquids (HCL) and 8) nonliquid sweets (NLS) as percentage of dietary sugar . Weight and calorie intake were significantly less after RYGB than after HGP after 6 mo (p less than or equal to 0.01) . Protein intake was significantly increased at all intervals after RYGB and at 6 and 12 mo after HGP (p less than 0.05) . After RYGB, intakes of SWS, MIC, and HCL were significantly decreased at all intervals (p less than 0.05) . SWS and MIC consumption was also significantly less after RYGB than after HGP (p less than or equal to 0.05) . Decreased SWS and MIC consumption in RYGB patients suggests that food-preference differences are partially responsible for the lower calorie intake and greater weight loss after RYGB than after HGP. Microbiologica, 1990 Jul, 13(3), 201 - 6 Fluconazole vs amphotericin B: "in vitro" comparative evaluation of the minimal inhibitory concentration (MIC) against yeasts isolated from AIDS patients; Lombardi G et al.; Fluconazole, a novel triazole antifungal drug, holds promise as a significant advance in the management of human fungal diseases . This new drug can be both orally and parenterally administered and is reported to be less toxic than other antifungal agents . The Authors studied the in vitro susceptibility of yeasts isolated from AIDS patients to this antimycotic drug, in order to evaluate if fluconazole's MICs were comparable to those of amphotericin B . A sample of 200 yeast strains (100 C.albicans, 20 C.parapsilosis, 20 C.tropicalis, 8 C.guilliermondii, 6 C.krusei, 6 C.pseudotropicalis, 24 T.glabrata and 16 Cr.neoformans) was tested . The results show an average MIC for amphotericin B (MIC90: 3.12 micrograms/ml) ten-fold lower than for fluconazole (MIC90: 100 micrograms/ml) . However, C.albicans and Cr.neoformans presented the same MIC value (3.12 micrograms/ml) both for fluconazole and for amphotericin B, suggesting that fluconazole could represent a valid alternative to amphotericin B in the treatment of fungal infections caused by these two agents. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 496 - 501 Prospects for standardisation of methods and guidelines for disc susceptibility testing; Williams JD; The disc diffusion method of susceptibility testing is widely used in diagnostic laboratories throughout the world . It is simple to perform and very suited to the clinical laboratory where a single isolate can be tested with a series of antibiotics in one experiment . For these two reasons the test is by far the commonest type of susceptibility method used . Other methods such as determination of the minimum inhibitory concentration or "breakpoint" methods are used in only a small number of laboratories . If standardisation of methods is to be achieved in order to agree on uniform reporting and guidelines, methods using disc tests are of the highest priority. Kekkaku, 1990 Jul, 65(7), 471 - 5 {Determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex}; Tsukamura M; The determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex (MAI complex) is influenced by the size of inoculation used in the determination . Such influences differ greatly according to the drugs . By increasing the number of colony-forming units (CFU) of the inoculation to 10(6)-fold, minimal inhibitory concentrations (MICs) of rifampicin and cycloserine have increased only 2-to 3-fold . However, MICs of ethionamide, streptomycin, enviomycin and ethambutol have increased 4-to 9-fold . In contrast, MICs of isoniazid and sulfadimethoxine have increased 30-to 35-fold . Since the determination of MICs of isoniazid and sulfadimethoxine are so greatly influenced by the size of inoculation, the determinations of MICs of these two drugs should be carried out by use of the "actual count" method (6, 7, 9) or the proportion method (8) . In the actual count method, the MIC is determined by inoculating 20-100 CFU . The determination of isoniazid susceptibility of M . tuberculosis (H37Rv) was influenced only slightly by the size of inoculation, but that of M . bovis (BCG) was influenced greatly as occurred in the determination of MAI complex strains. Chem Pharm Bull (Tokyo), 1990 Jul, 38(7), 2045 - 6 Hypotensive effects on spontaneously hypertensive rats and antifungal activity on various species of Fusarium oxysporum of diethylstilbestrol-related compounds; Inamori Y et al.; The diethylstilbestrol-related compounds 3,3'-dihydroxy-alpha, beta-diethyldiphenylethane (I), diethylstilbestrol (II) and hexestrol (III) showed hypotensive effects on spontaneously hypertensive rats (SHR) and antifungal activities against all Fusarium oxysporum sp . tested . As previously reported, I had strong hypotensive action on normotensive rats at the dose of 10 mg/kg, while II and III showed weak hypotensive effects on these rats at the same dose . In this work, all three compounds also had hypotensive actions on SHR at the same dose . I showed the strongest hypotensive effect (-80.0 +/- 5.0 mmHg, 10 mg/kg, i.v.) on both SHR and normotensive rats . The three compounds also had antifungal activities against five kinds of Fusarium oxysporum sp . tested . Especially, II strongly inhibited the growth of Fusarium oxysporum f . sp . raphani IFO-9972 (minimum inhibitory concentration (MIC): 1.0 micrograms/ml). J Med Microbiol, 1990 Jul, 32(3), 159 - 62 Transmissible trimethoprim resistance in strains of Escherichia coli isolated from cases of infantile diarrhoea; Lamikanra A et al.; Of 190 isolates of Escherichia coli from children aged up to 5 years with diarrhoea, 72 (37.9%) were resistant to trimethoprim and of the 70 isolates tested, 38 transferred high level trimethoprim resistance (MIC greater than 1000 mg/L) into E . coli EC 1005 . Of the enterotoxigenic isolates from which trimethoprim resistance was transferred, 41.2% also contained transmissible toxigenic characteristics . All the trimethoprim-resistant isolates were resistant to other antibiotics. Kansenshogaku Zasshi, 1990 Jun, 64(6), 687 - 92 {Evaluation of in vitro activity of rokitamycin against Chlamydia trachomatis}; Bannai H et al.; Evaluation of the in vitro activity of rokitamycin (RKM) against Chlamydia trachomatis in cycloheximide treated HeLa 229 cells and McCoy cells by comparing with five drugs including doxycycline (DOXY), minocycline (MINO), ofloxacin (OFLX), ampicillin (ABPC) and erythromycin (EM) with regard to assaying minimal inhibitory concentrations (MICs), minimal lethal concentrations (MLCs), and by yield reduction assays: 1) direct treatment of Chlamydial organisms with various concentrations of antibiotics before inoculation, 2) pre-treatment of host cell (HeLa 229) with the antibiotics before they are infected and 3) treatment of already infected cultures (48 hrs after infection) with antibiotics . The yield of Chlamydia was determined by both assaying the infectivity of Chlamydia and/or Chlamydiazyme value (from Abott Co Ltd USA) . It was found that similar MIC was obtained among the drugs tested (except EM) in both HeLa 229 cell and McCoy cell assay system . The MLC of RKM (0.3 micrograms/ml) was the same as that of OFLX and was significantly lower than that of other drugs tested . When Chlamydial organisms and the host cells were treated with various concentrations (25-0.1 micrograms/ml) of the drug, the infectivity and the growth of Chlamydia was noteworthily decreased with RKM treatment . Infectivity of Chlamydia in an already infected cultures also decreased with RKM treatment within 24 hours when comparing the value of the control . In other drugs treatment, 96 hours or more hours were required for obtaining the same infectivity as RKM.(ABSTRACT TRUNCATED AT 250 WORDS) Environ Health Perspect, 1990 Jun, 86, 323 - 6 Cytogenetic studies in human populations exposed to gas leak at Bhopal, India; Ghosh BB et al.; Frequencies of chromosomal abnormalities, sister chromatid exchanges, and replicative index were assessed following peripheral lymphocyte culture in 129 individuals from Bhopal, India . Of these, 83 persons (40 male and 43 female) had been exposed directly to the methyl isocyanate (MIC) gas after the accident at the Union Carbide plant on December 2 and 3, 1984 . The remaining 46 samples were taken from age-matched unexposed persons in the same city . Chromosome aberrations were recorded at first cycle metaphase (M1) and sister chromatid exchanges, at second cycle metaphase (M2), following standard schedule . The frequency of chromosomal aberrations was, in general, higher in individuals from the exposed populations, with the females showing a higher incidence . Nondisjunction of chromosomes or laggard was rare . The frequencies of sister chromatid exchanges and depression in mitotic and replicative indices could not be related to exposure or sex . The persistence of chromosomal abnormalities in the form of replicating minutes and exchange configurations, even 1114 days after exposure to the gas, may indicate a residual effect on T-cell precursors. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1017 - 9 Concentrations of oral lomefloxacin in serum and bronchial mucosa; Baldwin DR et al.; The bronchial mucosal concentrations of lomefloxacin were determined for specimens obtained by fiber-optic bronchoscopy and compared with simultaneous concentrations in serum . The 23 patients studied were given an oral dose of 400 mg once daily for 4 days to achieve steady-state levels . The median concentration in serum was 2.5 micrograms/ml (range, 1.0 to 5 micrograms/ml), and the median bronchial mucosal concentration was 5.0 micrograms/g (range, 0.7 to 18.6 micrograms/g) . The median percent penetration was 177% (range, 69 to 541%) . The concentrations in serum and mucosa exceeded the MIC for 90% of strains of organisms causing bronchial infections but not sufficiently to recommend lomefloxacin for the routine treatment of pneumococcal infections. Mycopathologia, 1990 Jun, 110(3), 157 - 61 In vitro activity of seven azole compounds against some clinical isolates of non-dermatophytic filamentous fungi and some dermatophytes; Oyeka CA et al.; The in vitro activity of seven azole compounds viz clotrimozole, isoconazole, bifanazole, fluconazole oxyconazole, Bay n 7133 and Bay L 9139 was investigated against 47 clinical isolates of pathogenic non-dermatophytic filamentous fungi and dermatophytic fungi . The isolates included Hendersonula toruloidea-26, Scytalidium hyalinium-5, Scytalidium japonicum-1, Trichophyton rubrum-5, Trichophyton tonsurans-3, Trichophyton mentagrophytes var . mentagrophytes-4, Epidemophyton floccosum-2, Microporum gypseum-2 isolates . The drugs were significantly more active against the dermatophytes (MIC range 0.025-1.56 micrograms/ml) than non-dermatophytes (MIC range 0.39-6.25 micrograms/ml) . Isoconazole showed more activity than the rest of the azole compound tested . Clotrimazole, fluconazole, oxyconazole, bifonazole were comparable in their inhibitory activity against both dermatophytes and non-dermatophytes . The azole derivatives, Bay n 7133 and Bay L 9139 showed higher MIC range i.e . gave a range of 0.39-1.56 micrograms/ml for dermatophytes and 1.56-6.25 micrograms/ml for non-dermatophytic filamentous fungi . The minimal fungicidal concentration (MFC) of all the drugs tested were mostly within 2-8 times their MIC values. Pathol Biol (Paris), 1990 Jun, 38(5 ( Pt 2)), 504 - 7 {Study of the intraperitoneal penetration of imipenem/cilastatin in acute peritonitis with perforation}; Peze P et al.; A study was performed to investigate the intraperitoneal penetration of Imipenem/cilastatin into inflammatory peritoneal fluid . Six patients undergoing abdominal surgery (acute peritonitis), were treated with Imipenem/cilastatin (4 perfusions of 0.5 g/day) during 5 days after the intervention . Plasma samples were obtained on day 1 and 4 at the pic and at the valley; peritoneal samples were obtained every days for 4 days, 1, 3 and 6 hours after the end of a perfusion . The samples were immediately stabilised following the manufacturer instructions and quick freezed at -80 degrees C . Dosages were performed using a microbiological assay . The mean peritoneal levels are above the MIC 90 of the more frequent bacteria which cause infection in abdominal surgery . Moreover none of the patients showed relapse of infection or complication during this treatment. J Med Chem, 1990 Jun, 33(6), 1656 - 62 Comparative reactivity of 1-carba-1-dethiacephalosporins with cephalosporins; Blaszczak LC et al.; Nine matched pairs of cephalosporins and their 1-carba-1-dethiacephalosporin analogues have been compared with regard to microbiological activity, beta-lactam carbonyl infrared absorption, and aqueous stability . In general the microbiological activity of the pairs of compounds were very similar across a broad range of bacteria . The infrared absorption bands for the beta-lactam carbonyls of the pairs indicated a general trend for the 1-carba-1-dethiacephalosporins to absorb at lower frequencies than the corresponding cephalosporins . All of the 1-carba-1-dethiacephalosporins did however present a striking stability enhancement over their cephalosporin counterparts at pH = 10 or 11 in water . This marked contrast of MIC similarity with the observed differences in chemical reactivity clearly demonstrates hydroxide ion catalyzed hydrolysis is not a good model for transpeptidase activity unless the compounds comprise a limited domain of structural type. Tubercle, 1990 Jun, 71(2), 109 - 15 In vitro activities against mycobacteria of two long-acting rifamycins, FCE22807 and CGP40/469A (SPA-S-565); Dickinson JM et al.; The in vitro activities of two new long-acting rifamycins, FCE22807 a derivative of FCE22250, and CGP40/469A (SPA-S-565) were studied . When compared with rifampicin, the minimal inhibitory concentrations (MIC) against Mycobacterium tuberculosis of both were 4 times lower but neither was particularly active against rifampicin-resistant strains of M . tuberculosis nor against M . avium-intracellulare-scrofulaceum complex strains . A drug is likely to be particularly effective in widely spaced intermittent dosage if it has a long half-life and high bactericidal activity . When tested against M . tuberculosis in the logarithmic and in the stationary phase of growth, FCE22807 was amongst the most bactericidal of the rifamycins while CGP40/469A had little bactericidal activity. Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Jun, 28(6), 875 - 81 {Isolation of Branhamella catarrhalis from sputum and clinical features of bronchopulmonary infection due to Branhamella catarrhalis}; Kinoshita A et al.; The authors investigated the isolation of Branhamella catarrhalis from sputum and the clinical features of bronchopulmonary infection due to B . catarrhalis from January of 1983 to December of 1987 at the Hokusyo Central Hospital . B . catarrhalis was cultured from 106 (3.8%) of 5,674 sputum specimens . The isolation rate did not vary during the 5 years from 1983 to 1987 . Approximately 70% of the patients had some underlying bronchopulmonary disease . The strains of beta-lactamase-positive B . catarrhalis have increased recently in our hospital . Using 4 diagnostic criteria for bronchopulmonary infection by B . catarrhalis, 24 cases were detected . MIC was measured in 97 strains of B . catarrhalis (beta-lactamase positive 63 strains, negative 34 strains) . beta-lactamase positive strains had a high MIC value for beta-lactam antibiotics, but antibiotics including beta-lactamase inhibitor markedly improved sensitivity to drugs . Negative strains showed good sensitivity to beta-lactam antibiotics . Cases of bronchopulmonary infection due to Branhamella catarrhalis and beta-lactamase-productive strains are increasing, therefore it is necessary to be careful in the choice of antibiotics. Hinyokika Kiyo, 1990 Jun, 36(6), 741 - 5 {Diffusion of ofloxacin (OFLX) into prostatic tissue in patients with benign prostatic hypertrophy}; Uchibayashi T et al.; Diffusion of ofloxacin (OFLX) into prostatic tissue was studied in 31 patients with benign prostatic hypertrophy . Concentrations of OFLX in the serum and prostatic tissue were measured at scheduled intervals after 200 mg OFLX oral administration . The mean OFLX level in prostatic tissue and tissue/serum ratio at 2 hours, 4 hours and 6 hours was 3.33 +/- 0.96 micrograms/g (1.25 +/- 0.28) in 10 patients, 2.21 +/- 0.55 micrograms/g (0.92 +/- 0.32) in 9 patients and 2.10 +/- 0.99 micrograms/g (1.01 +/- 0.23) in 12 patients, respectively . OFLX levels in prostatic tissue covered the minimum inhibitory concentration for several pathogenic bacteria detected from the infected prostatic fluid . Therefore, OFLX was thought to be a very useful drug for the treatment of bacterial prostatitis and postoperative infection of prostatic surgery. Mol Cell Biochem, 1990 May 10, 94(2), 133 - 46 MgCl2-sensitive and Gpp(NH)p-sensitive antagonist binding states of rat heart muscarinic receptors: preferential detection at ambient temperature assay and location in two subcellular fractions; Sulakhe PV et al.; Some novel observations dealing with antagonist binding to cardiac particulate muscarinic receptors are described . Gpp(NH)p increased (2-3 fold) the specific binding of {3H}-QNB or {3H}-NMS, both potent muscarinic antagonists, to washed particles (WP), but not microsomes (MIC), when the binding was conducted at 30 degrees C . Magnesium, on the other hand, increased (2-3 fold) the binding of these antagonists to MIC, but not to WP, under the same condition . The treatment of subcellular fractions with 0.2 mM N-ethylmaleimide (NEM), a sulfhydryl reagent, failed to significantly modify the respective stimulatory actions of either Gpp(NH)p on WP binding or of magnesium on MIC binding of these antagonists; treatment with dithiothreitol (1 mM) was also ineffective in this regard . Gpp(NH)p decreased Kd (WP) while magnesium increased Kd (MIC) for {3H}-QNB . Repeated freezing/thawing of isolated subcellular fractions abolished the stimulatory effect of magnesium on antagonist binding to MIC but not of Gpp(NH)p on WP antagonist binding; the freeze/thaw procedure per se increased MIC binding but not WP binding of these antagonists . When the binding was conducted at 4 degrees C (24 hr), the stimulatory effect of Gpp(NH)p on {3H}-QNB binding was enhanced (6-fold) in the case of WP and was detectable (80%) in the case of MIC . Under this condition, the stimulatory effect of magnesium on {3H}-QNB binding was also enhanced (5-fold) in the case of MIC and became evident (200%) in the case of WP . The results of this work support the following views: (a) antagonist-occupied cardiac muscarinic receptors are capable of interaction with guanine nucleotide binding proteins (G protein like Gi, Go) and such interaction influences antagonist binding properties (e.g . increased affinity) of the cardiac membrane-associated muscarinic receptors (b) magnesium influences (decreased affinity) antagonist binding properties by interacting with multiple sites of which some are likely associated with components other than G proteins of the particulate fractions (c) a pool of NEM-sensitive sulfhydryls involved in the regulation of Gpp(NH)p-sensitive agonist binding to cardiac muscarinic receptors is not involved in the regulation by either Gpp(NH)p or magnesium of antagonist binding in these subcellular fractions and (d) membrane fluidity and microenvironment surrounding the receptor and G proteins contribute to the actions of Gpp(NH)p and magnesium on antagonist binding. Fam Plann Perspect, 1990 May-Jun, 22(3), 128 - 30 Factors associated with postpartum care among Massachusetts users of the Maternal and Infant Care Program; Kogan MD et al.; PIP: Records of the 21 Maternal and Infant Care (MIC) offices run by the Massachusetts Department of Public Health located in community-based facilities in high-risk areas provided data for the period 1985-87 . MIC services include a postpartum visit within 2-6 weeks after birth . 24% of the deliveries in the MIC program were to teenagers . Unmarried women, high school dropouts, and minority group members were greatly overrepresented in the MIC program . 78% (10,854) of the women who received MIC care returned for a postpartum visit . Maternal age, educational status, parity, ethnicity, primary language, adequacy of prenatal care, length of maternal hospitalization, transfer of the infant to a neonatal intensive care unit, length of pregnancy, birth outcome, type of delivery, and birth weight were factors studied . The largest effect appeared to be correlated with adequacy of prenatal care utilization (the Kessner Index is used) . Only 63% of women with inadequate utilization returned, compared with 76% of those with intermediate care and 86%, adequate care . The higher the women's level of education, the more likely she was to have a postpartum visit . The more children she had, the less likely she was to return . 82% of those with 1st births returned and 70% of those with 4 or more children . Women who did not speak English were more likely to return, (82%) than those who did (78%) . NonEnglish speaking Asian women had the highest return rate (92%) . Women under age 26 were likely to return than older ones . Factors associated with postpartum care were analyzed by year of delivery, so time trends could be seen . In 1985 and 1986, 78.9% returned for postpartum care; in 1987, the figure decreased to 76.4% . The % with adequate prenatal care who returned for postpartum care declined each year, from 87.4% in 1985 to 85.9% in 1986, and 83.8% in 1987 . This was statistically significant . The % of Blacks who received postpartum care also declined, significantly . There was no change in the proportion getting adequate postpartum care among nonBlack groups . Factors associated with the lack of postpartum care in the multivariate analysis included Hispanic ethnicity, or later birth, and having a repeat cesarean section . The findings were shown to be stable across the years . In 1986 and 1987, women on the Healthy Start (a state-funded reimbursement program that pays for obstetric care of women with incomes between 100 and 185% of the poverty level) were less likely to miss their postpartum visit than those with commercial insurance . No To Hattatsu, 1990 May, 22(3), 209 - 15 {Microdensitometric study of maturation and fragility of the bone in male patients with cerebral palsy--the effect of long-term administration of 1 alpha-hydroxy vitamin D3 and the value of osteocalcin as a marker of bony growth}; Hayashi Y et al.; 1) We studied bony maturation and fragility in 48 male patients (4-28 years old) with cerebral palsy . They were divided into three groups; group A (drug free, mild motor handicapped), 10 cases, group B (anticonvulsants administrated, mild motor handicapped), 20 cases, group C (anticonvulsants administrated, severe motor handicapped) 18 cases . The indicator of bone mineral content (sigma GS/D) and metacarpal index (MCI) were analyzed by microdensitometric method . A positive correlation between age and sigma GS/D was detected in all groups but a positive correlation between age and MCI was found only in the group B . There was little difference in sigma GS/D and MIC between group A and group B, but those of group C were significantly decreased . These results suggest that increase of bone mineral is related with aging but metacarpal growth is variable, and a lack of daily activity has greater adverse effect on bony metabolism than administration of anticonvulsants . 2) The alterative rates of sigma GS/D (delta sigma GS/D/sigma GS/D/year) and MCI (delta MCI/MCI/year) after 1 alpha-hydroxy vitamin D3 (D3) treatment for 3 years or more were examined in 17 patients with bony atrophy, as compared with normal controls . The alterative rates of sigma GS/D and MCI were elevated in younger patients with D3 treatment but those were decreased in adult patients . Treatment with D3 remarkably increased bony growth in children . 3) In 37 patients, osteocalcin (OC) was measured by radioimmunoassay . OC was elevated in younger patients who were treated with D3.(ABSTRACT TRUNCATED AT 250 WORDS) Arch Environ Contam Toxicol, 1990 May-Jun, 19(3), 314 - 8 Acute toxicity of methyl isocyanate in mammals . II . Induction of hyperglycemia, lactic acidosis, uraemia, and hypothermia in rats; Jeevaratnam K et al.; When rats were administered methyl isocyanate (MIC) by inhalation or subcutaneous route it produced severe hyperglycemia, clinical lactic acidosis, highly elevated plasma urea, and reduced plasma cholinesterase activity with unaltered erythrocyte acetyl cholinesterase activity . Irrespective of the route of administration, MIC also caused severe hypothermia, which was not ameliorated by prior administration of atropine sulphate . Acute toxic effects of MIC are essentially similar by either route except for the intensity of the effects. J Toxicol Environ Health, 1990 May, 30(1), 1 - 14 Dissociation between maternal and fetal toxicity of methyl isocyanate in mice and rats; Varma DR et al.; The contribution of maternal hormonal changes and pulmonary damage on the fetal toxicity of methyl isocyanate (MIC) was studied in mice and rats . Exposure to MIC decreased maternal plasma progesterone levels in mice that lost but not in mice that retained pregnancy . Fetal toxicity of MIC was not related to changes in maternal plasma corticosterone levels . Neither chronic administration of progesterone nor the suppression of pulmonary edema with dexamethasone decreased fetal toxicity of MIC . Embryos exposed in utero or in vitro to MIC vapor exhibited a concentration-dependent decrease in growth in culture . An acute dose (3 mmol/kg) of the MIC metabolites (methylamine, dimethylamine, trimethylamine, dimethyl urea) did not exert fetal toxicity . These data suggest that the fetal toxicity of MIC is partly independent of maternal toxicity and may result from its transfer across the placenta and interaction with fetal tissues. Laryngoscope, 1990 May, 100(5), 536 - 40 Spectral analysis of airflow sounds in patent versus occluded tracheostomy tubes: a pilot study in tracheostomized adult patients; Rao AJ et al.; Cannula occlusion is a life-threatening postoperative complication of tracheostomy . Current management largely relies on nursing care for prevention of fatalities because no proven mechanical, machine-based support monitoring exists . The objective of this paper was to address the problem of monitoring the state of cannula patency, based on analysis of airflow acoustic spectral patterns in tracheostomized adult patients in the patent and partially occluded cannula . Tracheal airflow sounds were picked up via a condenser microphone air-coupled to the skin just below the tracheal stoma . Signal output from Mic was amplified, high-pass filtered, digital tape-recorded, and analyzed on a mainframe computer . Although airflow frequencies for patient cannulae were predominantly low-pitched (0.1 to 0.3 kHz), occluded tubes had discrete high-pitched spectral peaks (1.3 to 1.6 kHz) . These results suggest that frequency analysis of airflow sounds can identify a change in the status of cannula patency. J Antimicrob Chemother, 1990 May, 25(5), 745 - 50 Use of a non-radioactive DNA hybridization technique to study the effect of quinolone antibiotics on plasmid replication and curing; Phillips AC et al.; A biotin-labelled DNA probe was used to detect the presence of bacteria carrying plasmid DNA and to study the effect of ciprofloxacin and nalidixic acid on plasmid carriage . The colour intensity generated in dot-blot hybridization tests was measured with a computer-controlled image analysis system and was shown to be related to the number of plasmid copies present . Ciprofloxacin, at about 0.5 x MIC, reduced the plasmid copy number in a bacterial population, while nalidixic acid, used at a similar ratio to MIC, had a much smaller effect . The method could potentially be used to study the effect of antibiotics on plasmid replication and curing in any bacterial system for which a suitable DNA probe is available. Pathol Biol (Paris), 1990 May, 38(5), 431 - 5 {Evaluation of the Mycoplasma Plus and the SIR Mycoplasma kits for quantitative detection and antibiotic susceptibility testing of genital mycoplasma}; Renaudin H et al.; We compared the results obtained with two commercially available systems (Diagnostics Pasteur) for the quantitative identification and the antibiotic susceptibility testing of the genital mycoplasmas . Ureaplasma urealyticum and Mycoplasma hominis with established methodologies, i.e . isolation on agar with enumeration by dilutions in broth medium and MIC determinations . The Mycoplasma Plus system, consisting of six cups, was designed for the identification and quantitation of genital mycoplasmas and the detection of yeasts . Used in parallel in 150 clinical specimens, it detected U . urealyticum in 42 out of 43 and M . hominis in 10 out of 11 specimens positive by the established methodology . The SIR Mycoplasma antibiogram, consisting of 16 cups, provided for the testing of 1 or 2 concentrations (micrograms/ml) of each of 8 antibiotics: doxycycline, minocycline and lymecycline (4-8); erythromycin (1-4); josamycin (2-8); clindamycin (2); pristinamycin (2); and ofloxacin (1-4) . Using an inoculum of about 10(4)-10(5) organisms/ml, we found that major part of the results was in accord with those obtained with the MIC determined in broth for U . urealyticum and on agar for M . hominis . Strains intermediate or resistant to the tetracyclines were identified . Both systems seemed suitable for clinical laboratory use. J Med Chem, 1990 May, 33(5), 1353 - 60 Stereospecific synthesis and antiviral properties of different enantiomerically pure carbocyclic 2'-deoxyribonucleoside analogues derived from common chiral pools: (+)-(1R,5S)- and (-)-(1S,5R)-2-oxabicyclo{3.3.0}oct-6-en-3-one; Beres J et al.; Enantiomerically pure (+)- and (-)-carbocyclic thymidine, (-)-carbocyclic 3'-epi-thymidine, (+)-carbocyclic 3'-deoxy-3'-azidothymidine, (+)-carbocyclic 2,3'-O-anhydrothymidine, (+)-carbocyclic 3'-O,6'-methylenethymidine, and (+)-(6'S)-carbocyclic 6'-methylthymidine were synthesized in a stereospecific manner from common chiral pools of (+)-(1R,5S)- and (-)-(1S,5R)-2-oxabicyclo{3.3.0}oct-6-en-3-one and evaluated for antiviral activity . (+)-Carbathymidine and, to a lesser extent, (+)-carbocyclic 2'-deoxyadenosine proved to be effective against HSV-1 {minimum inhibitory concentration (MIC): 0.2 and 2 micrograms/mL, respectively} and HSV-2 (MIC: 2 and 20 micrograms/mL, respectively), but virtually inactive against TK- HSV-1 (MIC: 40 and 100 micrograms/mL, respectively) . (+)-Carbathymidine was also active against vaccinia virus (2 micrograms/mL) . None of the compounds had a specific effect on the replication of HIV or other RNA viruses. J Med Chem, 1990 May, 33(5), 1306 - 11 A model for compounds active against human rhinovirus-14 based on X-ray crystallography data; Diana GD et al.; A number of (oxazolinylphenyl)isoxazoles have been synthesized and tested against human rhinovirus-14 (HRV-14) . Several of the more active compounds have been examined by X-ray crystallography and their orientation in the compound binding site on the capsid protein of HRV-14 has been determined . Based on the minimum inhibitory concentration against HRV-14 and the X-ray conformation of the compounds, a model has been developed which distinguishes between the space-filling properties of the active and inactive compounds in this series . The model was generated by overlaying composite structures and comparing the van der Waals generated volume maps . The results of this study indicate that inactive compounds display areas of excessive bulk particularly around the phenyl ring, while the active compounds occupy space below the pore area of the compound binding site. Biokhimiia, 1990 May, 55(5), 856 - 64 {Interaction of model IgG complexes with lectin from Ricinus communis in solutions studied by light scattering method}; Sykulev IuK et al.; In order to demonstrate the participation of galactose-containing carbohydrate epitopes on the surface of model IgG complexes (MIC) during their interaction with high molecular weight ligands, MIC were obtained . The interaction of MIC with Ricinus communis agglutinin (RCA) was studied . The time-dependent changes in the intensity of light scattering in solutions containing MIC of different molecular masses were measured after addition of RCA . It was shown that the efficiency of MIC interaction with RCA depends on the molecular mass of the former . The binding of RCA to MIC is highly specific, it being completely abolished after addition of lactose (1-15 mM) . It was found that the final lactose concentration necessary for the complete inhibition of MIC interaction with RCA to take place, depends on the molecular mass of MIC . The data obtained point to the accessibility of IgG oligosaccharide antennae within the composition of MIC for the binding to high molecular weight ligands as well as to the increased density of galactose-containing epitopes on the surface of MIC resulting from the increase in their molecular mass. Kekkaku, 1990 Apr, 65(4), 257 - 62 {In-vitro combined effect of antituberculosis drugs on Mycobacterium avium complex}; Tsukamura M et al.; In-vitro combined activity of antituberculosis drugs on Mycobacterium avium complex strain 13034 (serotype 18) was observed . A twofold dilution series of each drug was combined with 17 additional drugs and the control without drug . Each medium was inoculated by a 0.02 ml-sample of four different bacterial suspensions, original suspension (10 mg wet weight per ml) and its 10(-5), 10(-6) and 10(-7) suspensions, and incubated at 37 degrees C for 28 days . The inoculation was made by a spiral loop that can deliver a 0.02 ml-sample by one inoculation . Since a total of media reached 6480 (1620 combinations x 4 different suspensions), only one strain was investigated in this study . Inoculation size used for determining minimal inhibitory concentrations was adjusted to 20 to 80 colony-forming units per medium . This was obtained by inoculating 10(-6) suspensions . The diameter of colonies was measured on media that were inoculated with 10(-7) suspensions . Since 96% confidence limits of determining minimal inhibitory concentrations are between 1/4 to fourfold, decrease or increase of the minimal inhibitory concentration equal to or above this level was regarded as significant . Such significant change of the minimal inhibitory concentrations occurred in combinations of drugs is shown in Table 2 . As shown in tables, no antagonism was observed . The combinations, in which significant decrease was seen, contained ethambutol, sulfadimethoxine and ethionamide . It was shown that these concentrations of the drugs cause marked delay of growth . In control medium, the diameter of colonies was 5-6 mm, whereas in media containing one of these drugs, it was 1 mm.(ABSTRACT TRUNCATED AT 250 WORDS) J Antimicrob Chemother, 1990 Apr, 25(4), 657 - 64 Plasma and dialysate levels of pefloxacin and its metabolites in CAPD patients with peritonitis; Rose TF et al.; Six patients with acute peritonitis undergoing continuous ambulatory peritoneal dialysis for end-stage renal failure received an 800 mg loading dose of pefloxacin mesylate orally followed by 400 mg twice daily orally for 10 or 21 days . Plasma and dialysate levels of both pefloxacin and its metabolites were measured . Plasma levels in excess of the MIC for all infective bacteria were achieved within 90 min and in dialysate within 4 h . No significant accumulation of pefloxacin or its metabolite norfloxacin was noted . However, both serum and dialysate levels of the metabolite pefloxacin N-oxide rose continuously during treatment . Plasma and dialysate levels of all three agents fell rapidly during the five days after treatment had stopped . No major side effects were observed, although two patients developed Achilles tendonitis. Mycoses, 1990 Apr, 33(4), 203 - 11 In vitro activities of polyene and imidazole antifungal agents against unusual opportunistic fungal pathogens; Rotowa NA et al.; Guidelines for the treatment of infections caused by unusual opportunistic fungi are limited and available in vitro data are scanty . In vitro susceptibility tests, employing an agar dilution procedure, were performed with amphotericin B (AMB), natamycin (NTC), itraconazole (ICZ), and ketoconazole (KTZ) . Two media were used: Kimmig's agar (KA) and Yeast Morphology Agar (YMA) . Fungi tested included isolates (n) of Acremonium spp . (10), Cunninghamella spp . (6), Fusarium spp . (18), Pseudallescheria boydii (14), and Trichosporon beigelii (5) . All Acremonium and Cunninghamella isolates were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but many appeared to be resistant to AMB, (MIC greater than or equal to 32 micrograms/ml), KTZ and ICZ (MIC greater than or equal to 128 micrograms/ml) . Most isolates of Fusarium spp . were susceptible to both AMB and NTC (MIC90 = 4 micrograms/ml); one isolate was cross-resistant to both polyenes (MIC greater than 32 micrograms/ml) . Only two of 18 Fusarium isolates appeared susceptible to the imidazoles (MIC less than or equal to 4 micrograms/ml); the remaining isolates exhibited high MICs (greater than or equal to 64 micrograms/ml) . All 14 isolates of P . boydii were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but four appeared to be resistant to AMB (MIC greater than or equal to 32 micrograms/ml) . Most isolates of P . boydii were susceptible to both KTZ (MIC less than or equal to 4 micrograms/ml) and ICZ (MIC less than or equal to 16 micrograms/ml) but two isolates appeared to be resistant (MIC greater than or equal to 16 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS) Farmaco, 1990 Apr, 45(4), 473 - 8 Pyrazole sulfanilamides: nitroderivatives of 1-phenyl-3-sulfanilamidopyrazole . Note XVI; Tironi C et al.; Synthesis and structural characterization of 3 sulfanilamido-1-phenylpyrazoles bearing on 1-phenyl group nitro substituent o-, m-, p-positioned are reported . All derivatives are analysed through 1H and 13C NMR spectroscopy . The MIC values obtained against Escherichia coli are briefly discussed in terms of structure-activity relationship. J Antimicrob Chemother, 1990 Apr, 25(4), 621 - 7 Relevance of the inoculum effect of antibiotics in the outcome of experimental infections caused by Escherichia coli; Soriano F et al.; The minimum dosage of antibiotics that reduced mortality in bacteraemic rats inoculated with two different Escherichia coli isolates was determined in an attempt to study the therapeutic importance of the inoculum effect . Low mortality rates (0-5%) at 48 h were obtained when antibiotics with minimal or no inoculum effect (ampicillin, cefuroxime, cefoxitin and gentamicin) were administered to yield serum levels 5 to 14 times the MIC, while antibiotics with a pronounced inoculum effect (piperacillin, cefotaxime and aztreonam) had to be administered to yield serum levels 57 to more than 1000 times the MIC determined with a standard (low) inoculum . All of the antibiotics with inoculum effect studied here are administered empirically in clinical practice at a higher dose than the microbiological and pharmacokinetic data would indicate (in order to reach peak serum concentrations exceeding the MICs of the pathogens by 4-10 times) . Our experiment suggests that such high and empirical doses of antibiotics with inoculum effect may be justified. J Cardiothorac Anesth, 1990 Apr, 4(2), 204 - 9 Cefazolin and netilmicin serum levels during and after cardiac surgery with cardiopulmonary bypass; Lehot JJ et al.; The kinetics of cefazolin and netilmicin were studied in 10 patients undergoing elective cardiac surgery with hemodilution and cardiopulmonary bypass (CPB) . During surgery, but before CPB, cefazolin, 25 mg/kg, and netilmicin, 2 mg/kg, were administered intravenously over 30 minutes . For the 48-hour period following CPB, cefazolin, 25 mg/kg, and netilmicin, 1 mg/kg, were administered intravenously every 8 hours . Initiation of CPB was accompanied by a 28% to 30% decrease in hematocrit and serum antibiotic levels . At the conclusion of surgery, cefazolin and netilmicin serum levels were 41 +/- 12 micrograms/L and 2.5 +/- 0.6 micrograms/mL (mean +/- SD), respectively . During the postoperative period, cefazolin levels were consistently greater than the minimum inhibitory concentration (MIC) for sensitive bacteria (4 micrograms/mL); average netilmicin levels were greater than MIC of sensitive bacteria (2 micrograms/mL) for 2 hours after antibiotic infusion . The netilmicin trough levels were 0.6 +/- 0.5 micrograms/mL . Pharmacokinetic parameters were determined using a model-independent method, and gave the following results during surgery: cefazolin--elimination half-life, 231 minutes, total body clearance, 1.05 mL/kg/min, and steady-state volume of distribution, 243 mL/kg . The values for netilmicin were 249 minutes, 1.18 mL/kg/min, and 353 mL/kg, respectively . Postoperatively there were no significant changes in the disposition of cefazolin, but the elimination half-life of netilmicin was shorter (124 minutes, P less than 0.01) and the total body clearance greater (3.58 mL/kg/min, P less than 0.01) than during surgery. Antimicrob Agents Chemother, 1990 Apr, 34(4), 674 - 5 Different doses of cefetamet pivoxil (Ro 15-8075) in the treatment of acute uncomplicated gonococcal urethritis in men; Tio TT et al.; In an open, dose-finding study, a 100% cure rate was observed in patients suffering from uncomplicated gonococcal urethritis who were treated with a single oral dose of either 1.2 g (n = 10), 0.8 g (n = 11), or 0.4 g (n = 10) of cefetamet pivoxil . The MICs of cefetamet for all gonococcal strains ranged from 0.001 to 0.12 micrograms/ml, and the MIC for 90% of the strains tested was 0.008 micrograms/ml . Cefetamet pivoxil was ineffective against Chlamydia trachomatis in 3 of 31 patients . Side effects were minor. Mycoses, 1990 Mar, 33(3), 140 - 5 Results of a combination treatment with natamycin and butylscopolamine in cases of intestinal Candida colonization; Gehring W et al.; The findings described show that Candida species can be found in the feces of approximately half a population of nonselected test persons and in the mouths of approximately a third . Intestinal Candida colonization was found in most of these persons after one feces examination, and in practically all of them after a second examination . 10 d of therapy with 400 mg natamycin per day in sugar-coated tablet form and 40 mg natamycin in the form of tablets for sucking produced a negative fungus test for the feces in only 20% of the cases . Although a combination of this therapy with 3 x 10 mg butylscopolamine per day improved short-term results significantly, the long-term results were hardly influenced at all . Typifying results according to the Warnock method showed that we are dealing with recurrences in practically all cases and not with new infections . Minimal inhibition concentrations (MIC) of natamycin showed no marked changes as a consequence of the natamycin treatment. Kansenshogaku Zasshi, 1990 Mar, 64(3), 310 - 20 {Study on the inhibitory effects of minocycline on genital Chlamydia trachomatis in McCoy cell culture}; Hosomura Y; In this study of Chlamydia trachomatis (C . trachomatis) from genital origin in McCoy cells, minocycline (MINO) was added to infected cell cultures at specific stages of their growth cycle . Sequential observations were made at each stage by electron microscope with the following results: 1) The minimal inhibitory concentration of MINO against C . trachomatis in McCoy cells was 0.025 micrograms/ml . 2) When MINO and chlamydial inoculation were simultaneously added (inoculum containing 1 microgram of MINO per ml), MINO did not inhibit attachment and invasion of elementary bodies (EBs) to McCoy cells in both cases of inoculation, with and without centrifugation . As 48 hours after inoculation 74% of the infectious EBs in McCoy cells were converted to early intermediate forms (IFs) . This suggests that MINO did not inhibit the transformation of EBs to early IFs . Under the influence of MINO, even after 48 hours, reticulate bodies (RBs) and chlamydial inclusions were not recognized . At the stages of transformation of infectious EBs to early IFs, duplication of the cell wall and electron lucent areas in the cytoplasm were observed . 3) Meanwhile, in the case of replacing the media with one containing MINO (1 microgram/ml) at 12 hours after inoculation, the conversion of RBs to late IFs was blocked . 4) Electron microscopically, the average numbers of late IFs and EBs per cross section of the inclusion at 24 hours after inoculation, were 0.64 and 0.17, respectively . At 48 hours after inoculation without MINO (control), the average numbers of late IFs and EBs were 10.5 and 65.6, respectively . When MINO (1 microgram/ml) was added at 24 hours after inoculation and observed at 48 hours, the average numbers of late IFs and EBs numbered 0.10 and 0.67, respectively . This indicates A) statistically, a significant decrease (0.64----0.10) for late IFs and a significant increase (0.17----0.67) for EBs compared with the average number of those at 24 hours after inoculation, B) when compared with the average number of those at 24 hours after inoculation, the sum of late IFs and EBs were nearly the same (0.64 + 0.17 not equal to 0.10 + 0.67), C) somewhat similar ratios of late IFs to EBs (10.5:65.6 = 1:6.2 not equal to 0.10:0.67 = 1:6.7) compared to the average number of those at 48 hours after inoculation without MINO (control) . B) suggests that the conversion of RBs to late IFs was blocked by MINO . A), B) and C) suggest that the conversion of late IFs to EBs was not inhibited by MINO.(ABSTRACT TRUNCATED AT 400 WORDS) Antiviral Res, 1990 Mar, 13(3), 139 - 49 Prophylactic ribavirin treatment of dengue type 1 infection in rhesus monkeys; Malinoski FJ et al.; The prophylactic efficacy of the broad-spectrum antiviral nucleoside analog ribavirin against flavivirus infection in non-human primates was investigated in a blinded, placebo-controlled study of rhesus monkeys infected with dengue virus . Both placebo- and ribavirin-treated monkeys developed viremia, as measured by direct plaque assay on Aedes albopictus C6/36 cells . Peak viremia occurred between days 3 and 9 after infection . No significant differences in time of onset, duration, or level of viremia were observed between placebo- and ribavirin-treated monkeys . Ribavirin induced predictable and reversible anemia and thrombocytosis . Serum ribavirin reached maximum levels of 30 microM by day 4, which approximates the in vitro minimum inhibitory concentration for dengue virus . Ribavirin appeared ineffective as a prophylactic drug for dengue type 1 viral infection, as evaluated by the magnitude of viremia in this monkey model. Invest Ophthalmol Vis Sci, 1990 Mar 1, 31(3), 502 - 5 Cefazolin levels after intravitreal injection . Effects of inflammation and surgery; Ficker L et al.; Cefazolin (2.25 mg) was injected into the vitreous cavity of phakic, aphakic, and aphakic/vitrectomized rabbits; inflamed eyes were compared to controls . Vitreous levels of cefazolin were determined at selected times from 2 to 48 hr, and the half-life was calculated . The effect of inflammation was to increase the half-life or to reduce the rate of elimination of cefazolin from the vitreous cavity . The drug was cleared substantially faster from aphakic/vitrectomized eyes than from phakic or aphakic eyes . Vitreous levels of cefazolin were above the MIC for most common gram-positive organisms causing endophthalmitis in all study groups at 24 hr, but in only the phakic inflamed eyes and in the aphakic eyes with intact vitreous at 48 hr. Am J Vet Res, 1990 Mar, 51(3), 381 - 5 Ocular and serum disposition kinetics of cloxacillin after topical administration of benzathine cloxacillin and intravenous administration of sodium cloxacillin to calves; Daigneault J et al.; Disposition kinetics of cloxacillin were examined in calves after topical administration of benzathine cloxacillin and single IV administration of sodium cloxacillin, and the susceptibility of 17 field isolates of Moraxella bovis was measured . For the IV pharmacokinetic phase, sodium cloxacillin was administered at dosage of 10 mg/kg of body weight to male Holstein calves (n = 6, weighing 146 to 170 kg), and serum concentration of cloxacillin was measured thereafter for 10 hours . For the ocular pharmacokinetic phase, 6 calves were given either of 4 benzathine cloxacillin topical formulations consisting of 50-, 125-, 250-, or 375-mg doses . Treatment was repeated every 10 days until all 4 benzathine cloxacillin dosages were tested in the same 6 calves . Blood and tears were collected for 72 hours after each benzathine cloxacillin formulation was administered, and the concentration of cloxacillin in each specimen was measured, using a bioassay . The minimal inhibitory concentration of cloxacillin for 17 field isolates of M bovis was determined by use of an agar pour-plate dilution assay . After single IV administration of sodium cloxacillin, its half-life, body clearance, and volume of distribution were 19.5 +/- 12.8 minutes, 18.3 +/- 2.2 ml/min.kg, and 496 +/- 290 ml/kg, respectively . After topical administration of benzathine cloxacillin, cloxacillin concentration in lacrimal fluid peaked between 30 and 45 minutes and ranged between 963 micrograms/ml and 3,256 micrograms/ml for the 125- and 375-mg doses, respectively . There was no detectable cloxacillin activity in the lacrimal fluid of any calf by 36 hours after topical administration of benzathine cloxacillin, and cloxacillin was not detected in the serum at any time.(ABSTRACT TRUNCATED AT 250 WORDS) Infection, 1990 Mar-Apr, 18(2), 101 - 4 A comparative study of cefamandole and ceftriaxone as prophylaxis in cardiac surgery; Neidhart P et al.; We compared the prophylactic use of cefamandole and ceftriaxone in 40 patients undergoing elective cardiac surgery . Postoperative wound infection occurred in one and two patients, respectively, in each group (n.s.), and bronchial superinfection in one patient in each group . In 12 additional patients drug concentrations in plasma and pericardial fluid were measured at different times following the administration of ceftriaxone . Plasma and pericardial fluid concentrations of ceftriaxone were above the minimal inhibitory concentration of susceptible microorganisms for up to 24 h after intravenous administration . We conclude, firstly, that the incidence of infection after cardiac surgery is low with both cefamandole and ceftriaxone prophylaxis . Secondly, efficient plasma and pericardial fluid levels of ceftriaxone last for up to 24 h after intravenous administration. Am Rev Respir Dis, 1990 Mar, 141(3), 640 - 7 Chronic cough . The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy; Irwin RS et al.; A successful, systematic, anatomic, diagnostic protocol for evaluating patients with chronic cough was presented in 1981 . To determine whether it was still valid, we prospectively evaluated, over a 22-month interval, 102 consecutive and unselected immunocompetent patients complaining of cough an average of 53 +/- 97 months (range, 3 wk to 50 yr) . Utilizing the anatomic, diagnostic protocol modified to include prolonged esophageal pH monitoring (EPM), the causes of cough were determined in 101 of 102 (99%) patients, leading to specific therapy that was successful in 98% . Cough was due to one condition in 73%, two in 23%, and three in 3% . Postnasal drip syndrome was a cause 41% of the time, asthma 24%, gastroesophageal reflux (GER) 21%, chronic bronchitis 5%, bronchiectasis 4%, and miscellaneous conditions 5% . Cough was the sole presenting manifestation of asthma and GER 28 and 43% of the time, respectively . While history, physical examination, methacholine inhalational challenge (MIC), and EPM yielded the most frequent true positive results, MIC was falsely positive 22% of the time in predicting that asthma was the cause of cough . Laboratory testing was particularly useful in ruling out suspected possibilities . We conclude that the anatomic diagnostic protocol is still valid and that it has well-defined strengths and limitations. Am Rev Respir Dis, 1990 Mar, 141(3), 626 - 30 Bactericidal activity in vitro of various rifamycins against Mycobacterium avium and Mycobacterium tuberculosis; Heifets LB et al.; Minimal inhibitory and bactericidal concentrations (MICs and MBCs) of rifampin (RMP), rifabutin (RBT), rifapentine (RPT), CGP-7040, and P-DEA, were determined for 50 M . avium strains in 7H12 liquid medium radiometrically under various pH conditions . Half were isolated from patients with AIDS and the other half from patients without AIDS but with pulmonary disease . The MICs and MBCs were also determined in 7H12 broth for M . tuberculosis strains . The MIC results obtained with M . tuberculosis strains, and the serum peak levels in humans, were used as standards for interpretation of the MICs and MBCs of the rifamycins for M . avium . The bactericidal activity of all rifamycins for M . avium was substantially lower than for M . tuberculosis . The majority of M . avium strains was within the "susceptible" category, e.g., comparable to susceptible M . tuberculosis strains, when tested with CGP-7040 and RPT, and all of them were "moderately susceptible" when tested with P-DEA . On the basis of in vitro bacteriostatic and bactericidal activity, it seems that three agents, RPT, P-DEA, and CGP-7040 have more potential than do RMP and RBT against M . avium disease. Rev Infect Dis, 1990 Mar-Apr, 12 Suppl 3, S304 - 6 Comparison of fluconazole and ketoconazole in experimental murine blastomycosis; Stevens DA et al.; Fluconazole, a new oral triazole antifungal agent, was tested against Blastomyces dermatitidis in vitro and in a murine model (pulmonary challenge) and compared with ketoconazole, an oral imidazole known to be effective against this agent in mice and in humans . Although fluconazole appeared less active than ketoconazole in vitro, in experiments involving 3 weeks of treatment and 2 months of observation, fluconazole was greater than 10 times as potent (mg/kg) in vivo against blastomycosis (prolongation of life) . In the model neither drug was curative at the doses and regimens used . A possible explanation for the efficacy of fluconazole in vivo is its favorable pharmacokinetic profile (i.e., prolonged serum concentrations that exceeded the MIC for the pathogen after oral administration) . Dosages of 100 mg/(kg.d) were tolerated for 3 weeks without evident toxicity. Rev Med Chil, 1990 Mar, 118(3), 291 - 5 {Concentration of cefotaxime in the exudate from ischemic ulcer after systemic and regional administration}; Acevedo A et al.; We evaluated the concentration of cefotaxime in the exudate from ischemic leg ulcers in 9 subjects with severe obstructive arterial disease . The administration of the drug was either systemic (1 g in 250 ml of saline given in 30 min) or regional at a vein of the foot while a tourniquet was applied at the level of the thigh during 30 min . Hygroscopic discs were used to collect samples of ulcer exudate at hourly intervals for 4 hr . Cefotaxime concentration was determined by HPL chromatography . A significantly greater concentration of antibiotic was obtained with regional as compared to systemic administration (46 +/- 16 vs 25 +/- 14, p less than 0.01) and a greater percentage of patients attained MIC 90 . A stable concentration of the drug was observed during the 4 hr period indicating a decreased rate of elimination of the antibiotic from the ulcer tissue . Thus, regional administration of antibiotics affords greater concentration than systemic administration, for treatment of ischemic leg ulcers. Ugeskr Laeger, 1990 Feb 5, 152(6), 375 - 9 {Advice on intravenous treatment with beta-lactams}; Schumacher H et al.; Beta-lactams (BL) are administered at present in dosages which are based only partly on controlled clinical investigations as these are difficult to carry out for all types of infections . Investigations of well-defined infections and animal experiments suggest that the optimal effect is obtained when the BL concentration is kept above the minimal inhibiting concentration (MIG) during treatment . In cases of intermittent BL treatment of serious infections and treatment of patients with compromised immune defence, it is considered advisable to keep the serum concentration constantly above the anticipated limit of sensitivity or MIC . On the basis of a review of the most important pharmacokinetic properties of BL, methods of measurement of the sensitivity of bacteria to BL and development of bacterial resistance to BL, a method is presented of calculating the individual doses and the intervals between doses as regards the sensitivities of the commonest human pathological bacteria to BL although the proposed dosages have not been tested clinically for all types of infections . Employing this, BL may easily be administered individually according to the severity of the infection and possible special conditions in the underlying disease in the patients . The individual doses and intervals between doses recommended in The Danish Medical Codex from 1988 are presented in tabular form and are compared with calculations of the time in which the serum concentration remains above the anticipated limit of sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) Planta Med, 1990 Feb, 56(1), 66 - 9 In vitro activity of protoanemonin, an antifungal agent; Martin ML et al.; Protoanemonin, the lactone of gamma-hydroxy-vinylacrylic acid, isolated from Pulsatilla alpina has in vitro activity against fungi . The MIC is 15 micrograms/ml and RNA inhibition seems to be the first target of the drug . The LD50 of protoanemonin in male Swiss albino mice was 190 mg/kg. J Med Assoc Thai, 1990 Feb, 73 Suppl 1, 28 - 32 Assessment of endocervical curettage in colposcopy; Linasmita V et al.; Colposcopy has become an accepted diagnostic procedure in the management of patients with abnormal cervical cytology . To assess the value of the endocervical curettage in colposcopy, a retrospective review of 125 cases who had the procedure done during the 20-month period (January 1986-August 1988) was carried out . The ECC were positive in 3 out of 57 (5.3%) patients with satisfactory examination and 24 out of 68 (35.3%) patients with unsatisfactory examination . In all 27 cases, there was insufficient tissue to make a diagnosis of invasive carcinoma . Of the 125 patients studied seventy-two (29 in the satisfactory group and 43 in the unsatisfactory group) underwent conization and/or hysterectomy . Endocervical curettage did not eliminate the need for cone biopsy in all cases of unsatisfactory colposcopy . The tissue diagnosis on ECC did not increase the diagnostic accuracy derived from the colposcopic directed biopsies in either group . There were 20 cases of invasive carcinoma (13 MIC, 7 invasive) in this study, the ECC were positive in 9 . We concluded that the ECC has limited value in colposcopy. J Chemother, 1990 Feb, 2(1), 8 - 10 In-vitro evaluation of a new oral cephalosporin, cefroxadine (CGP 9000); Shibl AM et al.; The in vitro activity of cefroxadine was studied and found to be at least comparable to that previously reported for cefalexin and cefradine . The activity of cefroxadine was superior to that of amoxicillin against tested isolates . Time-killing studies showed that the addition of 4 X minimum inhibitory concentration (MIC) of cefroxadine to growing cultures reduced viable counts by 4 log units within a 3 h incubation . A diffusion test with a 30 microgram cefroxadine disk produced acceptable interpretive results with tentative zone size breakpoints of less than or equal to 14 mm for resistance and greater than or equal to 17 mm for susceptibility. J Antimicrob Chemother, 1990 Feb, 25 Suppl B, 23 - 31 Pharmacokinetics of sodium fusidate after single and repeated infusions and oral administration of a new formulation; Taburet AM et al.; The pharmacokinetics of sodium fusidate were studied in eight healthy volunteers (five males and three females) aged 21 to 33 years (29.1 +/- 1.5), weight 46 to 79 kg (61.6 +/- 4.0 kg) . First, the subjects were given 500 mg of sodium fusidate by infusion over two hours; secondly, one month later, the volunteers were given 500 mg of fusidate by infusion every eight hours for three days; thirdly, two 250 mg tablets of a new film coated formulation were administered as a single dose . Plasma concentrations of fusidate were measured by HPLC . Peak plasma concentrations reached at the end of the first and the last infusions were 52 +/- 5 mg/l and 123 +/- 12 mg/l respectively . The following mean pharmacokinetic parameters were obtained after single intravenous administration: elimination half-life 10 +/- 1 h, total clearance 22 +/- 2 ml/min and volume of distribution 0.30 +/- 0.04 l/kg . After repeated administration the half-life and the volume of distribution remained unchanged whereas total clearance was halved (11 +/- 1 ml/min) . This leads to an experimental accumulation ratio (3.6 +/- 0.2) higher than the theoretical one (1.8 +/- 0.1; P less than 0.01) . Consequently, mean trough and peak steady state plasma concentrations (81 +/- 9 and 123 +/- 12 mg/l respectively) are higher than those expected from the single dose kinetics (33 +/- 4 and 76 +/- 7 mg/l respectively) . This dose regimen leads to concentrations well above the MIC for most sensitive strains.(ABSTRACT TRUNCATED AT 250 WORDS) J Dent Res, 1990 Feb, 69(2), 436 - 41 Prevention of population shifts in oral microbial communities in vitro by low fluoride concentrations; Bradshaw DJ et al.; A continuous culture system has been used to study the effects of low (sub-MIC) levels of sodium fluoride on the stability and metabolism of a defined oral microbial community . The microflora was also subjected to glucose pulses at pH 7.0, with and without subsequent pH control . At pH 7.0, a continuous supply of 1 mmol/L NaF reduced slightly the viable counts of the oral microflora, although their proportions were relatively unaffected . At pH 7.0, during glucose pulsing, 1 mmol/L NaF prevented the rise in proportions of A . viscosus and reduced the levels of B . intermedius . Glucose pulsing without pH control and in the absence of fluoride markedly inhibited the growth of many species, and L . casei, V . dispar, and S . mutans predominated in the culture . Fluoride (1 mmol/L), either pulsed with the glucose or provided continuously, reduced both the rate of change and the degree of fall in pH, and in doing so prevented the enrichment of S . mutans in the culture . Fluoride also reduced the pH-mediated inhibition of other members of the oral community, although S . sanguis was inhibited even further . Thus, even sub-MIC levels of fluoride may have a beneficial anti-bacterial effect on dental plaque by interfering with acid production . This would reduce the pH-mediated disruption to the balance of the microflora and suppress the selection of S . mutans. Am J Vet Res, 1990 Feb, 51(2), 197 - 9 Endometrial concentrations of ampicillin in mares after intrauterine infusion of the drug; Love CC et al.; Serum concentration of ampicillin, a semisynthetic penicillin, was measured in mares at various time intervals up to 24 hours after intrauterine infusion of 3 g of ampicillin . Blood samples were drawn immediately before infusion and at 1-, 4-, 10- and 24-hour intervals after infusion . At postinfusion hour 24, two endometrial biopsy specimens were obtained to measure endometrial concentrations of ampicillin . Blood was drawn twice as part of the 24-hour postinfusion sample collection, once before removal of the biopsy specimens and again 5 minutes after removal of the biopsy specimens . After drug infusion, more diestrous mares had detectable serum ampicillin concentration than did estrous mares for all samples, except the 24-hour prebiopsy sample . None of the 24-hour prebiopsy serum samples had detectable ampicillin concentration, but ampicillin was detected in the serum of 4 of 5 diestrous mares after endometrial biopsy . Endometrial concentrations of ampicillin were detectable at postinfusion hour 24 in estrous and diestrous mares, but were not different . All 24-hour biopsy specimens had ampicillin concentrations greater than the ampicillin minimal inhibitory concentration. J Am Acad Dermatol, 1990 Feb, 22(2 Pt 1), 211 - 5 Levels of itraconazole in skin blister fluid after a single oral dose and during repetitive administration; Schafer-Korting M et al.; Oral itraconazole is effective in the treatment of mycoses . To measure its concentrations in the tissue, levels of total and non-protein-bound itraconazole were determined in serum, suction-induced blister fluid, and cantharides-induced blister fluid . Six healthy subjects received 200 mg as a single dose, followed by 100 mg/day for 10 days . Itraconazole binding in suction-induced blister fluid (99.54%) and cantharides-induced blister fluid (99.77%) was calculated from plasma protein binding (99.8%) . The single-dose study showed the drug levels in blister fluid to increase more slowly than those in serum . The terminal half-life of itraconazole in serum was 22.5 +/- 3.2 hours . Suction- and cantharides-induced blister fluid levels declined in parallel . After the final dose, itraconazole penetration into cantharides-induced blister fluid was only 70% . Moreover, trough levels of unbound itraconazole in suction- and cantharides-induced blister fluid were 0.239 +/- 0.115 and 0.334 +/- 0.101 ng/ml and thus were significantly lower than free itraconazole levels in serum (0.422 +/- 0.125 ng/ml) . Thus a distribution equilibrium between serum and blister fluids was not obtained . Free drug concentrations in suction- and cantharides-induced blister fluid were far lower than the minimal inhibitory concentration values for Candida ssp . and dermatophytes. Pneumologie, 1990 Feb, 44 Suppl 1, 504 - 6 {Resistance testing of M . avium-intracellulare and M . tuberculosis of AIDS patients with new drugs and drug combinations}; Mauch H et al.; The minimal inhibitory concentration (MIC) of rifabutin for M . tuberculosis was 0.006 to 0.06 micrograms/ml, and 0.12 to 0.25 micrograms/l for clofazimine . Accordingly, M . tuberculosis is inhibited by concentrations of these two medications that are far lower than the levels normally found in the serum . In the case of M . avium, the MIC of the new drugs such as rifabutin and clofazimine are, in contrast to the MICs for M . tuberculosis, merely of the order of the achievable serum concentrations . The minimum bactericidal concentrations of these two substances are much higher than the bacteriostatic concentrations, which probably explains the frequent therapeutic failures, while in the case of ciprofloxacin, the prevailing situation is much more favourable . The growth of all M . avium strains is inhibited (= sensitive) when elevated concentrations (double "breakpoint" concentrations) of a triple-drug combination comprising rifampicin, ethambutol and ciprofloxacin, or a combination of ethambutol, rifampicin, ciprofloxacin and prothionamid are tested at "normal breakpoint" concentrations. J Infect Dis, 1990 Feb, 161(2), 261 - 5 Penicillin tolerance in Arcanobacterium haemolyticum; Nyman M et al.; It was previously found that Arcanobacterium haemolyticum, which can cause tonsillitis with exanthema, is not eradicated from the pharynx by administration of phenoxymethylpenicillin, despite minimum inhibitory concentration values of 0.015-1.0 micrograms/ml . Therefore, recent clinical isolates were studied for penicillin tolerance by using a disk diffusion screening test and a pour plate assay . Macrobroth dilution minimum inhibitory and bactericidal concentrations and antibiotic kill kinetics were determined for 4 isolates . Tolerance was present in 38 of 40 clinical isolates with the disk diffusion assay . With the pour plate assay all 40 isolates were tolerant, 34 of them highly tolerant . The presence of the tolerant phenotype was confirmed by macrobroth dilution assays . It is concluded that A . haemolyticum is often penicillin-tolerant, suggesting that phenoxymethylpenicillin administration would be ineffective in eradicating A . haemolyticum from the pharynx. Schweiz Med Wochenschr, 1990 Jan 27, 120(4), 92 - 7 {Penicillinase-producing strains of N . gonorrhoeae (PPNG) in the Zurich area, 1981-1988: incidence, antibiotic sensitivity and plasmid profile (3)}; Schlapfer G et al.; During the period 1981 to 1988 2688 strains of N . gonorrhoeae from patients with gonorrhea were investigated at the Department of Dermatology . Zurich University Hospital . The frequency of gonorrhea decreased by 86% (from 566 in 1981 to 76 in 1988) . The proportion of PPNG strains varied between 3.5% and 6.5% until 1986 and increased to 20% in 1988 . If chromosomal penicillin resistant strains are included, in 1988 25% of all isolated N . gonorrhoeae strains were resistant to penicillin . Until 1984 West African and South East Asian countries were almost exclusively the source of the PPNG strains . In 1988 our PPNG strains were acquired in all five continents . Since 1985 roughly 20% of the PPNG infections have been acquired in Zurich . 95 out of 125 PPNG strains between 1981 and 1988 were examined for plasmids . 85 out of 95 PPNG strains contained the 4.4-MD plasmid ("Asia plasmid") and 8 out of 95 the 3.2-MD plasmid ("Africa plasmid"), while 63 out of 95 PPNG strains additionally contained the 24,6-MD transfer plasmid . Antibiotic resistance was as follows: all PPNG strains were resistant to penicillin (MIC greater than 1 microgram/ml) . 80% to 100% were resistant to tetracycline (MIC greater than 1 microgram/ml), and 100% were sensitive to spectinomycin (MIC less than 30 micrograms/ml) and to thiamphenicol (MIC less than 2 micrograms/ml) respectively. Zentralbl Mikrobiol, 1990, 145(3), 187 - 93 Potential for the development of tolerance by Aspergillus amstelodami, A . repens and A . ruber after repeated exposure to potassium sorbate; Vinas I et al.; Three strains of A . amstelodami, A . repens and A . ruber were exposed to various levels of potassium sorbate, and the MICs were determined . Selected strains of the molds were then repeatedly exposed to subinhibitory levels of the compound to determine whether increased tolerance might develop . The MIC of sorbate (pH 5.5 or 6.5) for 3 species of Aspergillus was 0.07% . Increasing levels of sorbate resulted in increasing growth suppression of the molds . The 3 Aspergillus species were tested for increased tolerance to potassium sorbate, and none was found . They developed a slight increase in tolerance dependent upon pH and the mold strain by subculturing at low levels of sorbate. Z Gesamte Inn Med, 1990 Jan 1, 45(1), 8 - 11 {Dietary iodine deficiency in East Germany following introduction of interdisciplinary preventive use of iodine}; Bauch K et al.; The interdisciplinary iodine prophylaxis introduced in 1985/86 comprises the iodination of 84% of the packaged salt with 32 mg KIO3/kg salt and the use of iodized mixtures of mineral substances in animal production . At the beginning of this measure with an average renal ioduria of 19.0 +/- 1.0 micrograms J/g creatinine in the GDR there was at least still an iodine deficiency of 2nd degree . It increased from north to south: 20.3 +/- 1.0 in contrast 13.4 +/- 1.5 micrograms J/g creatinine . In the middle of 1986 a clear improvement of the supply with iodine began . The renal iodurias had more than doubled . For the GDR the mean ioduria was 43.4 +/- 0.9 . The relation from north to south had, if anything, inverted: 37.3 +/- 2.1 in the north, 42-49 micrograms J/g creatinine in the centre and south of the GDR . Nearly one third of the population no more undergoes an iodine deficiency . The intrathyroidal iodine content increases . The improved supply with iodine among others is evident in: reduction of the connatal goiter below 1%, reduction of the recall rate in the TSH hypothyroidism newborn screening, normal thyroid gland mass of the newborn, reduction of the goiter frequency in children and adolescents, transient increase of the frequency of hyperthyroidism, in particular based on functional autonomies in persons older than forty years . In animal production losses of produce amounting to 181 Mic/a were eliminated. Antimicrob Agents Chemother, 1990 Jan, 34(1), 65 - 70 Activities of ciprofloxacin and ofloxacin against rapidly growing mycobacteria with demonstration of acquired resistance following single-drug therapy; Wallace RJ Jr et al.; The susceptibility to ciprofloxacin of 548 clinical isolates of rapidly growing mycobacteria belonging to eight subgroups or species was determined . The 170 isolates of Mycobacterium fortuitum biovar.fortuitum were most susceptible; the MIC for 90% of the organisms was 0.125 micrograms/ml . The other biovariants of M . fortuitum, M . smegmatis, and the M . chelonae-like organisms were less susceptible; the modal MIC was 0.5 micrograms/ml, and the MIC for 90% of organisms was 1.0 micrograms/ml . The two subspecies of M . chelonae were generally resistant, with only 8% of 206 isolates falling in the moderately susceptible category (MIC, 2 micrograms/ml) and only 2% falling in the susceptible category (MIC, less than or equal to 1 micrograms/ml) . MICs of ofloxacin averaged 1 to 2 dilutions higher than those of ciprofloxacin for all subgroups tested . Three patients with M . fortuitum cutaneous disease relapsed after an initial response to therapy with ciprofloxacin, and their isolate was shown to have acquired drug resistance . Mutational frequencies for M . fortuitum with ciprofloxacin were relatively high (10(-5) to 10(-7), and MICs for single-step mutants were similar to those for the clinically resistant strains . Thus, despite the excellent activity of ciprofloxacin against rapidly growing mycobacterial groups other than M . chelonae, single-drug therapy should be used with caution because of the risk of development of mutational resistance. J Antibiot (Tokyo), 1990 Jan, 43(1), 70 - 5 6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase . I . Racemic 6-ethylidenepenems; Basker MJ et al.; The dehydration of various 6-(1-hydroxyethyl)penems to give E- and Z-6-ethylidenepenems is described . Both isomers have been shown to be potent broad spectrum inhibitors of bacterial beta-lactamases capable of reducing the MIC values of beta-lactam antibiotics such as amoxycillin and cephaloridine against a wide range of resistant organisms. Equine Vet J, 1990 Jan, 22(1), 51 - 3 Pharmacokinetics of trimethoprim-sulphamethoxazole in two-day-old foals after a single intravenous injection; Brown MP et al.; Six healthy two-day-old foals (3 pony foals and 3 horse foals) were given a single intravenous (iv) injection of trimethoprim (TMP)--sulphamethoxazole (SMZ) at a dosage of 2.5 mg of TMP/kg bodyweight (bwt) and 12.5 mg of SMZ/kg bwt . Serum TMP and SMZ concentrations were measured serially during a 24 hour period . The overall elimination rate constant (K) for TMP in the pony and horse foals was 0.45/h, whereas the K values for SMZ for the pony and horse foals were 0.12/h and 0.07/h, respectively (no significant difference; P greater than 0.05) . Based on published minimum inhibitory concentration values for equine pathogens (Adamson et al 1985), the primary indication for the use of TMP/SMZ in foals may be in the treatment of infections caused by gram-positive bacteria . A dosage of 2.5 mg of TMP/kg bwt and 12.5 mg of SMZ/kg bwt, given iv at 12 h intervals would be appropriate. J Med Microbiol, 1990 Jan, 31(1), 37 - 44 The effect of antibiotics that inhibit cell-wall, protein, and DNA synthesis on the growth and morphology of Legionella pneumophila; Rodgers FG et al.; The response of Legionella pneumophila to antibiotics that inhibit cell-wall, protein and DNA synthesis was examined by electronmicroscopy, MIC estimations and viable counts . Ampicillin, cefotaxime, methicillin, erythromycin, rifampicin and ciprofloxacin, each used separately at 20 times their respective MIC values, showed activity against L . pneumophila in these studies . The inhibitors of cell-wall synthesis--ampicillin, cefotaxime and methicillin--effected the greatest bactericidal activity and induced the most extensive morphological changes, which included the formation of membranous lesions through which cytoplasmic contents were lost . In terms of ultrastructural damage and loss of viability, the inhibitors of protein and DNA synthesis were less effective than the antibiotics that acted on the microbial cell wall . Erythromycin- and rifampicin-treated cells possessed irregular membranes and were partially or fully lysed, whereas ciprofloxacin induced abnormally elongated organisms with intermittently lysed and detached inner membranes . These results illustrated the ability of antibiotics of putative clinical value, with diverse modes of action, to affect the ultrastructural cytology as well as the viability of L . pneumophila in vitro. Pharmacotherapy, 1990, 10(6), 373 - 7 The effect of tourniquet inflation on cefazolin tissue penetration during total knee arthroplasty; Friedrich LV et al.; Patients undergoing total knee arthroplasty were randomized to tourniquet inflation 1, 2, or 5 minutes after a 1-g dose of cefazolin . Serum, soft tissue, and bone samples were obtained at 10, 30, and 60 minutes after inflation, immediately prior to tourniquet release (PTR), and 5 minutes after release . Areas under the concentration-time curve (AUC10-PTR) were calculated using the linear trapezoidal method and normalized to actual body weight, creatinine clearance, and length of tourniquet inflation . The percentage of penetration was calculated using the normalized values for the respective AUCs . Differences among the groups were analyzed using analysis of variance or the Kruskal-Wallis test where appropriate . Groups were similar for age, actual body weight, duration of tourniquet inflation, and creatinine clearance (p greater than 0.05) . The median percentages of penetration for soft tissue and bone at 5, 2, and 1 minute were 14.5% and 4.6%, 6.7% and 3.0%, and 5.9% and 4.6%, respectively . Only the percentage of soft tissue penetration between 5 and 1 minute was significantly different (p = 0.015) . Gender and type of anesthesia (general, epidural) had no effect on cefazolin penetration into soft tissue or bone . Although increasing the time interval between cefazolin administration and tourniquet inflation resulted in higher soft tissue drug concentrations, a 1-minute interval resulted in soft tissue and bone cefazolin concentrations at or above the minimum inhibitory concentration for microorganisms likely to be encountered in this surgical procedure. Microbiol Immunol, 1990, 34(8), 653 - 63 Effect of Tween 80 on the growth of Mycobacterium avium complex; Masaki S et al.; The effect of Tween 80 on the growth of Mycobacterium avium complex (MAC) in liquid culture condition was investigated . Observation of the colony-forming units (CFU) and the morphology of MAC with transmission and scanning electron microscopy showed that Tween 80 at 0.05% in the medium (ca . 0.5 mg/ml) had bacteriostatic action and caused cell elongation . Tween 80 at 0.5% or more in the medium (ca . 5 mg/ml) reduced the quantity of MAC glycolipids and also led to false positive or positive results in biochemical tests for mycobacterial identification using nitrate reductase, urease, or arylsulfatase . To determine whether or not surfactants could reduce the MAC permeability barrier, the minimal inhibitory concentration (MIC) of antituberculosis drugs on MAC was determined in liquid medium with or without several kinds of surfactants including Tween 80 . Five surfactants including Tween 80 increased the activity of antituberculosis drugs to MAC . These findings suggest that Tween 80 acts directly on the cell wall of MAC. Chemotherapy, 1990, 36(4), 308 - 20 Combinations of antifungal and antineoplastic drugs with interactive effects on inhibition of yeast growth; Ghannoum MA et al.; Interactive effects among antifungal and antineoplastic drugs contributed to toxicities when combinations of these drugs were used to inhibit the growth of five Candida spp . Drug interactions were measured by growth inhibition in both liquid and solid media, by viable cell counts and by examination using scanning electron microscopy . Large cooperative effects on toxicity were demonstrated between some antineoplastic and antifungal drugs . For example, positive cooperativity was seen between the antineoplastic drug 5-fluorouracil and combinations of the antifungal agents amphotericin B and miconazole nitrate . Smaller, and often negative, interactions occurred between the antineoplastic drug cyclophosphamide and antifungal drugs . The levels of drugs required for inhibition in combination drug treatments were critically dependent upon the ratios as well as the absolute concentrations of the drugs tested . Drug combinations were selected which inhibit yeast growth at concentrations far below the individual MIC <