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Biomedical subjects

J Maslow

Publications and source records attributed to J Maslow.

5 recordsLinked to original sources

Long-term outcomes of treatment of Mycobacterium avium complex bacteremia using a clarithromycin-containing regimen.

OBJECTIVES: To describe the long-term outcomes of treatment of AIDS-related Mycobacterium avium complex (MAC) bacteremia using a standard clarithromycin-based regimen. DESIGN: Retrospective study of patients with MAC bacteremia diagnosed between April 1992 and April 1995. SETTING: An urban AIDS clinic SUBJECTS: One hundred seventy-six consecutive patients with MAC bacteremia. INTERVENTIONS: Clarithromycin 500 mg twice daily, ethambutol 800 or 1200 mg daily, and clofazimine 100 mg daily. MAIN OUTCOME MEASURES: Late treatment failure (defined as a positive blood culture more than 90 days after starting treatment), clarithromycin susceptibility of initial and treatment-failure isolates, DNA fingerprinting of isolates from treatment failures. RESULTS: Two out of 176 (1.1%) baseline isolates were resistant to clarithromycin. One hundred and fifty-one patients were treated for MAC bacteremia, 144 (95%) with the standard regimen. Of the 117 patients who survived > 90 days after starting therapy, 25 (21%) met the criteria for late treatment failure. Of the 22 treatment-failure isolates available for susceptibility testing, 19 (86%) were resistant to clarithromycin. Therefore, 13% of patients treated using the standard regimen (19 out of 144) had treatment failure associated with the emergence of clarithromycin resistance. Using logistic regression, non-compliance was associated with treatment failure (P = 0.02). Fourteen out of the 17 (82%) evaluable paired isolates had identical DNA fingerprint patterns, whereas three pairs showed that a different strain of MAC was present at the time of treatment failure. CONCLUSIONS: Initial resistance to clarithromycin was rare during this period. However, late treatment failure associated with the emergence of clarithromycin resistance was relatively common during long-term follow-up. Most late treatment failures represented emergence of clarithromycin resistance in the initial strain.

AIDS-Related Opportunistic Infections↗

Epidemiologic typing systems.

Microbial strain typing is a useful adjunct to clinical epidemiology. Phenotypic typing systems examine expressed characteristics, whereas genotypic systems, including recent PCR-based systems, examine chromosomal or plasmid DNA. Typing systems have evaluated bacteria, fungi, and viruses successfully. The criteria used to assess the utility of each system include typeability, reproducibility, and discriminatory power.

Bacterial Typing Techniques↗

Quantitative differences in adhesiveness of type 1 fimbriated Escherichia coli due to structural differences in fimH genes.

Type 1 fimbriae are heteropolymeric surface organelles responsible for the D-mannose-sensitive (MS) adhesion of Escherichia coli. We recently reported that variation of receptor specificity of type 1 fimbriae can result solely from minor alterations in the structure of the gene for the FimH adhesin subunit. To further study the relationship between allelic variation of the fimH gene and adhesive properties of type 1 fimbriae, the fimH genes from five additional strains were cloned and used to complement the FimH deletion in E. coli KB18. When the parental and recombinant strains were tested for adhesion to immobilized mannan, a wide quantitative range in the ability of bacteria to adhere was noted. The differences in adhesion do not appear to be due to differences in the levels of fimbriation or relative levels of incorporation of FimH, because these parameters were similar in low-adhesion and high-adhesion strains. The nucleotide sequence for each of the fimH genes was determined. Analysis of deduced FimH sequences allowed identification of two sequence homology groups, based on the presence of Asn-70 and Ser-78 or Ser-70 and Asn-78 residues. The consensus sequences for each group conferred very low adhesion activity, and this low-adhesion phenotype predominated among a group of 43 fecal isolates. Strains isolated from a different host niche, the urinary tract, expressed type 1 fimbriae that conferred an increased level of adhesion. The results presented here strongly suggest that the quantitative variations in MS adhesion are due primarily to structural differences in the FimH adhesin. The observed differences in MS adhesion among populations of E. coli isolated from different host niches call attention to the possibility that phenotypic variants of FimH may play a functional role in populations dynamics.

Adhesins, Bacterial↗

The relationship between pharmacokinetics and pharmacodynamic action as applied to in vivo pA2: application to the analgesic effect of morphine.

When the pA2 of an antagonist is determined in vivo, administered doses are used rather than the peak or steady-state tissue concentrations. The present report examines the error which can arise in this method and also presents a method for determining the pA2 from data obtained at times after peak. We applied this time-dependent analysis to time-dose-response data obtained with morphine-naloxone in the rat, using tail compression as the nociceptive stimulus. Good agreement between pA2 values was found: 8.0 with peak effect data, and 8.1 with the time-dependent method. Further, this analysis yielded 20 minutes as the half-life of naloxone. It is concluded that the time-dependent method provides a check on the pA2 in vivo and confirms the utility of this constant in classifying receptors. The appendix contains methodology for application to other agonist-antagonist combinations classified according to their kinetics.

Analgesics↗