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Biomedical subjects

H Nadler

Publications and source records attributed to H Nadler.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of the in vitro activity of and pathogen responses to sparfloxacin with those of other agents in the treatment of respiratory tract, urinary tract, and skin and skin-structure infections.

The in vitro activity of and pathogen responses to sparfloxacin were compared with those of standard therapies for the treatment of patients with community-acquired pneumonia, complicated skin or skin-structure infections, urinary tract infections, acute bacterial exacerbations of chronic bronchitis, and acute maxillary sinusitis in 7 multicenter controlled trials in North America. Sparfloxacin was administered orally as a 400-mg loading dose followed by 200 mg once daily for up to 10 days. The bacteriologic efficacy of sparfloxacin (84% to 95%) was comparable to that of comparator drugs (77% to 100%). Sparfloxacin was generally 2 to 8 times more active (minimum inhibitory concentration for 90% of strains tested [MIC90]: 0.03 to 0.5 microg/mL) than comparators against common pathogens isolated in community-acquired infections, especially Streptococcus pneumoniae, including penicillin-resistant strains; Moraxella catarrhalis; Haemophilus influenzae; Streptococcus pyogenes; and Staphylococcus aureus. Sparfloxacin was also effective against Chlamydia and Mycoplasma species. The emergence of resistance was uncommon during sparfloxacin therapy (0.3% of 1100 cases). Higher area under the plasma concentration-time curve/MIC and maximum plasma concentration/MIC ratios for sparfloxacin were associated with clinical and bacteriologic efficacy, whereas lower ratios were associated with clinical and bacteriologic failure. The clinical efficacy of sparfloxacin (80% to 95%) was comparable to that obtained with the comparator drugs (71% to 92%). In addition, sparfloxacin was well tolerated and had an overall frequency of related adverse events similar to that of the comparators. There was a higher frequency of photosensitivity reactions but a lower level of digestive adverse events with sparfloxacin compared with comparators. Sparfloxacin is a suitable therapeutic alternative for the empiric treatment of respiratory tract infections owing to its favorable pharmacokinetic profile and activity against typical and atypical respiratory tract pathogens, even in geographic areas with a high incidence of penicillin resistance.

Anti-Bacterial Agents↗
PubMed1999

Practical approach to the identification of clinically relevant Enterococcus species.

Enterococci have become important nosocomial pathogens, with Enterococcus faecalis and then Enterococcus faecium predominating. Because of the emergence of glycopeptide (vancomycin and teicoplanin) resistance in enterococci, laboratories have been required to screen for resistant strains and to identify them to the species level. This has resulted in the need for accurate identification of species less commonly associated with clinical infections, such as Enterococcus casseliflavus and Enterococcus gallinarum, which are inherently resistant to the glycopeptides. Studies evaluating commonly used commercial identification systems, have found error rates for enterococcal species identification of 2-21% for E. faecalis, 5-9% for E. faecium, and 14-79% for other species. Reporting errors may have adverse effects on the management of clinical infections, as well as in the control of multidrug-resistant strain outbreaks. The purpose of this document is to present a simplified approach to the identification of Enterococcus species that uses a combination of rapid, readily available, and inexpensive tests.

Anti-Bacterial Agents↗
PubMed1995

Comparison of the activity of meropenem with that of other agents in the treatment of intraabdominal, obstetric/gynecologic, and skin and soft tissue.

Meropenem, a new carbapenem with improved stability in the presence of human dehydropeptidase-I[1], was evaluated in three prospective, multicenter, randomized, controlled clinical trials in North America. We compared the in vitro activity of meropenem and conventional antimicrobial agents for the treatment of intraabdominal, obstetric/gynecologic, and skin or soft tissue infections as well as the responses of pathogens to all of these agents. The trials of the drug for intraabdominal infection were double blind, and those for the obstetric/gynecologic and soft tissue infections were open labeled. Overall, MICs of meropenem for pathogens were lower, and the pathogen response rates were at least comparable to those for the following comparative agents: clindamycin plus tobramycin (for intraabdominal infections); clindamycin plus gentamicin (for obstetric/gynecologic infections); and imipenem and cilastatin (for skin or soft tissue infections). Meropenem has high in vitro potency and covers a broad spectrum of anaerobic and aerobic pathogens.

Abdomen↗
PubMed1995

A compilation of meropenem tissue distribution data.

Meropenem body fluid and tissue concentration data from both published studies and samples obtained during efficacy evaluation have been compiled and presented according to a consistent format to facilitate comparison. The concentration data have been compared with the mode MIC data available for the pathogens isolated during the clinical evaluation of meropenem. These data support the widespread and rapid penetration of meropenem into the interstitial fluid of those tissues not protected by a tight epithelial barrier. Furthermore, they suggest that the proposed dosages of meropenem 500 mg or 1 g tds would provide an adequate duration of cover at tissue sites for the treatment of a range of commonly occurring pathogens. A higher dosage of 40 mg/kg or 2 g in adults given tds would be recommended for meningitis based on the penetration of meropenem into CSF. Overall, the tissue and body fluid data presented confirm the expectation, based on the plasma concentrations and theoretical arguments, that meropenem is rapidly and readily distributed into the interstitial fluid, thereby producing concentrations in tissues likely to be clinically effective. This is consistent with the available clinical data on the therapeutic efficacy of meropenem.

Carbapenems↗
PubMed1993

Antibacterial activity of meropenem and selected comparative agents against anaerobic bacteria at seven North American centers.

The antibacterial activity of meropenem and comparative agents against approximately 1,000 anaerobes was determined using the disk dilution methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The organisms represented 27 species of six genera and included the most common pathogens. Meropenem and imipenem were the most active drugs and were comparable in overall activity, generally exhibiting an MIC90 of < or = 1 micrograms/mL. In contrast, the MICs of cefoxitin, clindamycin, and metronidazole were 32, 16, and 2 micrograms/mL, respectively. Meropenem was two- to fourfold more active than imipenem against selected Bacteroides species, Clostridium species, and Fusobacterium species. At a concentration of 1 microgram/mL, meropenem was more active than imipenem against cefoxitin-resistant Bacteroides fragilis or Bacteroides thetaiotaomicron. At a concentration of < or = 0.5 micrograms/mL, meropenem was more active than imipenem against clindamycin-resistant Bacteroides distasonis. At a concentration of 2 micrograms/mL, meropenem was more active than imipenem against cefoxitin-resistant or clindamycin-resistant Clostridium difficile. Thus, meropenem's high potency and broad-spectrum activity against common, rare, and drug-resistant anaerobes confirms its utility in the treatment of mixed anaerobic and aerobic infections.

Anti-Bacterial Agents↗
PubMed1992

Hawkinsinuria in two families.

Hawkinsinuria, a disorder of tyrosine metabolism has been documented in two families in the United States, in one of which there was clear evidence of autosomal dominant inheritance. Metabolic acidosis and failure to thrive appear to be confined to infancy. Tyrosyl metabolites and 5-oxoproline are also found only in infancy, while 4-hydroxycyclohexylacetic acid was present only with time. The disease may be detected by organic acid analysis or by staining an electropherogram for sulfur containing compounds.

Acidosis↗
PubMed1989

Development of a meropenem susceptibility disc: drug content, preliminary interpretive and quality control criteria and potency bioassay.

Laboratory studies were conducted to develop an appropriate susceptibility disc for meropenem. Laboratory-prepared paper discs containing 5, 10, and 20 micrograms of meropenem were investigated. Agar dilution MICs and agar disc diffusion tests were performed with 367 rapidly growing clinical isolates by methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Agar disc diffusion tests with 10 micrograms meropenem discs acceptably defined organisms as susceptible or resistant. The preliminary interpretive zone size criteria for 10 micrograms meropenem discs were: susceptible, greater than or equal to 14 mm, and resistant, less than or equal to 10 mm, by application of the NCCLS imipenem MIC interpretive susceptible and resistant breakpoints to the meropenem data. A total of 270 agar disc diffusion assays were performed with each of four ATCC reference strains, using prototype discs (Becton Dickinson (BBL] containing 10 micrograms meropenem. The preliminary quality control limits for agar disc diffusion tests with these discs are: Escherichia coli ATCC 25922, 28-32 mm; Pseudomonas aeruginosa ATCC 27853, 26-31 mm; Staphylococcus aureus ATCC 25923, 33-39 mm; and Enterococcus faecalis ATCC 29212, 19-23 mm. Further studies are necessary to re-evaluate both the preliminary interpretive and quality control criteria before definitive limits can be established. A reproducible, large plate bioassay with Enterococcus faecalis ATCC 29212 was developed to monitor meropenem disc potency.

Bacteria↗
PubMed1987

Evaluation of rapid SYS system as screen for Yersinia enterocolitica in the United States.

Clinical isolates (n = 150) from stool specimens were selected for evaluation of the Rapid SYS system (Analytab Products, Plainview, N.Y.) as a screening test for Shigella spp., Yersinia enterocolitica, and Salmonella spp. The Gram-Negative Identification Card (Vitek Systems, Inc., Hazelwood, Mo.) was used for identification. Although acceptable performance of the Rapid SYS system was described, the interpretative criteria provided by the vendor for previous studies led to inappropriate screening for Y. enterocolitica, particularly biotype 1. When corrected screening criteria were used for the present study, the sensitivity for the detection of 76 enteric pathogens was 98.7%. Of the 76 pathogens, 1 of 21 Shigella spp. was not detected. However, specificity was only 16.6% when 72 selected nonpathogens frequently encountered in stools were eliminated. Although the Rapid SYS system can identify Shigella spp., Y. enterocolitica, and Salmonella spp., only phenylalanine deaminase-producing and cytochrome oxidase-producing organisms can be eliminated from additional testing. Therefore, the Rapid SYS system cannot be used as a three-pathogen screen in the United States or in other geographic locales where Y. enterocolitica biotype 1 may be encountered.

Bacteriological Techniques↗
PubMed1987

Analysis of fetal intestinal enzymes in amniotic fluid for the prenatal diagnosis of cystic fibrosis.

Amniotic-fluid intestinal alkaline phosphatase activity, gamma-glutamyltranspeptidase activity, and leucine-aminopeptidase activity were quantitated to assess their reliability for the prenatal diagnosis of cystic fibrosis. The results indicate that for each of these enzymes an arbitrary cutoff point could be chosen that would enable one to correctly predict the outcome for the majority of at-risk pregnancies. However, some false positives and false negatives occurred with each enzyme. To obtain optimal diagnostic discrimination, the three enzyme values obtained for each sample were combined into a single linear discriminant function that proved to be a more accurate indicator of the outcome of the pregnancy. This was especially important for those cases in which the predicted outcome as based on the individual enzyme results was in disagreement. From the cases studied here, it appears that this method can be expected to give a correct prediction in approximately 96.5% of all 25%-at-risk pregnancies. False positives can be expected in approximately 1.4% of the pregnancies and false negatives in approximately 2.2%.

Alkaline Phosphatase↗
PubMed1982

A genetic approach to reveal the action of the opiate receptor in selected neuroblastoma-glioma cells. Interaction with alpha-adrenoceptors, calmodulin and Ca2+-ATPase.

Three clones of neuroblastoma-glioma cells that contain low amounts of calmodulin were selected from the NG108-15 cells after several treatments with high concentrations of chlorpromazine. Purified membranes of the three clones had decreased numbers of both alpha-adrenergic and opiate receptors, monitored with [3H]yohimbine and [3H,D-Ala2]methionine encephalinamide, respectively. No changes were observed in the affinity of these radioactive ligands to the receptors of the selected cells as compared to the parent cells. Addition of bovine brain calmodulin did not affect the binding of [3H,D-Ala2]methionine encephalinamide to the membranes of the selected cells and they had the same number of acetylcholine receptors, determined with 1-quinuclidinyl-[phenyl-4-3H]-benzilate, as the parent NG108-15 cells. The basal ATPase activity in the membranes of the selected cells was 35-50% of the parent cells, with a decreased V value and no significant change in the affinity constant Ka to ATP. Addition of Ca2+ to the purified membranes increased the V of the ATPase in the selected as well as the parent cells but the V of the selected cells remained lower than that of the parent cells. Ca2+ had no effect on the Ka to ATP in either cell type. The Ca2+-dependent ATPase activity of both the parent and the selected cells was also calmodulin-dependent dependent since it was blocked in vitro by chlorpromazine. The co-regulation of opiate and adrenergic receptors and their interaction with calmodulin and Ca2+-ATPase is discussed in view of recent observations indicating biochemical and physiological association between opiates, Ca2+ and adrenergic compounds.

Animals↗
PubMed1982

Effects of acute and chronic morphine treatment of calmodulin activity of rat brain.

The cyclic AMP-phosphodiesterase assay was used to quantitate the amount of calmodulin activity in various brain areas of male rats treated acutely or chronically for 5 days with morphine. The acute treatment with morphine decreased calmodulin activity in the mitochondrial-synaptosomal P2 fraction of the striatum, midbrain, and thalamus but had no effect on the cerebellum, which contains a low density of opiate receptors. The decrease in calmodulin activity by morphine was dose-dependent and was blocked by the opiate antagonist naloxone. In contrast, chronic treatment of rats with morphine increased calmodulin activity in the mitochondrial-synaptosomal P2 of the striatum, midbrain, cerebral cortex, and thalamus. A highly sensitive Ca2+/Mg2+-ATPase assay was also used to quantitate the amount of calmodulin activity in subcellular fractions obtained from the striatum. Chronic morphine treatment caused a significant increase in calmodulin activity in the membrane containing microsomal, synaptosomal, and mitochondrial layers but only a small change in the layer that contained the soluble proteins and the synaptic vesicles. It is suggested that alteration of the content of calmodulin in specific subcellular sites may have a central role in opiate action and addiction via regulation of multiple calmodulin-sensitive biochemical pathways.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Accuracy and reproducibility of the Oxi/Ferm system in identifying a select group of unusual gram-negative bacilli.

The Oxi/Ferm (O/F) identification system was compared in a double-blind study to a conventional test battery for the characterization of 96 reference and clinical strains consisting of 83 nonfermentative and 13 oxidase-producing, fermentative gram-negative bacilli. The O/F tube and supplemental tests correctly identified 84% of the nonfermentative and 77% of the oxidase-producing, fermentative bacilli. However, when the supplemental tests were excluded and the biochemical profiles generated by all nine O/F tube reactions were examined, the profile accuracy reached 95% (79 of 83) for the nonfermentative and 93% (12 of 13) for oxidase-producing, fermentative bacilli. Seven of the nine O/F substrate reactions demonstrated less than or equal to 89% agreement with conventional reactions, whereas the urea and arginine reactions provided 82 and 85% agreement, respectively. Replicate O/F tests with six selected organisms demonstrated 97% identification reproducibility and 84% overall substrate reproducibility. The mean O/F identification time was 2.6 days as compared to 3.3 days for the conventional system. Although this study suggests that the O/F system is a convenient, rapid, and accurate alternative to conventional identification methods, several modifications are recommended.

Bacteria↗
PubMed1979

New motility medium for nonfermenting bacilli.

Researchers compared use of a semisolid agar plate to wet mount examinations of broth cultures (16 to 18 hours) for the detection of motility of 96 reference and clinical strains of gram-negative rods. In this double blind study, 83 nonfermentative and 13 oxidase-producing, fermentative bacilli were tested by the two methods. Overall accuracy of the semisolid agar motility test was 96.8 percent compared to 89.6 percent for the broth method. Reproducibility of agar plate tests using selected reference strains was 100 percent in contrast to 90 percent for broth examinations. These findings indicate that the semisolid agar plate offers a convenient and more accurate method than wet mount examination for determining motility of unusual gram-negative bacilli.

Bacillus↗
PubMed1976

Absence of a serum factor in patients with cystic fibrosis.

A serum factor was demonstrated in normal individuals which (1) enhances the incorporation of L-[3H]fucose into cultured human skin fibroblasts, (2) is nondialyzable, (3) is heat labile at 50 degrees, (4) is present in the noneuglobulin fraction, and (5) appears to be deficient in serum from patients with cystic fibrosis. The specific activity of L-[3H]fucose incorporated into skin fibroblasts from normal individuals in the presence of serum from 12 control subjects was 3,337 +/- 168 cpm/mg protein in contrast to 2,294 +/- 172, the activity obtained either in the presence of serum from 10 age-matched patients with cystic fibrosis or in the absence of serum. These differences were significant at P less than 0.001. In comparison, no significant difference was detected in the amount of L-[3H]fucose incorporated into skin fibroblasts derived from normal individuals and patients with cystic fibrosis. The plasma membrane of cultured skin fibroblasts derived from patients with cystic fibrosis appears to be grossly unaltered in its protein and L-fucose labeling pattern.

Cell Membrane↗