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Biomedical subjects

D Bauer

Publications and source records attributed to D Bauer.

At least 91 records · Page 5Linked to original sources

Verapamil-mediated sensitization of doxorubicin-selected pleiotropic resistance in human sarcoma cells: selectivity for drugs which produce DNA scission.

The effects of verapamil on the cytotoxicity and accumulation of multiple drugs were studied in a model of pleiotropic resistance generated by doxorubicin (DOX) selection of the human sarcoma cell line MES-SA. The in vitro sensitivity of the DOX-resistant variant (named Dx5), which is 50- to 100-fold resistant to DOX compared to MES-SA, was enhanced approximately 7-fold by verapamil (3 micrograms/ml). In addition, the cytotoxicity of several agents to which the Dx5 line displays cross-resistance, i.e., daunorubicin, dactinomycin, mitoxantrone, and etoposide, was also enhanced 2- to 14-fold by verapamil. These agents share the properties of DNA intercalation and/or interaction with topoisomerase II. In contrast, verapamil did not alter the sensitivity of Dx5 to several other agents to which cross-resistance had been demonstrated, i.e., vincristine, vinblastine, colchicine, mitomycin C, and melphalan; nor did verapamil enhance the cytotoxicity of DOX or other agents against the DOX-sensitive parent, MES-SA. The sensitizing effect of verapamil did not correlate well with its effects on intracellular drug accumulation. [14C]DPX accumulation was increased by 30-40% in Dx5 but not in MES-SA cells in the presence of verapamil. [3H]Vinblastine accumulation was increased by 24-72% in both MES-SA and Dx5 cells in the presence of verapamil, although cytotoxicity of the Vinca alkaloids was not affected. In this human sarcoma model of DOX-selected pleiotropic resistance, verapamil partially reversed the resistance to DOX, as well as four of the nine drugs for which cross-resistance had been demonstrated in Dx5. The potentiation by verapamil of the cytotoxicity of some but not all of these antitumor agents suggests that factors other than altered drug transport may be responsible. The pattern of sensitization, restricted to agents which produce DNA strand scission by interaction with topoisomerase II, suggests that verapamil may be acting to promote the formation or inhibit the repair of such DNA strand breaks.

Animals

Active immunization of NMRI mice against Serratia marcescens.

Phenol-hot water lipopolysaccharide (LPS) extracts of Serratia marcescens strains CDC O3:H1, CDC O6:H3, NEW CDC O14:H12, and SH 186 (serotype O6/O14:H12) significantly protected NMRI mice against intraperitoneal challenge with the more mouse virulent homologous strains; overall, there was moderate cross-protection against the minority of heterologous challenge strains. Trichloroacetic acid LPS extracts and K-antigen extracts of strains NEW CDC O14:H12 and SH 186 also proved protective antigens. The purified metalloproteases of strains SH 186 and SF 178 (serotype O6/O14:H12) effected active murine immunization. Neither active nor passive immunization of NMRI mice with E. coli Rc mutant J5 afforded significant protection against various challenge strains of S. marcescens.

Animals

Learning preferences, values, and student satisfaction.

This study sought to determine the relative importance of values and learning preferences for educational satisfaction and to examine differences in value and learning preferences among undergraduate and graduate occupational therapy students and undergraduate physical therapy students. Although all three groups conformed to a profile of preferring teacher-structured, concrete, interpersonal learning, the graduate occupational therapy students appeared to give greater emphasis to universal social values and to have a stronger preference for abstract learning than both groups of undergraduates. The undergraduates expressed significantly greater satisfaction with their education than the graduate occupational therapy students; for each of the three groups educational satisfaction correlated with a different set of values or learning preferences.

Adult

[Problems in the biological monitoring of benzene exposure].

The biological monitoring of workers exposed to benzene containing mixtures by phenol analysis in urine is complicated by the facts that varying amounts of phenolic compounds are also produced by other precursors than benzene and that coexposure with other chemicals can cause interactions in metabolism and elimination rates. In order to overcome these difficulties it is proposed a) to abandon the colorimetric methods and to use only gas chromatography as a standard and reference method, b) as an overall monitoring concept always to determine phenol pre-exposure values as well as the cresol and creatinine concentrations in urine, and to combine biological monitoring whenever possible with personal air sampling.

Benzene

Gentamicin- and methicillin-resistant, clinical isolates of Staphylococcus aureus: comparative in vitro and in vivo efficacy of alternative antimicrobial drugs.

Six representative clinical isolates of gentamicin- and methicillin-resistant (GRMR) Staphylococcus aureus, constituting phage groups II and III, were susceptible only to amikacin, cefamandole, clindamycin, fosfomycin, fusidic acid, netilmicin, nitrofurantoin, trimethoprim-sulfamethoxazole, and vancomycin (Bauer-Kirby test). With few exceptions, the minimal bactericidal concentrations of the beta-lactam and aminoglycoside antibiotics tested, fusidic acid, and irregularly those of vancomycin, but not those of fosfomycin and rifampin, exceeded minimal inhibitory concentrations values by at least 8-fold. In vitro, combinations of rifampin with cefamandole, cefazolin, cefotaxime, erythromycin, fosfomycin, fusidic acid, netilmicin, and vancomycin yielded indifferent effects. The GRMR S. aureus strains were refractory against 50, 65, and 80 vol% of fresh defibrinated blood; following reduction of viable counts at 2 h (greater than or equal to 90%), rebound growth invariably occurred within 4 h after exposure. Combined human blood (55 vol%)-antibiotic assays revealed rifampin as the most effective drug, followed by vancomycin, fusidic acid, and cefamandole, in that order. Blood plus cefotaxime, cefazolin, or netilmicin yielded indifferent effects; fosfomycin failed in vitro. In terms of speed of recovery and survival data (chi 2 test), cyclophosphamide-pretreated, i.e., leukopenic NMRI mice responded best to chemotherapy with rifampin, followed by vancomycin, cefamandole, netilmicin, and fosfomycin, in that order; cefazolin yielded variable results.

Animals

Chemotherapeutic efficacy of cefotaxime and failure of fosfomycin in murine Salmonella typhimurium infection.

Six clinical isolates and 1 reference strain of Salmonella typhimurium were sensitive to conventional antibiotics (ampicillin, chloramphenicol, cotrimoxazole), cefotaxime (CTX), and fosfomycin ( FOSFO ). All 7 strains carried a 55 megadalton plasmid ( Birnboim - Doly agarose gel electrophoresis technique) and were of comparable virulence for outbred NMRI mice (LD50 values = range of 1.7 X 10(5)-1.0 X 10(6) CFU; intraperitoneal route). CTX (5 mg/25 g mouse/day, divided into 2 doses; duration = 7 days) proved efficacious against 3 selected strains (No. H 8800, 14, and 20) of S. typhimurium (p less than 0.01). FOSFO (same therapeutic regimen) failed in this regard; following transitory improvement of diseased animals (days 2-4), the mortality of treated animals eventually approached that of untreated control animals. Administration of 15 mg FOSFO /mouse/day likewise failed to enhance murine survival. Reisolated S. typhimurium bacteria of these 3 assay strains still were susceptible to FOSFO . In vitro, CTX likewise surpassed FOSFO in bactericidal activity against the same 3 S. typhimurium strains on a weight-for-weight basis in various biological fluids (human midstream urine; human defibrinated blood; murine thioglycolate-induced macrophage-rich peritoneal exudate).

Animals

Characterization of two clinical, multiple-drug-resistant isolates of Enterobacter cloacae.

Two multiple drug resistant Enterobacter cloacae isolates (Nos. 460 and 493) varied phenotypically in bacteriocin susceptibility in the absence of significant O antigen variation. Both isolates were susceptible to chloramphenicol, nitrofurantoin, polymyxin B, nalidixic acid, norfloxacin, and enoxacin only. One isolate carried a non-conjugative resistance (R) plasmid, whereas the other isolate contained a conjugative, 'curable' R plasmid and a cryptic plasmid. Both wild-type isolates constitutively produced a chromosomal cephalosporinase (nitrocefin hydrolysis); 'cured' variants of E. cloacae isolate No. 493, which had become susceptible for lamoxactam, produced a cefazolin-inducible beta-lactamase. The two E. cloacae isolates, including their 'cured' variants, were of low-grade virulence for outbred NMRI mice. Both isolates differed somewhat in susceptibility to defibrinated human blood. Inhibitory (0.25 microgram/ml), but not subinhibitory (0.125 microgram/ml) concentrations of norfloxacin and enoxacin combined with human blood yielded additive effects against both E. cloacae isolates.

Adult

[Major hypokalemia with rhabdomyolysis secondary to the intake of a nonalcoholic aniseed aperitif].

A case of exogenous hypermineralocorticism secondary to absorption of an alcohol-free liquorice beverage is reported here. The patient was a 53 year old man with known alcoholic liver cirrhosis who had stopped drinking alcohol one year earlier. He was admitted to the hospital for fever and myalgia without hypertension. Laboratory tests showed severe hypokalemia (1.7 mmol/l), metabolic acidosis and enzyme abnormalities compatible with rhabdomyolysis. Urinary potassium excretion was high. Plasma renin activity and aldosterone levels were low. Symptoms were those of exogenous hypermineralocorticism. One month earlier, the patient had drunk 0,25 1 per day of an alcohol-free licorice beverage for two weeks. Clinical and biological symptoms disappeared with potassium loading alone. Three weeks later, when serum potassium levels remained normal, the ingestion of the same amounts of the same beverage produced an important decrease in serum potassium levels. Intoxication by liquorice is a well-known cause of pseudoprimary hyperaldosteronism. But the case reported here has some unique features. It is, to our knowledge, the first case reported in the literature, although a few cases have been brought to the attention of the poison center in Marseille. The amount of beverage ingested was small (0.35 g/day of glycyrrhizinic acid) as compared to the usual threshhold of toxicity (0.7 g/day). The toxic effects lasted two weeks after discontinuing ingestion. Cirrhotic patients may be more susceptible than others but the main consumers of this type of beverage are presumably ex-alcoholics.

Beverages

[Effects of neuroleptics on liver function, the hematopoietic system, blood pressure and temperature regulation. Comparison of clozapine, perazine and haloperidol by evaluating medical records].

The frequency of disturbances of the liver function, of leucopoiesis, blood pressure and temperature regulation under clozapine in comparison with perazine and haloperidol in 478 patients (partly being treated repeatedly) was investigated by means of case histories of the Psychiatric Clinic of Tübingen from October 1974 up to June 1978. Within the time of the investigation no case of jaundice arose, however non-symptomatic increases of the liver values could be observed. The three drugs did not differ in this respect. Within the time of the investigation no case of agranulocytosis was observed. Only one leucopenia under clozapine, one under perazine, and six under haloperidol occurred. Concerning cardio-vascular effects of the neuroleptic medication, in 4.1% of the patients under clozapine therapy, 4.3% under haloperidol therapy and 10.3% under perazine therapy hypotension could be observed. Under clozapine 15.2% of the patients showed a rise of temperature, under perazine 3.2% and under haloperidol 2.8% of the patients. 83.3% of cases with elevated temperature under clozapine occurred during the first two weeks of treatment.

Adult

Plasmid-independent resistance of 'gray' colony variants of a strain of Serratia marcescens resistant to amikacin, cefotaxime and lamoxactam.

A multiple-drug-resistant strain of Serratia marcescens (serotype O14:H12; bacteriocin type 18), which was recovered repeatedly from the respiratory tract of an intensive care unit patient, yielded 'gray' colony phenotypic variants which were greater than or equal to four-fold less susceptible to amikacin, cefotaxime, and lamoxactam, but not to netilmicin and N-formimidoyl thienamycin, as compared with 'opaque' (wild-type) colony variants. The 'gray' variants proved phenotypically highly unstable and displayed comparable low virulence for NMRI mice (intraperitoneal route). The 'opaque' and 'gray' variants of this strain carried a nonconjugative, 46-megadalton resistance (R) plasmid, as determined by DNA agarose gel electrophoresis. The R-plasmid-mediated resistance against chloramphenicol, gentamicin, kanamycin, mezlocillin, piperacillin, triple sulfonamides, and cotrimoxazole, as demonstrated with 'curing' experiments. The mechanism of the novel amikacin-beta-lactam antibiotic resistance phenomenon remained undetermined.

Amikacin

A comparison of play behavior in nonhospitalized and hospitalized children.

Because play is extremely sensitive to environmental conditions, extended hospitalization may have adverse effects on normal play development in young children. This study compared the playfulness, as well as the level of play development, of three 2-year-old children who had been hospitalized most of their lives for tracheostomies, and three 2-year-olds living at home. Data on the children's play were gathered by videotaping in two standardized play settings and one free play setting. Statistically significant differences in the developmental level of play and in playfulness (i.e., the degree of liveliness and joy exhibited) were found between the two groups in all three settings, and the play age of all six children varied by setting. Quantitative data analysis was supported by qualitative findings. Although the differences between the groups cannot be conclusively attributed to hospitalization alone, certain features of the hospital environment appear to have hampered the development of play.

Child Behavior

Resistance-plasmid- and protease-independent murine virulence of a multiple-drug-resistant strain of Serratia marcescens.

The multiple-drug-resistant Serratia marcescens isolate SH 186 (serotype 06/014:H12, bacteriocin type 18) carried a 44 megadalton, nonconjugative resistance (R-) plasmid as demonstrated with 'curing' experiments and the DNA agarose gel electrophoresis technique. 'Cured' variants, which had lost part of or the entire R-plasmid, proved as virulent for outbred NMRI mice (intraperitoneal route) as the wild-type parent strain. Therefore, the virulence of this S. marcescens strain was plasmid-independent. Protease-deficient variants of this strain as well as protease-negative variants of two additional S. marcescens strains displayed comparable murine virulence. None of 19 representative S. marcescens strains, including isolate SH 186, gave rise to guinea pig keratoconjunctivitis (negative Anton-Sereny tests), i.e., were non-invasive; NMRI mice pretreated with either cyclophosphamide (leukopenia), type II carrageenan (blockade of macrophages) or with zymosan (depletion of complement) revealed essentially unaltered susceptibility to S. marcescens. However, mice pretreated with cyclophosphamide followed by zymosan were significantly more susceptible for 4 tests strains of S. marcescens, including isolate SH 186. Thus, neutrophil granulocytes and complement were required for murine defense against intraperitoneal infection with S. marcescens.

Animals

Industrial hygiene air monitoring of phenylhydrazine.

Two gas chromatographic (GC) methods for the analysis of phenylhydrazine have been examined with phenyl- and rho-chlorophenylhydrazine and a new method using thin-layer chromatography (TLC) was developed. The NIOSH GC method (2-furalphenylhydrazone derivatization), which is classified as "proposed", was found to yield two derivatization peaks, which could only be separated with capillary columns. The other GC method (acetone phenylhydrazone derivatization) gave a single peak, however, of limited stability. In the newly developed TLC method the fluorescamine derivative of phenylhydrazine is separated and detected either visually or with a TLC-fluorescence scanner after fluorescence enhancement with paraffin wax. With ordinary TLC techniques the quantification of phenylhydrazine was possible down to 200 pg per spot. The sensitivity of the TLC method is generally sufficient for the requirements of industrial hygiene air monitoring of phenylhydrazine.

Air

Human exposure to styrene. IV. Industrial hygiene investigations and biological monitoring in the polyester industry.

An industrial hygiene study of 10 glassfiber reinforced polyester plants (including 90 workers) was undertaken to investigate the styrene exposure in this industry and to estimate biological limit values (BLV's) for the urinary metabolites of styrene: mandelic (MA) and phenylglyoxylic acids (PGA). Time weighted average (TWA) styrene exposures were found ranging from 2 to 200 ppm. The urinary elimination of metabolites correlated well with exposure and the BLV's corresponding to an 8-h exposure at 100 ppm were consistent with earlier laboratory findings (end-of-shift sample: MA 1640, PGA 510, MA + PGA 2150; next-morning sample: MA 330, PGA 330, MA + PGA 660 mg/g creat.). Total metabolites (MA + PGA) in the next-morning sample or mandelic acid in the end-of-shift sample are recommended for routine monitoring of exposure to styrene. The study revealed the need for further research on how to reduce styrene exposure in this industry.

Air