Gastroenterology, 1993 Nov, 105(5), 1370 - 7 Distribution and characterization of vasoactive intestinal polypeptide binding in canine lower esophageal sphincter; Mao YK et al.; BACKGROUND: Vasoactive intestinal polypeptide (VIP) may be a nonadrenergic, noncholinergic inhibitory transmitter in the lower esophageal sphincter (LES) . There is no biochemical evidence of VIP receptors in the LES . METHODS: Using membranes from canine LES, VIP receptor distribution and characterization were analyzed by radioligand binding and cross-linking experiments . RESULTS: High densities of saturable VIP receptors were found (maximum bound {Bmax}, 539.2 fmol/mg in the synaptosome-enriched fraction {P2} and 732.7 fmol/mg in the smooth muscle, plasma membrane-enriched fraction {Mic II}), with high affinity for 125I-VIP (dissociation constant {Kd}, 1.38 nmol/L in P2 and 1.40 nmol/L in Mic II) . Competition binding studies suggested the presence of two binding sites, a high-affinity (inhibitor constant {Ki1}, 0.064 nmol/L) and a low-affinity (Ki2, 2.68 nmol/L) binding site in P2 membranes, but only one binding site (Ki, 1.18 nmol/L) in Mic II membranes . Guanosine triphosphate-gamma-s pretreatment eliminated high-affinity binding in P2 membranes by conversion to binding sites of lower affinity (Ki, 2.82 nmol/L) . Studies with a cross-linking agent identified VIP receptors in synaptosomal and smooth muscle plasma membrane fractions; a single polypeptide of approximately 60 kilodaltons was found in each membrane . CONCLUSIONS: Specific VIP receptors exist in both synaptosomal and smooth muscle plasma membrane of canine LES. Chest, 1993 Nov, 104(5), 1553 - 62 Mechanical insufflation-exsufflation . Comparison of peak expiratory flows with manually assisted and unassisted coughing techniques; Bach JR; Pulmonary complications are major causes of morbidity and mortality for patients with severe expiratory muscle weakness . The purpose of this study was to compare peak cough expiratory flows (PCEFs) during unassisted and assisted coughing and review the long-term use of mechanical insufflation-exsufflation (MI-E) for 46 neuromuscular ventilator users . These individuals used noninvasive methods of ventilatory support for a mean of 21.1 h/d for 17.3 +/- 15.5 years . They relied on manually assisted coughing and/or MI-E during periods of productive airway secretion . They reported a mean of 0.7 +/- 1.2 cases of pneumonia and other serious pulmonary complications and 2.8 +/- 5.6 hospitalizations during the 16.4-year period and no complications of MI-E . A sample of 21 of these patients with a mean forced vital capacity of 490 +/- 370 ml had a mean maximum insufflation capacity (MIC) achieved by a combination of air stacking of ventilator insufflations and glossopharyngeal breathing of 1,670 +/- 540 ml . The PCEFs for this sample were: following an unassisted inspiration, 1.81 +/- 1.03 L/s; following a MIC maneuver, 3.37 +/- 1.07 L/s; with manual assistance by abdominal compression following a MIC maneuver, 4.27 +/- 1.29 L/s; and with MI-E, 7.47 +/- 1.02 L/s . Each PCEF was significantly greater than the preceding, respectively (p < 0.01) . We conclude that manually assisted coughing and MI-E are effective and safe methods for facilitating airway secretion clearance for neuromuscular ventilator users who would otherwise be managed by endotracheal suctioning . Severely decreased MIC, but not necessarily vital capacity, is an indication for tracheostomy. Diagn Microbiol Infect Dis, 1993 Nov-Dec, 17(4), 283 - 91 Antiviral susceptibility testing of cytomegalovirus from primary culture using shell vial assay to detect the late viral antigen; Lipson SM et al.; Susceptibility testing of 68 cytomegalovirus (CMV) peripheral blood isolates to Ganciclovir (DHPG) and 11 blood isolates to Foscarnet (PFA), was performed on primary culture isolates using the shell vial assay methodology (SVA-IFA, that is, quantitation of fluorescent focus units, FFUs), with an anti-CMV monoclonal antibody to the late viral antigen . A positive reaction in monolayer cultures of MRC-5 cells was characterized by cytoplasmic fluorescence with inclusions at both or more commonly off one end of the elongated fibroblast nucleus . Isolates from conventional MRC-5 tube cultures displaying a 1+ (10% cytopathic effect) were inoculated into shell vials containing DHPG concentrations of 0, 1.5, 3, 6, 12, or 24 microliters/ml shell vials containing 400, 500, 800, or 1200 microM PFA . The optimal readability of monolayers (expressed as FFUs per monolayer) occurred at 96 h after treatment with DHPG and at 36-48 h with PFA . Resistance to DHPG was determined at the concentration of antiviral agent necessary to reduce the number of FFUs to 90% or 50% of the control {that is, the 90% minimum inhibitory concentration (MIC90) or MIC50} . Six of 68 isolates showed an MIC90 > 12 or an MIC50 > 1.5 microgram/ml, and were considered DHPG resistant . Three of the six isolates were from AIDS patients with late-stage disease who had never received DHPG therapy . All but one (specimen 2400) DHPG-resistant isolates revealed MIC90 values to a PFA concentration of 500 microM, which is considered an achievable peak plasma level in patients undergoing PFA therapy . The single DHPG- and FPA-resistant isolate was obtained from a patient displaying marked clinical resistance to both drugs.(ABSTRACT TRUNCATED AT 250 WORDS) Infect Immun, 1993 Oct, 61(10), 4382 - 91 Molecular epidemiology of penicillin-resistant pneumococci isolated in Nairobi, Kenya; Kell CM et al.; A total of 26% of the pneumococci isolated from an outpatient clinic in Nairobi, Kenya, during 1991 to 1992 had intermediate levels of penicillin resistance . Gene fingerprinting and DNA sequencing were used to distinguish the penicillin-binding protein (PBP) 1A, 2B, and 2X genes in 23 resistant isolates . Isolates were grouped into those that had identical forms of each of the three PBP genes (fingerprint groups) and those that had identical rRNA gene restriction patterns (ribotypes) . Both methods divided the isolates into 11 groups . In a few cases, horizontal gene transfer appeared to have distributed an identical altered PBP gene into different pneumococcal lineages . Eight isolates were indistinguishable by ribotyping or multilocus enzyme electrophoresis and contained identical PBP 1A genes . Although these isolates were therefore members of the same clone, they were divided into two fingerprint groups which contained different PBP 2X and 2B genes . Presumably, members of this clone have acquired different altered PBP 2X and 2B genes on two separate occasions . One of these fingerprint groups contained isolates of serotype 14, whereas the other contained isolates of both serotypes 14 and 7 . The identification of isolates in the latter group that are identical by all criteria, except serotype, implies the occurrence of a change in serotype . The predominant serotypes of the penicillin-resistant pneumococci from Nairobi were serotypes 14 and 19 . In both cases, isolates of the same serotype which required the same MIC of penicillin were not members of a single clone, indicating that identity of serotype and MIC are not sufficient criteria for defining clones of resistant pneumococci even when the bacteria are isolated from a single clinic. New Microbiol, 1993 Oct, 16(4), 359 - 65 Enhancement of the antitrichomonal activity of 5-nitroimidazole derivatives by hydrogen peroxide; Mattana A et al.; The in vitro sensitivity of nine Trichomonas vaginalis isolates to commonly employed 5-nitroimidazoles (metronidazole, nimorazole, ornidazole and tinidazole) was evaluated in absence and in presence of sub-inhibitory concentrations of hydrogen peroxide (H2O2) . Co-incubation with H2O2 and 5-nitroimidazole compounds decreased the MIC values of the strains exhibiting cross-resistance to these drugs . It was suggested that H2O2 produced in the inflammatory process during trichomonal infection could enhance the therapeutic effect of 5-nitroimidazole drugs. Am J Trop Med Hyg, 1993 Oct, 49(4), 460 - 4 Chloroquine bioassay using malaria microcultures; Kotecka BM et al.; The in vitro microculture technique was used to develop a relatively simple bioassay for estimating chloroquine (CQ) in plasma or serum . Chloroquine concentrations were determined by multiplying the maximum inhibitory dilution of plasma/serum required to inhibit growth of the CQ-sensitive FC27 isolate of Plasmodium falciparum by the minimum inhibitory concentration of CQ against the same isolate . Human serum samples spiked with CQ gave similar measurements using both bioassay and high-performance liquid chromatography . The antimalarial activity of plasma or serum samples collected from 13 patients treated with CQ was equivalent to the sum of the combined activity of CQ and its metabolite, mono-desethylchloroquine . The concentration of these components using the bioassay could be expressed conveniently in terms of CQ concentration equivalents . This bioassay can be used to estimate drug concentrations without the use of sophisticated methods or equipment . Since it is based on the microculture technique, it can be easily carried out in conjunction with the drug susceptibility test to assess CQ treatment failures in malaria patients. Am Rev Respir Dis, 1993 Sep, 148(3), 650 - 5 Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis; Ellard GA et al.; Tuberculous meningitis is a very serious form of tuberculosis . In the absence of randomized controlled trials of alternative treatment regimens, its management depends on employing potent drugs that penetrate well into the cerebrospinal fluid (CSF) . The penetration of isoniazid, rifampin, and streptomycin into the CSF of 27 Chinese patients was studied using fluorimetric and microbiologic procedures . Isoniazid rapidly diffused into the CSF, peak concentrations in excess of 3 mg/L, or over 30 times its minimal inhibitory concentration (MIC) against Mycobacterium tuberculosis being attained within 4 hr . In contrast, rifampin and streptomycin penetrated very slowly across the meninges, and CSF levels only slightly in excess of their MICs against M . tuberculosis were achieved . The penetration of the drugs into the CSF correlated poorly with differences in their partitioning between octanol/water and cyclohexane/water but could be predicted using a simple model based on their renal clearance rates and plasma protein binding . It is recommended that patients with tuberculous meningitis should be treated for at least 9 months with a combination of isoniazid, rifampin, and pyrazinamide, which may be supplemented in the first 2 mo with streptomycin. Eur J Epidemiol, 1993 Sep, 9(5), 553 - 8 In vitro susceptibility of mycelial and yeast forms of Penicillium marneffei to amphotericin B, fluconazole, 5-fluorocytosine and itraconazole; Sekhon AS et al.; The mycelial (25 degrees C) and yeast-like (37 degrees C) forms of Penicillium marneffei clinical and type strains were investigated for their in vitro susceptibility to amphotericin B (AmB), 5-fluorocytosine (5-FC), fluconazole (FLU) and itraconazole (ITZ), using Bacto antibiotic medium 3, yeast-nitrogen, Sabouraud's dextrose (pH 5.7) and high resolution (pH 7.1) broth media (1ml/tube), respectively . Results indicated that the minimal inhibitory and minimal fungicidal concentrations (MICs and MFCs) for the mycelial cultures of P . marneffei to AmB were in the range 0.78-1.56 and 0.78-3.125 micrograms/ml, respectively, as against 3.125-25 micrograms (MICs) for the yeast form cultures . The MFCs to AmB for the yeast form were one dilution higher . The MICs to FLU were generally lower for the yeast form (6.25-25 micrograms) than the mycelial form (25-50 micrograms/ml), whereas MFCs for the mycelial cultures were > 100 micrograms as compared to 6.25-100 micrograms for their yeast form . The MICs for the mycelial form to 5-FC ranged from < 0.195-0.39 microgram . Higher MICs (6.25 micrograms) were recorded for their yeast form . The MFCs to 5-FC for the yeast form were 25-100 micrograms/ml . The MICs for the mycelial form to ITZ ranged from < 0.195 to 3.125 micrograms/ml . Higher values (< 0.195-50 micrograms) were recorded for their yeast-like form . The MFCs to ITZ for mycelial and yeast forms ranged from < 0.195-0.39 and 25-100 micrograms/ml, respectively . Results indicate that P . marneffei's yeast form is more sensitive to FLU and ITZ (8 of 10 strains) while the mycelial form displayed greater susceptibility to AmB and 5-FC . The MICs for ITZ remained steady in SD medium, pH 5.7 to 7.1 . However, some strains gave higher MIC values (0.39-1.56 micrograms/ml) when tested in the HR. Mikrobiologiia, 1993 Sep-Oct, 62(5), 843 - 8 {Metal resistance of gram-negative bacteria isolated from soil and waste waters of industrial regions}; Anisimova LA et al.; Metals resistance of 112 strains of gram-negative bacteria isolated from soil and wastes around Nizniy Novgorod plants were investigated . MIC of metals varied in range between 1-10 mM Ni2+, Co2+, 1-6 mM Zn2+, 1-4 mM Cd2+, CrO4(2-), and 0.1-0.3 mM TeO3(2-) . Bacteria with phenotypes NiCo and NiZnTe are revealed most frequent (25.6 and 6.4% accordingly) . Plasmid DNAs with size between 2-70 kbp were found in 50% isolated strains . It was shown that resistance to cobalt of unidentified gram-negative bacterium is determined by plasmid genes . Recombinant plasmid contained fragment DNA controlling resistance to cadmium and zinc from Pseudomonas spp . strain was constructed by using helper plasmid pULB113. Zentralbl Bakteriol, 1993 Sep, 280(1-2), 279 - 85 Activity of antibiotics and azole antimycotics against Helicobacter pylori; von Recklinghausen G et al.; The bacteristatic and bactericidal activities of six antibiotics from different substance classes against Helicobacter pylori were determined . Ampicillin, imipenem, tetracycline, and amikacin inhibit the growth of all isolates at concentrations achievable in serum . Cefpirome and ofloxacin are ineffective against three and two of 41 strains, respectively . However, the minimum bactericidal concentrations (MBC) of the substances are two- to sixteen-fold higher than the minimum inhibitory concentrations (MIC) . There is sufficient bactericidal activity of ampicillin and imipenem against all strains, but amikacin, ofloxacin, tetracycline, and cefpirome are unable to kill 2, 8, 12, and 18 of 25 strains, respectively, at concentrations achievable in serum . Differences between MIC and MBC of antibiotics may contribute to the explanation of therapy failures . In addition, the inhibitory activity of seven nitroimidazole antimycotics and the triazole fluconazole was evaluated . The nitroimidazole MICs range from 2 to 64 mg/l, with tioconazole, miconazole, bifonazole, and ketoconazole as the most active substances . Fluconazole, however, was ineffective at concentrations < or = 128 mg/l . The efficacy of the nitroimidazole antimycotics against H . pylori in vivo should be tested in a clinical trial. J Antimicrob Chemother, 1993 Sep, 32(3), 445 - 51 In-vitro activity of three new fluoroquinolones and synergy with ansamycins against Mycobacterium leprae; Dhople AM et al.; The efficacy of three fluorinated quinolones, clinafloxacin (PD 127391), sparfloxacin (PD 131501) and PD 131628, either alone or in combination with rifampicin/rifabutin, against Mycobacterium leprae was evaluated in vitro using two biochemical parameters to measure the metabolic activity of the organism . Clinafloxacin was found to be most effective with an MIC of 0.75 mg/L, followed by sparfloxacin (MIC 1.5 mg/L) and PD131628 (MIC 3.0 mg/L) . When combined with rifampicin each of the three quinolones were additive to the activity . However, when combined with rifabutin, both clinafloxacin and sparfloxacin demonstrated pronounced synergic activity . Incorporation of clinafloxacin and rifabutin in a multi-drug therapy regimen is suggested. Pharmacotherapy, 1993 Sep-Oct, 13(5), 504 - 7 Predictors of trough concentrations of oral ciprofloxacin; Paladino JA et al.; Patients enrolled in a fixed-dose clinical trial of oral ciprofloxacin had trough concentrations measured to document absorption and monitor compliance . The objective was to determine whether any demographic characteristics might be important predictors of the concentrations . Stepwise multivariate linear regression revealed no correlation between ciprofloxacin trough concentrations and serum creatinine, estimated creatinine clearance (Clcr), weight, height, body surface area, or gender . However, age exhibited a direct linear relationship with trough concentrations (Y in microgram/ml), Y = 0.020.age--0.541 (p < 0.003) . We conclude that for patients with Clcr 30 ml/minute or above, age is a more important predictor of ciprofloxacin trough concentration than renal function . Dosage adjustment should not be arbitrary but should be guided by minimum inhibitory concentration, clinical response, and side effects. Antimicrob Agents Chemother, 1993 Sep, 37(9), 1997 - 9 Susceptibility of Mycobacterium kansasii to ofloxacin, sparfloxacin, clarithromycin, azithromycin, and fusidic acid; Witzig RS et al.; The MICs of ofloxacin, sparfloxacin, clarithromycin, azithromycin, and fusidic acid for clinical isolates of Mycobacterium kansasii were determined by the radiometric (BACTEC) method . All drugs except azithromycin elicited MICs for 90% of the strains tested that were lower than previously reported achievable maximum concentrations in serum . Ofloxacin, sparfloxacin, and clarithromycin had the largest maximum concentration in serum/MIC for 90% of strains ratio of the drugs tested. Antimicrob Agents Chemother, 1993 Sep, 37(9), 1746 - 8 In vitro activity of azithromycin (CP-62,993) against Chlamydia trachomatis and Chlamydia pneumoniae; Agacfidan A et al.; The in vitro susceptibilities of 49 strains of Chlamydia trachomatis and 3 strains of Chlamydia pneumoniae to azithromycin and tetracycline or doxycycline were determined . The MIC of azithromycin ranged from < or = 0.06 to 1.0 micrograms/ml, the MIC of tetracycline ranged from 0.03 to 0.12 micrograms/ml, and the MIC of doxycycline ranged from 0.015 to 0.06 micrograms/ml against C . trachomatis . The MIC ranges for C . pneumoniae were 0.12 to 0.25 micrograms/ml for azithromycin and 0.06 to 0.12 micrograms/ml for tetracycline . All minimal chlamydicidal concentrations were either equal to the MIC or one or two dilutions higher . No strains resistant to these antibiotics were detected . In vitro activity shows that azithromycin is highly active against C . trachomatis and C . pneumoniae. J Vet Pharmacol Ther, 1993 Sep, 16(3), 317 - 27 A study of the disposition of procaine penicillin G in feedlot steers following intramuscular and subcutaneous injection; Papich MG et al.; The disposition of an aqueous suspension of procaine penicillin G (300,000 U/mL) was studied in feedlot steers . Four groups of three steers were used . Steers in groups 1 and 2 received procaine penicillin G once daily for 5 days intramuscularly (i.m.) at a dose of 24,000 U/kg (group 1) or of 66,000 U/kg (group 2) . The injection on the last day was administered in the gluteal muscle . Steers in group 3 (i.m . neck injection) and group 4 {subcutaneous (s.c.) injection} each received a single dose of procaine penicillin G at a dose of 66,000 U/kg . From every animal, after the last injection in groups 1 and 2 and following the single injection in groups 3 and 4, a series of blood samples was taken at fixed time intervals . The plasma from these samples was analysed for penicillin G by a high performance liquid chromatography (HPLC) assay in order to determine the disposition of penicillin . The maximum plasma concentration (Cmax) and the area under the curve (AUC) were significantly different between groups 1 and 2, but we found no difference in the disappearance rate constant between these two groups . Group 4 single s.c . injections produced a lower mean Cmax (1.85 +/- 0.27 microgram/mL) than the mean Cmax (4.24 +/- 1.08 micrograms/mL) produced in group 3 by i.m . injections into the neck muscle or the mean Cmax (2.63 +/- 0.27 microgram/mL) produced in group 2 by i.m . injections into the gluteal muscle . However the mean Cmax produced by i.m . injections into the neck muscles (group 3) was higher than the mean Cmax produced by i.m . injections into the gluteal muscle (group 2) . Additionally, the disappearance t1/2 was longer (18.08 h) in group 4 following the s.c . injection and shorter (8.85 h) in group 3 following the i.m . neck injection, than the t1/2 following administration of the same dose i.m . into the gluteal muscle (15.96 h) in group 2 . In this study, when procaine penicillin G was injected into the gluteal muscle, doses of 66,000 U/kg were necessary to produce plasma concentrations that were above a minimum inhibitory concentration (MIC) for penicillin G of 1.0 microgram/mL as compared to doses of 24,000 U/kg. Clin Infect Dis, 1993 Sep, 17(3), 491 - 5 Clinical pharmacokinetics of continuous intravenous administration of penicillins; Visser LG et al.; Theoretically, continuous intravenous administration of beta-lactam antibiotics has advantages over intermittent administration because of the close relationship between efficacy and the time the plasma concentration remains above the minimal inhibitory concentration that has been found in vitro . The aim of the present study was to establish the pharmacokinetic parameters of benzylpenicillin and cloxacillin administration in patients receiving high-dose benzylpenicillin or cloxacillin therapy by continuous infusion . A major part of the interindividual variation in the plasma concentrations at steady-state was attributable to variation in renal function, as estimated by the creatinine clearance . On the basis of these results, a nomogram was constructed that can be used to determine on an individualized basis the total daily dose of benzylpenicillin or cloxacillin necessary for each patient to obtain therapeutic plasma concentrations. Indian Pediatr, 1993 Sep, 30(9), 1091 - 8 Serum concentrations of rifampicin and isoniazid in tuberculosis; Seth V et al.; Ninety-four patients, 1-13 years of age suffering from different types of tuberculosis were investigated for serum rifampicin (RIF) and isoniazid (INH) concentrations using microbiological and fluorimetric methods, respectively . Of these, 64 (68.1%) had pulmonary primary complex (PPC); 20 (21.3%) progressive primary disease (PPD) and 10 (10.6%) tuberculous meningitis (TBM) . Patients with PPC, PPD and TBM were given two-drug (6HR), three drug (2HRZ, 4HR) and four drug (2SHRZ, 4HRE, 3HE) regimens, respectively . RIF and INH were administered in a dose of 12 and 10 mg/kg/day, respectively . After 10-12 days of continuous therapy, their serum concentrations were estimated at 0, 2, 4, 6, 8 hours for RIF and 0, 1, 3, 5, 7 hours for INH . For RIF, the time to achieve maximum concentrations (Tmax) was 2 hours, range of mean of maximum concentration (Cmax) 3.38 to 3.88 micrograms/ml, terminal half life elimination (T1/2) 3.03 to 3.81 hours and area under serum concentration curve (AUC) 0-8 hours 24.7 to 28.3 micrograms/ml hours in different forms of tuberculosis . INH had a Tmax of 1 h, Cmax 4.38 to 8.17 micrograms/ml, T1/2 4.0 to 4.98 hours and AUC 0-7 hours 34.1 to 57.5 micrograms/ml hours . The concentrations achieved at 7-8 hours with these dosages were much above those required for therapeutic efficacy (minimum inhibitory concentration), being 50 to 250 times for RIF and 35-60 times for INH . We recommend pharmacokinetic studies with lower doses of RIF and INH for less toxic, equally effective and cheaper antitubercular chemotherapy. Mycoses, 1993 Sep-Oct, 36(9-10), 305 - 11 In vitro susceptibility of public indoor swimming pool fungi to three disinfectants; Bobichon H et al.; The floors of indoor swimming pools are contaminated by yeasts, dermatophytes and other saprophytic species . Previous epidemiological studies have revealed that the fungi persist even after cleaning . Three disinfectants were tested in vitro against fungi standard isolated from swimming pool floors . Minimum inhibitory concentration (MIC) tests and AFNOR standard T72-201 were carried out . Adilon and Decalcite, commonly used in swimming pools, were ineffective against most of the fungi, while Nobactel, recommended elsewhere, was particularly effective against the studied fungi . In addition to the necessary technical modifications of the methods, this study highlights the need to choose effective antifungal compounds and to alternate cleaning products to minimize acquired resistance. Kinderarztl Prax, 1993 Aug, 61(6), 211 - 4 {Oral ciprofloxacin therapy in juvenile patients with cystic fibrosis--results of a prospective pilot study}; Sollich V et al.; Efficacy and safety of oral ciprofloxacin were studied in a prospective study at three cystic fibrosis centres, covering 24 in-patients suffering from cystic fibrosis and acute bronchopulmonary exacerbation . The patients were between 10 and 17 years of age . Pseudomonas infection was present in 75% of these patients . Despite frequent persistence of the pathogens, clinical improvement was noted in 75% of the treated children . A definite increase of the average MIC was not seen in 20 cases of persisting strains . No serious side effects occurred during the 14-day oral treatment course . Ciprofloxacin is a useful alternative to conventional parenteral treatment with antibiotics in patients suffering from cystic fibrosis and infections of the airways. Clin Infect Dis, 1993 Aug, 17 Suppl 1, S215 - 8 Effect of pH, inoculum size, and incubation time on the susceptibility of Ureaplasma urealyticum to erythromycin in vitro; Kenny GE et al.; Determinations of the susceptibility of Ureaplasma urealyticum to erythromycin in vitro as measured by the broth dilution method have shown wide variations with minimal inhibitory concentrations (MICs) from 0.04 to > or = 8 micrograms/mL, indicating a need for standardization . The effects of pH, inoculum size, and incubation were studied . In the broth dilution test, pH had an important effect . The apparent MIC was 4- to 16-fold higher at pH 6.0 than at pH 7.0, with the MIC falling progressively from values of 8 to > or = 8 micrograms/mL to values of 0.25 to 1 microgram/mL as the pH of the medium was increased in steps to pH 7.0 . Large inocula also inflated the MICs 2- to 4-fold . In addition, the time of incubation influenced the apparent MIC, with increases of 4- to 16-fold between days 1 and 5 . In agar dilution assays, MICs decreased from 2 micrograms/mL at pH 6.2 to 0.5 microgram/mL at pH 6.6 . Since pH, inoculum level, and incubation time appear to be responsible for most of the variation in results, we propose that susceptibility testing for ureaplasmas can be improved by using medium with a more neutral pH than that usually used (pH 6) and by standardizing the inoculum size and incubation period. Enferm Infecc Microbiol Clin, 1993 Aug-Sep, 11(7), 352 - 8 {Characterization of plasmids in Escherichia coli strains}; Chaves J et al.; BACKGROUND: Strains of Escherichia coli are frequently plasmid carriers . In this species, resistance to beta-lactam antibiotics is almost always conditioned by the production of enzymes coded by plasmidic genes . The present is a study of the plasmids of 44 ampicillin-sensitive strains and 134 ampicillin-resistant (ampS and ampR) . The possibility that the number and size of the plasmids are different and that this data may be added to the information to be considered in these two groups of strains is suggested . METHODS: The 178 strains selected had been isolated from human products . Sensitivity to ampicillin was studied by diffusion and was confirmed with the study of MIC (Mueller-Hinton agar, innoculum: 5 x 10 CFU) . The plasmid type beta-lactamases were identified by analytical isoelectrofocus . Characterization of the plasmids was performed according to a variant of the Birnboim and Doly alkaline lysis technique . RESULTS: Among the ampR and ampS strains no plasmid were observed in 9 (6.72%) and 11 (25%) respectively . The mean number of plasmids was 2.53 and 1.57, ranging between 0-10 and 0-5 . The number of strains with plasmids larger than, or equal to, 38 Kb was 113 and 27 respectively . The largest plasmids observed in the ampS strains were of 99 Kb and in the ampR of 109 Kb . A total of 3.73% of the ampR strains presented plasmids larger than 99 Kb and 8.20% more than 5 plasmids . CONCLUSIONS: No plasmids, presence of up to five and sizes smaller than or equal to 99 Kb were observed in strains of ampS and ampR . The presence of more than five and/or plasmids larger than or equal to 100 Kb was observed in 11.94% of the ampR. Pneumologie, 1993 Aug, 47(8), 497 - 500 {Determination of the minimal inhibitory concentration of chemotherapeutic drugs with various methods against Mycobacterium avium}; Rusch-Gerdes S; The MIC's were determined for 11 antibiotics by the radiometric method, photometrically with the liquid medium Lockemann and conventionally with Lowenstein-Jensen-medium against Mycobacterium avium complex . Both liquid media (Bactec and Lockemann) agreed, whereas the conventional method gave higher MIC's . Tween 80 should be avoided in all media and diluent fluids, because Tween 80 changes the cell-wall-structure and therefore the minimal inhibition concentrations could be changed . The reporting time for the results was 4 days by the radiometric and 3 weeks by the photometric method. Masui, 1993 Aug, 42(8), 1190 - 3 {Immobilization of a sensitive plant, Mimosa pudica L., by volatile anesthetics}; Okazaki N et al.; The disappearance of thigmonastic mobility of a sensitive plant, Mimosa pudica L., caused by volatile anesthetic agents such as methoxyflurane, chloroform, halothane, enflurane or sevoflurane revealed that the response to anesthetic agents in plants maybe similar to that in animals . In terms of reversible anesthesia, animals seem to equal plants in order of potency of anesthetics, and the minimum immobilizing concentration (MIC; %) in the plant shows a good correlation with MAC in the human (MICplant = 5.8 MAChuman + 0.01, r2 = 0.946) . These phenomena suggest the existence of a certain common mechanism in anesthesia between animals and plants. Dis Colon Rectum, 1993 Aug, 36(8), 751 - 6 Minimally invasive colectomy: are the potential benefits realized? Peters WR, Bartels TL. Laparoscopic surgical techniques have recently been applied to various types of colon resection . Early reports have focused on the technical feasibility of these procedures, and it has not yet been clearly shown that such procedures benefit the patient . We reviewed our experience with 28 attempted minimally invasive colectomies (MICs) performed over a nine-month period . Laparoscopic or laparoscopic-assisted resections were successfully completed in 24 of these patients . We compared the results of surgery in these 24 patients with a group of 33 patients undergoing similar procedures at the same institution by the same surgeon in the nine months preceding the laparoscopic experience . The two groups of patients were similar with respect to age, weight, and the types of procedures performed . However, the postoperative length of stay for patients undergoing MIC (4.8 days) was significantly shorter than for those undergoing open colectomies (8.2 days) . Patients undergoing MIC also regained bowel function significantly earlier than those undergoing open colectomy . The operative times for the minimally invasive procedures were significantly longer than for those undergoing open colectomy . No surgically related deaths were encountered, and morbidity was 13 percent . None of the four patients converted from laparoscopic to open colectomy suffered complications as a result of the attempted laparoscopic procedure . We conclude that MIC can be safely performed and does appear to reduce the duration of postoperative ileus and decrease the length of postoperative hospitalization. Biol Psychol, 1993 Aug, 36(1-2), 119 - 29 Application of impedance cardiography during exercise; Miles DS et al.; Impedance cardiography has been used over the last 30 years to measure stroke volume on a beat-by-beat basis . Cardiac output has been successfully measured with either upper or lower body exercise during light or moderate workloads . With strenuous exercise, movement artifacts severely limit the acquisition of a quality impedance cardiogram . Advances in computer technology and signal conditioning techniques have created the next generation of impedance cardiograph systems . The purpose of this study was to evaluate such a system, the noninvasive continuous cardiac output monitor (NCCOM3-R7), at rest and during submaximal upright cycle exercise . In addition, the relationships between thoracic impedance (Z(o)), first derivative of the change in thoracic impedance (dZ/dt) and posture were evaluated using the NCCOM3-R7 and the Minnesota impedance cardiograph 304B (MIC) . Twenty-eight healthy men and women participated . The Z(o) progressively increased when moving from the supine to seated to standing position with both instruments . However, the NCCOM3-R7 yielded lower Z(o) values and higher dZ/dt values compared with the MIC for all postures . Z(o) and dZ/dt values appear to be dependent upon factors such as posture, gender, electrical current, and characteristics of the instrumentation . Exercise cardiac output values seemed reasonable for most subjects, although population subsets exist where the accuracy must be questioned . The general consensus supported by the impedance literature and reaffirmed by the present observations is that impedance cardiography provides a reasonable estimate of the directional changes in stroke volume and cardiac output during exercise and can be used to monitor changes in thoracic fluid balance . As this technology evolves and is further refined, it will undoubtedly play an increasing role in environmental medicine, exercise stress testing, cardiac rehabilitation, and sports medicine. Int Ophthalmol, 1993 Aug, 17(4), 217 - 22 Intravitreal penetration of oral pefloxacin in humans; Oncel M et al.; We measured vitreous and serum levels of pefloxacin after oral administration . Twenty patients with retinal detachments undergoing vitrectomy were recruited into this study . Each patient received 400 mg pefloxacin orally 1 to 12 hours before vitrectomy . Vitreous fluid (0.1 mL) was aspirated at surgery . Vitreous levels of pefloxacin were determined by high-performance liquid chromatography . Six hours after oral administration, an average level of 1.37 microgram/mL of pefloxacin was measured in the vitreous samples . These levels were well above the minimum inhibitory concentration (MIC) for most organisms termed sensitive to pefloxacin . Oral administration of pefloxacin may play an important role in the prevention or management of endophthalmitis. Appl Environ Microbiol, 1993 Aug, 59(8), 2657 - 65 Interference of humic acids and DNA extracted directly from soil in detection and transformation of recombinant DNA from bacteria and a yeast; Tebbe CC et al.; A two-step protocol for the extraction and purification of total DNA from soil samples was developed . Crude DNA extracts (100 microliters from 5 g of soil) were contaminated with humic acids at concentrations of 0.7 to 3.3 micrograms/microliters, depending on the type of soil extracted . The coextracted humic acid fraction of a clay silt was similar to a commercially available standard humic acid mixture, as determined by electrophoretic mobility in agarose gels, UV fluorescence, and inhibition assays with DNA-transforming enzymes . Restriction endonucleases were inhibited at humic acid concentrations of 0.5 to 17.2 micrograms/ml for the commercial product and 0.8 to 51.7 micrograms/ml for the coextracted humic acids . DNase I was less susceptible (MIC of standard humic acids, 912 micrograms/ml), and RNase could not be inhibited at all (MIC, > 7.6 mg/ml) . High inhibitory susceptibilities for humic acids were observed with Taq polymerase . For three Taq polymerases from different commercial sources, MICs were 0.08 to 0.64 micrograms of the standard humic acids per ml and 0.24 to 0.48 micrograms of the coextracted humic acids per ml . The addition of T4 gene 32 protein increased the MIC for one Taq polymerase to 5.12 micrograms/ml . Humic acids decreased nonradioactive detection in DNA-DNA slot blot hybridizations at amounts of 0.1 micrograms and inhibited transformation of competent Escherichia coli HB101 with a broad-host-range plasmid, pUN1, at concentrations of 100 micrograms/ml . Purification of crude DNA with ion-exchange chromatography resulted in removal of 97% of the initially coextracted humic acids.(ABSTRACT TRUNCATED AT 250 WORDS) Pediatr Nurs, 1993 Jul-Aug, 19(4), 351 - 4, 364 Comparison of two skin-level gastrostomy feeding tubes for infants and children; Haas-Beckert B et al.; Gastrostomy tubes have improved technically over the last 10 years . New to the market are skin-level devices, which are low-profile in design and avoid many problems of standard gastrostomy tubes . Two skin-level devices, the Button and the MIC-KEY, are appropriately designed for infants and children and are compared. Biochem Mol Biol Int, 1993 Jul, 30(3), 411 - 7 Role of lipid peroxidation in impairment of mitochondrial function at complex I by methyl isocyanate treatment of rats in vivo; Jeevaratnam K et al.; The subcutaneous administration of methyl isocyanate (MIC) in 1.0 LD50 dose in rats caused a significant effect on hepatic mitochondrial function only at complex I region of the respiratory chain . MIC administration at 1.0 LD50 dose also resulted in significant increases in malondialdehyde and ferrous ion concentration in liver mitochondria . It is suggested that the augmented lipid peroxidation in hepatic mitochondria, catalyzed by iron, possibly mobilized from intracellular stores leads to the inhibition of enzymes of mitochondrial respiration at complex I region, in vivo, in rats receiving a lethal dose of MIC subcutaneously. J Am Soc Nephrol, 1993 Jul, 4(1), 81 - 90 Can pharmacokinetic dosing decrease nephrotoxicity associated with aminoglycoside therapy; Leehey DJ et al.; A randomized, controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy . Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were randomly assigned to one of three groups: usual physician-directed dosing (Group 1), pharmacist-assisted dosing (Group 2), or pharmacist-directed dosing (Group 3) . Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group . Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher ratios of mean peak level to minimum inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels . Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups . However, the incidence of nephrotoxicity (> or = 100% increase in serum creatinine) was not different among the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectively) . Similarly, severity of toxicity was not affected by the dosing intervention . Risk factors for toxicity included duration of therapy, shock, treatment with furosemide, older age, and liver disease . After controlling for these factors, the dosing intervention still had no effect on nephrotoxicity . It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy. Am J Vet Res, 1993 Jul, 54(7), 1122 - 7 Penetration of danofloxacin into the respiratory tract tissues and secretions in calves; Friis C; Pharmacokinetic determinants of danofloxacin (1.25 mg/kg of body weight, IV) and its penetration into the respiratory tract tissues were studied in sixteen 4- to 6-week-old calves . The disposition curve was best described by an open 3-compartment model . Mean elimination half-life was 7.4 hours and the steady-state volume of distribution was 4.3 L/kg . The large volume of distribution was confirmed by a rapid and high penetration of the drug into respiratory tract tissues and secretions . In all structures (lung tissue, bronchial mucosa, bronchial secretions, and nasal secretions), danofloxacin concentration peaked 1 hour after drug administration . The area under the curve ratio for concentrations in tissue or secretions to concentrations in plasma was approximately 5 for lung tissue, 3 for bronchial mucosa, 0.85 for bronchial secretions, and 0.42 for nasal secretions . Protein binding of danofloxacin was 49% in plasma, 31% in bronchial secretions, and 14% in nasal secretions, resulting in consistently higher free danoflaxacin concentrations in bronchial secretions than in plasma . Accumulation of danofloxacin within bronchial mucosa and the high concentration of free drug in bronchial secretions suggested that an active process may be involved in the transport of danofloxacin across the airway epithelium . The dose of danofloxacin administered provided drug concentrations above the minimal inhibitory concentration of common respiratory pathogens for up to 12 hours in bronchial mucosa, up to 8 hours in bronchial secretions, and up to 4 hours in nasal secretions. J Infect, 1993 Jul, 27(1), 67 - 70 Disseminated Trichosporon beigelii infection causing skin lesions in a renal transplant patient; Mirza SH; A 45-year-old renal transplant patient presented with a recent history of small reddish nodular lesions on thighs, back and face . Biopsy of the nodules revealed numerous hyphae . Trichosporon beigelii was isolated from the biopsy specimen . Marked improvement occurred after 2 weeks' treatment with fluconazole, although its MIC was 16 mg/l. Antimicrob Agents Chemother, 1993 Jul, 37(7), 1556 - 7 Ciprofloxacin susceptibility testing by MIC and disk elution of drug-resistant Mycobacterium tuberculosis and Mycobacterium avium complex; LaBombardi VJ et al.; The ability to provide susceptibility data for certain species of mycobacteria can be clinically useful . In this study, the disk elution method for susceptibility testing was adapted for testing ciprofloxacin against mycobacterial isolates . Of the 75 Mycobacterium tuberculosis isolates tested, including 23 multiply drug-resistant isolates, 96% were susceptible to ciprofloxacin at a breakpoint concentration of 2 micrograms/ml. J Clin Microbiol, 1993 Jul, 31(7), 1924 - 6 Levofloxacin disk potency and tentative interpretive criteria for susceptibility tests; Pfaller MA et al.; Levofloxacin disk susceptibility test criteria were evaluated by testing 350 bacterial isolates . Either 5- or 10-micrograms disks could be used satisfactorily . A 5-micrograms levofloxacin disk with zone size breakpoints of < or = 12 mm for resistance (MIC, > or = 8.0 micrograms/ml) and > or = 16 mm for susceptibility (MIC, < or = 2.0 micrograms/ml) is recommended. Chemotherapy, 1993 Jul-Aug, 39(4), 272 - 7 Kinetics of filamentation of Escherichia coli induced by different sub-MICs of ceftibuten at different times; Braga PC et al.; Subinhibitory concentrations of some antibiotics are able to inhibit adhesion of bacteria to human host cells, to facilitate phagocytosis and to modify the shape of the bacteria cell wall, e.g., variable degrees of filamentation occur frequently in gram-negative bacteria . The kinetics of filamentation of Escherichia coli were investigated by incubation for various periods up to 18 h, with different subinhibitory concentrations of ceftibuten, from 1/2 to 1/128 of the MIC, corresponding to 0.25-0.003 micrograms/ml . Normal shapes, short and long filamentation and bacterial ghosts were observed . The morphological changes in the bacterial cells were influenced by the duration of exposure and by the antibiotic concentration . The greatest filamentation did not occur at 1/2 MIC, the concentration of ceftibuten closest to the MIC, but at 1/8 MIC, and filamentation plus ghosts were maximal between 8 and 18 h of incubation . The morphological changes observed clearly show that ceftibuten has a greater affinity for and impairs the function of penicillin-binding protein 3 (involved in synthesis of peptidoglycan for cross walls) more than other cephalosporins, such as cephaloridine or cefoxitin. J Am Acad Dermatol, 1993 Jul, 29(1), S37 - 41 Kinetics and spectrum of activity of oral antifungals: the therapeutic implications; Meinhof W; As a wider variety of organisms are being identified in superficial fungal infections, more accurate methods of identification may be required to determine fungal susceptibility . The sensitivity of available methods, such as the minimal inhibitory concentration test, is reviewed . The sensitivities of causative pathogens and the pharmacokinetics of the oral antifungal agents are described . Griseofulvin has a low affinity and ketoconazole a high affinity for keratin, but both require long-term administration to be effective . The pharmacokinetic profiles of terbinafine and itraconazole allow effective short-term treatment with high rates of clinical and mycologic cure . All four agents are active against dermatophytes . Ketoconazole has a broader spectrum of activity but is limited by a rare incidence of hepatotoxicity . Itraconazole has the broadest spectrum of activity. Environ Health Perspect, 1993 Jul, 101 Suppl 2, 125 - 30 Environmental release of chemicals and reproductive ecology; Bajaj JS et al.; Reproductive ecology is defined as "the study of causes and mechanisms of the effects of environmental risk factors on reproductive health and the methods of their prevention and management." Major areas of concern, within the purview of this paper, relate to adverse pregnancy outcomes, effects on target tissues in the male and the female, and alterations in the control and regulatory mechanisms of reproductive processes . Teratogenic potential of chemicals, released as a result of accidents and catastrophes, is of critical significance . Congenital Minamata disease is due to transplacental fetal toxicity caused by accidental ingestion of methyl mercury . Generalized disorders of ectodermal tissue following prenatal exposure to polychlorinated biphenyls have been reported in Taiwan and Japan . The Bhopal gas disaster, a catastrophic industrial accident, was due to a leak of toxic gas, methyl isocyanate (MIC), in the pesticide manufacturing process . The outcome of pregnancy was studied in female survivors of MIC exposure . The spontaneous abortion rate was nearly four times more common in the affected areas as compared to the control area (24.2% versus 5.6%; p < 0.0001) . Furthermore, while stillbirth rate was found to be similar in the affected and control areas, the perinatal and neonatal mortality rates were observed to be higher in the affected area . The rate of congenital malformations in the affected and control areas did not show any significant difference . Chromosomal aberrations and sister chromatid exchange (SCE) frequencies were investigated in human survivors of exposure . The observed SCE frequencies in control and exposed groups indicated that mutagenesis has been induced . Strategies for the management, prediction, and preventability of such disasters are outlined. J Antimicrob Chemother, 1993 Jul, 32(1), 45 - 9 Comparison of three methods for the determination of the sensitivity of Helicobacter pylori to metronidazole; Hirschl AM et al.; A comparison of various methods for the determination of the sensitivity of Helicobacter pylori to metronidazole was undertaken . The validity of the agar dilution, the disc diffusion and the Epsilometer (E) test was studied using a total of 86 strains, 16 of which were known to be resistant to metronidazole . All tests were carried out on Mueller-Hinton agar with 5% sheep blood . The results of the disc diffusion and the E-test were highly significantly (P < 0.001) associated with those of the agar dilution test, which was taken as a standard (r = -0.96 and r = 0.96, respectively) . Investigation of the accuracy of the repetitive (n = 10) testing ten sensitive and one resistant strains, showed that the disc diffusion test led to a systematic and significant (2p < 0.001) underestimation of the MIC values calculated from the inhibition zone diameters via linear regression . In contrast, the results of the E-test did not differ significantly from those of the agar dilution test . The precision of the agar dilution test was significantly worse (2p < 0.005) than the E-test and the disc diffusion test . Because of its accuracy and significantly better precision, the E-test is recommended as the best and simplest method for routine antibiotic sensitivity testing of H . pylori. Antibiot Khimioter, 1993 Jul, 38(7), 34 - 6 {Efficacy of rifampicin in experimental plague infection}; Makarovskaia LN et al.; The effect of rifampicin on the plague microbe was studied in vitro and in albino mice with experimental plague infection . The rifampicin MIC with respect to 50 strains of the plague microbe of different origin in the tests on the Hottinger agar ranged from 1.6 to 6.4 micrograms/ml . High efficacy of rifampicin was shown in the prophylaxis and treatment of experimental plague when used in doses of 25 and 50 mg/kg once every 24 hours for 5 to 7 days . Rifampicin prevented the development of plague in at least 80 per cent of the albino mice when it was administered 1, 3, 6 and 24 hours prior to the infection . The antibiotic had a prolonged action and preserved its high efficacy after the administration at intervals of 48 and 72 hours. Mater Med Pol, 1993 Jul-Dec, 25(3-4), 143 - 4 Anticandidal activity of flunarizine; Krajewska-Kulak E et al.; Susceptibility of 138 yeast-like strains from patients were tested against flunarizine (Flu), ketoconazole (Ktz), and the combination of Ktz with Flu, using Sabouraud dextrose broth . The minimal inhibitory concentrations (MIC)s for 101 strains of C . albicans were: Flu 319+ 30.1 micrograms/ml, Ktz 27.9 + 9.1 micrograms/ml . The combination of Ktz and Flu in various ratios (1:1, 1:2, 2:1) was found to exert a synergistic effect and the mean values of the following combinations were: Ktz+Flu 6.26 + 0.25, 4.8 + 0.27, 5.41 + 0.25 micrograms/ml . These results were significantly different (p < 0.001) when compared with ketoconazole alone . Our findings indicate that flunarizine (calcium channel blocker) increases the antifungal activity of Ktz against C . albicans in vitro. Cas Lek Cesk, 1993 Jun 28, 132(13), 406 - 9 {Naftifin--laboratory and clinical experience with a new antimycotic from the allylamine group}; Otcenasek M et al.; The authors evaluated the effectiveness of naftifin on a broad spectrum of 42 types of agents causing mycoses . Using the microdilution method, the authors assessed minimal inhibiting concentrations (MIC) of this antimycotic agent in 107 clinical isolates . Naftifin displayed a selective antifungal activity: excellent sensitivity was found in dermatophytes (MIC 90% = 0.39 mg.l-1), Aspergillae were medium sensitive (MIC = 0.09-12.5 mg.l-1) . The majority of yeasts and filamentous fungi from the group of Zygomycetes was resistant to naftifin . The therapeutic results in 57 subjects with dermatomycoses corresponded to the results of in vitro tests of the antimycotic agent . Most successful as treatment of dermatophytoses at extra-intertriginous sites and treatment of pityriasis versicolor; manifestation of candidoses were not affected . The commercial preparation used--Fetimin cream--is considered by the authors a suitable alternative of hitherto used local antimycotics, in particular preparations from the azole series. Am J Ophthalmol, 1993 Jun 15, 115(6), 770 - 4 Effects of inflammation and surgery on amikacin levels in the vitreous cavity; Mandell BA et al.; Intraocular injection of amikacin is increasingly used in the treatment of endophthalmitis . We injected 400 micrograms of amikacin into the vitreous cavity of rabbit eyes to study its pharmacokinetics . Phakic, aphakic, and aphakic vitrectomized eyes were injected, and inflamed eyes were compared to control eyes . Vitreous concentrations were determined at two, eight, 24, and 48 hours, and clearance rates were calculated . Amikacin is cleared considerably more quickly from aphakic (half-life, 14.3 hours) than phakic control eyes (half-life, 25.5 hours) and even more quickly from aphakic vitrectomized eyes (half-life, 7.0 hours) . Inflammation substantially increased the rate of clearance in aphakic eyes . In inflamed aphakic and aphakic vitrectomized eyes, vitreous drug levels were equal to or below the minimal inhibitory concentration for most organisms considered sensitive to amikacin at 24 hours . Supplementation of intraocular antibiotics may therefore be required in clinical settings. Indian J Malariol, 1993 Jun, 30(2), 67 - 73 In vitro activity of fluoroquinolones against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum; Tripathi KD et al.; The in vitro activity of three fluoroquinolones--ciprofloxacin, norfloxacin and ofloxacin--was studied on four laboratory-adapted strains (one chloroquine-resistant) and one fresh isolate of P . falciparum from Delhi by the schizont maturation inhibition microtest . The IC50 concentrations (mean +/- SD) were found to be as: ciprofloxacin 6.38 +/- 1.34 micrograms/ml, norfloxacin 11.24 +/- 1.27 micrograms/ml, and ofloxacin 22.3 +/- 3.11 micrograms/ml, while the MIC values were 32 micrograms/ml, 64 micrograms/ml and 128 micrograms/ml for the three drugs in the same order . The IC50 and MIC values for chloroquine-resistant strain were not significantly different from those for the chloroquine-sensitive strains . We conclude that there is little interstrain variability in the in vitro susceptibility of P . falciparum to fluoroquinolones, and that there is no cross resistance between them and chloroquine . The reported variability in clinical response of falciparum malaria to fluoroquinolones is not likely to be due to variation in parasite sensitivity. J Chemother, 1993 Jun, 5(3), 155 - 8 In vitro activity of azithromycin against Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis in comparison with erythromycin, roxithromycin and minocycline; Rumpianesi F et al.; The in vitro activity of azithromycin against 40 strains of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis was investigated in comparison with erythromycin, roxithromycin and minocycline . All C . trachomatis strains were inhibited by azithromycin at a concentration < or = 0.5 microgram/ml . The initial minimum inhibitory concentration (MIC) of the drug for U . urealyticum was 4 microgram/ml, whereas some resistance against the drug was shown by M . hominis . Erythromycin and roxithromycin presented almost comparable activities, whereas minocycline was slightly more active than macrolides against C . trachomatis (MIC < or = 0.25) and more active against M . hominis (initial MIC < or = 1 micrograms/ml) . Only 97% of U . urealyticum strains were susceptible to 8 micrograms/ml of minocycline. Antimicrob Agents Chemother, 1993 Jun, 37(6), 1247 - 52 Novel gyrA point mutation in a strain of Escherichia coli resistant to fluoroquinolones but not to nalidixic acid; Cambau E et al.; We have previously described a clinical isolate of Escherichia coli (Q2) that is highly resistant to fluoroquinolones (MIC of ciprofloxacin, 16 micrograms/ml) but susceptible to nalidixic acid (MIC of nalidixic acid, 4 micrograms/ml) (N . Moniot-Ville, J . Guibert, N . Moreau, J.F . Acar, E . Collatz, and L . Gutmann, Antimicrob . Agents Chemother . 35:519-523, 1991) . Transformation of strain Q2 with a plasmid carrying the wild-type gyrA gene from E . coli K-12(pAFF801) resulted in a 32-fold decrease in the MIC of ciprofloxacin, suggesting that at least one mutation in gyrA was involved in the resistance of Q2 . Intragenic gyrA fragments of 668 and 2,500 bp from strain Q2 were amplified by the polymerase chain reaction . We sequenced the 668-bp fragment and identified a single novel point mutation (transition from G to A at position 242), leading to an amino acid substitution (Gly-81 to Asp) in the gyrase A subunit . We constructed hybrid plasmids by substituting either the 668-bp fragment or the 2,500-bp fragment from Q2 DNA, both of which contained the gyrA point mutation, for the corresponding fragments in wild-type gyrA (2,625 bp) of E . coli K-12 . When introduced into E . coli KNK453 (gyrA temperature sensitive), both plasmids conferred an eightfold increase in the MIC of ciprofloxacin, but only a twofold increase in the MIC of nalidixic acid . When introduced into E . coli Q2, neither plasmid conferred any change in the MICs of ciprofloxacin or nalidixic acid, suggesting that only the point mutation found in gyrA was involved in the resistance that we observed. Biol Pharm Bull, 1993 Jun, 16(6), 594 - 9 Effects of aluminium-containing antacid on bioavailability of ofloxacin following oral administration of pivaloyloxymethyl ester of ofloxacin as prodrug; Maeda Y et al.; We newly synthesized a pivaloyloxymethyl ester of ofloxacin (OFLX-PVM) as prodrug in order to avoid the chelate formation between new quinolone and metal cations such as Al3+, Mg2+, Ca2+, or Fe2+ in the gastrointestinal tract . This compound was rapidly hydrolyzed in an incubation experiment by 43% in plasma, by 92% in small intestinal mucosal homogenates, and by 97% in liver homogenates during 0.5 h incubation, but was resistant to hydrolysis by pancreatic enzymes . In everted gut sac experiments, this compound was efficiently absorbed even in the presence of aluminium ion, whereas the absorption of ofloxacin (OFLX) was decreased significantly by the presence of aluminium ion . Minimal inhibitory concentration (MIC) values of OFLX-PVM were far higher than OFLX . Effects of aluminium hydroxide on the oral bioavailability of OFLX and OFLX-PVM were investigated in rabbits . The area under the plasma concentration-versus-time curve from zero to 24 h (AUC0-24h) following oral administration of OFLX was decreased significantly by 47.6% by combined administration with aluminium hydroxide, but AUC0-24h values of OFLX-PVM coadministered with and without aluminium hydroxide were similar to that of OFLX alone . These observations indicate that this new compound is likely to offer a prodrug for avoidance of interaction between new quinolone and metal cations. J Antimicrob Chemother, 1993 Jun, 31(6), 939 - 48 Once- versus twice-daily amikacin regimen: efficacy and safety in systemic gram-negative infections . Scandinavian Amikacin Once Daily Study Group; Maller R et al.; Three hundred and sixteen patients with serious infections verified or suspected to be of Gram-negative aetiology were treated in an open, randomized, comparative multicentre study with amikacin 15 mg/kg/day given either as a single dose or in two divided doses at 12 h intervals . Two hundred patients were evaluated for efficacy and all 316 for safety . The efficacy of both dosage regimens was very good with a satisfactory clinical response in 90% of the patients . There were no significant differences between the two regimens regarding efficacy and safety . This was also confirmed in an analysis according to the principle of 'intention-to-treat' including all randomized patients . In 218 patients additional therapy, most commonly with piperacillin or ampicillin, was considered necessary . The mean peak serum concentration of amikacin was 40.9 mg/L in the once-daily group, which is 10 x MIC for most Gram-negative bacteria, compared to 24.4 mg/L in the twice-daily group, which is 6 x MIC . Mean trough serum concentrations after 24 h were 1.8 mg/L in the once-daily group and 3.1 mg/L after 12 h in the twice-daily group . These serum concentrations were often close to or just below the MICs of the isolated pathogens . Drug related adverse reactions were seen in 40 (13%) of the patients . Among the adverse reactions with possible or probable relation to amikacin were 20 nephrotoxic events, nine in the once-daily group and 11 in the twice-daily group . A multivariate analysis of selective causative factors and nephrotoxic events gave a low correlation for once- vs twice-daily amikacin therapy . Five ototoxic events were observed, three in the once-daily group and two in the twice-daily group . One patient in the once-daily group experienced nausea in connection with amikacin infusions. Southeast Asian J Trop Med Public Health, 1993 Jun, 24(2), 221 - 5 Mefloquine monitoring in acute uncomplicated malaria treated with Fansimef and Lariam; Na Bangchang K et al.; Mefloquine levels were compared between Plasmodium falciparum malaria patients with sensitive response and those with treatment failure who received 3 drug regimens of mefloquine (46 patients with MSP 3 tablets (Fansimef), 38 and 34 with mefloquine (Lariam) 750 mg and 1,250 mg) . Mefloquine concentrations on Day-1 in any regimens in patients with treatment failure were significantly lower than those from the sensitive response, whereas there was no difference in the concentrations on Day-7 . However, MIC values of mefloquine prior to drug treatment were comparable in both groups . The study suggests that pre-treatment in vitro sensitivity testing was a non-reliable indicator of clinical outcome . Mefloquine concentration on the first day after treatment is a better predictor of the treatment outcome. Ann Trop Med Parasitol, 1993 Jun, 87(3), 235 - 9 In vitro sensitivity of southern African isolates of Plasmodium falciparum to halofantrine; Freese JA et al.; Twenty southern African isolates of Plasmodium falciparum and a 'control' Gambian strain were tested in vitro for their sensitivity to halofantrine . The concentration required to inhibit 50% of parasite growth, the IC50, ranged from 0.039 to 15.000 nmol/litre, with a mean of 4.619 nmol/litre . These IC50 values were comparable with those obtained in studies carried out in West Africa but were higher than the IC50 of South-East Asian isolates . All 21 isolates examined in the present study had minimum inhibitory concentrations (MIC) of 32 nmol/litre or less, with a median MIC value of 8 nmol/litre . Halofantrine was equally active against chloroquine-sensitive and chloroquine-resistant isolates and was also active against pyrimethamine-resistant strains . Indications are that this drug would be suitable for the treatment of P . falciparum malaria in the southern African region. Vet Microbiol, 1993 Jun, 35(3-4), 187 - 92 Basis for the evaluation of the microbiological risks due to veterinary drug residues in food; Boisseau J; The history of the establishment of safe residue levels is reviewed . Current international agreements within the FAO/WHO Codex Alimentarius programme and EC legislation establish these levels on the basis of toxicology studies . In addition to conventional toxicological effects, other effects such as the effects of drugs on the immune system, and pharmacological effects should be taken into account . The latter also include specific effects of residues of veterinary antibiotics on the human gut flora . The methods for the assessment of these effects are evaluated . Studies in human volunteers enable the establishment of a no-effect level in conditions which are the most closely mimicking the conditions of use . However, they are less favourable from a practical and ethical point of view . Studies with animal models can be used; for example human intestinal flora can be inoculated to gnotobiotic mice . These models need nevertheless to be further validated . Studies in vitro, such as those to determine the MIC, are relatively simple to carry out and inexpensive, but are not always representative of the relevant bacteria, and may not take into account factors such as, Ph, anaerobiosis and the barrier effect. Appl Microbiol Biotechnol, 1993 Jun, 39(3), 363 - 7 Determination of anti-Aspergillus activity of antifungal agents based on the dynamic growth rate of a single hypha; Oh K et al.; The dynamic growth rate of a single hypha of Aspergillus niger was analysed using an automatic system . A colony of A . niger was in contact with saline, saline containing an antifungal agent, and flushing saline, in sequence . The growth rate of a test hypha selected arbitrarily from the colony responded dynamically to the antifungal agent . The minimum concentration that caused the complete inhibition of hyphal growth was defined as the minimum inhibitory concentration (MIC) . The MIC values obtained were compared with those determined by conventional methods based on increasing rate of colony diameter or dry matter weight. Presse Med, 1993 May 29, 22(19), 914 - 8 {Pneumonia caused by resistant pneumococci}; Leophonte P et al.; During the last few years, acquired resistance of pneumococci to the main families of normally active antibiotics has appeared . This resistance is now worldwide but unevenly distributed: in Europe, for instance, it predominates in Spain and Hungary . In France, according to the national Registry, resistance to penicillins, which was less than 5 percent in 1988, rose to 16.9 percent in 1991 . More than 80 percent of resistant strains are found among 4 stereotypes (6, 9, 19, 23) and more than 50 percent belong to stereotype 23F exclusively . The incidence of penicillin-resistant has been evaluated at 8.5 percent in the year 1991-92 . The most significant risk factor is a previous treatment with beta-lactam antibiotics, but some authors also blame frequent pneumonias in the previous year, nosocomial pneumonia, or hospitalization during the previous 3 months . There are no specific clinico-radiological features . The incidence of resistant strains is said to be higher in HIV seropositive subjects . Amoxicillin administered in high doses remains the reference treatment for strains with intermediate susceptibility (minimal inhibitory concentration {MIC} between 0.1 and 1.0 microgram/ml) . Strains with a more than 1 microgram/ml MIC require beta-lactam antibiotics such as ceftriaxone, cefotaxime of imipenem in high doses . Pristinamycin still has good in vitro activity on resistant strains . Prevention rests on isolation of infected patients, treatment of healthy carriers and wide prescription of anti-pneumococcus vaccine. Antimicrob Agents Chemother, 1993 May, 37(5), 1177 - 9 Activities of the triazole D0870 in vitro and against murine blastomycosis; Clemons KV et al.; The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis . In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces dermatitidis (MIC = 0.048 microgram/ml; minimal fungicidal concentration = 0.097 microgram/ml) . In vivo, D0870 was approximately 100-fold more active than fluconazole on the basis of milligrams per kilogram of body weight given once daily (QD) against blastomycosis . D0870 doses of both 1 or 10 mg/kg given QD and 10 or 100 mg/kg given every other day prolonged survival (P < 0.001) over fluconazole (100 mg/kg given QD) . A D0870 dosage of 1 mg/kg QD was equivalent to fluconazole given at 100 mg/kg in reduction of lung burdens of B . dermatitidis, and D0870 administered at 10 mg/kg QD and 10 or 100 mg/kg every other day caused greater reduction (P < 0.001) . However, D0870 at 100 mg/kg given QD was lethally toxic, whereas fluconazole at 100 mg/kg was not . These results indicate that D0870 is an effective therapy for murine blastomycosis and should be further tested. Antimicrob Agents Chemother, 1993 May, 37(5), 1102 - 7 Clonal viability measurements on Plasmodium falciparum to assess in vitro schizonticidal activity of leupeptin, chloroquine, and 5-fluoroorotate; Young RD et al.; Until now, the in vitro activity of potential antimalarial agents has been evaluated primarily by monitoring decreases in parasite proliferation . These traditional assays do not distinguish between compounds that arrest proliferation of parasites and compounds that kill them . In this report, a more complex in vitro cytocidal assay for Plasmodium falciparum is described . This assay measures the clonal viability of P . falciparum after the parasites have been treated with an antimalarial agent . The new assay was used to assess cytocidal activities of three antimalarial agents that work through unrelated mechanisms . Leupeptin, a protease inhibitor, arrested the proliferation of W2 clones of P . falciparum at a MIC of 50 microM, but at least 80% of leupeptin-treated cells were viable as judged by the cytocidal assay . On the other hand, chloroquine at 1 microM, its MIC for W2 cells, not only arrested parasite proliferation but also killed more than 99% of the cells . Earlier studies had shown that treatment of P . falciparum with 100 nM 5-fluoroorotate for 48 h was sufficient to inhibit parasite proliferation and parasite thymidylate synthase but not enough to cause significant incorporation of 5-fluoropyrimidines in parasite nucleic acids . By using the new schizonticidal assay, these conditions were found to be necessary and sufficient to kill all parasites in culture . Results of these studies are consistent with the hypothesis that 5-fluoroorotate-based inactivation of P . falciparum thymidylate synthase triggers a lethal mechanism against malarial parasites. Surg Gynecol Obstet, 1993 May, 176(5), 480 - 3 A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem; Pederzoli P et al.; Recent evidence of pancreatic penetration of several antibiotics active against the usual flora found in pancreatic sepsis, at therapeutic minimal inhibitory concentration, prompted the authors to perform a randomized, multicenter, clinical trial on imipenem prophylaxis in acute pancreatitis . Seventy-four patients with computed tomographic (CT) scans demonstrating necrotizing pancreatitis within 72 hours of onset were randomly assigned to two groups receiving no antibiotic treatment or 0.5 gram of prophylactic imipenem administered intravenously every eight hours for two weeks . Pancreatic sepsis was always detected by means of cultures (percutaneous CT or ultrasound-guided needle aspiration and intraoperative samples) . The incidence of pancreatic sepsis was much less in treated patients (12.2 versus 30.3 percent, p < 0.01) . Therefore, the authors recommend prophylactic use of imipenem in patients with acute necrotizing pancreatitis. J Antimicrob Chemother, 1993 May, 31(5), 725 - 30 In-vitro evaluation of clarithromycin, temafloxacin, and ethambutol in combination against Mycobacterium avium complex; Gevaudan MJ et al.; The in-vitro activity of clarithromycin, temafloxacin, and ethambutol were assessed by MIC, FIC and intra-macrophage killing determinations alone and in various combinations against ten pigmented and ten non-pigmented strains of Mycobacterium avium complex bacteria . Alone, either clarithromycin or temafloxacin were found to be active against M . avium, but the best results were obtained from combinations of drugs . Clarithromycin and temafloxacin together were found to have an additive effect against two of ten pigmented variants and one of ten non-pigmented variants . Clarithromycin and ethambutol demonstrated a synergistic effect against two pigmented and one non-pigmented strain, and an additive effect against five and three pigmented and non-pigmented strains, respectively . For temafloxacin and ethambutol, additive effects were observed in four and two pigmented and non-pigmented strains, respectively . In cultures of macrophages both clarithromycin and temafloxacin alone reduced the numbers of bacteria growing intracellularly after six days, but the most effective bactericidal combination was clarithromycin, temafloxacin, and ethambutol together. World J Surg, 1993 May-Jun, 17(3), 393 - 7 Effect of peritoneal fluid pH on outcome of aminoglycoside treatment of intraabdominal infections; Simmen HP et al.; Netilmicin and clindamycin were administered to 47 patients with an intraabdominal infection who underwent emergency laparotomy . Thirty-one patients were cured, seven were improved, and therapy failed in nine patients despite the fact that all aerobic bacteria isolated from these patients were sensitive to netilmicin as determined by standard in vitro susceptibility tests . The pH of peritoneal and drainage fluid collected intraoperatively and during follow-up correlated with clinical outcome . Acidic pH was found in 21 of 33 (64%) specimens sampled from patients with therapeutic failure compared to 17 of 80 (21%) obtained from the categories "cured" and "improved" (p < 0.001) . Netilmicin concentrations in serum or peritoneal/drainage fluid did not correlate with clinical outcome . Netilmicin levels were above the minimal inhibitory concentration of the pathogens in 59 of 64 (92%) drainage fluid specimens in which aerobic bacteria were isolated . Aerobic bacteria were isolated in 91% of drainage fluid specimens if the pH was less than 7.0, compared to 37% if pH was more than 7.0 (p < 0.001) . Reduction of pH antagonized aminoglycoside activity in vitro against clinical isolates of Escherichia coli . Surgical reexploration should be considered in cases of deterioration following a laparotomy associated with detection of acidic drainage fluid. J Antimicrob Chemother, 1993 May, 31 Suppl D, 159 - 66 The post-antibiotic sub-MIC effect in vitro and in vivo; Cars O et al.; The post-antibiotic effect (PAE) has been recognized as a pharmacodynamic parameter which may influence optimal dosage intervals . During the post-antibiotic phase, various bacteria have been shown to be very sensitive to a repeated exposure to the same antibiotic . A long period of growth suppression may be obtained when a low concentration (< or = 0.3 x MIC) is added to bacteria previously exposed to a supra-inhibitory concentration . This phenomenon has been named the post-antibiotic sub-MIC effect (PA SME) . Since a period with sub-inhibitory concentrations will often exist between the doses when intermittent dosing of antibiotics is used, the PA SME probably reflects the in-vivo situation more closely than the PAE . The published literature on the PA SME is reviewed and its possible role in antibiotic dosing discussed. J Antimicrob Chemother, 1993 May, 31 Suppl D, 137 - 48 Medical relevance of low concentrations of antibiotics; Lorian V; Low concentrations of antibiotics or sub-minimum inhibitory concentrations (sub-MIC) have been shown in vitro to alter the ultrastructure and antigenicity of bacteria, their adherence to epithelial cells, their synthesis and excretion of pathogenic enzymes and their rate of growth . The same effects have been detected when low concentrations of antibiotic act on bacteria in vivo . Animal experiments as well as clinical investigations have demonstrated therapeutic results with sub-MICs at the site of infection. J Antimicrob Chemother, 1993 May, 31(5), 673 - 80 The accessibility of cross-reactive anti-lipopolysaccharide-core monoclonal antibodies to Escherichia coli grown in sub-MICs of temocillin and other antibiotics; Edmond DM et al.; Two broadly cross-reactive anti-lipopolysaccharide core monoclonal antibodies WN1 222.5 and SZ27/150.3 were used in an ELISA system to detect the accessibility of core epitopes in Escherichia coli (four clinical isolates and NCTC 10418) grown to early stationary phase in the absence and presence of a half, a quarter and an eighth the MIC of temocillin, ampicillin, chloramphenicol, gentamicin and ciprofloxacin . The bacteria were coated on to ELISA microtitre plates . By comparing ELISA-titre ratios, temocillin induced a significantly large increase in binding of WN1 222.5 to all strains except NCTC 10418 . Ampicillin and chloramphenicol induced a small increase in the binding of WN1 222.5 in some instances . Ciprofloxacin and gentamicin caused no increase in binding . Lipopolysaccharide SZ27/150.3 was only tested against temocillin-grown bacteria, but binding was not increased significantly compared with WN1 222.5 . The results obtained demonstrate the potential use of temocillin to improve the clinical efficacy of immunotherapeutic monoclonal antibodies in Gram-negative sepsis. Ukr Biokhim Zh, 1993 May-Jun, 65(3), 29 - 33 {Carbohydrate-binding proteins--lectins and glycosidases in plants of Anthurium genus}; Tkachenko VI et al.; The content of lectins and activity of glycosidases have been estimated in seeds and vegetative organs of 5 strains of plants of Anthurium genus . In seeds of all the investigated strains lectins were detected with the selectivity toward the N-acetyl-galactosamine (minimal inhibitory concentration of sugar was 0.1-0.2 mM) and an anti-A blood group specificity . Lectins of Anthuriums selectively bound O-type glycosidic chains and revealed high affinity toward mucins (salivary or ovary cysts origin) . Lectins were not detected in vegetative parts of Anthuriums . In seeds of plants the following glycosidases were detected in the diminishing activity order: alpha-galactosidase, alpha-mannosidase, beta-galactosidase, beta-glucosaminidase. Hum Exp Toxicol, 1993 May, 12(3), 253 - 7 Modulation of biochemical and cytological profile of bronchoalveolar lavage constituents in rats following split-dose multiple inhalation exposure to methyl isocyanate; Gupta GS et al.; 1 . Studies were carried out to explore the acute pulmonary effects of equal, split-dose, multiple inhalation exposures of rats to methyl isocyanate (MIC), (0.32 mg l-1, 8 min x 10 exposures) as reflected by alterations in bronchoalveolar lavage fluid (BALF) constituents and to evaluate recovery, if any, following survival in a MIC-free environment, 10 d after the last MIC exposure . 2 . In the BALF of MIC-exposed rats, there was an increase in the total number of cells and the number of cells showing enhanced dye uptake and reduction of nitroblue tetrazolium chloride . The cell-free BALF showed increases in total protein, sialic acids and lactic acid contents and lactate dehydrogenase activity . 3 . In rats exposed to MIC and sacrificed 10 d after survival in a MIC-free environment, there was a reduction in the cellular and biochemical constituents of BALF . The phagocytic potential of macrophages was, however, also decreased under this regime. J Chemother, 1993 Apr, 5(2), 103 - 6 Control of intracellular growth of Mycobacterium fortuitum by human monocytes in vitro; Nziramasanga P et al.; The ability of human monocytes to phagocytize and respond to infection by Mycobacterium fortuitum was tested using the method of Crowle and May . The monocytes were obtained from heparinized donor blood samples and separated from lymphocytes by adherence to plastic surfaces . M . fortuitum infection was performed immediately . Intracellular viability was indicated by colony forming units (CFU) done at 2 hour intervals . Monocytes were found to cause a rapid reduction in CFU during the first 2 hours of incubation . The rate of killing of M . fortuitum decreased thereafter but continued for the entire 8-hour study period . In parallel tests, ciprofloxacin and ofloxacin were added to the culture medium . Increased intracellular killing was observed with drug concentrations above 2 x MIC in both cases . Ofloxacin showed better antimycobacterial effects than ciprofloxacin. Antimicrob Agents Chemother, 1993 Apr, 37(4), 911 - 3 In vitro activities of new macrolides and rifapentine against Brucella spp; Garcia-Rodriguez JA et al.; We have tested the in vitro activities of streptomycin, rifampin, tetracyclines, trimethoprim-sulfamethoxazole, erythromycin, four new macrolides (roxithromycin, azithromycin, clarithromycin, and dirithromycin), and rifapentine against 62 strains of Brucella spp . Azithromycin and clarithromycin were, respectively, eight- and twofold more active than erythromycins (MIC for 90% of strains = 2, 8, and 16 micrograms/ml, respectively) . The activity of rifapentine was similar to that of rifampin (MIC for 90% of strains = 1 microgram/ml). Epidemiol Infect, 1993 Apr, 110(2), 253 - 9 Human isolates of apramycin-resistant Escherichia coli which contain the genes for the AAC(3)IV enzyme; Hunter JE et al.; Gentamicin-resistant Escherichia coli isolated at different periods from patients in two hospitals were tested for resistance to the aminoglycoside antibiotic apramycin . Twenty-four of 93 (26%) gentamicin-resistant isolates collected from the Royal Liverpool Hospital between 1981 and 1990 were resistant to apramycin . Thirteen isolates were highly resistant to apramycin (minimal inhibitory concentration (MIC) > or = 1024 micrograms/ml), were also resistant to gentamicin, netilmicin and tobramycin, and hybridized with a DNA probe derived from the aminoglycoside acetyltransferase (3)IV (AAC(3)IV) gene . The proportion of gentamicin-resistant isolates which had high level resistance to apramycin increased from 7% in 1981-5 to 24% in 1986-90 . Twelve gentamicin-resistant E . coli from Guy's and St Thomas's Hospital isolated between 1977 and 1980 were also tested for resistance to apramycin . For five of these isolates the MICs of apramycin was 32-256 micrograms/ml . None was shown to have a conjugative plasmid carrying resistance to apramycin and only one hybridized with the DNA probe for the AAC(3)IV enzyme. Antimicrob Agents Chemother, 1993 Apr, 37(4), 696 - 701 Mutations in the gyrA gene of a highly fluoroquinolone-resistant clinical isolate of Escherichia coli; Heisig P et al.; We have determined the DNA sequence of the gyrA gene of the fluoroquinolone-resistant Escherichia coli isolate 205096 (MIC of ciprofloxacin, 128 micrograms/ml), which was recently demonstrated to be a gyrA mutant (P . Heisig and B . Wiedemann, Antimicrob . Agents Chemother . 35:2031-2036, 1991) . Compared with the gyrA+ gene of E . coli K-12, 55 nucleotide changes were found . Three of these resulted in amino acid exchanges: Ser-83-->Leu, Asp-87-->Gly, and Asp-678-->Glu . A 0.7-kb DNA fragment containing two of these mutations (Ser-83-->Leu and Asp-87-->Gly) was isolated and fused in frame to the residual 3' coding region of gyrA+ in a plasmid to yield a chimeric gyrA gene (gyrA#) . After introduction into E . coli 205096, this gyrA# gene does not increase the fluoroquinolone susceptibility of the resulting heterodiploid strain in a dominance test, while the gyrA+ gene does . The ciprofloxacin concentration necessary to inhibit by 90% (IC90) the supercoiling activity of gyrase isolated from E . coli 205096 is above 2,000 micrograms/ml . An identical result was found for gyrase reconstituted in vitro from the gyrB+ gene product and the chimeric gyrA# gene product . This is more than a 4,000-fold increase compared with the IC90 determined for gyrase from E . coli K-12 (gyrA+) (IC90, 0.5 microgram of ciprofloxacin per ml) . No indications for the involvement of the gyrB gene or for alterations in quinolone permeation were found. Oncology, 1993 Apr, 50 Suppl 1, 31 - 4 Mitomycin, ifosfamide, and cisplatin in non-small cell lung cancer; Cullen MH; Mitomycin, ifosfamide, and cisplatin have demonstrated the best single-agent activity thus far in patients with non-small cell lung cancer (NSCLC), the most common malignant disease in the western world . For this reason, we initiated a phase II study, giving these three agents in combination (designated MIC) to 74 patients with inoperable NSCLC . Sixty-six patients were evaluable for response, of whom 30 (45%) demonstrated a partial response and 7 (11%) a complete response . These results, along with those obtained in two other phase II trials of MIC in NSCLC, promoted us to begin a large-scale, multicenter, phase III study of MIC in patients with inoperable limited-stage NSCLC . In this ongoing study, patients have been randomized to receive treatment with MIC and radiotherapy or radiotherapy alone . We hope to resolve the issue of whether a survival advantage is conferred on NSCLC patients treated with radiotherapy in combination with this promising chemotherapeutic regimen. Eur J Ophthalmol, 1993 Apr-Jun, 3(2), 61 - 5 Intraocular levels of cefuroxime in inflamed rabbit eyes; Koul S et al.; The pharmacokinetics of cefuroxime was studied in the inflamed rabbit eye employing subconjunctival, intravitreal and combined intravitreal-intravenous routes of administration to study the intraocular levels and the duration of minimum inhibitory concentrations (MIC) of the antibiotic in the vitreous and in the aqueous . A standard inoculum of viable S . aureus was injected into the vitreous of 36 pigmented rabbits to establish experimental endophthalmitis . A biological method was used for the antibiotic assay . Penetration of systemically and subconjunctivally administered-cefuroxime into the inflamed vitreous was poor . Intraocular inflammation increased the clearance of the intravitreally injected cefuroxime . A dose of 75 mg subconjunctivally produced levels in the aqueous far exceeding MIC for over six hours . Penetration of intravitreally injected cefuroxime into the aqueous was poor, inconsistent and short lasting . Following a single intravitreal injection of 1000 micrograms cefuroxime, levels exceeding the MIC for common ocular pathogens persisted in the vitreous for at least 24 hours but supplementation with intravenous cefuroxime neither increased the intraocular levels nor delayed the clearance of the intravitreally injected antibiotic. Pathol Biol (Paris), 1993 Apr, 41(4), 313 - 5 In vitro evaluation of activities of azithromycin, clarithromycin and sparfloxacin against Chlamydia trachomatis; Lefevre JC et al.; The in vitro activities of azithromycin, clarithromycin and sparfloxacin were evaluated by studying inhibition of in vitro Chlamydia trachomatis propagation in McCoy cells, comparatively with erythromycin, ofloxacin and tetracycline . Fifteen clinical isolates of C . trachomatis were tested with an inoculum of 5.10(3) inclusion--forming units in a 96--well microtiter plate . Minimal inhibitory concentration (MIC) ranges were as follows: azithromycin, 0.06 to 0.125 microgram/ml; clarithromycin, 0.008 microgram/ml; erythromycin, 0.06 to 0.125 microgram/ml; ofloxacin 0.5 to 1 microgram/mg; sparfloxacin, 0.03 to 0.06 microgram/ml; and tetracycline 0.125 to 0.25 microgram/ml . Minimal bactericidal concentration (MBC) ranges, calculated from passage into antibiotic--free medium, were as follows: azithromycin 0.25 to 0.5 microgram/ml; clarithromycin, 0.03 to 0.125 microgram/ml; erythromycin, 0.25 to 2 micrograms/ml; ofloxacin, 0.5 to 1 microgram ml; sparfloxacin, 0.03-0.06 microgram/ml; and tetracycline, 1 to 4 micrograms/ml . Clarithromycin and sparfloxacin showed the greatest activity and clinical studies of these agents in C . trachomatis infections are therefore indicated. Biochim Biophys Acta, 1993 Mar 5, 1162(1-2), 143 - 8 Methylisocyanate and actin polymerization: the in vitro effects of carbamylation; Kuckel CL et al.; Uremia has been implicated in cataractogenesis due to protein carbamylation by cyanate derived from urea . The present study was designed to directly identify the effects of carbamylation on actin polymerization and the possible contribution to cataract formation . The susceptibility of actin to carbamylation is expected because of the 19 lysines distributed along its length . The lysines of actin were selectively carbamylated by methylisocyanate (MIC) at pH 8.0 and 4 degrees C and actin polymerization assayed by high-shear viscometry, fluorescence and transmission electron microscopy . Our results provide evidence that non-enzymatic carbamylation of the lysine residues prevents the polymerization of actin . In addition, this carbamylated actin inhibited the polymerization of nascent, unmodified actin . High-shear viscosity measurements demonstrated decreased initial apparent rates and decreased steady-states (final specific viscosities) of polymerization . Fluorescence measurements showed decreased relative intensities of fluorescence versus control and confirmed the inhibitory effects of carbamylation by MIC on the steady state of F-actin . Transmission electron microscopy (TEM) showed the presence of disorganized filaments when carbamylated actin was added to polymerizing unmodified actin . Our results suggest that carbamylation of actin can cause a loss of ordered filament structure and shape of the lens fiber cell, thus predisposing it to cataract development. Cesk Epidemiol Mikrobiol Imunol, 1993 Mar, 42(1), 29 - 34 {Testing the sensitivity of opportunistic agents of mycoses to antimycotic drugs in vitro}; Otcenasek M et al.; The authors tried to standardize the method of assessment of the minimal inhibitory concentration (MIC) of antimycotics for the evaluation of the sensitivity of opportunistic causal agents of mycoses . They paid attention to factors which cause deterioration of the reproducibility of tests and lead to intra- and interlaboratory variability of results . In conjunction with this the authors drew attention to the lack of uniformity of views on the application of these tests in clinical practice . In the author's view the reservation pertaining in particular to an inadequate correlation of results in vitro and in vivo do not cast doubts on the expedience of laboratory assessment of sensitivity . Testing of systemic antimycotics with a low pharmacotherapeutic index and a relatively high frequency of secondary resistance is particularly justified . In those instances assessment of MIC values is a significant component of monitoring of adequate antifungal chemotherapy, in particular when antimycotics are administered for prolonged periods to patients with altered immunity. Clin Investig, 1993 Mar, 71(3), 221 - 5 HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors; Boehm BO et al.; The prevalence of circulating autoantibodies against thyroperoxidase (mic-TPO) was determined in 3,000 healthy blood donors (age range: 23 to 60 years) from the Hamburg area . Of the blood donors, 153 (5.1%) were found to have high titer of mic-TPO (> 350 IU/ml) . Only two autoantibody positive subjects (0.06%) were chemically hyper- and hypothyroid, respectively . Analysis of HLA-DR specificities revealed that HLA-DR specificities DR3 and DR5 were significantly increased when compared to controls (n = 1,863) . Comparison of the autoantibody-positive probands with a group of disease controls, i.e., Graves' patients and patients with lymphocytic thyroiditis, revealed a higher prevalence of HLA-DR3-positive HLA haplotypes in the disease controls when compared to autoantibody positives . Individuals with a mic-TPO level greater than 2,000 IU/ml were almost exclusively found to have one HLA-DR3 or HLA-DR5 positive HLA haplotype . We conclude that a high prevalence of high-titer mic-TPO can be found in healthy blood donors . Circulating signs of thyroid autoimmunity were associated with HLA specificities also found to be associated with autoimmune thyroid diseases. Ir J Med Sci, 1993 Mar, 162(3), 91 - 4 Prevalence of metronidazole-resistant Helicobacter pylori in dyspeptic patients; Xia HX et al.; Susceptibility to metronidazole of 213 clinical strains of H . pylori from dyspeptic patients was determined by a plate dilution method . Seventy two (33.8%) of the strains were resistant to metronidazole (MIC > 8 mg/L), 20 of these were from 24 patients who had received previously metronidazole (83.3%), giving a primary (pretreatment) resistance rate of 27.5% (52/189) . The resistance rate was higher in women than in men, especially aged 50 to 59 years old (43.6% vs 23.3%, p < 0.001) . The resistance rate was lower in patients at 60 or over (9.8%), but similar between the younger patients groups (38.8% - 49.0%) . There was no difference in the resistance rate between peptic ulcer disease (32.6%) and nonulcer dyspepsia (34.7%) . These data indicated that metronidazole resistance in H . pylori is absolutely associated with previous use of the drug, and the higher resistance rate in women may be due to the more frequent prescription of the drug for their gynaecological infection or operation . Therefore, testing of susceptibility of H . pylori to metronidazole is important . A new susceptibility testing technique, the E-test was evaluated in this study and found to give comparable results to the plate dilution method and also had the advantage of being simple to perform. Antimicrob Agents Chemother, 1993 Mar, 37(3), 610 - 2 Efficacy of ampicillin-sulbactam versus that of cefoxitin for treatment of Escherichia coli infections in a rat intra-abdominal abscess model; Rice LB et al.; We examined the efficacy of ampicillin-sulbactam (2:1) and cefoxitin in the treatment of infections caused by Escherichia coli strains exhibiting increasing levels of beta-lactamase-mediated resistance to ampicillin-sulbactam in the rat intra-abdominal abscess model . Cefoxitin was superior to ampicillin-sulbactam in the treatment of infections caused by all strains . Treatment with ampicillin-sulbactam resulted in a statistically significant decrease in CFU per gram of abscess in comparison with treatment with ampicillin alone for both the moderately resistant and the resistant strains, with an inverse correlation between the MIC and the absolute decrease in CFU per gram of abscess. Mycoses, 1993 Mar-Apr, 36(3-4), 125 - 30 Susceptibility testing of Candida species for fluconazole: the role of buffering in the agar dilution assay; Werner E et al.; The role of buffering in the determination of the minimal inhibitory concentration (MIC) of fluconazole was studied with Candida species . Agar dilution tests were performed on media (pH 7.25) buffered with either phosphate or morpholinopropane-sulfonic acid (MOPS) or endomethylene-tetrahydrophthalic acid (EMTA), 0.1 mol l-1 each, or on the unbuffered medium . It consisted of casitone and glucose supplemented with FeCl3 and MgSO4 . The MICs recorded after 24 h at 37 degrees C extended from 0.1 mg l-1 to > or = 100 mg l-1 on the phosphate and EMTA medium, being concordant on both media . On the MOPS medium and the unbuffered medium the readings were also concordant; the MICs, however, were mostly 25 mg l-1 or higher . This increase of the values--up to six dilution steps--could not be correlated with the amount of acid secreted by the single strains . EMTA proved to be an alternative to phosphate in this system, and because it allows a faster growth of the yeasts it might be superior to phosphate . The concordance of the MIC values in the presence of such different buffer compounds tends to suggest that they indeed indicate the strongest inhibition attainable in vitro by fluconazole . MOPS was confirmed to be of no use in this system. Mycoses, 1993 Mar-Apr, 36(3-4), 101 - 3 Kinetics of amorolfine in human nails; Polak A; Amorolfine penetrates rapidly into the nail after topical application . The kinetics of penetration follow an exponential law as expected, and the level of amorolfine measured in the nail (at least in the upper levels) already exceeds the MIC of most fungi causing onychomycosis after only 24 h of contact . After topical application amorolfine is detectable in the nail earlier and in higher concentrations than terbinafine and itraconazole after oral application. Southeast Asian J Trop Med Public Health, 1993 Mar, 24(1), 49 - 52 Intramuscular artemether in female patients with uncomplicated falciparum malaria; Bunnag D et al.; Thirty-three female patients suffering from acute uncomplicated falciparum malaria were treated with intramuscular artemether for 5 days during May-October 1990 . Fourteen patients received 160 mg as an initial dose, followed by 80 mg daily for 4 days . Nineteen patients with low body weight (mean weight of 36.5 kg) were given artemether at 3.2/kg as a loading dose and followed by 1.6 mg/kg/dose for another 4 days . The geometric mean of parasitemia was 17,378/microliters (range 640-234,720) . The mean fever (FCT) and parasite clearance time (PCT) were 41.8 and 49.4 hours, respectively . Two patients had probable intercurrent infection with FCT of over 7 days . Thirty-one patients had completed the 28-day follow-up . The cure rate was 90.3% (28/31) . Three patients had RI type of response . Mild and transient adverse effects were experienced in eleven patients; these consisted of pain at the injection sites, vomiting, dizziness, abdominal pain, palpitation and diarrhea . These symptoms may in part be due to symptom complex of malaria . The MIC of chloroquine, quinine, quinidine and mefloquine was performed in all patients but only 25 isolates were successfully cultured and tested . The MIC of all tested drugs were shown to be higher than that of previous studies, suggesting that there is a rapid increase of mefloquine resistant strains of falciparum malaria . In conclusion, artemether proves to be effective against multiple drug resistant falciparum malaria (including mefloquine resistant strains) and can be considered as an alternative antimalarial to mefloquine . The drug was well tolerated in female patients with mild and transient side-effects.(ABSTRACT TRUNCATED AT 250 WORDS) Pathol Biol (Paris), 1993 Mar, 41(3), 242 - 8 {Clinical pharmacokinetics of ceftriaxone during the third trimester of pregnancy and study of its transplacental passage in two patients}; Bourget P et al.; The purpose of this study was to determine ceftriaxone (CTX) pharmacokinetics during pregnancy . Six women (26 to 34 years of age) admitted for chorioamnionitis (n = 4) or pyelonephritis (n = 2) were included . Gestational age ranged from 29 1/7 to 40 5/7 weeks . Initial intravenous treatment was ceftriaxone (CTX) (2 g/d), tobramycin (3 mg/kd/d) and ornidazole (1 g/d) . Blood specimens were collected during the first treatment day (D1) to determine the primary pharmacokinetic profile of CTX then at steady-state (D7) to look for systemic accumulation . In two patients, transplacental passage of CTX was evaluated by determining the ratio of fetal and maternal concentrations (F/M) at delivery . Plasma CTX levels were determined using high-performance liquid chromatography . A noncompartmental method was used for pharmacokinetic analysis . Each patient served as her own control . Data obtained on D1 and D7 were compared using Wilcoxon's test (values of p < or = 0.05 were considered significant) . A group of healthy controls given a similar regimen was also used . 1) Tolerance was outstanding, recovery was achieved in every case, and there were no premature deliveries . 2) No evidence of accumulation of CTX was found and kinetic profiles on D1 and D7 were not significantly different . 3) Mean kinetic parameter values were closely similar to those found in healthy volunteers . 4) Residual levels of total CTX and free CTX determined after 24 hours were greater than the minimal inhibitory concentration (MICs) of susceptible organisms . 5) The usual recommended dosage of CTX (2 g/d) proved adequate during the third trimester of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) Indian J Malariol, 1993 Mar, 30(1), 29 - 35 In-vivo and in-vitro sensitivity of Plasmodium falciparum to chloroquine at Indian Oil Corporation, Mathura (U.P.); Dua VK et al.; In vivo and in vitro susceptibility of Plasmodium falciparum to chloroquine were conducted at Indian Oil Corporation (IOC), Mathura, India . 18 out of 31 cases showed resistance {minimum inhibitory concentration (MIC) 8 pmol} in in vitro study . EC50 and EC90 values estimated from log-probit analysis for resistant isolates were 0.66 and 1.44 microM/litre, and for sensitive isolates 0.28 and 0.96 microM/litre blood respectively . In vivo tests identified 13 cases (40.62%) as resistant and 19 cases (59.73%) as sensitive out of 32 cases . All the cases belonged to IOC, Mathura complex, or its vicinity. Hum Exp Toxicol, 1993 Mar, 12(2), 135 - 9 Do the hydrolysis products, methylamine and N,N'-dimethylurea, play any role in the methyl isocyanate-induced haematological and biochemical changes in rabbits? Jeevaratnam K, Sugendran K, Vaidyanathan CS. The subcutaneous administration of methyl isocyanate (MIC) to female rabbits, resulted in significant increases in haemoglobin concentration, erythrocyte volume fraction and leucocyte number in blood, as well as plasma total proteins, and urea . The present study was designed to investigate whether the hydrolytic products of MIC, methylamine (MA) and N,N'-dimethylurea (DMU) play any role in eliciting these changes . Both MA and DMU administered subcutaneously in an equimolar dose to that of 1.0 LD50 MIC, 2.2 mmol kg-1, had no influence on these parameters, although there was a marginal increase in the plasma urea level shortly after the administration of DMU . This study establishes that the observed haematological and biochemical changes induced by MIC intoxication in rabbits are mostly due to MIC. J Biol Chem, 1993 Feb 15, 268(5), 3238 - 44 The topology of the anchor subunit of dimethyl sulfoxide reductase of Escherichia coli; Weiner JH et al.; The terminal electron transfer enzyme Me2SO reductase of Escherichia coli is a heterotrimeric enzyme composed of a membrane extrinsic catalytic dimer (DmsAB) and a membrane intrinsic polytopic anchor subunit (DmsC) . The topology of DmsC has been studied using phoA (alkaline phosphatase) and blaM (beta-lactamase) gene fusions . The results of analyzing the properties of proteins produced by the fusions suggests a structure with eight transmembrane helices . Both the amino and carboxyl termini are exposed to the periplasm . The entire DmsC polypeptide is necessary to anchor DmsAB to the membrane as fusions with truncated DmsC were not functional and soluble DmsAB accumulated in the cytoplasm . A dmsC-phoA fusion in the termination codon of dmsC generated a chimeric enzyme with functional Me2SO reductase and alkaline phosphatase activity . Quantitation of the minimal inhibitory concentration of ampicillin for the dmsC-blaM fusions indicated that different transmembrane helices had differing signal sequence activity. J Neurosci Res, 1993 Feb 15, 34(3), 357 - 63 Microglial conditioned medium promotes survival and development of cultured mesencephalic neurons from embryonic rat brain; Nagata K et al.; We previously reported that microglial conditioned medium (Mic-CM) has a neurotrophic effect on cultured rat neocortical neurons {Nakajima et al . (1989): Biomed Res 10:411-423} . In order to investigate the interaction between microglia and neurons in more detail, we determined the effects of Mic-CM on the primary cultured mesencephalic neurons from 16-day embryonic rats . The addition of Mic-CM to the culture medium significantly enhanced the survivability of neurons and promoted neurite extension in a low cell-density culture condition . In a high cell-density culture condition, Mic-CM markedly increased dopamine uptake, which was quantified by assessing the specific {3H}dopamine uptake, and also increased the dopamine content of cultured cells . Furthermore, the number of mesencephalic dopaminergic neurons, which was determined by quantitative analysis of tyrosine hydroxylase (TH)-immunoreactive cells, increased significantly in the presence of Mic-CM . These results suggest that Mic-CM enhances survival or maturation of TH-positive neurons present in cultures of the embryonic mesencephalon and that these neurotrophic effects may be due to a diffusible factor(s) from microglia. Antimicrob Agents Chemother, 1993 Feb, 37(2), 363 - 5 Anti-Trichophyton mentagrophytes activity and percutaneous permeation of butenafine in guinea pigs; Arika T et al.; We examined anti-Trichophyton mentagrophytes activity, cutaneous penetration, and skin localization of butenafine, a novel benzylamine antifungal agent . The following results were obtained . (i) In the guinea pig dorsal skin trichophytosis model, butenafine produced complete eradication of fungi from infected sites . Clotrimazole was active when animals were infected with 10(4) or 10(5) cells but was almost inactive when the inoculum size was 10(6) cells . (ii) The MICs of butenafine and clotrimazole against arthrospores of T . mentagrophytes KD-04 were 0.025 and 0.39 microgram/ml, respectively . (iii) When 0.2 ml of a 1% 14C-butenafine solution was applied for 23 h/day for 7 days, high radioactivity corresponding to 250 to 500 micrograms of butenafine per g of skin in the epidermis, including the horny layer, was observed . (iv) Butenafine penetrates through transepidermal and transfollicular routes . The excellent therapeutic efficacy of butenafine on experimental dermatophytosis may be attributed to its low MIC and good penetration and distribution in the horny layer and hair follicles, where fungi reside. Infect Immun, 1993 Feb, 61(2), 512 - 9 Antibiotics enhance binding by human lipid A-reactive monoclonal antibody HA-1A to smooth gram-negative bacteria; Siegel SA et al.; The effect of antibiotic exposure of phenotypically smooth gram-negative bacteria on binding by the human lipid A-reactive monoclonal antibody HA-1A (trademark of Centocor, Inc.) was examined by liquid-phase immunoassay and by dual-parameter flow cytometry (fluorescence-activated cell sorter {FACS}) analysis . HA-1A exhibited dose-dependent binding to untreated rough gram-negative bacteria such as the Escherichia coli D21F2 Re chemotype strain but little binding to untreated smooth strains such as E . coli O111:B4, or to gram-positive bacteria . However, overnight incubation of E . coli O111:B4 with inhibitory concentrations of ceftazidime produced dose-dependent enhancement of HA-1A binding . Similar augmentation of HA-1A binding was observed when other smooth strains were exposed to cell wall-active agents . Dual-parameter FACS analysis of E . coli O111:B4 exposed overnight to two times the MIC of ceftazidime revealed a decrease in forward light scatter, indicating a reduction in average cell size or bacterial fragmentation, accompanied by a striking increase in lipid A-inhibitable HA-1A binding . Moreover, ceftriaxone, but not gentamicin, produced a marked increase in propidium iodide uptake, indicating an increase in bacterial cell permeability, and a corresponding enhancement of HA-1A binding . Antibiotic-induced enhancement of HA-1A binding to smooth strains of gram-negative bacteria thus appears related to specific alterations in bacterial cell morphology resulting in exposure of the epitope recognized by HA-1A. Antimicrob Agents Chemother, 1993 Feb, 37(2), 297 - 300 Efficacy of oral WIN 54954 for prophylaxis of experimental rhinovirus infection; Turner RB et al.; The efficacy of oral WIN 54954 for the prevention of rhinovirus infection and illness was tested in two randomized, double-blinded, placebo-controlled volunteer challenge studies . Volunteers were inoculated with rhinovirus type 39 (MIC of WIN 54954, 0.17 microgram/ml) or rhinovirus type 23 (MIC, 0.016 microgram/ml) . The volunteers received two doses of drug (600 mg per dose) or placebo on the first day; this was followed by three doses on each of the subsequent 5 days . All volunteers were challenged with virus after the third dose of study drug . No significant antiviral or clinical effect was detected in either study . Pharmacokinetic studies revealed that on the last day of drug administration, 38 of 39 (97%) volunteers had trough levels of WIN 54954 in plasma greater than the MIC for the respective virus . Nasal wash specimens collected on the same day revealed a detectable level in only 6 of 24 (25%) volunteers at the peak (range, 6 to 24 ng/ml) and in only 2 of 14 (14%) volunteers at the trough (range, 6 and 7 ng/ml) . These results suggest that the lack of efficacy of WIN 54954 against rhinovirus may be related to an inability to deliver sufficient drug to the site of viral infection. J Antimicrob Chemother, 1993 Jan, 31(1), 117 - 28 Reactivity and protective capacity of a polyclonal antiserum derived from mice immunized with antibiotic exposed Escherichia coli; Raponi G et al.; The murine immune response to Escherichia coli O6:K-alone or pre-exposed to 0.1 x MIC of aztreonam was investigated . Relative to mice immunized with untreated bacteria, mice immunized with antibiotic-treated microorganisms presented a significantly enhanced protection towards a challenge of 100 x LD50 of viable E . coli O6:K- . Previous injection of 0.1 mL of serum drawn from mice immunized with treated and untreated bacteria protected non-immunized mice towards a challenge of 10 x LD50 of viable E . coli O6:K-- . Serum from mice immunized with treated bacteria also protected non-immunized mice towards a lethal challenge of E . coli O111 . The antiserum contained high titre of IgG antibodies that cross-reacted with lipopolysaccharide isolated from smooth and rough Gram-negative bacteria . Immunoblotting showed additional bands of reactivity to the untreated E . coli O6:K- . Immunization with antibiotic-treated bacteria led to the production of type specific and cross reactive antibodies that protected animals against viable homologous and heterologous lethal challenges. J Antimicrob Chemother, 1993 Jan, 31(1), 105 - 9 Synergy of cefotaxime and fosfomycin against penicillin-resistant pneumococci; Barakett V et al.; The killing kinetics of cefotaxime and fosfomycin, alone and in combination, against seven clinical isolates of penicillin-resistant pneumococci were studied . The antibiotics were tested at 1 x, 2 x and 4 x the MIC for each individual isolate . The results showed a synergic interaction of the two antibiotics for three of the seven strains . This strategy may be useful clinically. J Appl Toxicol, 1993 Jan-Feb, 13(1), 15 - 8 Influence of methylamine and N,N'-dimethylurea, the hydrolysis products of methyl isocyanate, on its systemic toxicity; Jeevaratnam K et al.; Subcutaneous administration of the LD50 dose of methyl isocyanate (MIC) to rats induced severe hyperglycaemia, lactic acidosis and uraemia in rats . Neither methylamine (MA) nor N,N'-dimethylurea (DMU), the hydrolysis products of MIC, administered in equimolar doses had any influence on these parameters except for a marginal transient increase in plasma urea by DMU . Methyl isocyanate administration led to haemoconcentration, resulting in an increase in the plasma concentration of total proteins and a decrease in both the plasma concentration of albumin and the plasma cholinesterase activity . The hydrolysis products of MIC had no influence on any of these parameters . Thus, it seems reasonable to suggest that the systemic effects of MIC are caused by MIC per se, in spite of its high hydrolytic instability. Arch Dis Child, 1993 Jan, 68(1 Spec No), 54 - 7 Transplacental transfer of cefuroxime in uncomplicated pregnancies and those complicated by hydrops or changes in amniotic fluid volume; Holt DE et al.; The transplacental transfer of cefuroxime was determined at antenatal fetal blood sampling in a cross sectional study of 78 patients between 15-35 weeks' gestation, 8-138 minutes after a maternal intravenous dose of 750 mg . Mean serum cefuroxime concentration, measured by high performance liquid chromatography, was 7.4 (95% confidence interval (CI) 6.8 to 8.1) mg/l in control fetuses; concentrations in hydropic fetuses were similar (6.2 mg/l, CI 4.7 to 7.7) but in fetuses with oligohydramnios they were significantly lower, (4.9 mg/l, CI 3.6 to 6.2) . Antibiotic concentration did not correlate with gestational age and remained unchanged by transfusion of packed red cells . We conclude that (i) fetal serum concentrations of cefuroxime obtained after a maternal dose of 750 mg are only adequate for prophylaxis against organisms with a minimum inhibitory concentration of < 4 mg/l and (ii) transplacental passage of cefuroxime is significantly reduced in the presence of oligohydramnios. Res Vet Sci, 1993 Jan, 54(1), 32 - 9 Effect of stage of oestrous cycle on tylosin disposition in genital tract secretions of cows; Cester CC et al.; The influence of physiological state (oestrous or luteal phase) on tylosin disposition in genital secretions was examined after intravenous administration of tylosin to cows . Six healthy, cyclic and non