mic

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-lactating dairy cows with controlled oestrous cycles were given a single slow intravenous injection of tylosin, at a dose of 10 mg kg-1 . Plasma and genital fluid were regularly sampled up to 48 hours after injection . Tylosin diffused from blood to the genital tract and accumulated in genital secretions whatever the stage of the oestrous cycle: the secretion to plasma ratio was 3.45 +/- 2.54 during oestrous and 4.75 +/- 3.24 during the luteal phase . The area under the concentration-time curve (AUC) and the mean residence time (MRT) were significantly higher in genital secretions than in plasma . The AUC and the MRT in genital secretions showed no significant differences during the oestrous cycle . The minimal inhibitory concentrations (MIC) of tylosin for 25 strains of Actinomyces pyogenes were between 0.032 (12 strains) and 0.063 micrograms ml-1 (13 strains) . Simulations based on the mean values of pharmacokinetic parameters determined in genital secretions, gave tylosin concentrations higher than the MIC for at least 36 hours . It was concluded that after an intravenous administration of tylosin, effective concentrations were achieved in genital secretions of the cyclic cow whatever its hormonal status which supported its use for the treatment of genital tract infections.

J Clin Pathol, 1993 Jan, 46(1), 51 - 5
Histopathological findings in oesophageal carcinoma with and without preoperative chemotherapy; Darnton SJ et al.; AIMS: To investigate the pathological effects of preoperative chemotherapy on oesophageal carcinoma . METHODS: Qualitative and quantitative changes in oesophageal carcinoma after preoperative chemotherapy were assessed by examination of biopsy specimens before treatment and resected specimens . RESULTS: Of 13 patients with adenocarcinoma treated with 5-fluorouracil, adriamycin, and mitomycin (FAM), nine showed minor histological changes compared with 14 control cases . All 12 patients with squamous carcinoma treated with preoperative mitomycin, ifosfamide, and cisplatin (MIC) showed noticeable histological changes when compared with the 13 control cases . Changes included complete ablation (n = 1) and partial regression (n = 5) of the tumour . A quantitative estimate of the proportion of tumour to stroma showed no difference between control adenocarcinomas and those treated with chemotherapy . There was, however, a significant reduction (p < 0.01) in the proportion of tumour to stroma in the treated squamous group compared with the controls . There was no relation between the degree of response in squamous carcinomas and the degree of differentiation of the tumour . Patients in which squamous carcinomas responded well, as assessed quantitatively, showed a tendency to better survival at one year . CONCLUSIONS: Histopathological changes attributable to chemotherapy can be observed in oesophageal carcinoma . The response of squamous carcinoma to MIC is histologically more evident than that of adenocarcinoma to FAM . A quantitative technique may be useful in assessing the effect of chemotherapy in oesophageal squamous carcinoma.

Mikrobiyol Bul, 1993 Jan, 27(1), 31 - 5
{In vitro activity of ofloxacin and ciprofloxacin against Mycobacterium tuberculosis strains}; Aysev AD; The activity of Ofloxacin and Ciprofloxacin against 50 strains of M . tuberculosis were investigated in-vitro on Lowenstein-Jensen medium . Minimal Inhibitory Concentration (MIC90) of Ofloxacin and Ciprofloxacin were found 1 mg/L and 4 mg/L, respectively . There were no difference in susceptibility to Ofloxacin and Ciprofloxacin between strains which were susceptible or resistant to Standard Anti-tubercular drugs.

Exp Brain Res, 1993, 95(1), 15 - 27
Primate frontal cortex: neuronal activity following attentional versus intentional cues; Boussaoud D et al.; We examined neuronal activity in three parts of the primate frontal cortex: the dorsal (PMd) and ventral (PMv) premotor cortex and a ventrolateral part of the dorsolateral prefrontal (PF) cortex . Two monkeys fixated a 0.2 degrees white square in the center of a video display while depressing a switch located between two touch pads . On each trial, a spatial-attentional/mnemonic (SAM) cue was presented first . The SAM cue consisted of one 2 degrees x 2 degrees square, usually red or green, and its location indicated where a conditional motor instruction would appear after a delay period . The stimulus event containing the motor instruction, termed the motor instructional/conditional (MIC) cue, could be of two general types . It might consist of a single 2 degrees x 2 degrees square stimulus identical to one of the SAM cues presented at the same location as the SAM cue on that trial . When the MIC cue was a single square, it instructed the monkey to move its forelimb to one of the two touch pads according to the following conditional rule: a green MIC cue meant that contact with the right touch pad would be rewarded on that trial and a red MIC cue instructed a movement to the left touch pad . Alternatively, the MIC cue might consist of two 2 degrees x 2 degrees squares, only one of which was at the SAM-cue location: in those cases, one square was red and the other was green . The colored square at the SAM cue location for that trial was the instructing stimulus, and the other part of the MIC cue was irrelevant . When, after a variable delay period, the MIC cue disappeared, the monkey had to touch the appropriate target within 1 s to receive a reward and could break visual fixation . The experimental design allowed comparison of frontal cortical activity when one stimulus, identical in retinocentric, craniocentric, and allocentric spatial location as well as all other stimulus parameters, had two different meanings for the animal's behavior . When a stimulus was the SAM cue, it led to either a reorientation of spatial attention to its location, or the storage of its location in spatial memory . By contrast, when it was the MIC cue, the same stimulus instructed a motor act to be executed after a delay period . For the majority of PMd neurons (55%), post-MIC cue activity exceeded post-SAM cue activity.(ABSTRACT TRUNCATED AT 400 WORDS)

J Med Vet Mycol, 1993, 31(2), 161 - 4
Antimycotic susceptibility testing of agents of black grain eumycetoma; Venugopal PV et al.; Antimycotic susceptibility testing of 17 strains of eumycetes including Madurella mycetomatis, Madurella grisea, Pyrenochaeta romeroi, Exophiala jeanselmei and Leptosphaeria tompkinsii, isolated from cases of black grain mycetoma, was carried out against ketoconazole, itraconazole, miconazole and econazole by broth microdilution and agar dilution methods . Itraconazole and ketoconazole were more active inhibiting 50% of the strains (MIC 50) at 0.5 and 1 microgram ml-1 and 90% (MIC 90) at 2.5 and 5 micrograms ml-1, respectively . The MIC 50s of econazole and miconazole were 2.5 and 5 micrograms ml-1 and MIC 90s 10 micrograms ml-1 for both drugs.

J Appl Toxicol, 1993 Jan-Feb, 13(1), 33 - 7
Alterations in hepatic biochemistry of mice intoxicated with MIC, carbaryl and thiram; Gupta M et al.; The effect of different doses of methyl isocyanate (MIC), carbaryl and thiram on liver microsomal mixed-function oxygenases (MFO) was studied in adult Swiss Portan mice by intraperitoneal (i.p.) injection for different durations . The LD50 dose of all three toxicants after 0.75 h of administration could increase cytochrome P-450 and cytochrome b5 contents (82-143%), and the 1/4 LD50 of these compounds could elicit the same effect after 168 h (168-393%) . The 1/4 LD50 dose of thiram decreased the cytochrome P-450 content below the control level (69.62%) in 0.75 h and the same dose of MIC could decrease the cytochrome P-450 level by 40% compared to the control after 3 days of consecutive injection . The activities of drug-metabolizing enzymes (aminopyrine demethylase--NADH and NADPH-linked--and aniline hydroxylase) were found to increase with all three compounds in general . Marked changes in the activity of the marker enzyme glucose-6-phosphatase were also seen after i.p . injection if MIC, carbaryl and thiram . These findings suggested that these compounds were hepatotoxic, which could be due to their carbamylating nature.

Am J Vet Res, 1993 Jan, 54(1), 99 - 102
Effect of heparin on hemagglutination by pseudorabies virus; Ohashi S et al.; Heparin inhibited hemagglutination (HA) by pseudorabies virus (PRV), but not HA by Akabane virus, bovine adenovirus type 7, Fukuoka virus, Getah virus, Japanese encephalitis virus, and parainfluenza virus type 3 belonging to the families Bunyaviridae, Adenoviridae, Rhabdoviridae, Togaviridae, Flavivi-idae, and Paramyxoviridae, respectively . The minimal inhibitory concentration of heparin required to inhibit 8 HA U of PRV ranged from 0.005 to 0.01 U/ml . Mouse erythrocytes failed to combine with the HA inhibitory factor of heparin . On the other hand, mouse erythrocytes treated with heparinase had greatly reduced agglutinability by PRV . Virus-heparin complex formation could be observed by sedimenting heparin with the virus particles.

Int J Clin Pharmacol Res, 1993, 13(2), 65 - 8
Lack of activities of amikacin and sulphamethoxazole against Mycobacterium avium-intracellulare; Yew WW et al.; Twenty clinical isolates of Mycobacterium avium-intracellulare were tested with amikacin and sulphamethoxazole for in-vitro susceptibilities . The MICs and MBCs of the former drug ranged from 8 to > 64 mg/L (median MIC: 64 mg/L, median MBC: > 64 mg/L) . The MICs and MBCs of the latter drug were found to be > 256 mg/L . Each of eight patients with invasive pulmonary disease due to these organisms was treated with amikacin for six months and with cotrimoxazole (sulphamethoxazole-trimethoprim) for one year . Only one patient had sustained bacteriological conversion . Three patients showed a transient reduction of bacillary load during the period of amikacin administration . The rest all failed to show response . Thus sulphamethoxazole was found to have no activity against Mycobacterium avium-intracellulare, and amikacin has doubtful activity when used alone in treatment of M . avium-intracellulare infection.

G E N, 1993 Jan-Mar, 47(1), 10 - 5
{Measurement of esophageal pH during 24 hours in children . Preliminary report}; Gonzalez I et al.; A preliminary report is presented regarding the 24 hours continuous pH monitoring of 40 patients from 1 month to 19 years of age with clinical features of gastro-esophageal reflux confirmed by at least one of the diagnostic methods utilized (radiology, endoscopy, esophageal biopsy) . The equipment used was a MIC GASTROGRAPH with 1.2 and 3 mm catheters according to age and using the methodology suggested by ESPGAN . Patients with reflux index of more than 10% had all other pH indexes and other diagnostic methods abnormal . The area of the curve below pH 4 correlated directly with the presence of esophagitis . Patients with post history of esophageal atresia and caustic esophagitis had marked alterations of pH . PH monitoring with the modern methodology currently available is of great help to quantify severity of acid reflux, to distinguish between physiologic pathologic reflux and to decide treatment.

Med Dosw Mikrobiol, 1993, 45(1), 61 - 4
{Interaction of cefotaxime and normal human serum in the bacteriocidal process against strains of Escherichia coli producing surface K1 antigen}; Franiczek R et al.; A comparison was made regarding susceptibility of strains of E . coli to bactericidal activity of normal human serum . It was found that when among strains with K1 antigen over 40% were resistant to normal human serum, strains without this antigen were resistant in only 15% . Sub-doses of cefotaxime (1/2 and 1/3 MIC) together with normal human serum strong bactericidal action against strains of K1-possessing E . coli resistant to serum . Sub-doses of cefotaxime cause occurrence of elongated form of bacteria, starting one hour after addition of the antibiotic . Elongated forms of bacteria are not loosing antigen K1 and this suggest that it probably does not exert a role in protection of bacteria against synergistic action of both studied factors.

Clin Ther, 1993, 15 Suppl B, 32 - 6
Effect of lansoprazole on Helicobacter pylori; Lamouliatte H; Helicobacter pylori has been identified as a major factor in duodenal ulcerogenesis . After H pylori eradication, the recurrence rate of duodenal ulcers falls dramatically and cure of this chronic relapsing disease has been claimed by several authors . H pylori eradication was first attempted with bismuth salts alone or with antibiotics . H2-receptor antagonists are not effective against H pylori, although proton pump inhibitors such as omeprazole and lansoprazole are active in vitro against H pylori . Their minimum inhibitory concentration is close to that of the imidazoles (metronidazole, tinidazole): proton pump inhibitors and imidazoles have common structural features . Consequently, lansoprazole has been tested in monotherapy and triple therapy . In monotherapy, the H pylori clearance rate with lansoprazole 30 mg during 4 weeks was 40% in our study and 19% in a study by Jhala et al . No eradication was achieved . These results were in agreement with those of another proton pump inhibitor . In triple therapy, two studies used the same regimen in nonulcer dyspepsia patients: lansoprazole 30 mg/day for 2 weeks, amoxicillin 2 g/day for 2 weeks, and tinidazole 1 g/day for 2 weeks . Pooled data from these two French trials show that H pylori eradication was achieved in 14/17 patients (82.4%) . Lansoprazole administered concomitantly with two antibiotics is effective in the eradication of H pylori and is as effective as other triple therapy regimens with bismuth salts, or with other proton pump inhibitors . One of the most important problems is metronidazole resistance of H pylori strains . Antibiotics such as new macrolides (clarithromycin or roxithromycin) should be tested in a triple therapy regimen against H pylori strains with lower primary resistance.

Med Dosw Mikrobiol, 1993, 45(3), 273 - 6
{Occurrence of methicillin-resistant strains in Poland and their characteristics}; Piechowicz L et al.; The investigation was performed on 923 strains of S . aureus isolated from clinical material obtained from several regions of Poland . Resistance to methicillin was tested by a dilution method on a solid Mueller-Hinton medium supplemented with 2% of NaCl . Strains exhibiting MIC higher than 4 micrograms/ml were determined as resistant . Resistance to other antibiotics (P, Am, CB, CF, CH, MA, Ge, Bs, E, L, Dx) was tested by a disc method . Bacteriophage typing of S . aureus was performed by a method described by Blair and Williams in RTD and RTD x 100, using basic set of phages and additional phages (88, 89, 187) . MRSA were present in various regions of the country with similar frequency (from 3.3% to 8.3%) . In one center only the percentage was as high as 52.3% . High percentage of MRSA was noted in burned patients (59.9) and these strains were obtained at one center . Within the MRSA III phage group was dominating as well as non-typable strains and inhibited at 100 x RTD-35.4% . MRSA most frequently were typing with phages 88-40.9%, 89-35.0%, 85-24.0%, and they rarely belonged to the phage group II . Among MRSA strains higher percentage of antibiotic-resistance was noted, as compared with other strains . About 60% of MRSA strains were resistant to 6-8 antibiotics . The dominating resistance concerned penicillins, cephalosporins, aminoglycosides, tetracyclines and erythromycin.

Microbiol Immunol, 1993, 37(12), 979 - 81
Effect of heparin on hemagglutinin of herpes simplex virus type 1; Noda M et al.; Heparin inhibited the hemagglutinin activity of herpes simplex virus (HSV) type 1 . The minimal inhibitory concentration of heparin required to inhibit 8 hemagglutination (HA) U of HSV ranged from 0.005 to 0.01 U/ml . Mouse erythrocytes failed to combine with the HA inhibitory factor of heparin . On the other hand, mouse erythrocytes treated with heparinase had greatly reduced agglutinability by HSV . Virus-heparin complex formation was observed by sedimenting heparin with the virus particles.

Vet Res, 1993, 24(6), 494 - 502
Influence of tiamulin concentration in feed on its bioavailability in piglets; Riond JL et al.; Tiamulin pharmacokinetic parameters were determined in 8 2-month-old male improved Swiss Landrace piglets after intake of 2,000 mg/kg feed, 500 mg/kg feed, 12.5 mg/ml aqueous solution administered via a stomach tube and 180 mg/kg feed offered ad libitum . In all cases, the total tiamulin dose received was 10 mg/kg body weight (bw) per day . For the 2,000 mg/kg and 500 mg/kg treatments, animals were restrictively fed a commercial mix in amounts corresponding to 3-fold their maintenance requirement of digestible energy . The piglets first individually received the amount of medicated feed and immediately thereafter the rest of the daily ration . The highest tiamulin serum concentrations (Cmax), the largest area under the curve (AUC0-->infinity), the largest absorption rate constant (Ka), and the shortest time at which the maximum serum concentration occurred (tmax) were obtained after administration via stomach tube followed in the respective order by the 2,000 mg/kg, 500 mg/kg and 180 mg/kg treatments . Ad libitum feeding of the medicated mix at 180 mg/kg failed to provide tiamulin serum concentration above minimum inhibitory concentrations (MIC) of some representative microorganisms . In conclusion, tiamulin concentration in medicated feed strongly influences its rate and extent of absorption and consequently serum concentrations . Larger tiamulin concentration in feed enhances its bioavailability . The common practice adopted by national regulatory agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration agencies for the registration of a new drug is to conduct pharmacokinetic studies after administration via a stomach tube . This practice should be reevaluated because this mode of administration does not correspond to that in routine use.

Ann Otolaryngol Chir Cervicofac, 1993, 110(7), 393 - 8
{Pharmacokinetic study of antibiotics in otitis}; Begue P et al.; Antibiotic concentrations in middle ear fluid can be determined in the purulent effusions of acute otitis media or in chronic effusions at the time of myringotomy with tympanostomy tube insertion . Measurements are usually made using microbiological methods . The concentration of betalactamines in middle ear fluid is 20 to 40% serum concentrations . Therefore, in the treatment of otitis media, it is necessary to use high doses of antibiotics, so that the concentration in the middle ear fluid is higher than the minimum inhibitory concentration (MIC) for the most frequent infecting organisms . Sulfamides penetrate well into the middle ear . On the other hand, the concentration of macrolides is not significant until two or three doses have been delivered and a steady state is reached . While direct measurements of the antibiotic concentrations in middle ear fluid can provide information concerning the effectiveness of the antibiotic relative to the MIC, they do not replace clinical trials in confirming the indications of new antibiotic molecules in the treatment of otitis media . In addition, direct measurements are delicate and show great interindividual variations.

Antibiot Khimioter, 1993 Jan, 38(1), 39 - 42
{Ceftriaxone in prevention and treatment of experimental plague infection}; Ryzhko IV et al.; Ceftriaxone (rocefin), a 3rd generation cephalosporin with prolonged action, was highly efficient (ED50 0.12 to 0.38 mg/mouse) against experimental plague in albino mice infected either by Fra+ or Fra- strains of the plague microbe . The daily doses of the antibiotic (0.5-1.0-2.0 mg/mouse) provided 85-100 per cent survival of the animals . All the strains (15) of the plague microbe isolated from different natural foci and different objects were highly sensitive to ceftriaxone . The MIC was 0.02 to 0.05 microgram/ml.

Antibiot Khimioter, 1993 Jan, 38(1), 33 - 8
{An animal experiment on transplacental transport of ceftazidime at various terms of pregnancy}; Kasabulatov KK et al.; The experiments on rats revealed good transplacental transfer of ceftazidime to the fetus . The level of the transfer increased with increasing of the pregnancy term . The antibiotic concentration in the fetal tissues exceeded the MIC for opportunistic organisms . The ceftazidime concentrations in the amniotic fluid were equal to the therapeutic ones at the early and late terms of the pregnancy . At the early terms of the pregnancy the antibiotic transferred to the amniotic fluid transplacentally . The data are in favour of recommending ceftazidime for prophylaxis and treatment of fetal intrauterine infections.

Yao Xue Xue Bao, 1993, 28(9), 655 - 60
{Effect of DGAVP and Org2766 on intracellular free Ca2+ concentration in dissociated brain cells}; Zhang WN et al.; Intracellular free calcium concentration ({Ca2+}i) was measured with Fura-2 in freshly dissociated brain cells isolated from newborn (1-2 day) mouse pups using AR-CM-MIC cation measurement system, and the effects of DGAVP and Org2766 on the changes in {Ca2+}i induced by the protein synthesis inhibitor anisomycin (ANI) were studied . The results indicate that anisomycin caused dose-dependent increases in {Ca2+}i; and DGAVP itself showed no significant effect on {Ca2+}i, but an appropriate dose of DGAVP antagonized the increases induced by the selective dose-range of ANI, suggesting that the antagonism of ANI-induced inhibition of protein synthesis by DGAVP was likely achieved by preventing ANI from increasing {Ca2+}i, but this mechanism did not apply to the other neuropeptide Org2766 . Therefore, we suppose that the mechanism of the two neuropeptides are different in terms of their effect on intracellular free calcium concentration.

Wien Med Wochenschr, 1993, 143(12), 312 - 21
{Microinvasive CT-controlled tumor therapy of soft tissue and skeletal metastases}; Gronemeyer DH et al.; Micro-invasive CT-guided intratumoral therapy (MIC-ITT) when used in combination with sympathectomy can be an excellent palliative treatment with little impairment of the patient . Rapid as well as complete reduction of pain without systemic side effects can be achieved under local anesthesia in patients in advanced tumor stages by the direct instillation of 50 to 96% alcohol and/or a locally efficacious low toxic cytostatic (Mitoxantron) under CT guidance . CT enables not only exact puncture without injuring endangered structures but also a controlled application of medication . The interventions can be performed with special probes with a diameter of 18 to 25 G . The study population consisted of 145 patients who received a total of 434 treatments . Repeated micro invasive intratumoral treatment was performed on 110 patients with bone and soft tissue metastases (Group I, 335 single treatments) and on 35 patients with vertebral metastases (Group II, 109 single treatments) . In all patients conventional therapeutic strategies had been exhausted or were no longer applicable on the basis of a reduced Karnofsky Index . Treatment was performed in combination with sympathetic neurolysis at the upper tumor pole in all cases . The maximum follow-up time was 30 months . Pain reduction was estimated on a visual analogic scale . In Group I up to time of death a pain reduction of 75% or better was achieved in 88 patients (80%) . A reduction in tumor size concomitant with a stabilization of the tumor region could be shown in 25% in this group, no change in 62% and progression in 13% . In Group II a pain reduction greater than 75% was achieved in 84% as well as a reduction in tumor size (< 50%) in 18% of the patients . Necrotic zones could be shown in 27% and calcification of tumor area in 35% . No change in tumor size was found in 66% of the patients, progression in 16% . All treatments were free of complications . On the whole the results of this therapeutic approach are encouraging . In particular one aspect should be mentioned: with respect to palliative treatment the reduction of tumor size is not crucial . The decisive factor is the improvement in quality of life of the patient using an intervention which impairs the patient only minimally . Furthermore this micro invasive approach should always involve the combination of local tumor treatment with treatment or lysis of the autonomic sympathetic nervous system in tumor vicinity.(ABSTRACT TRUNCATED AT 400 WORDS)

Fundam Appl Toxicol, 1993 Jan, 20(1), 57 - 67
Autoradiographic analyses of guinea pig airway tissues following inhalation exposure to 14C-labeled methyl isocyanate; Kennedy AL et al.; Through the use of radioactively labeled methyl isocyanate (MIC), the deposition, penetration, and clearance of this highly reactive compound in the airway at the tissue and cellular levels have been directly examined . Guinea pigs were exposed to 14C-MIC vapors at concentrations ranging from 0.38 to 15.2 ppm for periods of 1-6 hr . Solubilization of tissues from these animals showed the airway tissues to have the highest level of radioactivity . In the nasal region, 14C deposition, as monitored by histoautoradiography, was limited to the epithelial layer, was related to dose, and was dependent on the specific epithelial cell type . The squamous epithelium was minimally labeled on the surface and the label did not penetrate the cell layer . However, radioactivity was detected throughout the entire nasal respiratory epithelial layer . The lack of nasal deposition in tracheotomized animals demonstrated that the 14C accumulation at this site was due to the scrubbing action of the nasal region with no contribution from blood recirculation . Cellular localization in the tracheobronchial region showed epithelial and subepithelial deposition in a dose-dependent manner with accumulation of the label at the subepithelial region . Radioactivity penetrated to the level of the terminal bronchiole but was not detected in the alveolar region . The persistence of airway radioactivity over the 48-hr postexposure period monitored suggests the covalent modification of airway macromolecules . Despite its broad specificity and high reactivity, MIC undergoes selective reactions in the airways which are dependent on respiratory region and cell type.

Biochem Int, 1992 Dec, 28(4), 745 - 50
Monitoring of haemoglobin-methyl isocyanate adduct by high-performance liquid chromatography with diode array detector; Venkateswaran KS et al.; Carbamylation of haemoglobin by methyl isocyanate (MIC) was detected by high-performance liquid chromatography (HPLC) using a photodiode array detector following cyclisation of the N-terminal valine into methyl isopropyl hydantoin (MIH) . MIH was also synthesised by reaction of MIC with valine, the chromatographic conditions standardised and the spectrum derived by a photodiode array detector recorded for confirmation of the identity of MIH . This HPLC method is specific, sensitive and suitable for the detection of exposure of blood samples to methyl isocyanate.

Toxicol Appl Pharmacol, 1992 Dec, 117(2), 172 - 9
In vitro and in vivo effect of methyl isocyanate on rat liver mitochondrial respiration; Jeevaratnam K et al.; Previous work has shown that irrespective of the route of exposure methyl isocyanate (MIC) caused acute lactic acidosis in rats (Jeevaratnam et al., Arch . Environ . Contam . Toxicol . 19, 314-319, 1990) and the hypoxia was of stagnant type due to tissue hypoperfusion resulting from hypovolemic hypotension in rabbits administered MIC subcutaneously (Jeevarathinam et al., Toxicology 51, 223-240, 1988) . The present study was designed to investigate whether MIC could induce histotoxic hyperoxia through its effects on mitochondrial respiration . Male Wistar rats were used for liver mitochondrial and submitochondrial particle (SMP) preparation . Addition of MIC to tightly coupled mitochondria in vitro resulted in stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation . The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (five- to sixfold) to the inhibitory action of MIC than succinate while cytochrome oxidase remained unaffected . MIC induced twofold delay in the onset of anerobiosis, and cytochrome b reduction in SMP with NADH in vitro confirms inhibition of electron transport at complex I region . MIC also stimulated the ATPase activity in tightly coupled mitochondria while lipid peroxidation remained unaffected . As its hydrolysis products, methylamine and N,N'-dimethylurea failed to elicit any change in vitro; these effects reveal that MIC per se acts as an inhibitor of electron transport and a weak uncoupler . Administration of MIC sc at lethal dose caused a similar change only with NAD(+)-linked substrates, reflecting impairment of mitochondrial respiration at complex I region and thereby induction of histotoxic hypoxia in vivo.

Tuber Lung Dis, 1992 Dec, 73(6), 378 - 83
Treatment of tuberculosis in HIV infection; Grosset JH; Whether tuberculosis patients received short-course chemotherapy with treatment of isoniazid (INH) and rifampicin (RIF), combined or not with pyrazinamide (PZA) and ethambutol (EMB) or streptomycin (SM), or long term chemotherapy with INH, SM and thiacetazone (Tb1), the rate of sputum culture conversion was similar in HIV-positive and HIV-negative patients . To prevent relapses it was recommended to treat patients for a minimum of 9 months and for at least 6 months after culture conversion, or even to administer INH for life after the end of treatment . However, no difference was observed in the percentage of relapses between HIV-positive and HIV-negative patients . Side-effects were observed in approximately 20% of HIV-positive patients treated with INH + RIF + PZA + EMB (or SM) or with INH + SM + Tb1, Tb1 being responsible for epidermal necrolysis, in some cases fatal . The mean survival of HIV-patients with tuberculosis was from 10 to 18 months after the diagnosis of tuberculosis . Other opportunistic infections could have been the main cause of death . Acquired drug resistance is not a common complication of tuberculosis treatment in HIV-positive patients, but several epidemics of nosocomial transmission of multiple drug-resistant tuberculosis have recently been observed in the USA . Sparfloxacin, a new fluoroquinolone with a long half-life and low MIC (0.25-0.50 mg/l) against Mycobacterium tuberculosis, is a promising drug against tuberculosis.

Am Rev Respir Dis, 1992 Dec, 146(6), 1445 - 7
In vitro activity of the new quinolone lomefloxacin against Mycobacterium tuberculosis; Piersimoni C et al.; Minimal inhibitory concentrations (MIC) of ciprofloxacin, ofloxacin and lomefloxacin were determined for 90 Mycobacterium tuberculosis strains isolated from both AIDS and other patients . Eleven (12.2%) of these strains showed in vitro resistance to one or more first-line antituberculosis drugs . Susceptibility tests were done in 7H12 broth by the radiometric method . The MIC range for ciprofloxacin was 0.125 to 4.0 micrograms/ml; for ofloxacin, 0.25 to 4.0; and for lomefloxacin 0.5 to 4.0 micrograms/ml . On the basis of our data, we believe that the following MIC, when determined in 7H12 broth radiometrically, should be used as break points to classify the strain as susceptible: ciprofloxacin and ofloxacin, 1 microgram/ml or less; lomefloxacin, 2 micrograms/ml or less . Lomefloxacin on a once-daily basis deserves further evaluation as a potential supplementary drug for the treatment of tuberculosis.

Trop Med Parasitol, 1992 Dec, 43(4), 223 - 5
An in vitro bioassay for quantification of melarsoprol in serum and cerebrospinal fluid; Burri C et al.; A biological assay was developed for measuring melarsoprol in serum and cerebrospinal fluid of patients with human African trypanosomiasis . Trypanosomes were cultivated in microtiter plates for 72 hours with melarsoprol (Mel B) in concentrations of 1.25 micrograms/ml to 2.2 ng/ml . The minimum inhibitory concentration of Mel B for a reference Trypanosoma brucei rhodesiense clone was determined by microscopical examination . Samples of serum or cerebrospinal fluid were incubated under the same conditions and the highest dilution determined which caused death of all trypanosomes . The melarsoprol concentration of the sample was then calculated using the sample dilution and the determined minimal inhibitory concentration of the trypanosome population used for the assay . The test was validated using a number of reference samples and it was used for melarsoprol determination in serum- and cerebrospinal fluid samples taken from two treated patients . A sample size of 100 microliters was sufficient to perform the assay . The lower detection limit was 9 ng/ml (22.6 nmol/ml) . The assay has potential for measuring other trypanocidal drugs in body fluids.

J Antimicrob Chemother, 1992 Nov, 30(5), 661 - 72
Prevalence of resistance to beta-lactam antibiotics in Escherichia coli isolated from blood from 1969-1991; Shannon K et al.; MICs of beta-lactam antibiotics were determined for blood culture isolates of Escherichia coli from patients in St . Thomas' Hospital, London between 1969 and 1991 . There was correlation between MICs of carbenicillin and those of amoxycillin (Kendall's coefficient of rank correlation, tau = 0.67), mezlocillin (tau = 0.73), cephaloridine (tau = 0.64) and amoxycillin/clavulanic acid (tau = 0.72), but less correlation between MICs of carbenicillin and cefuroxime (tau = 0.31) . During the two decades, the geometric mean MICs increased for carbenicillin (6.6-fold increase in mean MIC), mezlocillin (3.4-fold increase in mean MIC), cephaloridine (two-fold increase in mean MIC) and, to a smaller extent, amoxycillin/clavulanic acid (1.2-fold increase in mean MIC), but not for cefuroxime . These changes were the result of increases in the proportion of isolates that were resistant to carbenicillin and not of changes in the phenotype of carbenicillin-resistant isolates.

J Clin Pathol, 1992 Nov, 45(11), 979 - 83
Effects of chemotherapy on ultrastructure of oesophageal adenocarcinoma; Darnton SJ et al.; AIMS: To compare and contrast the ultrastructural appearance of resected oesophageal adenocarcinomas treated with preoperative chemotherapy with that of non-treated resected controls; and to determine the usefulness of this method in the assessment of the effectiveness of the chemotherapeutic regimen . METHODS: Ten resected oesophageal adenocarcinomas treated with preoperative chemotherapy--mitomycin-C, ifosfamide, and cisplatin (MIC)--were examined by transmission electron microscopy and their appearance compared with that of 13 concurrent untreated resected oesophageal adenocarcinomas . RESULTS: The treated adenocarcinomas showed cytotoxic damage although complete tumour eradication was not achieved . In all 10 treated cases a variable proportion of the neoplastic cells showed unusual degenerative and necrotic changes not seen in untreated cases . In the most affected carcinomas the stroma contained increased numbers of inflammatory cells . CONCLUSIONS: This ultrastructural method is useful for the assessment of the in vivo effect of MIC.

Antimicrob Agents Chemother, 1992 Nov, 36(11), 2529 - 32
Susceptibility of Rickettsia conorii, R . rickettsii, and Coxiella burnetii to PD 127,391, PD 131,628, pefloxacin, ofloxacin, and ciprofloxacin; Jabarit-Aldighieri N et al.; Plaque formation and dye uptake assays were used to measure the MICs of PD 127,391 and PD 131,628 against Rickettsia species . The MICs of PD 127,391 were 0.25 microgram/ml for Rickettsia rickettsii and 0.125 to 0.25 microgram/ml for Rickettsia conorii . The MICs of PD 131,628 were 0.25 to 0.5 microgram/ml for R . rickettsii and 0.5 microgram/ml for R . conorii . As determined by the shell vial technique, 15 strains of Coxiella burnetii were susceptible to PD 127,391 and PD 131,628 (MIC, < or = 1 microgram/ml), while one strain of C . burnetii (MP10) was of intermediate susceptibility.

Mycoses, 1992 Nov-Dec, 35(11-12), 335 - 42
Low voltage scanning electron microscopy study of naftifine activity on Microsporum canis; Butty P et al.; Scanning electron microscopy (SEM) is at present considered a good way to observe the morphological alterations induced by an antifungal on pathogenic fungi . Owing to its high precision, low voltage scanning electron microscopy (LVSEM) improves the quality of observations . The Microsporum canis morphology alterations induced by naftifine at a concentration of 0.9 microgram ml-1 (10 times the minimum inhibitory concentration (MIC) for 7 days were studied in LVSEM . The young lateral ramifications and the aborted buds take on a granulous aspect . These granulations can be localized as brassard shapes around hyphae . The mycelial filaments often appear irregularly swollen with bulbous tips . Macroconidia are selectively covered with a microfibrillar network . In addition, LVSEM on control samples reveals pavimentous angular structures on the macroconidial surface and fine granulations on the filament surface of M . canis unknown until now . A cytological study with transmission electron microscopy (TEM) of filaments altered by naftifine permitted us to observe the disorganization of cell wall fibrillar structure, an excessive plasma membrane undulation and an intracytoplasmic accumulation of large vesicles with probably lipidic contents.

Can J Physiol Pharmacol, 1992 Nov, 70(11), 1518 - 22
Reduced sensitivity to dexamethasone of pancreatic islets from obese (fa/fa) rats; Chan C et al.; The direct effects of dexamethasone exposure on insulin secretion from islets of fa/fa rats and their lean littermates (Fa/?) were compared . After 72 h culture in 1 nM dexamethasone, glucose (27.5 mM)-stimulated insulin secretion over 90 min from islets of lean rats was significantly decreased compared with islets cultured without dexamethasone (12.9 +/- 1.4 vs . 5.7 +/- 1.0% of total islet content, p < 0.05) . Higher doses of dexamethasone for 24-48 h culture produced similar effects . For islets of fa/fa rats, the minimum inhibitory concentration of dexamethasone was 10-fold higher, and islets required at least 48 h exposure for inhibitory effects to be observed . Dexamethasone also decreased the insulin response by islets to glybenclamide, indicating that dexamethasone effects were not specific to glucose transport or metabolism . The results suggest that islets of fa/fa rats may be less sensitive to direct inhibitory effects of glucocorticoids on glucose-stimulated insulin release than islets of lean animals.

J Antimicrob Chemother, 1992 Nov, 30(5), 597 - 602
Post-antibiotic effect of ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin for Pseudomonas cepacia; Kumar A et al.; The post-antibiotic effects (PAE) of ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin were studied for ten strains of Pseudomonas cepacia isolated from patients with cystic fibrosis . Antibiotic concentrations used for exposure were either the MIC of each agent for the sensitive isolates or the recommended sensitivity breakpoint concentrations for the resistant isolates . After 2 h of exposure, cultures were rapidly diluted 1000-fold to eliminate the antibiotic . Out of the ten isolates, there were eight sensitive to ceftazidime, six to ciprofloxacin, six to imipenem, nine to piperacillin and five to tobramycin . All antibiotics tested demonstrated PAE for some isolates of P . cepacia, however, each antibiotic failed to produce a PAE for at least one isolate . The mean PAE was 1.35 h for ceftazidime, 2.38 h for ciprofloxacin, 2.39 h for imipenem, 2.16 h for piperacillin and 1.77 h for tobramycin . Imipenem demonstrated PAE of > or = 0.5 h for all sensitive isolates tested; ceftazidime, piperacillin, ciprofloxacin and tobramycin demonstrated PAE of > or = 0.5 h for 6/8, 8/9, 5/6 and 2/5 sensitive isolates, respectively . These data indicate that several antibiotics have significant (> or = 0.5 h) PAE for isolates of P . cepacia.

Cancer, 1992 Oct 15, 70(8), 2121 - 8
Microinvasive carcinoma of the cervix; Sevin BU et al.; BACKGROUND . Microinvasive carcinoma of the cervix (MIC) has been poorly defined in the past and is still a focus of persistent controversy . In 1985, the International Federation of Gynecology and Obstetrics (FIGO) defined Stage IA as "preclinical invasive carcinoma, diagnosed by microscopy only," subdividing it into Stage IA1 or "minimal microscopic stromal invasion," and Stage IA2 or "tumor with invasive component 5 mm or less in depth taken from the base of the epithelium and 7 mm or less in horizontal spread." In 1974, the Society of Gynecologic Oncologists (SGO) defined MIC as any lesion with a depth of invasion of 3 mm or less from the base of the epithelium, without lymphatic or vascular space invasion . METHODS . To assess the risk of lymph node metastasis and treatment failures, pathologic material and clinical data on 370 patients with Stage I carcinoma of the cervix, who were treated by radical hysterectomy and pelvic-aortic node dissection, were reviewed . Histopathologic analysis of tumors was based on a uniform format, including measurement of the maximum depth of invasion, the width and length of the horizontal tumor spread, invasive growth pattern, cell type, tumor grade, and lymphatic or vascular space involvement . RESULTS . Of the 370 patients, 110 had a depth of invasion of 5 mm or less . Of these, 54 patients fulfilled the SGO definition of MIC; 42, the new FIGO Stage IA2 definition; and 27, both definitions . None of the patients with MIC, as defined by either the SGO or the new FIGO Stage IA2, had lymph node metastases or tumor recurrence . These data support the conclusion that MIC, defined by either the SGO or FIGO definitions, have a low risk for lymph node metastasis or recurrent carcinoma . A review of the literature indicated a recurrence rate for Stage IA2 of 4.2% . In addition to depth of invasion, lymph vascular space invasion is a better predictor of lymph node metastasis and recurrence than the surface dimension . CONCLUSIONS . The authors recommend adoption of the SGO definition of MIC . Patients with a depth of invasion of 3 mm or less without lymph vascular space invasion safely can be treated conservatively.

J Infect Dis, 1992 Oct, 166(4), 923 - 6
Postantibiotic effect of amikacin and rifapentine against Mycobacterium avium complex; Bermudez LE et al.; Postantibiotic effect (PAE) has received little attention in the therapy of chronic intracellular infections, such as those caused by mycobacteria . Amikacin is active therapeutically against Mycobacterium avium complex, even though serum levels exceed the MIC for only a few hours . To determine the PAE of amikacin and rifapentine for M . avium, bacteria were exposed to concentrations of 1x, 4x, and 10x the MIC of each drug for up to 120 min . Regrowth of M . avium was compared with similarly diluted untreated cultures . No PAE was observed on an inoculum of 10(4) bacteria when rifapentine was used at 5x MIC, although a slight inhibition of growth was obtained at 10x MIC for 2 h . For amikacin, PAE was observed up to 48 h at concentrations of 4x and 8x MIC and exposure times of 30-120 min . A PAE of 22 h was seen with 10(7) cfu of M . avium during incubation for 30 min with amikacin at 4x MIC . These results show that amikacin, unlike rifapentine, has a long PAE against M . avium.

Mikrobiyol Bul, 1992 Oct, 26(4), 333 - 7
{Development of resistance in bacteria interacting with subinhibitory antibiotic concentrations}; Cokca F et al.; In order to determine the role of subinhibitory concentrations of antibiotics in resistance development, we performed an in vitro trial in which E . coli gained resistance after exposure to low concentrations of ampicillin in serial passages, while MIC values for amikacin and gentamicin increased 2 and 4 times, respectively . Pseudomonas also became resistant to ceftazidime whereas the MIC value for ciprofloxacin increased 10 times . There was not any significant change in susceptibility of S . aureus to vancomycin and amoxicillin + clavulanate.

Antonie Van Leeuwenhoek, 1992 Oct, 62(3), 225 - 30
Hyalohyphomycosis caused by Paecilomyces variotii: a case report, animal pathogenicity and 'in vitro' sensitivity; Naidu J et al.; A case of cutaneous infection in a 25-year-old male caused by Paecilomyces variotii is described . Animal pathogenicity studies with normal and cortisone-treated mice revealed the predeliction of P . variotii for skin and liver in both normal and cortisone-treated mice and for lungs and heart only in immunosuppressed mice . 5-fluorocytosine gave the best MIC value for P . variotii in vitro . This report documents for the first time that P . variotii causes cutaneous infection.

Mutat Res, 1992 Oct, 283(2), 97 - 106
Selective reactivities of isocyanates towards DNA bases and genotoxicity of methylcarbamoylation of DNA; Tamura N et al.; The reactivities of methyl isocyanate (MIC) and phenyl isocyanate (PIC) with DNA, and the genotoxicity of MIC were investigated . MIC and PIC reacted with the exocyclic amino group of deoxycytidine, deoxyadenosine and deoxyguanosine to produce carbamoylated products . The reactions of both isocyanates with deoxycytidine were 2 and 4 orders of magnitude higher than with deoxyadenosine and deoxyguanosine, respectively . To explore the genotoxicity of MIC, M13mp9 RF DNA was modified with MIC and then introduced into E . coli . The plaque-forming efficiencies of DNA decreased with increasing dose levels, and the decreases were more pronounced in Uvr endonuclease-deficient strains (uvrA, uvrB and uvrC) than in the Uvr endonuclease-proficient strain, JM103 . The differences in survival in JM103 and uvr- strains suggest that the methylcarbonyl adducts can be removed by the uvr excision-repair system . Modification of M13mp9 RF DNA with MIC induced MIC-dose-related, SOS-dependent mutations in the beta-galactosidase locus . These results demonstrate the genotoxic response of MIC-modified DNA in E . coli.

J Antimicrob Chemother, 1992 Oct, 30(4), 497 - 507
Potentiation of azithromycin activity against Escherichia coli by human serum ultrafiltrate; Pruul H et al.; In this study we investigated the influence of serum ultrafiltrate on the activities of azithromycin, other macrolides and unrelated antibiotics against Escherichia coli . In the presence of serum ultrafiltrate the MIC of azithromycin was decreased by 10-fold . The activities of erythromycin and roxithromycin were also enhanced, although to a lesser extent . The potentiation of activity was inhibited by divalent cations and by pre-treatment of the ultrafiltrate with trypsin . Potentiation of azithromycin activity was associated with a pH-independent, early increase in bactericidal activity and inhibition of bacterial metabolism . We postulate that low molecular weight proteinaceous components of normal human serum interact with azithromycin and other macrolides to alter the susceptibility of Gram-negative bacteria to the antibiotics, possibly through increased macrolide penetration across the bacterial cell membrane permeability barriers.

Antimicrob Agents Chemother, 1992 Sep, 36(9), 1987 - 90
Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system; Brown BA et al.; MICs of clarithromycin against 324 clinical isolates belonging to eight species of slowly growing nontuberculous mycobacteria were determined by using a broth microdilution system . Isolates were inoculated into twofold drug dilutions in Middlebrook 7H9 broth (pH corrected to 7.4) and then incubated at 30 degrees C for 7 days for Mycobacterium marinum and for 14 days for all other species . The MIC for 90% of the strains (MIC90) was less than or equal to 0.5 micrograms/ml for isolates of Mycobacterium gordonae (6 strains), Mycobacterium scrofulaceum (5 strains), Mycobacterium szulgai (6 strains), and Mycobacterium kansasii (35 strains) . MICs for M . marinum (25 strains) and Mycobacterium avium complex (237 strains) were higher, but 100% and 89% of the strains, respectively, were susceptible to less than or equal to 4 micrograms/ml . In contrast, MICs for five of six M . simiae strains were greater than 8 micrograms/ml, and the range of MICs for Mycobacterium nonchromogenicum varied from less than or equal to 0.125 to 8 micrograms/ml . For the 237 isolates of M . avium complex, the MIC50 was 2 micrograms/ml and the MIC90 was 8 micrograms/ml . MICs for most isolates (77%) were in the 1- to 4-micrograms/ml range . For the 80 isolates in this group known to be from AIDS patients, the MIC50 was 4 micrograms/ml and the MIC90 was 8 micrograms/ml . These MIC studies combined with preliminary clinical trials suggest that clarithromycin may be useful for drug therapy of most species of the slowly growing nontuberculous mycobacteria except M . simiae.

Am J Cardiol, 1992 Sep 1, 70(6), 582 - 6
Normalization of impaired response of platelets to prostaglandin E1/I2 and synthesis of prostacyclin by insulin in unstable angina pectoris and in acute myocardial infarction; Kahn NN et al.; The minimal inhibitory concentration of prostaglandin E1 (used as a probe for prostacyclin {PGI2}) needed to inhibit platelet aggregation (36 +/- 16 nM) in normal volunteers (n = 40) increased (64 +/- 30 nM) in patients (n = 46) with acute coronary artery disease . Bolus injection of insulin in 20 patients, 0.1 U/kg body weight 4 times a day (every 6 hours) for 7 days decreased the minimal inhibitory concentration of prostaglandin E1 from 64 +/- 30 to 26 +/- 12 nM (p less than 0.001) . Twenty other patients who received only saline solution had no decrease in minimal inhibitory concentration of the prostanoid . The bolus injection of insulin also increased the plasma level of PGI2 (9 +/- 2 pM) two-fold in these patients (28 +/- 10 pM) . Administration of aspirin inhibited the insulin-induced increase of plasma prostanoid level . Patients in the placebo group had no increase in plasma PGI2 level . The bolus injection of insulin administered only once to another group of patients (n = 6) demonstrated that the hormonal effects were maximally increased within an hour of insulin administration, and were directly related to the increased insulin level in plasma . These results indicated the feasibility of using physiologic quantities of insulin for controlling of platelet aggregation through resensitization of platelet response to prostaglandin and increased synthesis of PGI2 in vivo in acute coronary artery disease.

Eur J Clin Microbiol Infect Dis, 1992 Sep, 11(9), 777 - 81
Results of a multicentre European survey in 1991 of metronidazole resistance in Helicobacter pylori . European Study Group on Antibiotic Susceptibility of Helicobacter pylori; Loceryl nail lacquer--realization of a new galenical approach to onychomycosis therapy; Pharma Division Preclinical Development, F . Hoffmann-La Roche Ltd, Basel, SwitzerlandLoceryl nail lacquer was developed to provide the effective antifungal drug, amorolfine, in a once-weekly dosage regimen combined with a convenient mode of application . Traditional formulations such as creams and nail solutions do not fulfil these requirements because they are wiped or washed off very rapidly . Amorolfine nail lacquer builds a non-water-soluble film on the nail plate, and this film remains in place for 1 week . The film contains a high concentration of amorolfine and forms a depot from which the drug is delivered and which allows the drug to permeate the nail plate . The film-forming polymer and the solvent were optimized for drug release, stability, and convenience of application (drying time, no gloss, transparency) . In preclinical development, porcine hoof horn was used as a screening model to differentiate between formulations and dosage strengths with respect to the penetration rate . A high drug concentration of 11.72 micrograms/specimen (10 mm in diameter) was reached in the hoof horn after 6 h, increasing to 39.5 micrograms/specimen within 7 days, the maximum duration of the investigation . The drug concentration achieved was far above its minimum inhibitory concentration . Furthermore, the penetration model clearly indicated that amorolfine crossed the horn barrier and was found in the moistened gauze which simulated the nail bed . After a 7-day penetration period, 1.8% of the applied dose (500 micrograms) was available under the nail.

J Antimicrob Chemother, 1992 Sep, 30(3), 303 - 11
Inhibition of Chlamydia trachomatis growth in mouse fibroblasts by liposome-encapsulated tetracycline; al-Awadhi H et al.; The in-vitro susceptibility of Chlamydia trachomatis to liposome-encapsulated tetracycline was determined and compared with free tetracycline . Anionic, cationic and neutral small unilamellar liposomes were used in this study . Chlamydia-infected mouse fibroblast monolayers were continuously exposed to varying concentrations of antibiotic, incubated for 48 h and Giemsa stained . The minimum inhibitory concentration (MIC) for anionic, cationic and neutral liposomes containing tetracycline were 0.38, 0.08 and 0.04 mg/L, respectively . This was approximately 2, 10, and 20 times more efficient than free tetracycline (MIC, 0.79 mg/L) . Neutral liposomes displayed no visible toxic side-effects on the host cells . When compared with free tetracycline, neutral liposomes were the most efficient for the delivery of inhibitory concentrations of tetracycline to chlamydia-infected mouse fibroblast L cell cultures.

Diagn Microbiol Infect Dis, 1992 Sep-Oct, 15(7), 609 - 12
Evaluation of the teicoplanin broth microdilution and disk diffusion susceptibility tests and recommended interpretive criteria; Kenny MT et al.; Comparative teicoplanin in vitro susceptibility data were generated for 1201 Gram-positive US clinical trial isolates using standardized broth microdilution and disk diffusion techniques . Based on the results of this study, the following interpretive criteria for teicoplanin are recommended: for MIC tests, less than or equal to 8 micrograms/ml = susceptible, 16 micrograms/ml = moderately susceptible, and greater than or equal to 32 micrograms/ml = resistant; and for disk (30 micrograms) tests, greater than or equal to 14 mm = susceptible, 11-13 mm = intermediate, and less than or equal to 10 mm = resistant.

Antimicrob Agents Chemother, 1992 Sep, 36(9), 1805 - 9
Standardized susceptibility testing of fluconazole: an international collaborative study; Pfaller MA et al.; An international collaborative study of broth dilution (MIC) and disk diffusion susceptibility testing of fluconazole was conducted by using a chemically defined medium (High-Resolution Antifungal Assay Medium; Oxoid Ltd., Basingstoke, United Kingdom) and standard test methods performed in eight reference laboratories . Ten yeast isolates were tested by each test method in duplicate on each of 3 separate days . The intralaboratory reproducibility of the MIC test was excellent; 95.7% of the replicate tests (n = 220) were within 2 doubling dilutions of the other values in the set for the eight laboratories . The intralaboratory reproducibility of the disk test was also good, with 91% of the replicate tests (n = 234) agreeing with each other within an arbitrarily chosen value of 4 mm . Interlaboratory agreement of MIC test results was acceptable, with 84% of the MICs agreeing within 2 doubling dilutions . In contrast, the interlaboratory agreement of the disk test was not good, with only 59% of test results agreeing within 4 mm . Comparison of the rank order of MICs obtained in each laboratory with the reference rank order gave an agreement of 70 to 80% (median, 80%) with the MIC test and 70 to 90% (median, 80%) with the disk test . These preliminary results are encouraging for the development of standardized testing methods for testing fluconazole.

J Pharmacol Exp Ther, 1992 Sep, 262(3), 1203 - 8
Kinetic disposition of temafloxacin and ciprofloxacin in a murine model of pneumococcal pneumonia . Relevance for drug efficacy; Vallee E et al.; The authors studied whether pharmacokinetic parameters could explain differences in the in vivo antipneumococcal activity of temafloxacin and ciprofloxacin in a mouse model of pneumonia . The effects of infection on the disposition and clearance mechanisms of the two drugs were evaluated after a single administration (100 mg/kg s.c.) relative to noninfected controls . Effective drug concentrations and possible drug inactivation at sites of infection were assessed using both microbiological (active drug levels) and high-performance liquid chromatography (total drug levels) procedures and by recording bacterial clearance in blood and lung homogenates . Pulmonary bacterial clearance was correlated more closely to concentrations in serum than to those in lung homogenates, probably because they better reflect interstitial fluid concentrations . Neither the serum and lung concentrations nor the clearance of ciprofloxacin were modified greatly by infection . Ciprofloxacin was not inactivated at sites of infection . Temafloxacin exhibited higher serum concentrations and tissue penetration than ciprofloxacin . The differences between the two drugs in noninfected controls were accentuated, with apparent retention of temafloxacin in infected mice resulting in more persistent activity in lung and serum . The renal failure observed in infected mice did not apparently account for the reduction in the total clearance of temafloxacin, suggesting its probable trapping at sites of infection . The observation that serum (and tissue) concentrations of temafloxacin exceeded the minimal inhibitory concentration of the test organism over the whole dosing interval (12 hr), could account for its efficacy in severe pneumococcal disease.

Epidemiol Prev, 1992 Sep, 14(52), 22 - 31
Health effects of the Bhopal gas leak: a review; Dhara R; The methyl isocyanate (MIC) gas leak from the Union Carbide plant at Bhopal, India in 1984 was the worst industrial disaster in history . Exposure estimates of gas concentrations in the area range from 85 to 0.12 ppm . Of the approximately 200,000 persons exposed, 3598 deaths have resulted as of November 1989 . Chronic inflammatory damage to the eyes and lungs appears to be the main cause of morbidity . Reproductive health problems in the form of increased spontaneous abortions and psychological problems have been reported . Questions about the nature of MIC toxicity have been raised by the persistence of multi-systemic symptoms in survivors . Animal studies using radio-labeled MIC given by the inhalation route have shown that the radio-label is capable of crossing the lung membranes and being distributed to many organs of the body . This paper reviews health effects of gas exposure from published studies and discusses some of the clinical and epidemiological issues being debated.

Sci Total Environ, 1992 Aug 12, 123-124, 591 - 603
Mathematical descriptions of accelerated transformation of 1,3-dichloropropene in soil; a microbiological assessment; Vink JP et al.; The rate of transformation of the soil fumigant (Z)-and (E)-1,3-dichloropropene in moist soil layers was measured at incubation temperatures of 5 degrees C, 10 degrees C and 20 degrees C . 'DD95' was added to four characterized soil layers, in amounts corresponding to realistic field contents after fumigation . Rapid transformation immediately after application was observed in layers with low initial contents (30-300 micrograms/kg dm) and could well be described with a first-order rate model . Incubation at higher doses (5-15 mg/kg dm respectively) showed distinctly different transformation pathways . Degradation curves could well be computed using a microbiological interspective competition (MIC) model for moist soil . The transformation rate is inversely correlated to microorganism population size and growth . Transformation curves described by MIC are characterized by a lag-time, a period of accelerated transformation and a period of decreasing transformation rates . At low temperatures, DT50 values of more than 20 days could be observed . First-order rate computations did not exceed 8 days . The use of different mathematical discriptions for various soil layers and soil temperatures permits simulation of DD95-transformation by microorganisms in the soil profile throughout the growing season.

Biochemistry, 1992 Jul 28, 31(29), 6646 - 59
Hydroxyethylene isostere inhibitors of human immunodeficiency virus-1 protease: structure-activity analysis using enzyme kinetics, X-ray crystallography, and infected T-cell assays; Dreyer GB et al.; Analogues of peptides ranging in size from three to six amino acids and containing the hydroxyethylene dipeptide isosteres Phe psi Gly, Phe psi Ala, Phe psi NorVal, Phe psi Leu, and Phe psi Phe, where psi denotes replacement of CONH by (S)-CH(OH)CH2, were synthesized and studied as HIV-1 protease inhibitors . Inhibition constants (Ki) with purified HIV-1 protease depend strongly on the isostere in the order Phe psi Gly greater than Phe psi Ala greater than Phe psi NorVal greater than Phe psi Leu greater than Phe psi Phe and decrease with increasing length of the peptide analogue, converging to a value of 0.4 nM . Ki values are progressively less dependent on inhibitor length as the size of the P1' side chain within the isostere increases . The structures of HIV-1 protease complexed with the inhibitors Ala-Ala-X-Val-Val-OMe, where X is Phe psi Gly, Phe psi Ala, Phe psi NorVal, and Phe psi Phe, have been determined by X-ray crystallography (resolution 2.3-3.2 A) . The crystals exhibit symmetry consistent with space group P6(1) with strong noncrystallographic 2-fold symmetry, and the inhibitors all exhibit 2-fold disorder . The inhibitors bind in similar conformations, forming conserved hydrogen bonds with the enzyme . The Phe psi Gly inhibitor adopts an altered conformation that places its P3' valine side chain partially in the hydrophobic S1' pocket, thus suggesting an explanation for the greater dependence of the Ki value on inhibitor length in the Phe psi Gly series . From the kinetic and crystallographic data, a minimal inhibitor model for tight-binding inhibition is derived in which the enzyme subsites S2-S2' are optimally occupied . The Ki values for several compounds are compared with their potencies as inhibitors of proteolytic processing in T-cell cultures chronically infected with HIV-1 (MIC values) and as inhibitors of acute infectivity (IC50 values) . There is a rank-order correspondence, but a 20-1000-fold difference, between the values of Ki and those of MIC or IC50 . IC50 values can approach those of Ki but are highly dependent on the conditions of the acute infectivity assay and are influenced by physiochemical properties of the inhibitors such as solubility.

Chest, 1992 Aug, 102(2), 347 - 55
Sensitivity and specificity of bronchial provocation testing . An evaluation of four techniques in exercise-induced bronchospasm; Eliasson AH et al.; The thresholds used to define a positive result for bronchial provocation challenges (BPC) are arbitrary . Requiring smaller decrements in expired flow to define a positive study would capture more cases of reactive airways (increased sensitivity) but would include some "normal" responses (decreased specificity) . To examine the relationship between threshold definition and the ability to correctly classify subjects as either normal or as having airways hyperresponsiveness (AHR), four different BPC tests were administered on different days to 20 patients with a clinical diagnosis of exercise-induced bronchospasm (EIB) and 20 control subjects . The four BPC tests were indoor exercise on a cycle ergometer, methacholine inhalation challenge (MIC), eucapnic voluntary hyperventilation (EVH) with dry gas, and EVH with cold gas . Our results indicate that the thresholds which best separate the two groups are different for each of the four BPC techniques . For methacholine inhalation (MIC), a fall in FEV1 (d%FEV1) of 15 percent or greater at 188 cumulative breath units was 100 percent specific for AHR but had a sensitivity of only 55 percent . Eucapnic voluntary hyperventilation (EVH) with room temperature dry gas was 100 percent specific at a d%FEV1 of 11 percent, but, at that threshold, sensitivity was only 50 percent . EVH with cold air was 100 percent specific at a d%FEV1 of 12 percent but sensitivity was only 35 percent . The bicycle ergometer challenge was far too insensitive to be of value in evaluating AHR . Based on their respective receiver operating characteristic curves, the best separation of the two subject groups occurred at a d%FEV1 of 5 percent and 12 percent for the two EVH techniques and MIC, respectively . An individual's response to one test was highly correlated with the response to either of the other two (r = 0.66, p less than 0.001 for dry vs cold gas EVH; r = 0.56, p less than 0.001 for dry gas EVH vs methacholine; and r = 0.69, p less than 0.001 for cold gas EVH vs methacholine) . Thus, MIC and EVH techniques are equally useful in defining AHR and each has its optimal threshold for a positive test result.

Pediatr Pulmonol, 1992 Aug, 13(4), 215 - 21
Diet in infancy and bronchial hyperreactivity later in childhood; Poysa L et al.; Sixty-seven atopy-prone children (atopic family group, AFG) and 52 children with no family history of atopy (NAFG) were followed for 10 years . During infancy, the mothers of the newborn AFG children were advised to adjust their infants' diet, with a view toward minimizing the risk of atopy, and not to keep pets . Pulmonary function tests, methacholine inhalation challenge (MIC), and skin prick tests (SPT) were done in order to evaluate the bronchial reactivity and skin reactivity in the two groups . A pathological result in MIC was found in 20 (30%) of the AFG children and in 10 (19%) of the NAFG children . Such results of MIC were more common in the children with positive SPT results than in those without (67% vs . 24%) . In regard to the diet consumed in infancy, MIC was pathological in 23% of children with and in 36% without prophylactic diet in infancy . For MIC, using the new, Spira electro 2 dosimeter equipment, the sensitivity was 75% and specificity 97%, but the predictive value for diagnosing bronchial asthma was only 25% . The important advantage of our method is that the degree of bronchial reactivity can be estimated by responses to increasing provocative doses . Our observations confirm that the new method is suitable for detecting bronchial asthma in clinical practice but it seems not to be optimal for epidemiological studies . We concluded that later bronchial hyperreactivity can not be diminished by avoiding home pets or providing a hypoallergenic diet during infancy.

Antimicrob Agents Chemother, 1992 Aug, 36(8), 1788 - 90
In vitro susceptibilities of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone; Agger WA et al.; We determined the in vitro susceptibilities of eight Borrelia burgdorferi isolates to five oral cephalosporins . MICs for B . burgdorferi 297 were 23 micrograms/ml (cephalexin), 45 micrograms/ml (cefadroxil), 91 micrograms/ml (cefaclor), 0.13 microgram/ml (cefuroxime), 0.8 microgram/ml (cefixime), and 0.02 microgram/ml (ceftriaxone) . When B . burgdorferi isolates were exposed to concentrations twice the MIC of cefuroxime, cefixime, or ceftriaxone, at least 72 h of incubation was required to kill 99% of the organisms.

Antimicrob Agents Chemother, 1992 Aug, 36(8), 1619 - 25
Innovative endpoint determination system for antifungal susceptibility testing of yeasts; Tellier R et al.; Fungal infections and antifungal resistance are increasingly recognized . Antifungal susceptibility testing remains unstandardized, and a particularly important problem is endpoint determination . In this paper we propose the yeast metabolic reduction of the tetrazolium salt 2,3-bis(2- methoxy-4-nitro-5-sulfophenyl)-5-{(phenylamino)carbonyl}-2H-tetraz olium hydroxide (XTT) as a colorimetric endpoint which is quantitative and objective . Amphotericin B, fluorocytosine, and fluconazole dose-response curves were obtained, and a metabolic MIC could be determined by using precise criteria.

Arzneimittelforschung, 1992 Aug, 42(8), 1031 - 6
Effect of gyrase inhibitors on some eukaryotic short-term test systems . DNase I in vitro nucleic acid synthesis and DNA repair in primary cultures of chicken embryo and rat cells; Tempel K et al.; DNase I activity was diminished by ciprofloxacin (CFL), nalidixic acid, norfloxacin, and ofloxacin in a dose-dependent manner, the MIC's (minimal significantly inhibiting concentrations) being 3.2, 2.8, 2.4, and 7.6 micrograms/ml, resp., in phase I-reaction (increase in DNA hyperchromicity) and 21, 20, 55, and 56 micrograms/ml, resp., in phase II-reaction (formation of acid-soluble products) . The Line-weaver-Burk plots indicated inhibition by substrate (phase I) and uncompetitive inhibition (phase II) . The decrease in scheduled DNA synthesis by CFL showed MIC's of 270, 100, 1000, and 850 micrograms/ml in chicken embryo brain (B) and liver (L) cells and in rat thymic (T) and splenic (S) cells, resp . With regard to ribonucleic acid synthesis, MIC values of 82, 82, 12.5, and 48 micrograms/ml CFL were determined, resp . Within a concentration range of 25-1600 micrograms/ml, no principal differences existed between the 4-quinolones used . In T-cells, DNA repair as induced by X-irradiation or UV-light and determined by nucleoid sedimentation was inhibited by CFL (greater than 100 micrograms/ml) . The present results demonstrate biological effects of 4-quinolones on eukaryotic systems at remarkably low concentrations . In this context, the possibility of interactions with DNA catabolizing enzyme systems and synergistic effects with DNA/chromatin-damaging agents should be considered further.

Antimicrob Agents Chemother, 1992 Aug, 36(8), 1611 - 3
Activity of azithromycin against Mycobacterium avium infection in beige mice; Cynamon MH et al.; The comparative activities of azithromycin and clarithromycin and the activities of azithromycin alone and in combination with other antimycobacterial agents were evaluated in the beige mouse model of disseminated Mycobacterium avium complex infection . Azithromycin was similar in activity to clarithromycin . Azithromycin plus clofazimine plus ethambutol reduced the number of splenic organisms more than azithromycin alone, while the combination was less active than azithromycin alone for bacteria in lungs . Rifabutin had activity similar to that of azithromycin for organisms in spleens and lungs . Rifabutin plus azithromycin was more active than either agent alone for organisms in spleens, but the combination's activity was not significantly different from that of rifabutin for organisms in lungs . The activity of azithromycin against several M . avium complex isolates was evaluated . The reduction of viable cell counts in spleens ranged from 1.7 to 0.8 log units . For the three isolates studied, there was little correlation between the in vitro MIC and the in vivo activity.

Hindustan Antibiot Bull, 1992 Aug-Nov, 34(3-4), 104 - 7
In vitro evaluation of three topical antimycotics against ring-worm fungi singly and in combination; Rai MK et al.; Three antimycotic drugs, viz., Miconazole nitrate, Econazole nitrate and ciclopirox olamine were tested singly and in combination of miconazole nitrate and Econazole nitrate, Miconazole nitrate and Ciclopirox olamine, and Econazole nitrate and Ciclopirox olamine to evaluate in vitro efficacy against Trichophyton mentagrophytes and Macrosporum nanum . The best efficacy was shown by Ciclopirox olamine (MIC 0.78 microgram/ml) and a combination of Miconazole nitrate and Econazole nitrate (MIC 0.78 microgram/ml).

Diagn Microbiol Infect Dis, 1992 Jul, 15(5), 479 - 82
E-Test as a routine MIC tool for reference work; Olsson-Liljequist B; The usefulness of the E-Test, a method for determining minimum inhibitory concentrations of antibiotics against bacteria, in the reference work of susceptibility testing is described . Examples are given on the establishment of reference collections of bacterial strains and on quality control, areas that should also be valid for routine clinical bacteriology laboratories.

APMIS, 1992 Jul, 100(7), 663 - 7
Susceptibility of strains of the Mycobacterium tuberculosis complex to fusidic acid; Fuursted K et al.; The activity of fusidic acid was studied in 40 strains of M . tuberculosis (of which 20 strains were mono- or multiresistant to standard antituberculosis drugs) and 10 strains of M . bovis . Minimum inhibitory concentration (MIC) was determined by the radiometric (BACTEC) broth method . The MIC for the 50 strains varied between 8 and 32 mg/l, with a MIC90 of 16 mg/l for M . tuberculosis and a MIC90 of 32 mg/l for M . bovis . Minimal bactericidal concentration (MBC, defined as the lowest concentration of fusidic acid which killed 99% or more of the population) varied between 32 mg/l and 500 mg/l, with a MBC90 of 250 mg/l for M . tuberculosis and 500 mg/l for M . bovis . No cross-resistance to other antituberculosis drugs (ethambutol, isoniazid, rifampicin, streptomycin, pyrazinamide, ofloxacin, ciprofloxacin) was observed as strains resistant to one or more standard antituberculosis drugs were as susceptible to fusidin as sensitive strains of M . tuberculosis . No synergism or antagonism could be demonstrated when fusidic acid was combined with either ethambutol, isoniazid, rifampicin or streptomycin against strains of M . tuberculosis resistant to one or more standard antituberculosis drugs . Addition of pooled human serum to the medium increased both MIC and MBC by factors of 4 and 8 at serum concentrations of 10% and 50%, respectively . Single-step mutation to high-level resistance to fusidic acid at a frequency of less than 1.7 x 10(-8) could be readily selected at four times the MIC . These fusidic acid-resistant organisms had a generation time 2.0-2.7 x longer than their parent organisms.

Cancer Genet Cytogenet, 1992 Jul 1, 61(1), 14 - 25
Prognostic impact of karyotype and immunologic phenotype in 125 adult patients with de novo AML; Marosi C et al.; One hundred-twenty-five adult patients with de novo acute myeloid leukemia (AML) were treated according to a standard 7 + 3 induction regimen . Karyotype and immunological phenotype of blasts examined prior to treatment were correlated with each other, with response to treatment and duration of survival . The following monoclonal antibodies (mAbs) were used for immunological phenotyping: VIM-D5 (CD15), MY7 (CD13), MY9 (CD33), VIM-2 (CDw65), VIM-13 (CD14), 63D3 (CD14), VID-1 (anti HLA-DR), WT1 (CD7), CLB-Ery3 (antiblood group H antigen), C17-27 (CD61), and an antiserum against TdT . Despite a considerable overlap between the individual groups, patients with specific aberrations as defined by the MIC classification (n = 39) showed distinct, characteristic, myeloid or myelomonocytic immunophenotypes . In M2/t(8;21) there was a significant association with negativity to CD13, in M3/t(15;17) with negativity to CD15 and HLA-DR, whereas in M4/inv(16) expression of blood group H antigen was unexpectedly found . The response to therapy, as well as rate of complete remission as duration of survival, was better in patients with M2/t(8;21), M3/t(15;17), and M4Eo/inv(16) as compared to all other patients and significantly worse in patients with M5a/t/del(11)(q23) . In 35 patients with normal karyotype and 16 patients with cytogenetic anomalies not presently associated with FAB subtypes the expected correlations of rather immature myeloid immunologic phenotypes with M1 and M2 morphology and CD14 expression in monoblastic leukemias was found . Remission rate and survival were significantly worse in 19 patients with complex nonrandom aberrations, where blast cell expression of blood group H antigen and of TdT were significantly increased.

Zentralbl Bakteriol, 1992 Jul, 277(2), 204 - 9
In vitro and in vivo activities of KRM-1648, a newly synthesized benzoxazinorifamycin, against Mycobacterium marinum; Yamamoto Y et al.; The in vitro and in vivo activities of KRM-1648, one of the newly synthesized benzoxazinorifamycins, against M . marinum were compared with those of rifampin . The MIC values of KRM-1648 determined by the agar dilution method on 7H11 medium against 10 strains of M . marinum were 32-128 times and even more below those of rifampin . In an in vivo experiment, KRM-1648 was markedly effective in terms of the incidence of gross skin lesions and the number of CFUs in the lungs and spleen . Its efficacy was much greater than that of rifampin.

Antimicrob Agents Chemother, 1992 Jul, 36(7), 1483 - 6
Levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery; Doi R et al.; It is not known whether a prophylactic antibiotic administered prior to surgery reaches adequate levels in the peritoneum, where peritonitis may take place . This study determined levels of cefmenoxime in sera and peritoneal tissues of patients undergoing gastrointestinal surgery . Fifteen patients who underwent elective gastrointestinal surgery received an intravenous drip infusion of cefmenoxime (2 g) over 1 h prior to surgery . In patients who underwent gastrectomy, the level of cefmenoxime in serum was 130.8 +/- 6.9 micrograms/ml at laparatomy and decreased to 5.0 +/- 0.7 micrograms/ml at 4 h . Levels in parietal peritoneal and omental tissues at laparotomy were 35.3 +/- 5.2 and 19.2 +/- 3.5 micrograms, respectively, and decreased time dependently . In patients who underwent cholecystectomy, the level of cefmenoxime in serum was 137.9 +/- 7.3 micrograms/ml at laparotomy and decreased to 5.0 +/- 1.2 micrograms/ml at 4 h . Levels in parietal peritoneal and omental tissues were 31.0 +/- 8.4 and 13.7 +/- 3.3 micrograms/g, respectively, and decreased time dependently . The level of cefmenoxime in serum correlated with the levels of cefmenoxime in parietal peritoneum (r = 0.64, P less than 0.01) and in omentum (r = 0.47, P less than 0.02) . In patients with appendicitis who received a bolus injection of 2 g of cefmenoxime, the level of drug in inflammatory omental tissue correlated with the level in serum . The levels in peritoneal tissue during surgery lasting up to 2 h were significantly greater than in MIC of cefmenoxime against almost all bacteria reported . A preoperative single dose of 2 g of cefmenoxime probably is effective as a prophylactic for intraoperative contamination.

Farmaco, 1992 Jul-Aug, 47(7-8), 1021 - 34
Pyrazolo{3,4-d}{1,2,3}triazole-1-carboxamides and 5-alkylaminopyrazolo{3,4-d}oxazoles: synthesis and evaluation of the in vitro antifungal activity; Vicentini CB et al.; A series of N-alkyl-N'-(4-diazo-5-pyrazolyl)-ureas (4) was thermally and photochemically converted into pyrazolo {3,4-d}{1,2,3}triazole derivatives (5,6) and 5-alkylaminopyrazolo{3,4-d}oxazoles (7) respectively . The products were tested for in vitro antifungal activity against Fusarium culmorum, Botrytis cinerea, Phoma betae, Pythium ultimum, Sclerotinia minor and Rhizoctonia solani . The MIC and ED50 values of compound (6) against some of the test fungi were comparable to those of the reference fungicides iprodione and mancozeb.

Trans R Soc Trop Med Hyg, 1992 Jul-Aug, 86(4), 368 - 71
The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro; Sowunmi A et al.; The clinical efficacy of two doses of mefloquine (15 and 25 mg/kg body weight) was evaluated in 85 children suffering from acute symptomatic falciparum malaria . The cure rate on day 28 was 100% in both groups . There was no significant difference (P > 0.05) in the mean parasite and fever clearance times in both groups (48.5 +/- 14.6 and 32.0 +/- 12.7 h respectively for the 25 mg/kg group and 49.0 +/- 15.1 and 30.0 +/- 13.3 h respectively for the 15 mg/kg group) . There was also no significant difference (P > 0.05) in these values between children with hyperparasitaemia (53.6 +/- 11.1 and 36.0 +/- 17.0 h respectively) and those without hyperparasitaemia (49.1 +/- 13.6 and 31.8 +/- 14.6 h respectively) . Recurrence of parasitaemia was observed after day 30 in 2 patients in the 15 mg/kg group and in 1 patient in the 25 mg/kg group . In vitro, 3 of 21 isolates showed reduced susceptibility to mefloquine, with minimum inhibitory concentrations (MIC) > 67 nM/litre . The MIC and 50%, 90% and 99% inhibitory concentrations were 200.8, 6.27, 31.7 and 119.6 nM/litre respectively . Four of 22 isolates were resistant to chloroquine (MIC > 108 nM/litre) . Isolates that showed low sensitivity to mefloquine in vitro were sensitive to chloroquine in vitro, and the 4 that were resistant to chloroquine were sensitive to mefloquine . Irrespective of MIC and dose of mefloquine, parasitaemia cleared in all subjects in 96 h or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann R Coll Surg Engl, 1992 Jul, 74(4), 274 - 6
Is antibiotic penetration compromised in the ischaemic tissues of patients undergoing amputation?
Kerin MJ, Greenstein D, Chisholm EM, Sheehan SJ, Kester RC.
Antibiotic prophylaxis is indicated for patients undergoing amputation for severe ischaemia or gangrene . However, the adequacy of tissue levels of antibiotics in ischaemic tissue is not known . In this study the serum and tissue antibiotic levels were measured after intravenous administration of metronidazole (15 mg/kg body weight) and cephradine (20 mg/kg body weight) . In 11 patients, venous samples were taken at time 0 (induction of anaesthesia) 10, 30 and 60 min . Samples of 2 g each of fat and muscle were collected from the amputation site and three distal sites . Metronidazole and cephradine levels were measured and the degree of limb ischaemia estimated preoperatively by an isotope limb blood flow method . Our results indicate that both metronidazole and cephradine penetrate ischaemic tissues to levels equivalent of a Mean Inhibitory Concentration (MIC) 50 for most organisms encountered in vascular surgery, and that the degree of ischaemia does not alter this.

Environ Health Perspect, 1992 Jul, 97, 241 - 53
Sequential respiratory, psychologic, and immunologic studies in relation to methyl isocyanate exposure over two years with model development; Kamat SR et al.; Of 113 methyl isocyanate (MIC)-exposed subjects studied initially at Bhopal, India, 79, 56, 68, and 87 were followed with clinical, lung function, radiographic, and immunologic tests at 3, 6, 12, 18, and 24 months . Though our cohort consisted of subjects at all ages showing a varied severity of initial illness, fewer females and young subjects were seen . Initially all had eye problems, but dominant symptoms were exertional dyspnea, cough, chest pain, sputum, and muscle weakness . A large number showed persistent depression mixed with anxiety, with disturbances of personality parameters . The early radiographic changes were lung edema, overinflation, enlarged heart, pleural scars, and consolidation . The persistent changes seen were interstitial deposits . Lung functions showed mainly restrictive changes with small airway obstruction; there was impairment of oxygen exchange . Oxygen exchange improved at 3-6 months, and spirometry improved at 12 months, only to decline later . The expiratory flow rates pertaining to large and medium airway function improved, but those for small airways remained low . There were changes of alveolitis in bronchoalveolar lavage fluid on fiber optic bronchoscopy, and in 11 cases positive MIC-specific antibodies to IgM, IgG, and IgE were demonstrated . On follow up, only 48% of the subjects were clinically stable, while 50% showed fluctuations . Thirty-two percent of the subjects had lung function fluctuations . Detailed sequential behavior over 2-4 years was predicted for dyspnea, forced vital capacity, maximum expiratory flow rate (0.25-0.75), peak expiratory flow rate, VO2, and depression score . A model for clinical behavior explained a total variance of 52.4% by using the factors of cough, PCO2 and X-ray zones in addition to above five parameters . The behavior of the railway colony group (1640 patients) revealed a similar pattern of illness . When this observed pattern of changes was transferred to the affected Bhopal city sections (with an equitable age-sex distribution), our model results were again validated . Thus the picture of MIC-induced disease seems similar despite the differences for age-sex and initial severity of illness in our cohort and in the population of Bhopal city as predicted by our model.

Antimicrob Agents Chemother, 1992 Jul, 36(7), 1573 - 4
In vitro activities of azithromycin, clarithromycin, L-ofloxacin, and other antibiotics against Chlamydia pneumoniae; Hammerschlag MR et al.; The in vitro susceptibilities of 11 strains of Chlamydia pneumoniae to azithromycin, clarithromycin, erythromycin, L-oflaxacin, and doxycycline were determined . Clarithromycin was the most active agent tested, with an MIC for 90% of strains and minimal chlamydiacidal concentration for 90% of strains of 0.03 microns/ml . The activity of azithromycin was similar to those of erythromycin and doxycycline, with MICs for 90% of strains of 0.125 to 0.25 microns/ml . However, the prolonged half-life and enhanced tissue penetration of azithromycin should allow for less frequent dosing and shorter duration of therapy than with erythromycin or clarithromycin . L-Ofloxacin had activity similar to that of ofloxacin, with MICs of 0.125 to 0.5 micron/ml . From the results of this in vitro study, azithromycin and clarithromycin appear to be effective antibiotics that may have a role in the treatment of infections due to C . pneumoniae.

Roum Arch Microbiol Immunol, 1992 Jul-Sep, 51(3), 171 - 82
Sensitivity to penicillin of S . pneumoniae strains isolated from various pathological conditions; Vereanu A et al.; 297 S . pneumoniae strains isolated from patients with different pneumococcal infections during 1990-1991 were tested for the sensitivity to antibiotics--by the diffusimetric method to 9 antibiotics (Penicillin (6 micrograms), Ampicillin (10 micrograms), Erythromycin (15 micrograms), Oxacyllin (5 micrograms), Streptomycin (50 micrograms), Tetracycline (50 micrograms), Chloramphenicol (50 micrograms), Rifampicin (6 micrograms), and Kanamycin (30 micrograms) and by MIC determination to Penicillin and Erythromycin . 30% of S . pneumoniae strains were resistant to Penicillin and Erythromycin corresponding to a MIC > or = 1 UP/ml or > or = 1 microgram E/ml . The most active antibiotics were Chloramphenicol and Rifampicin and the less active: Tetracycline, Kanamycin and Streptomycin . A relation between the origin and serotype of the strains and the sensitivity to antibiotics was revealed . The strains from the throat, conjunctive and otic secretions and belonging to serotypes 19, 6 and 14 showed the highest levels of resistance to all antibiotics . A good correlation between MIC and diffusion method results was observed to Erythromycin and no correlation to Penicillin . In this last case the results of MIC determination to Penicillin were better correlated with the results of inhibitions diameters to Oxacyllin, method which have to be recommended.

Zentralbl Bakteriol, 1992 Jun, 277(1), 100 - 5
In vitro activity of antifungal agents against clinical isolates of aspergilli; Otcenasek M; The growth-inhibitory effect of 9 antifungal agents against 32 strains of aspergilli belonging to 10 species was studied . MIC values were determined in a microtiter dilution method using Brain Heart Infusion Broth (polyenes, azoles) and a medium with Yeast Nitrogen Base (5-flucytosine) . Saperconazole was the most active agent against all isolates tested, the growth of 90% being inhibited at a concentration of 0.09 mg l-1 . The susceptibility profile of individual species differed only little, with the exception of high MIC values of polyenes in A . terreus . Nine isolates (28%) were resistant to 5-flucytosine . The intra-species variation of susceptibility studied in A . fumigatus was only little pronounced.

Nippon Rinsho, 1992 Jun, 50(6), 1194 - 9
{Diagnosis and classification of leukemia}; Okamura S et al.; Modern diagnosis and classification of leukemia are reviewed . The FAB (French, American, British) classification, introduced in the late 1970s has been the basis for most studies to date . During the 15 years since then, new categories such as M7 and M0 were added to the classification . The MIC proposal (morphology, immunology, cytogenetics) has been an important development which emerged from the knowledge about chromosomal changes and immunophenotyping . Improvement in diagnosis and classification will emerge from studies employing all the above techniques, including DNA analysis, in the 1990s.

Indian J Exp Biol, 1992 Jun, 30(6), 504 - 8
Inhalation toxicity of methylisocyanate: assessment of germ cell mutagenicity and reproductive effects in rats; Agarwal DK et al.; Adult male Wistar rats were exposed to methylisocyanate (MIC, 3.2 mg/l, single inhalation exposure for 8 min under static condition) or ethyl methanesulphonate (EMS, 150 mg/kg, single ip dose) for the assessment of germ cell mutagenicity and reproductive effects . Sequential matings of treated males with normal females on days 1-7, 8-14 and 15-21 post-exposure did not indicate any induction of dominant lethal mutation (increased frequency of preimplantation losses and early fetal deaths) by MIC but it was significantly induced by EMS as compared to respective controls . Males, necropsied after 21 days of exposure, showed no effect of MIC on epididymal sperm density and morphology . EMS also had no effect on sperm density but it significantly induced morphological abnormalities in sperm as compared to untreated controls . There was an acute and transitional reduction in reproductive performance (10-21%) of MIC-exposed males during days 1-14 post-exposure followed by recovery to the normal level during days 15-21 post-exposure . The progeny of MIC-exposed males was also normal in terms of litter size, litter weight, neonatal survival and body weight gain in litters up to 10 days post-partem . It is concluded with the evidence at hand that the observed failure of MIC to cause germ cell mutagenicity is related to its poor biodistribution to the target site(s) and a transient reduction in the reproductive performance of MIC-exposed males is a result of general stress and disconsolate copulation.

Ann Trop Med Parasitol, 1992 Jun, 86(3), 207 - 15
A new model for testing gametocytocidal effects of some antimalarial drugs on Plasmodium falciparum in vitro; Chutmongkonkul M et al.; A technique is described for obtaining pure gametocyte cultures of Plasmodium falciparum, using pyrimethamine at the minimum concentration for inhibition of asexual parasites . Routine cultures producing sexual stages were exposed to pyrimethamine on days 5 and 6 . These cultures grew synchronously and contained gametocytes of stages II, III and V on day 7, 9 and 15 of the cultures respectively . The pyrimethamine-treated gametocytes were more infective to mosquitoes than were untreated controls . This model for the culture of pure gametocytes was used to observe the activity of chloroquine, halofantrine, pyrimethamine and quinine on the gametocyte stage III of Plasmodium falciparum strain NF54 in vitro . NF54 was shown to be sensitive to chloroquine, quinine and pyrimethamine, but the results showed that halofantrine was the most effective drug in reducing the number of gametocytes . A concentration of 3 x 10(-9) M halofantrine was lethal to both asexual parasites and gametocytes . The gametocytocidal EC90 of chloroquine (1 x 10(-6) M) and that of quinine (9 x 10(-7) M) were equal to the minimum inhibitory concentration of asexual stages of isolates of P . falciparum considered as highly resistant to these drugs . A high concentration of pyrimethamine (1 x 10(-4) M) had, in contrast, little effect on gametocytes.

Enferm Infecc Microbiol Clin, 1992 Jun-Jul, 10(6), 334 - 9
{Penicillin-resistant pneumococci and the empirical use of penicillins in the treatment of community-acquired acute pneumonia}; Sanchez C et al.; The prevalence of penicillin-resistant pneumococci in our environment has raised questions about the effectiveness of penicillin as empiric treatment for community-acquired pneumonia cases . We followed prospectively all patients with community-acquired pneumonia from February 1989 through January 1990 . We also reviewed retrospectively the treatment and evolution of all patients with confirmed pneumococcal pneumonia diagnosed between January 1988 and January 1990 . A total of 115 patients with probable pneumococcal pneumonia were prospectively followed-up . Seventy-nine were treated with penicillin (benzyl- and aminopenicillin), and the remaining patients with macrolides, cephalosporin drugs or both . Five patients died (4%) . There is no significant differences between mortality in penicillin-treated patients (2 cases) when compared to patients with other treatments (3 cases) . Twenty-three patients have confirmed pneumococcal pneumonia . Among them, 8 (24%) had penicillin-resistant pneumococci (5 strains with MIC: 0.12-1 microgram/ml; 3 strains with MIC: 2 micrograms/ml) . No differences were recorded regarding demographic data, predisposing conditions, underlying diseases, severity of pneumonia or the outcome of treatment between penicillin and non-penicillin treatment groups . Also, no differences were seen in clinical response and mortality when patients with pneumonia due to penicillin-resistant pneumococci treated with penicillin were compared to the ones treated with other drugs . In two patients, initially treated with erythromycin, progression of the pneumonia was recorded . Erythromycin resistant pneumococci (MIC greater than 8 micrograms/ml) were recovered from transthoracic needle biopsy . Both patients recovered well when beta-lactam antibiotics were prescribed.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Ophthalmol, 1992 May 15, 113(5), 555 - 60
Vancomycin-enriched corneal storage medium; Steinemann TL et al.; Antibiotics in a corneal preservation solution probably have little effect during storage at 4 C, but are effective as the tissue is warmed . The tissue acts as a sponge, soaking up the antibiotic from the solution and releasing it into the eye, where the bactericidal effect is achieved . Currently, high concentrations of gentamicin (relative to the minimal inhibitory concentration) are used in the preserving solution for this purpose . Presumably, proportionately high concentrations of any proposed new antibiotic added to supplement the bactericidal effect of gentamicin, such as the vancomycin used in this study, would be required . However, neither the ability of donor tissue to tolerate high concentrations of vancomycin nor the stability of vancomycin at neutral pH in appropriate storage media has been documented . We evaluated the addition of vancomycin (100 micrograms/ml) to two corneal storage media that contained gentamicin in terms of stability of the antibiotic in solution and the effect on the endothelial cells of donor tissue stored for two weeks at 4 C . Vancomycin was stable in solution at neutral pH (7.2) during the five-month period of the study; the concentration exceeded 90 micrograms/ml for the first five weeks . The endothelial cells from donor tissue stored in the vancomycin-enriched media showed no notable differences from those stored in the same media without vancomycin in terms of cell shape, cell borders, cell swelling, and apical holes . The stability of vancomycin in storage and the absence of endothelial toxicity in vitro support the potential use of this antibiotic as a supplement to gentamicin for the prevention of endophthalmitis in patients receiving corneal transplants.

Res Vet Sci, 1992 May, 52(3), 391 - 3
Penetration of tinidazole into the gingival crevicular fluid in dogs; Sarkiala E et al.; Tinidazole was administered as a single oral dose of 15 mg kg-1 to 12 dogs, and its concentration in the plasma and gingival crevicular fluid (GCF) was measured at one and two hours by high performance liquid chromatography . Tinidazole was detectable in GCF in five dogs at one hour (6.8 +/- 2.6 micrograms ml-1) and in six dogs at two hours (9.2 +/- 1.4 micrograms ml-1) and in all plasma samples . In those animals with no detectable tinidazole in GCF, either the concentration of tinidazole in plasma was low or the volume of the GCF sample was insufficient for determination . The observed tinidazole levels in GCF exceeded the minimal inhibitory concentration values for most anaerobic oral bacteria.

Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4), 371 - 3
In vitro activity of beta-lactam drugs and sulbactam against Chlamydia trachomatis; Segreti J et al.; We tested the in vitro activity of ampicillin, ampicillin-sulbactam, cefoperazone, cefoperazone-sulbactam, and sulbactam against 18 recent clinical isolates of Chlamydia trachomatis and two ATCC strains . Ampicillin (MIC50, 256 micrograms/ml) and sulbactam (MIC50, 128 micrograms/ml) demonstrated some activity against C . trachomatis, but cefoperazone had little to no activity . At 2-3 dilutions below the MIC, C . trachomatis treated with ampicillin or sulbactam, but not cefoperazone, formed small inclusions that remained small on passage onto antibiotic-free McCoy cells . It appears that ampicillin and sulbactam suppress rather than kill C . trachomatis.

J Clin Microbiol, 1992 May, 30(5), 1297 - 300
Preliminary disk diffusion susceptibility testing criteria for cefdaloxime (RU29246, HR-916 metabolite), a new orally administered cephalosporin; Jones RN et al.; Cefdaloxime (formerly RU29246; Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J.) a new active component of the HR-916 ester, was tested by dilution and two disk (10- and 30-micrograms) diffusion susceptibility tests against 391 clinical isolates . Interpretive criteria were proposed for three potential MIC breakpoints of less than or equal to 1, less than or equal to 2, and less than or equal to 4 micrograms/ml . Analyses by regression line and error rate bounding methods minimized false-susceptible (very major) errors and produced a greater than or equal to 90% absolute interpretive agreement between susceptibility test methods . The less than or equal to 2-micrograms/ml breakpoint seemed optimal when 10-micrograms disks and the available human pharmacokinetics were used . The following inhibition zone diameter criteria were proposed: susceptible, greater than or equal to 19 mm; resistant, less than or equal to 15 mm . These recommendations for clinical trials should remain tentative until additional information about cefdaloxime formulations, pharmacokinetics, and patient outcomes can be correlated with in vitro susceptibility test results.

Clin Infect Dis, 1992 May, 14(5), 1027 - 33
Clinical features of human infection with Scedosporium inflatum; Wood GM et al.; We report on 17 Australian cases of human infection or colonization with Scedosporium inflatum . The spectrum of clinical manifestations was similar to that in infection caused by Scedosporium apiospermum . The patients were classified into three groups . Four immunocompetent patients who presented with localized infections of a joint, nail bed, eye, or sphenoidal sinus made up the first group . Our first case, in a boy with posttraumatic septic arthritis, responded to surgical drainage with amphotericin B followed by treatment with itraconazole . The other three cases were cured by surgery alone . The second group consisted of five immunocompromised patients who presented with disseminated infections in a variety of sites . Four of these patients did not respond to antifungal therapy and died . The fifth apparently responded to antifungal drugs after correction of his neutropenia . The third group included eight patients with asymptomatic colonization in the external ear (five cases) or respiratory secretions (three cases) . The nine isolates of S . inflatum tested by both disk and agar dilution methods were resistant to antifungal drugs . In our first case, which responded clinically to itraconazole, the MIC of this drug for the fungal isolate was 25 micrograms/mL . Thus S . inflatum can cause a broad spectrum of human infections whose severity and prognosis depend largely on the host's immune status.

J Bacteriol, 1992 May, 174(9), 3092 - 4
The arsenical ATPase efflux pump mediates tellurite resistance; Turner RJ et al.; The ars operon of the resistance plasmid R773 was found to produce moderate levels of resistance to tellurite . A MIC of 64 micrograms of TeO3(2-) per ml was found for Escherichia coli cells harboring plasmids which contained all three of the structural genes (arsA, arsB, and arsC) of the anion-translocating ATPase . MICs specified by plasmids carrying only one or two structural elements or the cloning vector alone were 2 to 4 micrograms/ml . The rate of TeO3(2-) uptake was found to be on the order of 55% less for cultures containing the resistance plasmids.

Antimicrob Agents Chemother, 1992 May, 36(5), 1097 - 101
Susceptibility testing of bacteria recovered from patients with peritonitis complicating continuous ambulatory peritoneal dialysis; Ludlam H et al.; Antagonism of antibiotic activity by peritoneal dialysate has been postulated to be a cause of failure of treatment of peritonitis complicating continuous ambulatory peritoneal dialysis . We evaluated by a case-control study whether unexpected treatment failure could be attributed to such antagonism . Bacteria isolated from 34 patient episodes of peritonitis treated with the same regimen of ciprofloxacin monotherapy were studied . Ciprofloxacin was significantly less active in dialysate than in Iso-Sensitest broth (IB) . The median MIC in IB was 0.5 microgram/ml, increasing to 2.0 micrograms/ml for both fresh dialysate (FD) (P = 0.003) and pooled dialysis effluent (PDE) (P = 0.03); the median MBC in IB was 8.0 micrograms/ml, increasing to 128.0 micrograms/ml in FD (P = 0.0002) and 64.0 micrograms/ml in PDE (P = 0.02) . However, no significant differences were found in the results for patients suffering unexpected treatment failure (relapse of peritonitis) compared with the results for patients whose infection resolved without sequel . In IB the median MICs for relapsers and nonrelapsers were 1.0 and 0.5 microgram/ml, respectively (P = 0.88); median MBCs were 32.0 and 4.0 micrograms/ml (P = 0.19) . In FD median MICs for relapsers and nonrelapsers were 2.0 and 1.0 micrograms/ml (P = 0.06); median MBCs were 128.0 micrograms/ml for both groups (P = 0.84) . In PDE the median MICs were 2.0 micrograms/ml for both groups (P = 0.78); median MBCs were 256.0 and 64.0 micrograms/ml (P = 0.17) . We therefore found no evidence to suggest that antagonism of antibiotic activity by dialysate is a cause of treatment failure or that conventional methods for laboratory susceptibility testing in peritonitis complicating continuous ambulatory peritoneal dialysis should be abandoned in favor of testing in media containing dialysate.

Pathol Biol (Paris), 1992 May, 40(5), 427 - 32
{Alteration of bacteria induced by subinhibitory concentrations of cefixime: consequences on bactericidal activity of human polynuclear neutrophils}; Labro MT et al.; Subinhibitory concentrations of most parenteral cephalosporins have been reported to alter bacterial infectivity and, in particular, to increase the susceptibility of altered bacteria to the killing effects of polymorphonuclear neutrophils (PMN) . Few data on this issue are available for oral cephalosporins . This study investigated the effects of sub-MIC concentrations of the new oral cephalosporin cefixime on two bacterial targets, i.e., S . aureus 209P (MIC 20 mg/l) and E . coli K12 (MIC 0.15 mg/l) . After overnight incubation (18 hours) with 10 or 5 mg/l cefixime, susceptibility of S . aureus to the killing effects of PMNs was increased two-fold as compared with control organisms and susceptibility to the O2-independent PMN bactericidal system (PMN extract) was also increased . In contrast, the susceptibility of E . coli to PMN and to cell-free bactericidal systems was identical for cefixime-exposed strains (0.1 and 0.05 mg/l) and for unexposed controls . However, cefixime-exposed E . coli were filamentous, suggesting that bactericidal efficacy in terms of the bacterial mass eliminated was enhanced in exposed strains . These data show that low levels of cefixime are capable of producing major alterations in susceptible and resistant bacteria and of increasing their susceptibility to PMN . These effects may be relevant in vivo, in particular when low concentrations of antibiotics persist over long periods in infected sites.

Rev Inst Med Trop Sao Paulo, 1992 May-Jun, 34(3), 259 - 62
{A comparative study between broth dilution and agar dilution technics in antibiograms for Candida}; Alves SH et al.; The performance of broth dilution method and agar dilution method were compared by MIC (minimal inhibitory concentration) and MFC (minimal fungicidal concentration) from Candida strains to polyene and imizadole antifungal agents . The concordance between these methods was drug dependent . The best percent of concordance were showed when the polyenes were tested . The problems of sensitivity test for yeasts to antifungal drugs are discussed.

Rev Inst Med Trop Sao Paulo, 1992 May-Jun, 34(3), 251 - 4
{The sensitivity of yeasts from the Candida genus isolated from cancer patients to polyene antifungals}; Alves SH et al.; Candida strains susceptibility from cancer patients were compared with Candida strains susceptibility from patients, without cancer by MIC (minimal inhibitory concentration) and MFC (minimal fungicidal concentration) to Amphotericin B and Nystatin . Broth dilution method and agar dilution method were the procedure employed . The authors find no significant differences between the studied groups . The problem of Candida resistance to polyene antifungals is discussed.

J Chromatogr, 1992 Apr 24, 597(1-2), 167 - 72
Kinetic aspects of membrane-based immunoaffinity chromatography; Nachman M; With a view towards the efficient large-scale purification of recombinant proteins, factors influencing antigen-antibody adsorption kinetics were studied in a model hollow-fiber membrane-based immunosorbent . Non-diffusion-controlled, homogeneous adsorption kinetics are approached in membranes . It is shown that adsorption kinetics, rather than mass transfer, first becomes limiting in membrane-based immunoaffinity chromatography (MIC) . Antigen adsorption is not kinetically limited, even at low feed-stream antigen concentrations . Binding efficients approach theoretical values when antibody coupling densities are decreased sufficiently . Antigen breakthrough during adsorption occurs near the membrane's observed binding capacity . The results of these kinetic studies were essential in the development of highly efficient and productive MIC systems for the purification of three recombinantly produced biotherapeutics, interferon-alpha 2a, interleukin-2 and interleukin-2 receptor.

Brain Res, 1992 Apr 17, 577(2), 285 - 92
Microglia isolated from rat brain secrete a urokinase-type plasminogen activator; Nakajima K et al.; In a previous study, we found particular proteases which degrade myelin basic protein (MBP) in a conditioned medium of cultured rat brain microglia . The MBP degrading activity in microglial-conditioned medium (Mic-CM) increased markedly in the presence of plasminogen . By Sephadex G-150 column chromatography, plasminogen-dependent MBP degrading activity was eluted at the position of about 47 kDa and 28 kDa . Furthermore slight plasminogen-dependent protease activity in the presence of fibrin (tissue plasminogen activator activity) was detected at a molecular weight of about 68 kDa . The two molecular forms (47 kDa and 28 kDa) of plasminogen-dependent protease were demonstrated by casein-zymography, and it was suggested that they were urokinase type-plasminogen activators (uPA) . This suggestion was confirmed by immunoblotting using anti-uPA antiserum . The unique 28 kDa type was considered to be produced from the 47 kDa form by limited proteolysis . Secretion of PA from microglia was demonstrated by cell zymography . In contrast, significant secretion of plasminogen activator inhibitor could not be detected in the Mic-CM . In addition, lipopolysaccharide significantly decreased the secretion of PA from microglia, while interleukin-1 and basic fibroblast growth factor enhanced the secretion.

J Chemother, 1992 Apr, 4(2), 88 - 94
The influence of serum proteins on biological activity of anticandidal peptides containing N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid; Kasprzak L et al.; The binding of several anticandidal peptides containing N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP) to serum proteins was studied using equilibrium dialysis . The affinity of these FMDP-peptides for serum albumin was low and well correlated with their biological activity against Candica albicans ATCC 26278 in serum albumin solution . This binding did not affect the biological activity of FMDP-peptides . On the other hand, substantial raising of MIC values was observed when anticandidal activity of FMDP peptides was assayed in the presence of complete serum proteins . This effect was likely to be a result of interaction with non-albumin components of serum proteins . Preliminary evidence points to the possibility of non-specific interaction with components containing sulfhydryl groups . In this study Nva-FMDP-Nva peptide was shown to be the most active compound in the serum protein solution . Moreover Nva-FMDP-Nva was most resistant to inactivation by serum components in comparison to other FMDP-peptides.

Enferm Infecc Microbiol Clin, 1992 Apr, 10(4), 216 - 9
{Renal tuberculosis treated with rifampicin, isoniazid and ofloxacin}; Alberte A et al.; We describe the results of eight patients with renal tuberculosis treated with rifampin, isoniazid and ofloxacin . Ofloxacin was given orally, 200 mg b.i.d . for 6 months . During the first three months, rifampin (600 mg/daily) and isoniazid (330 mg/daily) were added . All M . tuberculosis strains isolated were sensitive to ofloxacin (MIC 1 mg/l) . Follow-up cultures turned to be negative rapidly (during the first month of therapy), and no untoward effects were recorded . All patients had a 12-months follow-up period, and all were clinically cured . The treatment used was well accepted by all patients.

Am J Med Genet, 1992 Apr 15-May 1, 43(1-2), 505 - 9
Neuropsychological studies in families with fragile-X negative X-linked mental retardation; Cianchetti C et al.; Neuropsychological studies were performed in 82 subjects of 12 families with x-linked, fragile X negative, mental retardation (MR) . Subjects were examined with Wechsler tests (WPPSI, WISC-R or WAIS, according to their capabilities), Progressive Matrices, Bender or Santucci and memory tests . Physical findings in 5 families were characterised by micro-orchidism (MiO), microcephaly (MiC), short stature (SS) and non-specific facial features (XMR +/- MiO +/- MiC +/- SS) . The 11 males with MR had a very low IQ, ranging from 13 to 37 (mean 21.2 +/- 8.8); this did not constitute a profile definition . Among the females of their families, 4 had subnormal or borderline IQ, respectively 74, 66, 38 and 37 . A second group (2 families) had MiO but with normal stature and occipito-frontal circumference (XMR +/- MiO) . The 7 males with MR had an IQ ranging from 24 to 43 (mean 35.1 +/- 5.8) and showed frequently better results in performance than in verbal subtests . In these 2 families, 5 females had subnormal or borderline IQ, respectively 77, 72, 71, 70 and 20 . In the 5 families of the third group, XMR +/- MaO (fraX-), several affected males had macro-orchidism (MaO) and facial changes similar to those of fragile X syndrome . IQ variability, also in the same family (e.g.: the 3 brothers of family 3 had, respectively, an IQ of 26, 28 and 68; and 2 brothers of family 1 had an IQ of 13 and 63) and different profiles . Two females were severely affected (IQ 16 and 24), while another 4 had an IQ, respectively, of 63, 69, 71 and 72.

J Infect Dis, 1992 Apr, 165(4), 676 - 82
Beta-lactam enhancement of aminoglycoside activity under conditions of reduced pH and oxygen tension that may exist in infected tissues; Bryant RE et al.; Aminoglycoside activity is suppressed under conditions of low pH and oxygen tension that are likely to occur in infected tissues; the suppressive effects of these conditions are additive . Under aerobic conditions, the MIC of amikacin for 10 isolates of Escherichia coli was 4.8 +/- 0.7 micrograms/ml at pH 7.2 and increased to 40.0 +/- 8.2 micrograms/ml at pH 6.0 . Under anaerobic conditions, the MIC of amikacin for E . coli was 30.0 +/- 1.5 micrograms/ml at pH 7.2 and greater than 50.0 micrograms/ml at pH 6.0 . In vitro and in vivo studies of amikacin activity in an acidic and hypoxic milieu containing beta-lactamase demonstrated substantially enhanced bactericidal activity when amikacin and beta-lactams were used together . Under conditions of reduced pH and oxygen tension, cefotaxime enhanced {3H}-tobramycin uptake by E . coli 14-fold and {3H}amikacin uptake 7-fold and appeared to overcome the suppressive effect of those conditions on uptake of aminoglycosides by bacteria.

Arch Environ Contam Toxicol, 1992 Apr, 22(3), 300 - 4
Acute toxicity of methyl isocyanate in rabbit: in vitro and in vivo effects on rabbit erythrocyte membrane; Jeevaratnam K et al.; Methyl isocyanate (MIC) interaction with the rabbit erythrocyte membrane increased the fluidity of the membrane and decreased the osmotic fragility of erythrocytes both in vitro and in vivo in rabbits intoxicated with MIC subcutaneously . MIC inhibited both acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) activities of erythrocytes dose-dependently in vitro, while in vivo a decreased trend in ATPase activity with unaltered AChE activity was observed . MIC also caused significant decrease in plasma sodium level with corresponding increase in potassium level in rabbits . The observed effects are due to MIC, per se, as the hydrolysis products of MIC, methylamine and N,N'-dimethylurea did not affect the erythrocyte fluidity and enzymes activities both in vitro and in vivo while they increased the osmotic fragility of erythrocytes in vivo in rabbits administered subcutaneously in equimolar concentration to MIC dosage . Inhibition of Na(+)-K(+)-dependent ATPase with altered permeability to cations and also probably water transport of plasma membrane due to MIC interaction are envisaged.

Am Rev Respir Dis, 1992 Apr, 145(4 Pt 1), 856 - 8
Clarithromycin minimal inhibitory and bactericidal concentrations against Mycobacterium avium; Heifets LB et al.; Minimal inhibitory and bactericidal concentrations (MIC and MBC) of clarithromycin were determined with 49 Mycobacterium avium strains isolated from patients with acquired immunodeficiency syndrome . The inhibitory activity depended on the pH of the medium: the drug was more active at pH 7.4 and less active at pH 5.0, with activity at pH 6.8 in an intermediate position . The broth-determined MIC found at pH 7.4 were 0.25 and 0.5 micrograms/ml for most strains . The agar-determined MIC for most strains ranged from 1.0 to 4.0 micrograms/ml . The MBC of the drug were 8- to 64-fold higher than the MIC, which indicates that the efficacy of clarithromycin can be associated with its inhibitory rather than its bactericidal activity.

Oral Microbiol Immunol, 1992 Apr, 7(2), 113 - 7
Antibiotic resistance of the subgingival microbiota following local tetracycline therapy; Goodson JM et al.; The antibiotic resistance of the subgingival microbiota was studied by 3 approaches . First, we assessed the ability of subgingival isolates taken following therapy to grow on media containing tetracycline (TC) . Higher percentages of TC-resistant organisms appeared at TC fiber-treated periodontal sites and within the saliva 1 week after treatment as compared with pre-treatment levels . By 1 month, the percentage of TC-resistant organisms had returned to levels comparable to those seen before treatment . In the second approach, subgingival isolates taken following therapy were grown on media without antibiotics, and isolates were selected for Gram-stain and cell morphology determination . This study indicated that subgingival sites became colonized with gram-positive cocci in the same time period that an increase of TC-resistant isolates was observed in the first study . This may account for the transient increase in TC resistance, because many gram-positive cocci are intrinsically resistant to TC . In the third approach, the antibiotic resistance of subgingival gram-negative species was determined . The predominant cultivable microbiota of 9 sites from 3 subjects were isolated immediately before and 6 months after TC fiber treatment . Gram-negative rods were characterized and tested for sensitivity to TC (minimum inhibitory concentration {MIC} 1-128 micrograms/ml), penicillin at 80 micrograms/ml, and erythromycin at 8 micrograms/ml . None of the gram-negative rods were resistant to TC (MIC greater than or equal to 16 micrograms/ml), either before or after treatment . Before treatment 98% of the gram-negative rods were susceptible to TC at 1-2 micrograms/ml and after therapy 88% were susceptible.(ABSTRACT TRUNCATED AT 250 WORDS)

Am Rev Respir Dis, 1992 Mar, 145(3), 657 - 60
beta-Lactamase inhibitors and the inducibility of the beta-lactamase of Mycobacterium tuberculosis; Zhang Y et al.; Ten clinical isolates and the type strain (H37Rv) of Mycobacterium tuberculosis were shown to produce an intracellular beta-lactamase . Crude enzyme preparations were extracted from acetone cell powders by grinding with zirconium beads in 0.133 M glycine with 1.0% Triton X-100 . The enzymes had identical patterns on isoelectric focusing, with two major bands at isoelectric points of 4.9 and 5.1 . The beta-lactamase was highly susceptible to the new beta-lactamase inhibitor BRL 42715, with an I50 of 0.0001 microgram/ml . The enzyme was also susceptible to clavulanic acid with an I50 (0.05 microgram/ml), which was similar to the value for the common bacterial beta-lactamase TEM-1 (0.01 microgram/ml) . The latter result is consistent with previous MIC studies with M . tuberculosis, which have shown synergy between clavulanic acid and amoxicillin . BRL 42715 and clavulanic acid were more active than sulbactam, tazobactam, and cloxacillin . These studies support the potential value of penicillin/clavulanic acid and penicillin/BRL 42715 combinations in the treatment of tuberculosis.

Mycopathologia, 1992 Mar, 117(3), 145 - 52
Pathogenicity of Sporotrichum pruninosum and Cladosporium oxysporum, isolated from the bronchial secretions of a patient, for laboratory mice; Singh SM et al.; In this study we have demonstrated the occurrence of Sporotrichum pruinosum and Cladosporium oxysporum in the bronchial secretions of a patient with a presumptive diagnosis of tuberculosis . This observation coupled with the ability of both fungi to cause infection and elicit tissue responses in experimentally infected mice supported a probable etiologic relationship with the patient which could not be confirmed in the absence of histologic evidence . In vitro some antimycotics were tested against S . pruinosum and C . oxysporum by the agar dilution method . Oxiconazole with a minimum inhibitory concentration of 0.1 micrograms/ml-1 after 72 h and amorolfine at a concentration of 0.001 micrograms/ml-1 after 72 h were the most active ones against S . pruinosum and C . oxysporum respectively . It is suggested that the isolation of S . pruinosum and C . oxysporum from patients with bronchopulmonary disorders should be viewed with caution . Clinical and laboratory evaluation of such patients should be done critically before arriving at a firm diagnosis.

Antimicrob Agents Chemother, 1992 Mar, 36(3), 662 - 4
Resistance of Peptostreptococcus spp . to macrolides and lincosamides: inducible and constitutive phenotypes; Reig M et al.; The activities of erythromycin and clindamycin against 350 Peptostreptococcus strains were studied during a 5-year period (1986 to 1991) . In 5.1% of the Peptostreptococcus strains, which presented dissociated resistance (clindamycin MIC, less than or equal to 1 microgram/ml; erythromycin MIC, greater than 8 micrograms/ml), evidence of inducible macrolide-lincosamide resistance was shown . A total of 17.7% of the strains presented a constitutive phenotype; the clindamycin and erythromycin MICs for these strains were greater than 8 micrograms/ml.

J Vet Pharmacol Ther, 1992 Mar, 15(1), 53 - 61
Pharmacokinetics of spiramycin after intravenous, intramuscular and subcutaneous administration in lactating cows; Sanders P et al.; Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows . This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration . Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route . Plasma and milk were collected post injection . Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method . The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h) . An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves . Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes . The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes . Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk . However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagn Microbiol Infect Dis, 1992 Mar-Apr, 15(3), 253 - 8
Diffusion of teicoplanin and vancomycin in agar; Cavenaghi LA et al.; Teicoplanin, although more active than vancomycin {by minimum inhibitory concentration (MIC)}, produces smaller inhibition zones in sensitivity testing with 30-microgram disks . Our data support the hypothesis that this is due to lower diffusion of teicoplanin in agar media . After 6 hr of incubation, approximately 70% of vancomycin, but only 20% of teicoplanin entered the agar from a paper disk charged with 30 micrograms of antibiotic . This is due to a difference between the diffusion coefficients: 0.47 mm2/hr for teicoplanin and 0.72 mm2/hr for vancomycin . With the methodology used in this work, it is possible to calculate the range of concentrations of the antibiotic occurring at times likely to include the critical time--the time when the inhibition zone is formed--of most strains at any given distance from the reservoir . One can thus estimate the breakpoint diameter for a given MIC breakpoint; for example, an MIC breakpoint of less than or equal to 4 micrograms/ml would correspond to a greater than or equal to 15-mm breakpoint diameter for vancomycin (30-microgram disk) and a greater than or equal to 13-mm breakpoint diameter for teicoplanin (30-microgram disk).

Can J Microbiol, 1992 Mar, 38(3), 209 - 14
Fonsecaea pedrosoi: lipid composition and determination of susceptibility to amphotericin B; Gomes MH et al.; Conidia and mycelial cells of Fonsecaea pedrosoi ATCC 46428 were obtained for analyses of lipid composition . Total lipids, phospholipids, sterols, and qualitative sterols and fatty acid composition were determined . A higher lipid content was detected in conidia than in mycelial cells of Fonsecaea pedrosoi, which could not be attributed to total sterols and phospholipids . In both forms of this fungus, ergosterol was the only sterol detected . The minimal inhibitory concentration of amphotericin B was lower for conidia than for mycelium.

Hiroshima J Med Sci, 1992 Mar, 41(1), 13 - 7
Effects of subminimal inhibitory concentrations of ampicillin on hemagglutination of Escherichia coli; Nishimoto K et al.; The hemagglutination (HA) activity of Escherichia coli was enhanced by subminimal inhibitory concentrations (sub-MICs) of ampicillin . One half of the MIC of ampicillin caused a bacterial filamentation and diminished bacterial piliation (as observed by light and electron microscopies) as well as an increase of HA activity . HA activity, however, decreased after separation of ampicillin-treated bacteria . These results indicate that the increase in HA activity by ampicillin is mainly due to filament formation.

Eur J Clin Microbiol Infect Dis, 1992 Mar, 11(3), 265 - 7
In vitro activity of azithromycin and tetracycline against 358 clinical isolates of Brucella melitensis; Landinez R et al.; The in vitro activity of azithromycin against human pathogenic strains of Brucella melitensis was tested at three centres and compared to that of tetracycline, the standard antibiotic currently used for the treatment of human brucellosis . MIC determination was carried out . Tested concentration ranges for both azithromycin and tetracycline were between 0.03 and 16 micrograms/ml . Brucella melitensis biotype 1, strain M16 was employed as a control microorganism . A total of 358 Brucella melitensis strains from human blood cultures were tested . MIC90 (micrograms/ml) values ranged from 0.5 to 1.00 for azithromycin and were 0.25 for tetracycline . It was concluded that there was little difference in the sensitivity of pathogenic Brucella melitensis to azithromycin and tetracycline isolated from three different regions in Spain . These results encourage further investigations on the possible therapeutic role of azithromycin in brucellosis.

J Med Chem, 1992 Feb 21, 35(4), 716 - 24
Phenothiazines as lipid peroxidation inhibitors and cytoprotective agents; Yu MJ et al.; A series of phenothiazines was synthesized and evaluated as in vitro inhibitors of iron-dependent lipid peroxidation . The MIC (minimum tested concentration that gave greater than or equal to 50% inhibition) for 2-(10H-phenothiazin-2-yloxy)-N,N-dimethylethanolamine methanesulfonate (6) was 0.26 microM . Whereas methyl substitution at N-10 diminished activity nearly 100-fold, other structural modifications such as varying the amine group, the distance separating the amine substituent from the phenothiazine nucleus, and the linking group had little effect . Compound 6 was more effective than probucol, a known antioxidant, in blocking Cu2+ catalyzed oxidation of low-density lipoprotein (LDL) as measured by competitive scavenger receptor mediated degradation of 125I-labeled acetyl-LDL by mouse peritoneal macrophage cells in vitro . At a concentration of 5 microM, compound 6 also protected primary cultures of rat hippocampal neurons exposed to hydrogen peroxide (50 microM) when assessed 18 h later by fluorescein diacetate and propidium iodide uptake.

J Bacteriol, 1992 Feb, 174(4), 1288 - 92
Expression of bacterial mercuric ion reductase in Saccharomyces cerevisiae; Rensing C et al.; The gene merA coding for bacterial mercuric ion reductase was cloned under the control of the yeast promoter for alcohol dehydrogenase I in the yeast-Escherichia coli shuttle plasmid pADH040-2 and transformed into Saccharomyces cerevisiae AH22 . The resulting transformant harbored stable copies of the merA-containing hybrid plasmid, displayed a fivefold increase in the MIC of mercuric chloride, and synthesized mercuric ion reductase activity.

J Bacteriol, 1992 Feb, 174(4), 1205 - 12
Cloning and sequence analysis of the Chlamydia trachomatis spc ribosomal protein gene cluster; Kaul R et al.; We identified and sequenced a segment of Chlamydia trachomatis chromosomal DNA that shows homology to the Escherichia coli spc and distal region of the S10 ribosomal protein (r-protein) operons . Its sequence revealed a high degree of nucleotide and operon context conservation with the E . coli r-protein genes . The C . trachomatis spec operon contains the r-protein genes for L14, L24, L5, S8, L6, L18, S5, L15, and Sec Y along with the genes for r-proteins L16, L29, and S17 of the S10 operon . The two operons are separated by a 16-bp intragenic region which contains no transcription signals . However, a putative promoter for the transcription of the spc operon was found 162 nucleotides upstream of the CtrL14e start site; it revealed significant homology to the E . coli consensus promoter sequences . Interestingly, our results indicate the absence of any structure resembling an EcoS8 regulatory target site on C . trachomatis spc mRNA in spite of significant amino acid identity between E . coli and C . trachomatis r-proteins . Also, the intrinsic aminoglycoside resistance in C . trachomatis is unlikely to be mediated by CtrL6e since E . coli expressing CtrL6e remained susceptible to gentamicin (MIC less than 0.5 micrograms/ml).

Pediatrics, 1992 Feb, 89(2), 247 - 50
Cerebrospinal fluid isoniazid concentrations in children with tuberculous meningitis: the influence of dosage and acetylation status; Donald PR et al.; Cerebrospinal fluid (CSF) and plasma isoniazid (INH) concentrations were determined on 96 occasions in 38 children (median age 1.5 years) with tuberculous meningitis, and the effects of INH elimination status and test dosages of 10 mg/kg body weight and 20 mg/kg body weight was studied . Maximum cerebrospinal fluid INH concentrations were reached during the period 2 to 4 hours after dosing and cerebrospinal fluid and plasma INH concentrations did not differ significantly during this period . Cerebrospinal fluid INH concentrations following a dosage of 10 mg/kg (4.6 +/- 2.4 micrograms/mL) were, however, significantly lower than those following a dosage of 20 mg/kg (11.6 +/- 2.7 micrograms/mL) . Cerebrospinal fluid INH concentrations in faster acetylators at a dosage of 10 mg/kg (3.2 +/- 1.1 micrograms/mL) were significantly lower than in slower acetylators (7.7 +/- 1.3 micrograms/mL), as was the case with a dosage of 20 mg/kg, where faster acetylators had cerebrospinal fluid INH concentrations of 10.5 +/- 2.5 micrograms/mL compared with 14.1 +/- 1.4 microgram/mL in slower acetylators . Following dosages of both 10 mg/kg and 20 mg/kg, INH concentrations in excess of the minimal inhibitory concentration for Mycobacterium tuberculosis persisted in the CSF 12 to 14 hours later . Despite the patients' being young and frequently malnourished, suffering from advanced forms of tuberculous meningitis, and receiving high dosages of INH, rifampicin, and pyrazinamide, none developed any clinical signs of hepatotoxicity and in only one child did the serum bilirubin level rise to 19 micrograms/mL.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 486 - 8
Comparison of antifungal activity of amphotericin B deoxycholate suspension with that of amphotericin B cholesteryl sulfate colloidal dispersion; Hanson LH et al.; Complexing amphotericin B (AmB) with lipids or entrapping it in liposomes may increase its efficacy by reducing toxicity and affecting distribution . However, depending on the lipids involved, interference with antifungal activity has been shown . We compared the in vitro activity of AmB colloidal dispersion by cholesteryl sulfate (ABCD) to the standard AmB deoxycholate suspension (ABDS) against 41 isolates of 15 pathogenic species . Broth dilution MIC and minimum fungicidal concentration (MFC) ranges were similar, and the same number of isolates had lower MICs and MFCs with one drug as with the other . Differences between species were noted . In less than a third of comparisons, there were large (fourfold or more) decreases in ABCD activity relative to that of ABDS, and in approximately 1/10, there were large increases . Thus, ABCD complexing variably affects AmB activity . As ABCD pharmacokinetics and toxicology differ from those of ABDS, the significance of these results for in vivo activity needs to be determined.

Diagn Microbiol Infect Dis, 1992 Feb, 15(2), 135 - 40
Modification of the error-rate bounded classification scheme for use with two MIC break points; Brunden MN et al.; In antimicrobic susceptibility testing, minimum inhibitory concentration (MIC) susceptibility break points are defined by correlation of bacteriologic-clinical outcome data with MIC data for the infecting organisms . Disk diffusion {that is, zone-diameter (Z)} correlates are then established that provide for the prediction of organism susceptibility, while misclassification errors are kept to a minimum . The determination of Z break points through an error-rate-bounded classification scheme was first proposed by Metzler and DeHaan (1972) . This method involves one MIC break point that separates susceptible and resistant strains . More recently, researchers have preferred to use two MIC break points (susceptible and resistant) that separate susceptible, moderately susceptible, and resistant strains . There is no known methodology for determining the Z break points for this latter situation, other than enumerating solutions for all feasible Z break-point pairs and choosing among the results . Our interest lay in presenting a methodology for determining the Z break points once the MIC break points are established . By deriving an index as a function of Z break points, a search method for finding the optimal Z break points is given . For the data set examined, our index interval solution required only a small percentage of solutions to be examined.

J Antimicrob Chemother, 1992 Feb, 29(2), 115 - 20
Proposed mechanism for metronidazole resistance in Helicobacter pylori; Cederbrant G et al.; Metronidazole MIC values were determined for ten isolates of Helicobacter pylori . Under microaerobic conditions four were inhibited by less than 0.25 mg/L, two strains required 2.0 mg/L and four strains had MIC greater than 32 mg/L . The strains were tested for their susceptibility to metronidazole after varying lengths of anaerobic exposure prior to or during microaerobic incubation . The susceptibility was determined by E-test and traditional agar dilution technique . The level of susceptibility of primarily susceptible strains was not significantly affected by a 2 to 24 h period of anaerobic incubation . However, the effect on resistant strains was dramatic . These strains were increasingly susceptible when a 2 to 12 h period of anaerobicity was provided anytime during the first 48 h and fully susceptible (MIC less than 0.1 mg/L) if 24 h of anaerobicity was provided . When tested again under microaerobic conditions the strains exhibited their original MIC values . The composition of the medium did not influence the results . We propose that "metronidazole resistance" in H . pylori is due to a decreased ability of these strains to achieve a sufficiently low redox potential under microaerobic conditions for the necessary reduction of metronidazole, and that these strains during short periods of anaerobicity manage to reduce and "store" sufficient amounts of metronidazole to appear fully susceptible after subsequent microaerobic incubation . microaerobic incubation.

Am J Pathol, 1992 Feb, 140(2), 497 - 502
Human papillomavirus and the three group metaphase figure as markers of an increased risk for the development of cervical carcinoma; Claas EC et al.; In this study, the presence of atypical mitotic figures and human papilloma virus (HPV) genomes was related to the degree of cervical intraepithelial neoplasia (CIN) or microinvasive carcinoma (MIC) as found in 94 paraffin-embedded biopsies from cervical lesions . The results showed that the frequency of three group metaphase (TGM) figures, a special kind of atypical mitotic figure, as well as the presence of HPV 16 and 18 genomes increased with the degree of cervical intraepithelial neoplasia . TGM figures were observed in 24% of CIN2, up to 61% in CIN3 lesions, and in 83% of the microinvasive cervical carcinomas . HPV genomes were detected in 15% of CIN1, up to 75% in CIN3 lesions, and in 92% of the invasive carcinomas of the cervix . The combination of these two markers showed even a better association with a higher degree of cervical intraepithelial neoplasia . The results of these studies suggest that detection of particular HPV types, mainly HPV 16 and 18, and the presence of TGM figures can be considered as markers that indicate an increased risk for progression of cervical intraepithelial neoplasia to invasive carcinoma.

Biochim Biophys Acta, 1992 Jan 30, 1099(1), 51 - 6
Mechanism of energization of uptake of the fluorescent dye 2-(4-dimethylaminostyryl)-1-ethylpyridinium cation {DMP+} into an acrA strain of Escherichia coli; Sedgwick EG et al.; The mechanism of uptake of the fluorescent dye 2-(4-dimethylaminostyryl)-1-ethylpyridinium cation (DMP+) into cells and vesicles of the acrA strain AS-1 of Escherichia coli was examined . Uptake was energized by substrate oxidation and discharged by uncouplers . Uptake was enhanced by the presence of tetraphenylphosphonium cation, tetraphenylboron anion and tributyltin chloride, which may inhibit the efflux system for DMP+ . Uptake was inhibited by 5-methoxyindole-2-carboxylic acid (MIC) . By the use of ionophores with right-side-out vesicles loaded with monovalent cations it was shown that DMP+ uptake could be driven both by the establishment of a membrane potential across the vesicle membrane and by a H+/DMP+ antiport system . Attempts to demonstrate the latter mechanism in everted membrane vesicles were unsuccessful.

Biochem Biophys Res Commun, 1992 Jan 15, 182(1), 86 - 91
Antileishmanial activity of hamycin: a polyene antibiotic; Sarkar S et al.; Hamycin, a polyene antibiotic, now in extensive use in the treatment of candidiasis and otomycosis, is found to be remarkably effective in killing Leishmania donovani promastigotes in a liquid medium at a concentration of 0.2 microgram/ml . The glucose stimulated respiration and the uptake of 2-deoxy-D{U-14C}-glucose was inhibited in cells treated with the drug at a growth inhibitory concentration . An immediate release of isotopic glucose from preloaded cells could be demonstrated after exposure to hamycin . All the above effects could be effectively prevented in the presence of ergosterol . The primary site of action of hamycin on L . donovani promastigote cells appears to be membrane sterols that result in the loss of the permeability barrier to small metabolites . The lower minimum inhibitory concentration of hamycin compared to other established drugs warrants further study in the context of increasing reports of clinical resistance to pentavalent antimonials.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 180 - 4
Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M . chelonae-like organisms; Brown BA et al.; Susceptibilities to erythromycin by broth microdilution were compared with those to the newer macrolide clarithromycin for 223 isolates of rapidly growing mycobacteria belonging to seven taxonomic groups . Seventy-nine random isolates were also tested against azithromycin and roxithromycin . The MIC of clarithromycin for 90% of strains tested (MIC90) was 0.25 microgram/ml for isolates of Mycobacterium chelonae subsp . chelonae and 0.5 microgram/ml for M . chelonae subsp . abscessus, with 100% of strains inhibited by less than or equal to 1 microgram/ml . Clarithromycin was 10 to 50 times more active than erythromycin and four- to eightfold more active than the other newer macrolides against M . chelonae . MICs of clarithromycin frequently increased with prolonged incubation with isolates of M . chelonae subsp . abscessus but not M . chelonae subsp . chelonae . MICs of clarithromycin were much higher for M . fortuitum bv . fortuitum (MIC50, 2.0 microgram/ml; MIC90, greater than 8.0 microgram/ml) . The three newer macrolides had comparable activity against M . fortuitum bv . peregrinum (MIC90s of 0.5 to 2.0 microgram/ml compared with erythromycin MIC90s of greater than 8.0 microgram/ml) . Overall, clarithromycin was the most active agent, inhibiting all isolates of M . chelonae subsp . chelonae, M . chelonae subsp . abscessus, M . fortuitum bv . peregrinum, and the M . chelonae-like organisms and 35% of M . fortuitum bv . fortuitum at less than or equal to 1 microgram/ml . Clinical trials of the newer macrolides, especially clarithromycin, against these environmental mycobacterial species appear to be warranted.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 223 - 6
Effect of inoculum size on bacteriolytic activity of cefminox and four other beta-lactam antibiotics against Escherichia coli; Soriano F et al.; MICs and turbidimetric experiments revealed a negligible inoculum effect with two Escherichia coli strains exposed to cefminox and cefoxitin, whereas a marked inoculum effect was revealed after exposure to cefotaxime, ceftizoxime, and imipenem . The activities of the cephamycins were associated with spheroplast formation and bacteriolysis at concentrations close to the MIC, whereas the other agents induced the formation of filaments or, in the case of imipenem, rounded cells.

Vet Surg, 1992 Jan-Feb, 21(1), 1 - 4
Pharmacokinetic disposition of cefazolin in serum and tissue during canine total hip replacement; Richardson DC et al.; Intraoperative cefazolin concentrations were measured in serum, joint capsule, cancellous bone of the acetabulum, and proximal cancellous bone of the femur in 15 dogs undergoing total hip replacement . Cefazolin (22 mg/kg intravenously {IV}) was administered every hour for three doses . The mean peak serum concentrations (+/- SEM) were 387.79 +/- 27.56 micrograms/mL, 521.71 +/- 28.00 micrograms/mL, and 542.20 +/- 30.91 micrograms/mL, respectively . Mean serum concentrations just before administration of doses 2 and 3 were 51.77 +/- 2.39 micrograms/mL, and 64.84 +/- 3.46 micrograms/mL, respectively . The mean cefazolin concentrations in the joint capsule, cancellous bone of the acetabulum, and cancellous bone of the femur were 34.71 +/- 2.50 micrograms/g, 28.70 +/- 7.40 micrograms/g, and 36.20 +/- 3.80 micrograms/g, respectively . The minimum inhibitory concentration of cefazolin for 90% of the common contaminants (MIC90) in this clinic is less than or equal to 2 micrograms/mL or per gram of tissue . Serum concentrations never fell below 15 times the MIC90 (lowest trough, 35.93 micrograms/mL), and the lowest tissue concentration (6.57 micrograms/mL in cancellous bone from the acetabulum) was still more than 3 times the MIC90 . The mean tissue concentration was 15 times the MIC90.

Leukemia, 1992, 6 Suppl 2, 1 - 6
The classification of acute leukaemia; Catovsky D et al.; The standard methods for classifying acute leukaemias now include morphology, cytochemistry and membrane markers . Major advances in immunology, in particular the development of monoclonal antibodies (McAb) with lineage specificity, have provided objective positive criteria for the diagnosis of acute lymphoblastic leukaemia (ALL) . The FAB group has recognised the importance of McAb for the classification of some forms of acute myeloid leukaemia (AML), such as megakaryoblastic leukaemia, AML-M7, in which reactivity with McAb against platelet glycoproteins is a requirement for diagnosis . More recently the group has defined a type of myeloblastic leukaemia with minimal differentiation, AML-MO, in which myeloid cytochemistry is negative and the diagnosis is made by the expression of myeloid antigens and negative lymphoid markers in the blast cells . However, new problems have emerged with the wider use of McAb which now need to be addressed: the most important is the precise evaluation criteria for biphenotypic leukaemia for which we have proposed a scoring system in order to recognise the genuine cases which constitute a distinct disease entity . The role of karyotyping in the classification of acute leukaemia is gradually being defined (MIC proposals) and some forms of acute leukaemia can only be diagnosed by chromosome translocations, e.g . Ph+ ALL, resulting from t(9;22) and t(4;11) in infant ALL . Several translocations can also be demonstrated by molecular techniques . Cases with t(8;16) (p11;p13) are characterised by myelomonocytic features, erythrophagocytosis and fibrinolysis and represent a type of AML which can be defined primarily by its cytogenetic abnormality.

Dermatology, 1992, 184 Suppl 1, 25 - 9
Experience with amorolfine in the treatment of dermatomycoses; del Palacio A et al.; In a double-blind randomized comparative study, 75 patients were treated with amorolfine cream 0.125, 0.25 or 0.5% . At the end of treatment clinical cure rates of 80, 76 and 84%, respectively, and mycological cures of 72, 64 and 76% were obtained . At 2 months posttherapy follow-up relapse rates were 0, 12 and 12%, respectively . There was no significant difference between the three groups in terms of clinical and mycological response, duration of treatment or tolerance . In a double-blind parallel study, 40 patients were treated topically with either 0.5% amorolfine cream or 1% bifonazole cream . The percentages of combined clinical and mycological cures were 83.3 and 78.95%, respectively . There was no significant difference in terms of tolerance and clinical and mycological cure rates . All treatments were applied once daily . Posttreatment MIC values did not indicate development of resistance to either amorolfine or bifonazole.

Pharmacotherapy, 1992, 12(1), 50 - 5
Ex vivo protein binding of clindamycin in sera with normal and elevated alpha 1-acid glycoprotein concentrations; Kays MB et al.; Clindamycin is a lincosamide antibiotic that binds primarily to alpha 1-acid glycoprotein (AAG), an acute-phase serum protein . Many studies have shown that AAG concentrations increase in response to stress, including infection, myocardial infarction, and trauma . The objectives of this study were to determine the serum protein binding of various clindamycin concentrations in sera with normal and elevated AAG concentrations . Serum was obtained from 4 healthy volunteers and 12 patients with pathophysiologic conditions known to elevate serum AAG concentrations . Timing for collection was determined from the literature, corresponding with the expected peak concentration for each disease state . Samples were assayed for AAG by radial immunodiffusion and were spiked with clindamycin to achieve total concentrations of 10 micrograms/ml (n = 18), 4 micrograms/ml (n = 10), and 2 micrograms/ml (n = 7) . Protein binding was determined by ultrafiltration and subsequent high-performance liquid or gas chromatography . Protein binding was dependent on the serum concentrations of both AAG and clindamycin . When AAG concentrations increased from 101-150 mg/dl to 201 mg/dl or greater, mean protein binding increased from 81.2% to 92.4% (p = 0.1265) and from 61.3% to 88.6% (p less than 0.05) at clindamycin concentrations of 2 and 4 micrograms/ml, respectively . With AAG concentrations between 101 and 150 mg/dl, mean protein binding increased from 62.4% at 10 micrograms/ml to 81.2% at 2 micrograms/ml (p = 0.1514) . Since AAG concentrations may increase in certain patients, the concentration of free (pharmacologically active) drug may fall below the minimum inhibitory concentration for several pathogens earlier in a dosing interval.

Leuk Res, 1992, 16(2), 181 - 90
Morphologic immunophenotypic and cytogenetic patterns of adult acute myeloid leukemia in Saudi Arabia; Roberts GT et al.; During a 6-year period we received bone marrow (BM) and peripheral blood (PB) samples from 178 patients with acute myeloid leukemia (AML) . All patient BM, and occasionally, PB samples were characterized according to FAB criteria, and by immunophenotyping (IP) and cytogenetics (CG) . This report summarizes the findings in the 125 patients who were older than 15 years . Their mean and median ages were 39.4 and 37.0 years . There were 8 (6.4%) M1, 27 (21.6%) M2, 15 (12.0%) M3, 49 (39.2%) M4, 14 (11.2%) M5A, 9 (7.2%) M5B and 2 (1.6%) M6 . IP showed that HLA-DR was most strongly and frequently expressed by M1 blasts (53.5%, 86%) and least strongly and frequently expressed by M3 blasts (4.5%, 0%) . HLA-DR was also relatively strongly expressed by M4, M5A, M5B (21.5%, 43%; 34.9%, 69%; and 19.2%, 56%, respectively) . CD11b was uniformly weakly expressed by all FAB subgroups . CD13 was most strongly and frequently expressed by M4 (20%, 43%), and was relatively weakly and infrequently expressed by the other FAB subtypes (9.5%, 9.2%, 16.4%, 8.4%, 16.3%) . CD14 was moderately expressed by M4 (15.2%, 25%) and M5B (14.0%, 22%) and M1 (7.0%, 40%) . CD33 was most strongly expressed by M3 blasts (26.3% and 61%), and was most weakly expressed by M5B (10.6% and 22%) . Fourteen (11.2%) patients had blasts that showed lymphoid antigens (5 T, 5 B, 5 CALLA) in addition to myeloid characteristics . Fifty-four (51.9%) of 104 patients tested had one or more karyotypic abnormalities, the most frequent of which was 8+ . Only the t(15:17) was specific, and was seen in M3 . Four patients with anomalous IP had trisomy 21, one of whom also had 11q- . We conclude that Saudi Arabian AML shows FAB patterns similar to patients in the West, and that M3 patients have a characteristic IP and cytogenetic pattern . Apart from this the MIC classification failed to reveal characteristic modes.

Lung, 1992, 170(4), 235 - 41
Later development of asthma in patients with a negative methacholine inhalation challenge examined for suspected asthma; Puolijoki H et al.; A negative methacholine inhalation challenge (MIC) in a patient with suspected bronchial asthma is generally considered to make this diagnosis unlikely . Nevertheless, the patient may later develop asthma . To estimate the proportion that eventually becomes asthmatic, a 10 year follow-up study was carried out on 334 consecutive MIC-negative patients aged 14-80 years . The development of asthma among these patients was assessed on the basis of entitlement to preferential refund from the cost of antiasthmatic therapy granted for them under national health insurance . During the follow-up 30 patients (9%) were granted the refund . There was no significant difference between men and women in this respect . Patients who developed asthma were somewhat older than those who did not . A family history of allergy, allergic rhinitis, and positive reactions to skin prick tests were significantly more common in patients with future asthma . These patients also had a lower mean forced expiratory volume in 1 sec (FEV1) (% of predicted) and a higher mean increase in PEF after an inhaled sympathomimetic than those remaining free from asthma . In multivariate analyses with a logistic model, 3 risk indicators proved independent predictors of future asthma: age, positive family history of allergy, and FEV1 (% of predicted).

Rev Mal Respir, 1992, 9(4), 464 - 6
{Acquired rifampicin resistance during M . kansasii infection in a patient with AIDS}; Dautzenberg B et al.; A man with AIDS and M . kansasii lung infection received rifampicin and isoniazid for 9 months, combined with ethambutol for four months . The treatment was effective with sputum culture negativation, but relapse occurred . The minimal inhibitory concentration of rifampicin for the M . kansasii strain was respectively 0.2 microgram/ml at the onset and 128 micrograms/ml after the treatment, giving evidence of acquired resistance . A new treatment was initiated but is was ineffective.

Drugs Exp Clin Res, 1992, 18(6), 233 - 7
Sub-inhibitory concentrations of brodimoprim inhibit adhesion of E . coli to human uroepithelial cells; Braga PC et al.; Bacterial adhesion to mucosal surfaces is a prerequisite for infection . Several antibiotics at sub-inhibitory concentrations (sub-MICs) have been shown to affect the adhesive ability of bacteria, usually decreasing adherence in vitro . The aim of the present study was to investigate the effect of brodimoprim, a broad-spectrum antibiotic, on E . Coli adhesiveness to uroepithelial cells . Sub-inhibitory concentrations of brodimoprim, up to 1/16 MIC, significantly reduced the percentage of adhesion of E . Coli to epithelial cells . At these concentrations, brodimoprim strongly diminished the adhesiveness of E . Coli, causing the growth of filamentous shapes lacking in pili and therefore unable to adhere to epithelial cells.

Scand J Infect Dis, 1992, 24(5), 619 - 27
Delayed antibiotic-induced lysis of Escherichia coli in vitro is correlated with enhancement of LPS release; Van Den Berg C et al.; A kinetic turbidimetric Limulus amebocyte lysate (LAL) assay was used to study the effects of gentamicin, amoxycillin and ciprofloxacin (16 x MIC) upon release of lipopolysaccharide at different stages of a growing Escherichia coli 055:B5:H culture in vitro . In this model a linear correlation was present between the logarithms of colony counts and free LAL activities . Untreated E . coli grew from log values of 4.9 +/- 0.15 (low inoculum) and 6.8 +/- 0.08 cfu/ml (high inoculum) at t = 0 to 8.9 +/- 0.05 and 9.1 +/- 0.13 cfu/ml at t = 6 h, respectively . The log values of basal free LAL activities at low and high inoculum sizes were 1.9 +/- 0.07 and 3.3 +/- 0.14 endotoxin units/ml, increasing 2100- and 69-fold, respectively during a 6-h growth . Amoxycillin-induced lysis was not significantly associated with an increase in free LAL activity . Efficacy of bacterial killing by gentamicin was high, but free LAL activity increased only 3.2- and 7.7-fold at the low and high inoculum experiments, respectively . Ciprofloxacin induced cell filamentation during the experiments . At low and high inoculum conditions exposure to ciprofloxacin induced a 43- and 68-fold increase in free LAL activities, respectively . Our data indicate that (a) LPS is released as long as E . coli remain structurally intact; (b) LPS release is enhanced when bacterial biomass increases; and (c) are taken as evidence against the concept of lysis-correlated LPS release.

Acta Orthop Belg, 1992, 58 Suppl 1, 222 - 6
The use of gentamicin-PMMA chains in the treatment of infected tibial nonunion; Klemm K et al.; Local antibiotic therapy with gentamicin-PMMA chains and external fixation permit effective simultaneous therapy of both components of infected tibial pseudarthroses: sequestering osteomyelitis and pseudarthrosis . The local concentrations of gentamicin which can be achieved by implantation of gentamicin-PMMA chains are far above the MIC of most common pathogens . This form of local antibiotic therapy is superior to any form of systemic antibiotic therapy . The gentamicin-PMMA chains serve as well as space holders for the bone graft to promote bone consolidation in the absence of infection . The results can be improved by successful management of the soft tissue damage often associated with tibial pseudarthrosis . Pedicled or free muscle graft with microvascular anastomosis is the method of choice.

Retina, 1992, 12(3 Suppl), S3 - 6
Systemic antibiotic prophylaxis in penetrating ocular injuries . An experimental study; Alfaro DV et al.; Intraocular concentrations of systemically administered gentamicin and cefazolin in eyes after a standard penetrating ocular injury were measured to determine the effect of eye injury on ocular pharmacokinetics . Twenty pigmented rabbits were divided into two groups . A standard, 8-mm wound was made at the pars plana of one eye in each animal . Group 1 consisted of 10 rabbits that were treated with cefazolin (75 mg/kg), and Group 2 consisted of 10 rabbits that were given gentamicin (2 mg/kg) . Fellow eyes, which sustained no trauma, served as control eyes . All groups received intravenous injections every 8 hours for 72 hours, beginning immediately after repair of the wound . After 72 hours, samples were obtained from the anterior chamber, vitreous cavity, and serum . Standardized bioassays for detection of gentamicin or cefazolin were performed . Significant concentrations of intravitreal cefazolin (9.6 micrograms/ml) and gentamicin (0.60 micrograms/ml) were found in the traumatized eyes in comparison to control eyes (P = 0.0001; P = 0.006) . Cefazolin exhibited excellent penetration, achieving concentrations well above minimum inhibitory concentration values for most organisms . Gentamicin levels, however, were well below acceptable therapeutic levels . This study suggests that systemically administered cefazolin can achieve significant intravitreal penetration at minimum inhibitory concentrations after penetrating injury.

Chemotherapy, 1992, 38(3), 150 - 4
Diffusion of tosufloxacin into prostatic tissue; Uchibayashi T et al.; The diffusion of tosufloxacin (TFLX) into the prostatic tissue was studied in 25 patients with benign prostatic hypertrophy . TFLX concentrations in the serum and prostatic tissue were measured at scheduled intervals after oral administration of 450 mg of TFLX on the day before surgery, followed by administration of 150 mg of TFLX immediately before surgery . The mean TFLX levels in prostatic tissue (and tissue/serum levels) at 2, 4 and 6 h were 0.35 +/- 0.16 microgram/g (0.93 +/- 0.36) in 7 patients, 0.58 +/- 0.92 microgram/g (1.10 +/- 0.45) in 10 patients and 0.22 +/- 0.09 microgram/g (0.95 +/- 0.45) in 8 patients . The TFLX levels in prostatic tissue exceeded the minimum inhibitory concentration for several pathogenic bacteria detected in the infected prostatic fluid . Therefore, TFLX shows promise as a useful drug in the treatment of bacterial prostatitis and infections developing after prostatic surgery.

Clin Exp Pharmacol Physiol, 1992 Jan, 19(1), 25 - 30
Pharmacological evaluation of two novel analogues of mianserin: 2-N-carboxamidinonormianserin (FCC5) and 2-N-carboxamidonormianserin (FCC13); Leitch IM et al.; 1 . The pharmacological properties have been examined of FCC5 (2-N-carboxamidinonormianserin) and FCC13 (2-N-carboxamidonormianserin), two novel analogues of mianserin . 2 . FCC5 or FCC13 (100 micrograms/kg, i.v.) caused long-lasting (greater than 1 h) abolition of 5-hydroxytryptamine (5-HT) and histamine-induced bronchoconstriction in the anaesthetized guinea-pig . Both analogues had no effect (up to 1 mg/kg, i.v.) on bronchoconstriction caused by acetylcholine (25-50 micrograms/kg, i.v.) . 3 . The pressor effects of 5-HT in pithed rats were significantly attenuated by FCC5 (0.1 mg/kg, i.v.) or FCC13 (0.5 mg/kg, i.v.) . 4 . Oedema in the rat hind paw caused by intraplantar 5-HT was inhibited by FCC5 (ID50 0.76 mg/kg, i.p.; 2.7 mg/kg, p.o.) or FCC13 (ID50 0.65 mg/kg, i.p.; 5.8 mg/kg, p.o.) . 5 . In the central nervous system (CNS), FCC13 caused antagonism of 5-HT activity . It inhibited: (i) L-5-hydroxytryptophan (L-5-HTP)-induced head twitches in mice (ID50 1.85 mg/kg, i.p.), (ii) fenfluramine-induced facilitation of flexor reflex activity (FRA) in spinalized decerebrate rats (SDR) (IC50 0.57 mg/kg, i.p.) . 6 . FCC5 (less than or equal to 30 mg/kg, i.p . and less than or equal to 3 mg/kg, i.p., respectively) had no effect in either test . In contrast to mianserin, it also had no overt central actions as (less than or equal to 30 mg/kg, i.p.) had no effect on: (i) morphine-induced catalepsy (MIC) or (ii) clonidine-induced facilitation of FRA in SDR . However, high doses of FCC13 inhibited MIC (ID50 20 mg/kg, i.p.), but had no effect on (ii) (less than or equal to 10 mg/kg, i.p.) . 7 . Thus, FCC5 and FCC13 are potent, orally active H1 and 5-HT receptor antagonists . However, in contrast to FCC13 and mianserin, FCC5 did not cause CNS-mediated effects.

Rev Latinoam Microbiol, 1992 Jan-Mar, 34(1), 1 - 6
{Minimal inhibitory and bactericidal concentrations of some antiseptics and disinfectants against strains of hospital origin}; Fernandez-Crehuet Navajas R et al.; The MIC in solid media and the B.M.C . by the dilution-neutralization test using sterile water, was determined using 10 antiseptics and disinfectants with 70 strains of 10 species of Gram negative bacteria more frequently causing nosocomial infections in Ciudad Sanitaria Reina Sofia, Cordoba, in Spain . Relationship between the two tests was searched with no positive results . The more effective antiseptics were silver nitrate and chlorhexidine, the less active was phenol . Activity of some antiseptics was similar at 30 or 60 minutes of contact with the microorganisms.

Antimicrob Agents Chemother, 1992 Jan, 36(1), 100 - 7
In vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity; Andries K et al.; Pirodavir (R 77975) is the prototype of a novel class of broad-spectrum antipicornavirus compounds . Although its predecessor, R 61837, a substituted phenyl-pyridazinamine, was effective in inhibiting 80% of 100 serotypes tested (EC80) at concentrations above 32 micrograms/ml, pirodavir inhibits the same percentage of viruses at 0.064 micrograms/ml . Whereas R 61837 was active almost exclusively against rhinovirus serotypes of antiviral group B, pirodavir is broad spectrum in that it is highly active against both group A and group B rhinovirus serotypes . Pirodavir is also effective in inhibiting 16 enteroviruses, with an EC80 of 1.3 micrograms/ml . Susceptible rhinovirus serotypes were rendered noninfectious by direct contact with the antiviral compound . Their infectivity was not restored by dilution of virus-drug complexes, but was regained by organic solvent extraction of the compound for most serotypes . Neutralized viruses became stabilized to acid and heat, strongly suggesting a direct interaction of the compounds with viral capsid proteins . Mutants resistant to R 61837 (up to 85 times the MIC) were shown to bear some cross-resistance (up to 23 times the MIC) to the new compound, indicating that pirodavir also binds into the hydrophobic pocket beneath the canyon floor of rhinoviruses . Pirodavir acts at an early stage of the viral replication cycle (up to 40 min after infection) and reduces the yield of selected rhinoviruses 1,000- to 100,000-fold in a single round of replication . The mode of action appears to be serotype specific, since pirodavir was able to inhibit the adsorption of human rhinovirus 9 but not that of human rhinovirus 1A . Pirodavir is a novel capsid-binding antipicornavirus agent with potent in vitro activity against both group A and group B rhinovirus serotypes.

J Periodontol, 1992 Jan, 63(1), 52 - 7
Microbiological and clinical results of metronidazole plus amoxicillin therapy in Actinobacillus actinomycetemcomitans-associated periodontitis; van Winkelhoff AJ et al.; We report on the microbiological and clinical effects of mechanical debridement in combination with metronidazole plus amoxicillin therapy in 118 patients with Actinobacillus actinomycetemcomitans-associated periodontitis . Patients were categorized into 3 groups: 28 had localized periodontitis; 50 had generalized periodontitis, and 40 had refractory periodontitis . After initial treatment and metronidazole plus amoxicillin therapy 114 of 118 (96.6%) patients had no detectable A . actinomycetemcomitans . Significant reduction in pocket probing depth and gain of clinical attachment were achieved in almost all patients . Four patients were still positive for A . actinomycetemcomitans after therapy . Metronidazole resistance (MIC greater than 25 micrograms/ml) was observed in 2 of 4 strains from these patients . Patients still positive for A . actinomycetemcomitans or Porphyromonas gingivalis showed a significant higher bleeding tendency after therapy . It was concluded that mechanical periodontal treatment in combination with the metronidazole plus amoxicillin therapy is effective for subgingival suppression of A . actinomycetemcomitans in patients with severe periodontitis.

Rinsho Byori, 1992 Jan, 40(1), 73 - 80
{Evaluation of proposed criteria of disk susceptibility testing for tosufloxacin and lomefloxacin in NCCLS guidelines and WHO standards}; Aihara M et al.; Disk diffusion zone diameter breakpoint criteria for Tosufloxacin and Lomefloxacin were tentatively established by correlating MICs with 1-, 5- and 10 micrograms of Tosufloxacin disk inhibitory zone diameters and with 10 micrograms of Lomefloxacin disk of those to 418 clinical isolates representing 32 species . We recommend 5 micrograms disks for Tosufloxacin with the following breakpoints: Susceptible (MIC, less than or equal to 0.5 microgram/ml), greater than or equal to 22 mm; intermediate, 17 to 21 mm; and resistant (MIC, greater than or equal to 2.0 micrograms/ml), less than or equal to 16 mm . We recommend 10 micrograms disks for Lomefloxacin with the following breakpoints: Susceptible (MIC, less than or equal to 2.0 micrograms/ml), greater than or equal to 21 mm; intermediate, 16 to 20 mm; and resistant (MIC, greater than or equal to 8.0 micrograms/ml), less than or equal to 15 mm . Using these criteria for Tosufloxacin and Lomefloxacin, the occurrence rate of major errors in judging susceptibility and resistance was 0.48%.

J Antimicrob Chemother, 1992 Jan, 29(1), 27 - 33
Influence of outer membrane mutations on susceptibility of Escherichia coli to the dibasic macrolide azithromycin; Farmer S et al.; Azithromycin differs chemically from erythromycin by having an extra positive charge created by the presence of a methyl-substituted nitrogen in the 15-membered macrolide ring . This results in substantially increased potency against Gram-negative bacteria . Therefore, the possibility was considered that azithromycin was taken across the outer membrane of Escherichia coli by the self-promoted uptake route, which is utilized by other cationic antibiotics including polymyxins and aminoglycosides . Azithromycin, like polymyxin B and gentamicin, demonstrated equal activity against porin-sufficient and porin-deficient E . coli strains but its MIC was increased eight-fold by magnesium supplementation . Nevertheless, an outer membrane-altered mutant DC2 was eight-fold more susceptible than its parent strain UB1005 to azithromycin, indicating that the outer membrane was a permeability barrier to this macrolide . A mutant SC9252 which had an alteration in the self-promoted uptake of polymyxin and gentamicin, was more resistant to azithromycin, polymyxin and gentamicin compared to its parent SC9251 . Further azithromycin, like polymyxin B and gentamicin, was capable of weakly permeabilizing cells to the hydrophobic fluorophor 1-N-phenyl-naphthylamine, a process antagonized by Mg2+ . The monobasic macrolide erythromycin on the other hand was less affected by the SC9252 mutation, less effectively antagonized by Mg2+, and was a far less effective permeabilizer than dibasic azithromycin . These data are consistent with the hypothesis that the improved efficacy of azithromycin compared to erythromycin against E . coli reflects its better access to the self-promoted uptake pathway due to its additional positive charge.

Am Rev Respir Dis, 1992 Jan, 145(1), 212 - 4
Activity in vitro of rifabutin, FCE 22807, rifapentine, and rifampin against Mycobacterium microti and M . tuberculosis and their penetration into mouse peritoneal macrophages; Dhillon J et al.; The activities of the rifamycins, rifabutin, FCE 22807, rifapentine, and rifampin, were studied within unstimulated peritoneal macrophages infected with Mycobacterium microti and in cultures of M . microti and M . tuberculosis in 7H-9 medium without Tween 80 . In macrophage cultures, serial rifamycin concentrations were added after a 2.5 h phagocytosis period, and viable counts were done after incubation for 5 to 6 days . To ensure comparability with the daily drug replacements in the macrophage experiments, the period of exposure to serial rifamycin concentrations in 7H-9 medium was kept to only 3 days . The MICs of M . microti and M . tuberculosis were similar . The MICs of rifabutin and FCE 22807 were 2.5 times lower and that of rifapentine 1.7 times lower than the MIC of rifampin . None of the rifamycins were concentrated in macrophages, the MICs being higher in the macrophages than in vitro by a factor of 2-fold for rifabutin, 6.7-fold for rifampin, 20-fold for FCE 22807, and 26-fold for rifapentine.

Diagn Microbiol Infect Dis, 1992 Jan, 15(1), 21 - 34
In vitro susceptibility and synergy studies of Aspergillus species to conventional and new agents; Denning DW et al.; In vitro susceptibility data using a macrodilution broth method on greater than 100 isolates of Aspergillus spp . are presented . For amphotericin B (Amp B) (n = 105), 67% had minimum inhibitory concentrations (MICs) less than or equal to 2 micrograms/ml, and 90% had MICs less than or equal to 4 micrograms/ml; for 5-fluorocytosine {flucytosine (5FC) (n = 60), 35% had MICs less than or equal to 12.5 micrograms/ml; for miconazole (MCL) (n = 18), 39% had MICs less than or equal to 5 micrograms/ml; for ketoconazole (KTZ) four (13%) of 32 isolates had an MIC less than or equal to 3.1 micrograms/ml; for itraconazole (ITZ) (n = 88), 97% had MICs less than or equal to 6.3 micrograms/ml; and for saperconazole (SAP) (n = 20), 90% had MICs less than or equal to 3.1 micrograms/ml . Of Amp B minimum fungicidal concentrations (MFCs) (n = 25), 76% were less than or equal to 4 micrograms/ml; 5% of ketoconazole (n = 20) and no flucytosine (n = 38) MFCs were less than or equal to 25 micrograms/ml; for itraconazole (n = 60), 70% had MFCs less than or equal to 6.3 micrograms/ml, and for saperconazole (n = 20), 75% had MFCs less than or equal to 3.1 micrograms/ml . Drug interaction studies were also performed . For Amp B and rifampin 36 (92%) of 39 showed synergy, for Amp B and flucytosine six (23%) of 26 showed synergy and another six (23%) showed antagonism; 13 (50%) were indifferent . In five Amp B-itraconazole combination studies, synergy and indifference were seen in two each and an additive effect was observed in one . The published literature on in vitro testing methodology and results for Aspergillus spp . is also reviewed, and recommendations for the clinical use of in vitro susceptibility testing are made.

Drugs Exp Clin Res, 1992, 18(11-12), 443 - 6
In vitro and in vivo antidermatophytic activity of saperconazole, a new fluorinated triazole; Fu KP et al.; The in vitro activity of saperconazole against selected isolates of dermatophytes and its in vivo efficacy in a guinea pig dermatophytic infection model using Trichophyton mentagrophytes were evaluated . Susceptibility testing was determined with an agar dilution method in three media: yeast nitrogen base agar (YNBA), brain heart infusion agar (BHIA) and Sabouraud dextrose agar (SDA) . An inoculum of 1 x 10(5) CFU of T . mentagrophytes spores was placed onto the surface of these agars . Incubation was at 32 degrees C for 72 h . The MIC of saperconazole against all isolates was less than 1 microgram/ml, whereas the MIC ranged from 0.1 to > 128 micrograms/ml for fluconazole . The MIC range of saperconazole against Trichophyton species was < or = 0.002 to 0.25 micrograms/ml; against Microsporum species it was < 0.001 to 0.1 microgram/ml; and against Epidemophyton species was < or = 0.002 to 0.25 micrograms/ml . These data showed that saperconazole was the most active compound tested against these selected dermatophytes . The activities of saperconazole against T . mentagrophytes, T . rubrum and M . canis were not affected by the medium . The MICs against these organisms were < or = 0.008 micrograms/ml in SDA, YNBA or BHIA . There were 2- to 4-fold decreases in activity for fluconazole at the same conditions . In vivo, topical treatment with saperconazole at concentrations of 0.125% and 0.25% resulted in 50% and 75% microbiological cure rates, respectively, in the guinea pig topically infected with T . mentagrophytes.

Antimicrob Agents Chemother, 1991 Dec, 35(12), 2645 - 8
Effects of quinolones on nucleoid segregation in Escherichia coli; Georgopapadakou NH et al.; The effects of quinolone antibiotics on nucleoid segregation in growing Escherichia coli were examined by using fleroxacin (Ro 23-6240, AM 833) as a prototype compound . At levels that were close to its MIC and induced growth arrest and filamentation, fleroxacin caused large nucleoids to appear in midcell, suggesting inhibition of nucleoid segregation . With increasing fleroxacin concentrations, nucleoids became progressively smaller, suggesting inhibition of DNA replication . Removal of fleroxacin restored normal cell and nucleoid morphology in filaments with large nucleoids but not in filaments with small nucleoids . The results are consistent with inhibition of chromosome decatenation at low quinolone concentrations (bacteriostatic effect) and DNA supercoiling at high concentrations (bactericidal effect).

Eur J Clin Microbiol Infect Dis, 1991 Dec, 10(12), 1068 - 70
Analysis of beta-lactamase production in ampicillin-resistant Escherichia coli isolated from blood cultures 1983-1989; Arstila T et al.; From 1983 to 1989, 520 Escherichia coli blood culture pathogens were isolated from two hospitals in Turku, Finland . Ampicillin resistance (MIC greater than or equal to 16 micrograms/ml) of these isolates increased from 33% in 1983 to 66% in 1987, but decreased to 38-49% in 1988-1989 . Occurrence of TEM-1 beta-lactamase producing isolates increased only slightly from 14% in 1983 to 25% in 1989 among all Escherichia coli strains studied . Strains with ampicillin MIC values of 16 micrograms/ml and 32 micrograms/ml were mostly responsible for the increase in resistance . Among these isolates, TEM-1 or any other of the well known plasmid-mediated beta-lactamases were not found by hybridization or isoelectric focusing.

Jpn J Antibiot, 1991 Dec, 44(12), 1397 - 406
{A study on the disc sensitivity test for cefpirome}; Kanazawa Y et al.; Susceptibilities of 232 strains of 40 bacterial groups to cefpirome (CPR) were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zones by the single-disc method under the experimental conditions established by Kanazawa . The experiments demonstrated a significant correlation between MIC by the dilution method and diameter of inhibition zone in each of the conventional assay of over-night (about 16 hours) incubation, the delayed assay (about 24 hours incubation), and the rapid assay (about 3-4 or 5-6 hours incubation), thus confirming the applicability of the single-disc assay for CPR . Analysis of the data obtained by using CPR disc containing 30 micrograms revealed the primary regression equation to be: D (diameter, mm) = 26.7-9.2 log MIC (micrograms/ml) in the conventional assay, D = 33.8-12.7 log MIC (micrograms/ml) in the delayed assay, D = 21.2-6.7 log MIC (micrograms/ml) in 5-6 hours rapid assay, and D = 14.8-4.1 log MIC (micrograms/ml) in 3-4 hours rapid assay . The range of variations in MICs estimated from the diameter of inhibition zone by the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution test, as a reference for the experimental errors which may be involved in the estimation of MIC of CPR by the single-disc assay.

Zentralbl Bakteriol, 1991 Dec, 276(1), 63 - 7
Susceptibility to aminoglycosides of 63 strains of Stomatococcus mucilaginosus isolated from sputum; Chomarat M et al.; The MIC of 63 Stomatococcus mucilaginosus for 7 aminoglycosides was determined . Most of the strains were resistant to these antibiotics except to streptomycin . A natural resistance due to impermeability may be involved . One single strain was resistant to all these aminoglycosides where the concentration level of streptomycin was greater than 1000 mg/l . A chromosomal mutation is probably involved.

Zentralbl Bakteriol, 1991 Dec, 276(1), 54 - 62
In vitro activity and cross resistance studies with cefpodoxime; Grimm H; On the basis of MIC determinations and appropriate MIC breakpoints, 370 pathogens showed complete cross resistance between cefpodoxime and cefuroxime axetil, cefotiam hexetil, cefixime and cefotaxime in 69.7%, 80.3%, 92.2% and 87% of the strains, respectively . Cefpodoxime was superior to cefuroxime axetil in 28.7%, to cefotiam hexetil in 17.6%, to cefixime in 7% of strains and to cefotaxime not at all . On the other hand, we found cefpodoxime to be inferior to the cephalosporins mentioned in 1.6%, 2.1%, 0.8% and 13%, respectively.

J Clin Microbiol, 1991 Dec, 29(12), 2890 - 2
Disk diffusion susceptibility test interpretive criteria for GR69153, a new catechol-substituted cephalosporin; Jones RN et al.; GR69153 disk diffusion tests with 10- and 30-micrograms disks were evaluated against 383 rapidly growing aerobic pathogens . Very high absolute agreement (96.1 to 98.1%) was observed between the MICs and disk zone diameters, and no false-susceptible results were encountered with the proposed criteria . The 30-micrograms GR69153 disk with a susceptible-zone diameter of greater than or equal to 17 mm (MIC correlate, less than or equal to 8 micrograms/ml) and a resistant-zone diameter of less than or equal to 13 mm (MIC correlate, greater than 16 micrograms/ml) is recommended . GR69153 had a spectrum of activity slightly wider than that of ceftazidime against the species tested.

Dig Dis Sci, 1991 Dec, 36(12), 1782 - 6
Ascitic fluid and serum cefotaxime and desacetyl cefotaxime levels in patients treated for bacterial peritonitis; Runyon BA et al.; Forty-one episodes of ascitic fluid infection were treated with cefotaxime 2 g intravenously every 8 hr, and ascitic fluid and serum were sampled 6, 12, 24, 48, and 96 hr after the first dose of antibiotic . Concentrations of cefotaxime and desacetyl cefotaxime were measured in ascitic fluid and serum by high-performance liquid chromatography . There was essentially 100% penetration of cefotaxime and metabolite from serum into ascitic fluid at all time points . Ascitic fluid was sterilized in 94% of episodes after the first dose of antibiotic . The ascitic fluid concentration of cefotaxime 6 hr after the first dose of antibiotic was greater than 20 times the minimal inhibitory concentration of the drug for 90% of the isolated flora . This rapid ascitic fluid penetration of cefotaxime in high concentration explains the rapid sterilization of ascitic fluid by the drug in the setting of bacterial peritonitis and obviates the need to give a loading dose or intraperitoneal injection.

AIDS, 1991 Dec, 5(12), 1447 - 52
Inhibition of HIV-1 infection by alkylureas; Goldstein H et al.; The risk of infection by HIV-1 through transfusion of contaminated blood products has been markedly decreased but not eliminated by serological screening of donors . Methods are required to further minimize or eliminate the risk of infection of blood product recipients . We therefore examined the capacity of alkylureas to inhibit infectivity of HIV-1 . Incubation of free HIV-1 virions with alkylureas suppressed their infectivity, and the minimal inhibitory concentration of the alkylureas was related to the length of the alkyl chain . Butylurea, the most potent inhibitor of HIV-1, inhibited the infectivity of 10(5) median tissue culture infective dose (TCID)50 of HIV-1, chronically HIV-1-infected H9 cells and mononuclear cells from two HIV-1-infected patients . Size fractionation of HIV-1 following incubation with butylurea indicated that the structure of the virus was disrupted by butylurea . This study demonstrates that butylurea, at a concentration that has been shown not to affect red blood cell function, can inhibit infectivity of extracellular and intracellular HIV-1 . Since the HIV-1 inhibitory capacity of the alkylureas increases with the length of the alkyl side chain, it is likely that hydrophobic interactions between the alkylureas and HIV-1 are responsible for the observed effect.

Antimicrob Agents Chemother, 1991 Dec, 35(12), 2473 - 80
Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages; Rastogi N et al.; The MICs and MBCs of the new difluorinated quinolone drug sparfloxacin against type strains belonging to 21 species of mycobacteria were screened . The MICs and MBCs were within the range of 0.1 to 2.0 and 0.1 to 4.0 micrograms/ml, respectively (with an MBC/MIC ratio of 1 to 2), and against 18 of the 21 species tested, the drug showed significant bactericidal activity (at least 99% killing or more of the initial inoculum added) at concentrations well within the reported peak concentrations in serum (Cmax) in humans . MICs of sparfloxacin for 7 of 10 Mycobacterium avium complex strains were below the Cmax, with MBC/MIC ratios within the range of 2 to 4 . Enhancement of its activity by ethambutol, rifampin, amikacin, and clarithromycin (which were used at sublethal concentrations) assessed by using BACTEC radiometry revealed that its activity was further enhanced in 2 of 10 strains by rifampin and in 7 of 10 strains by ethambutol . The bactericidal effects of various drugs used alone as well as two-drug combinations used at Cmax levels were also screened against four strains of M . avium complex growing intracellularly in two different macrophage systems, namely, mouse bone marrow-derived macrophages and peripheral blood monocyte-derived human macrophages . Our results showed a satisfactory correlation between the extracellular and intracellular drug activity data.

J Immunol Methods, 1991 Nov 22, 144(2), 203 - 13
Assessment of the inhibitory effect of immunosuppressive agents on rat T cell interferon-gamma production using an ELISPOT assay; van der Meide PH et al.; The immunospot (ELISPOT) assay has proven to be an efficient and sensitive method for the enumeration of single cells secreting antibodies or cytokines . Here we show that the generation of interferon-gamma producing cells (IFN-gamma pc) in rat spleen cell cultures stimulated with concanavalin A (ConA) is dose-dependently inhibited by a wide variety of immunosuppressants such as cyclosporin A, FK506, hydrocortisone, dexamethasone, azathioprine and ART-18, a monoclonal antibody (mAb) with established immunosuppressive activity in organ transplantation and autoimmunity . The minimal inhibitory concentration (m.i.c.) correlated well with the reported m.i.c . in the mixed lymphocyte reaction (MLR) assay and the therapeutically effective plasma levels in vivo . Our data indicate that the IFN-gamma-specific immunospot assay is a powerful tool for determining the potency of immunosuppressive agents in vitro and provides a simple and accurate method for screening large numbers of agents with suspected immunosuppressive properties . The assay may additionally prove to be of value for determining the therapeutically effective doses of immunosuppressants that should be administered in vivo.

J Infect Dis, 1991 Nov, 164(5), 1003 - 6
Liposomal hamycin: reduced toxicity and improved antifungal efficacy in vitro and in vivo; Mehta RT et al.; Hamycin has been used to treat a variety of yeast and other fungal infections by oral, topical, and intraperitoneal routes . However, its parenteral use has been reported to be associated with high toxicity . Multilamellar liposomes composed of dimyristoyl phosphatidyl choline, dimyristoyl phosphatidyl glycerol, and various amounts of cholesterol were used as drug carriers for hamycin . The antifungal activity of hamycin was maintained after liposome encapsulation (MIC range, 0.6-1.2 micrograms/ml), and toxicity was reduced in vitro and in vivo as the concentration of cholesterol was increased to an appropriate ratio . Mice were treated with various doses of free or liposomal hamycin 2 days after infection . Although free drug did not significantly improve survival, liposomal hamycin at an equivalent dose (0.6 mg/kg) increased the survival from 18 to 38 days . Higher doses (1.2 and 1.8 mg/kg) showed further improvement in survival and reduction in numbers of colony-forming units in the kidneys . Liposome encapsulation resulted in improved therapeutic index of hamycin.

Antibiot Khimioter, 1991 Nov, 36(11), 30 - 4
{Myelotoxicity of epirubicin}; Gol'dberg ED et al.; Epirubicin (pharmorubicin, India), an antitumor antibiotic of the anthracycline group, was studied in regard to its effect on peripheral blood, bone marrow and lymphoid organs (the thymus and spleen) of CBA mice after its intraperitoneal administration in a single dose equal to the MIC (7.8 mg/kg) and in a course dose (1/5 of the MIC 5 times a day) . The cytogenetic impairments induced by the cytostatic were estimated on metaphase plates with the bone marrow specimens and by counting the peripheral blood erythrocytes with micronuclei (the micronuclear test) . It was shown that epirubicin induced cytogenetic disturbances in the hemopoietic cells within the first 72 hours . The antibiotic had a marked reversible effect on the erythroid population and lymphoid tissues and a moderate toxic action on the granulocyte population . The antibiotic did not affect thrombocytopoiesis . The single administrations had a more pronounced and prolonged myelotoxic and lymphotropic effect.

Kansenshogaku Zasshi, 1991 Nov, 65(11), 1446 - 50
{Studies on uptake of macrolide antibiotics by Chlamydia host cell}; Kosugi-Shiritani Y et al.; Minimum inhibitory concentration (MIC) of Macrolide antibiotic (ML) against C . trachomatis was found to greatly vary with the cell culture system used for the assay . We then investigated the ability of various cell cultures to uptake MLs in the relation to MIC determination . Penetration of the 14C-labeled MLs, Erythromycin, Jasamycin and Rokitamycin into cells was quantitatively studied by measuring the radioactivity incorporated into McCoy, HeLa229W and HeLa229F cells . It was found that HeLa229W cell showed the lowest MIC for the drugs, followed by HeLa229F cell and then by McCoy cell . Reversely, McCoy cell showed the lowest intracellular concentration of an ML, followed by HeLa229F cell and then by HeLa229W cell . These results indicate that MIC of an ML significantly varies depending on the ability of the test cell to uptake the drug.

J Antimicrob Chemother, 1991 Nov, 28(5), 627 - 37
Isomeric DNA ladder formation of a plasmid encoding tobramycin resistance from Escherichia coli; Singh M et al.; During a 20-month survey of resistance to three aminoglycosides (gentamicin, tobramycin, and amikacin) in Escherichia coli at a university hospital, six tobramycin-, kanamycin-resistant isolates containing a 50 kilobase conjugative R-plasmid which encoded an aminoglycoside phosphotransferase (APH-(3')) were isolated . The APH-(3') conferred resistance to kanamycin (MIC = 100 mg/L) but not to tobramycin (MIC = 20 mg/L) . In both the original isolates and transconjugants the six R-plasmids demonstrated an isomeric ladder in the range of 50-112 kb, which was enhanced by exposure of the bacterial cultures to tobramycin . pJFJ2522 is the prototype for this group of plasmids . Bacterial DNA gyrase reversed the isomeric DNA ladder in pJFJ25222 by increasing the supercoiling of the plasmid DNA . Regardless of the level of supercoiling, the plasmids produced indistinguishable restriction endonuclease fragment patterns . The clinical isolates containing these plasmids demonstrated different restriction fragment length polymorphism (RFLP) of their EcoRI digested genomic DNA using E . coli rRNA as a probe . Ladder formation was plasmid specific since other tobramycin R-plasmids did not form a ladder, but it was not host specific . pJFJ25222 formed a ladder in a recA- host and displayed the same restriction pattern in a recA- as in a recA+ environment . In conclusion, pJFJ2522 contains a new tobramycin resistance gene whose mechanism of resistance is not known and whose product probably influences the isomerization of the plasmid.

Clin Chem, 1991 Oct, 37(10 Pt 1), 1777 - 80
Comparison of thyroperoxidase and microsomal antibody assays in sera from patients with Graves disease; Massart C et al.; Anti-microsomal (anti-Mic Ab) and anti-thyroperoxidase antibody activities (anti-TPO Ab) were compared by using commercially available radioassay kits . Sera were collected from 52 patients with Graves disease before and after administration of carbimazole (1-methyl-2-thio-3-carbethoxyimidazole) . The two antibody concentrations were significantly correlated, both before treatment (r = 0.835, P less than 0.001, n = 52) and at the end of treatment (r = 0.584, P less than 0.001, n = 52) . Twenty-nine (Group I) of the 52 patients were in remission for two years after drug withdrawal, whereas 23 (Group II) relapsed . Within each group, the anti-Mic and anti-TPO Ab concentrations were significantly correlated (Group I: r = 0.781, P less than 0.0001; Group II: r = 0.866, P less than 0.0001) . Relapse vs nonrelapse was linked to the antibody positivities measured before treatment: 91% vs 65% (chi 2 = 4.75, P less than 0.02) for anti-Mic Ab and 87% vs 62% (chi 2 = 4.05, P less than 0.02) for anti-TPO Ab . We conclude that assays of anti-Mic and anti-TPO Ab are equally reliable analytically and equally informative clinically . Because of its rapid implementation, the anti-TPO assay may advantageously replace anti-Mic Ab assay, especially for forming a prognosis of Graves disease.

J Chemother, 1991 Oct, 3(5), 295 - 304
Antifungal activity of two benzofuran-imidazoles in different experimental conditions; Bellotti MG et al.; A number of experiments was performed in order to analyze the in vitro activity of two new benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66 . Studies included the determination of minimum inhibitory concentrations (MICs) on three culture media, at different pH values and at different inoculum sizes . Furthermore, the killing activity and induced resistance were determined . In all the experiments econazole, clotrimazole and bifonazole were the reference compounds . The best MIC values of the two new imidazoles were observed on modified Sabouraud's medium, at neutral pH and an inoculum size of 10(4) cells/ml . The two substances showed killing activity and no resistance was observed . On the whole, the more favorable results were obtained with the compound IM/B/4-66.

Antibiot Khimioter, 1991 Oct, 36(10), 5 - 8
{Comparative evaluation of various bacterial growth inhibitors as selective agents for isolation of soil Actinomyces}; Terekhova LP et al.; Tobramycin and dioxidine sensitivity of 57 strains belonging to 14 actinomycetes genera was studied . The cultures of Streptomyces were much more sensitive to tobramycin than the cultures of rare genera . The majority of the Streptomyces cultures showed a high resistance to dioxidine (MIC greater than or equal to 50 micrograms/ml) . At the same time the majority of the cultures of rare genera were inhibited by low concentrations of dioxidine (no more than 50 micrograms/ml) . For isolation of actinomycetes from soil samples, tobramycin, dioxidine, ceftriaxone and novobiocin were used . Tobramycin added in a concentration of 10 micrograms/ml to the Gauze agar organic medium No . 2 promoted a 2-fold increase in detection of actinomycetes of the rare genera as compared to the control . It was especially favourable for detection of cultures belonging to Micromonospora, Amycolatopsis, Streptosporangium and Nocardiopsis . Dioxidine in concentrations of 10 and 50 micrograms/ml inhibited the growth of the cultures belonging to rare genera . Ceftriaxone in the same concentrations inhibited the growth of the cultures of both Streptomyces and the rare genera . Novobiocin favoured detection of the cultures belonging to Amicolatopsis and Micromonospora . Therefore, among the tested compounds tobramycin and novobiocin appeared to be the most useful selective agents for isolation of actinomycetes of rare genera.

Antibiot Khimioter, 1991 Oct, 36(10), 42 - 4
{Pharmacokinetics of cefotaxime and desacetylcefotaxime in the blood serum and bronchial secretion in patients with chronic bronchitis after administration of a single 24-hour dose}; Kamnev IuV et al.; Concentrations of cefotaxime and its major active metabolite, desacetylcefotaxime, were determined in the serum and bronchial secretion of patients with chronic bronchitis aggravated after intramuscular injection of cefotaxime in a dose of 4 g once a day . Characteristic patterns of cefotaxime metabolism and high peak concentrations of desacetylcefotaxime in the serum (67.6 +/- 17.2 micrograms/ml) defined the prolonged retention of the metabolite both in the blood and bronchial secretion . The metabolite concentrations in more than half of the patients maintained within 2 micrograms/ml in the bronchial secretion by the 12th hour after the injection and in the blood serum by the 24th hour . Therefore, 4 g cefotaxime administered intramuscularly once a day provided the blood concentrations of the metabolite comparable with the MIC for the majority of the pathogens causing nosocomial infections of the respiratory tract practically within the whole period of the daily dosage . In the bronchial secretion such concentrations were attained within half of the period of the daily dosage.

DICP, 1991 Oct, 25(10), 1050 - 7
Mathematical examination of dual individualization principles (I): Relationships between AUC above MIC and area under the inhibitory curve for cefmenoxime, ciprofloxacin, and tobramycin; Schentag JJ et al.; Traditional antibiotic dosage adjustments target predetermined serum concentrations, whereas a host of in vitro studies and recent clinical trials establish that bacteria vary in their susceptibility . Dual individualization, which considers the variance in both antibiotic pharmacokinetics and bacterial susceptibility, has been employed to describe different rates of bacterial eradication in relation to varying serum concentrations . In patients with nosocomial pneumonia, one of the model compounds studied was cefmenoxime, where a target six-hour area under the serum concentration-time curve (AUC) of 140 micrograms.h/mL above minimum inhibitory concentration (MIC) was previously associated with bacterial eradication in an average of four days . The target AUC value of 140 micrograms.h/mL above MIC is unique to cefmenoxime . Ideally, there should be a dual individualized target useful to adjust the dose of any antibiotic . Computer simulations performed to evaluate this hypothesis suggested that each antibiotic had a unique value for target AUC above MIC . These simulations indicated that an optimal AUC above MIC was about 80 percent of the total AUC above the MIC . Predictable rates of bacterial eradication would presumably result from maintaining these relationships across the range of bacterial susceptibility and the range of serum concentration profiles . Each antibiotic has a unique and different 24-hour AUC over MIC value associated with bacterial eradication in 4 days . For cefmenoxime, the target was 540 area units over MIC per 24 hours, tobramycin with 34 area units, and ciprofloxacin with 23 area units per 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Arzneimittelforschung, 1991 Oct, 41(10), 1098 - 100
Pharmacological and microbiological evaluations of potential new long-acting local anaesthetics; al-Saadi D et al.; The results of the preliminary pharmacological and microbiological evaluations of certain new derivatives of dialkylaminoethyl-phenyl-ether hydrochloride, as potential long-acting local anaesthetics, are reported . The guinea pig intradermal wheal test was used for determining the activity and duration of local anaesthesia (WT) . These were assayed at concentrations of 0.5% w/v . Lidocaine hydrochloride, 1.0% w/v, was employed as the standard and normal saline, 0.9% w/v, as the control . The compounds showed outstanding activity profiles and duration of action with no apparent signs of both local and systemic side effects . In addition, the results of inhibition of the ciliated protozoan Tetrahymena pyriformis mobility by the aforementioned compounds are presented . A general relationship between the minimum inhibitory concentration (MIC) of these compounds to inhibit mobility of the whole T . pyriformis cells and the duration of anaesthesia was observed . Moreover, derivatives with tertiary or secondary butyl substituents in the benzene ring, irrespective of position or number, were superior to others and showed prolonged duration of anaesthesia and lower MIC . The dependence of both WT and MIC on partition coefficient (log P) of these compounds indicates that in both biological systems the anaesthetics interact strongly with hydrophobic structures of the T . pyriformis cells membrane resulting in fluidisation and loss of ciliary function.

Med Sci Law, 1991 Oct, 31(4), 294 - 8
GC-MS identification of MIC trimer: a constituent of tank residue in preserved autopsy blood of Bhopal gas victims; Chandra H et al.; Based on the external and internal findings of Bhopal gas disaster victims, it was apparent that the gases and particulate matter came out as an aerosol . This was possibly the pyrolysed, reformulated, reconjugated suspension of constituents of the tank E-610 of Union Carbide India Limited, Bhopal, while it was claimed to be methyl isocyanate (MIC) only . It was postulated by the manufacturer of MIC, that the material inhaled by the victims of the Bhopal gas disaster does not cross the lung barrier (UCC press conference on 14th December 1984) . It was observed that the more the victims ran, the more aerosol they inhaled and the fatalities were observed in such victims . The tissues, which were preserved in the deep freeze, were randomly selected and analysed by GC coupled with MS (ITD) Finnigan MAT, UK . 14 out of 34 autopsy cases showed MIC trimer peak in extracts of blood . This was one of the constituents of the aerosol and was also located in the tank residue, thereby proving that the trimer had passed the lung barrier.

Med Sci Law, 1991 Oct, 31(4), 289 - 93
GC-NPD and GC-MS analysis of preserved tissue of Bhopal gas disaster: evidence of methyl carbamylation in post-mortem blood; Sriramachari S et al.; Twenty-five preserved autopsy blood samples of Bhopal toxic gas exposed victims were analysed by gas chromatography (GC) coupled with either Nitrogen-Phosphorous detector (NPD) or mass spectrometer (MS) for the presence of methyl carbamyl valine in terms of valine methyl hydantoin (VMH) . 84% of these samples showed a positive test for VMH on GC-NPD and the identity of the peaks were further confirmed on GC-MS . The concentration of VMH in the gas-affected positive blood samples ranged from 2.56 to 51.28 nanomoles . These results indicate entry of methyl isocyanate (MIC), one of the constituents of the toxic cloud caused by the disaster, into the blood stream of victims who had inhaled gas.

Antimicrob Agents Chemother, 1991 Oct, 35(10), 2037 - 41
Use of ampicillin-sulbactam for treatment of experimental meningitis caused by a beta-lactamase-producing strain of Escherichia coli K-1; Guerra-Romero L et al.; We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1 . Ceftriaxone was used as a comparison drug . The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam {2:1 ratio, ampicillin concentration}) and 0.125 and 0.25 micrograms/ml (ceftriaxone) . All antibiotics were given by intravenous bolus injection in a number of dosing regimens . Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained . CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses) . This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h) . It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.

Jpn J Antibiot, 1991 Sep, 44(9), 1013 - 9
{In vitro antifungal activity of amorolfine against Malassezia species}; Uchida K et al.; In vitro antifungal activities of a new morpholine agent, amorolfine (MT-861) were investigated, against 39 strains of Malassezia furfur (11 stock cultures and 28 clinical isolates) and 8 strains (stock cultures) of Malassezia pachydermatis, in comparison with those of 2 reference drugs, clotrimazole (CTZ) and bifonazole (BFZ) . Of the 3 antifungal agents, MT-861 exhibited strongest antifungal activities against the stock cultures of M . furfur and M . pachydermatis with average MIC values of 0.428 and 0.174 micrograms/ml, respectively; and the average BFZ activity was less than 1/10, and the average CTZ activity was 1/100, of the average MT-861 activity . All of the clinical isolates of M . furfur also showed high susceptibilities, though they were more susceptible to BFZ and CTZ.

Antimicrob Agents Chemother, 1991 Sep, 35(9), 1925 - 7
In vitro susceptibility of Brucella melitensis to antibiotics; Rubinstein E et al.; The in vitro susceptibilities of 86 recent clinical isolates of Brucella melitensis to minocycline, streptomycin, co-trimoxazole, rifampin, and six fluoroquinolones were determined . Minocycline exhibited the lowest MIC and was followed by rifampin and streptomycin . Among the quinolones, WIN 57273 and ciprofloxacin were the most active agents . No antibiotic combination of these agents exhibited synergy against 15 selected isolates . In killing rate experiments, streptomycin exhibited the most rapid kill (less than 12 h), while a complete kill with minocycline, rifampin, and ciprofloxacin was delayed up to 48 h . The combinations of streptomycin with each of minocycline, rifampin, or ciprofloxacin exhibited the fastest kills (within 2 h), while with the other combinations, a complete kill was delayed up to 96 h . These results demonstrate the discrepancy between the results of various in vitro methods in evaluating the antibiotic susceptibility of B . melitensis.

Antimicrob Agents Chemother, 1991 Sep, 35(9), 1923 - 4
Effects of chlorpromazine on the cell envelope proteins of Escherichia coli; Amaral L et al.; Chlorpromazine (CPZ), at a concentration of 60 micrograms/ml of medium completely inhibited the replication of Escherichia coli . At concentrations below this MIC, CPZ caused transient induction of filamentation, such that by the end of 5 h, all of the cells were filaments, and by the end of 24 h, only rod-shaped E . coli were present . The reversion to normal morphology in the presence of CPZ was not due to either the degradation of CPZ or the selection of CPZ-resistant mutants . The electrophoretic pattern of proteins extracted from isolated cell envelopes of CPZ-induced filaments as well as from E . coli that reverted to normal morphology was distinctly different from that of the controls.

Antimicrob Agents Chemother, 1991 Sep, 35(9), 1753 - 9
Biosynthesis of peptidoglycan in Gaffkya homari: on the target(s) of benzylpenicillin; Sinha RK et al.; The formation of acceptor for the N epsilon-(D-Ala)-acceptor transpeptidase is an essential feature of nascent peptidoglycan processing . In Gaffkya homari the synthesis of cross-bridges in peptidoglycan includes a variety of penicillin-sensitive enzymes, e.g., transpeptidase, DD-carboxypeptidase, and LD-carboxypeptidase . To determine the primary target, we grew cultures in the presence of the MICs of benzylpenicillin (0.2 microgram/ml), methicillin (10 micrograms/ml), cephalothin (5 micrograms/ml), and cefoxitin (25 micrograms/ml) and examined the monomer-dimer composition of each peptidoglycan by high-performance liquid chromatography after muramidase digestion . From these studies it was recognized that of all the dimers, the synthesis of the predominant cross-bridge, diamidated octapeptide (-Ala-iso-D-Gln-Lys-D-Ala -Ala-iso-D-Gln-Lys-D-Ala), is most sensitive to the action of the beta-lactam at its MIC . The enhanced deamidation of the acceptor tetrapeptide, one of the substrates for the transpeptidase, is correlated with the inhibition of this cross-bridge . For example, at the MIC of benzylpenicillin, the ratio of amidated tetrapeptide to nonamidated tetrapeptide decreased from 2.8 in the control to 1.0 in the treated culture . From these results it would appear that a decrease in preferred acceptor for the transpeptidase results in the inhibition of synthesis of this major cross-bridge . Thus, the metabolism of the amide function of the monomer peptides may represent an additional feature of processing in the assembly of cross-bridged dimers in the peptidoglycan of this organism that is sensitive to the action of beta-lactam.

Kekkaku, 1991 Sep, 66(9), 635 - 8
{Mycobacterium examination system at the National Jewish Center in the States}; Haga T; Impressions on visit to Mycobacteriology Laboratory of National Jewish Center for Immunology and Respiratory Medicine are reported . The BACTEC and Gen-Probe Method are introduced to the laboratory system on mycobacterial examinations such as detection, identification, drug susceptibility and minimal inhibitory concentration test.

Hosp Pract (Off Ed), 1991 Sep, 26 Suppl 5, 7 - 13; discussion 52-4
Pharmacokinetics of ceftriaxone; Blumer J; Ceftriaxone fulfills many of the qualities of an ideal antibiotic: a prolonged elimination half-life, which results from a "restrictive" excretion pattern; saturable protein binding, which provides the theoretical basis for administering the total daily dose as a single bolus; and once-a-day dosing, which provides plasma and tissue concentrations that exceed the MIC for most susceptible pathogens for 24 hoursPublication Types:

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