PubMed Health⌕ Search

Biomedical subjects

K Rand

Publications and source records attributed to K Rand.

17 recordsLinked to original sources
PubMed2004

Impact of tazobactam pharmacokinetics on the antimicrobial effect of piperacillin-tazobactam combinations.

Pharmacokinetic-pharmacodynamic (PK-PD) modelling was used to study the impact of the pharmacokinetics of tazobactam on the antimicrobial effect of piperacillin-tazobactam combinations. An in vitro experiment using a novel dilution system was performed to compare the effects of two conditions of the combination therapy against Escherichia coli ATCC35218, a beta-lactamase producing bacterium. Both conditions simulated the same initial concentrations of piperacillin and tazobactam, but different elimination half-lives for tazobactam. The killing and regrowth kinetics of E. coli clearly indicated that there is a difference in the antimicrobial effects when there is a difference in the pharmacokinetics of tazobactam in the combination therapy. The results show that for equal piperacillin exposure, different tazobactam half-lives will have a significant effect on antimicrobial outcome.

Anti-Bacterial Agents↗
PubMed1998

Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease.

Although first suggested at the turn of the 20th century, there is a renewed interest in the infectious theory of atherosclerosis. Studies done in many laboratories around the world over the past several years have shown an association between markers of inflammation and coronary atherosclerosis with an exacerbation of the inflammatory process during acute myocardial ischemia, particularly in the early stages of reperfusion. It is also being recognized that the traditional risk factors, such as smoking, dyslipidemia, hypertension and diabetes mellitus, do not explain the presence of coronary atherosclerosis in a large proportion of patients. We believe that in certain genetically susceptible people, infection with very common organisms, such as Chlamydia pneumoniae or cytomegalovirus, may lead to a localized infection and a chronic inflammatory reaction. Persistence of infection may relate to the degree of inflammation and severity of atherosclerosis. Early trials with appropriate antibiotic agents in some patients with a recent history of acute myocardial infarction have led to very salutary results. If patients with an infectious basis of atherosclerosis can be identified, a therapy directed at eradication of the offending organism may be appropriate.

Animals↗
PubMed1997

Pharmacokinetic-pharmacodynamic modelling of the in vitro antiinfective effect of piperacillin-tazobactam combinations.

PURPOSE: The aim of the study was to investigate the in vitro antiinfective effect of piperacillin-tazobactam (PIP-TZB) combinations on Escherichia coli in simulations of free concentration time profiles of both drugs, similar to those obtained in human tissue after i.v. bolus administrations. METHODS: An in vitro dilution model was used to expose E. coli ATCC 35218 (beta-lactamase producer) to various piperacillin-tazobactam concentration profiles obtained after i.v. bolus multiple dose, using different dose ratio combinations (1:4, 1:8, 1:16) and dosing regimens, ranging from once-a-day to 4 times a day. The antimicrobial effect was evaluated by determination of the number of bacteria over time. The concentration of PIP in the model was determined by HPLC. RESULTS: A modified Emax model was used to describe the pharmacodynamic effect. The model was linked with the piperacillin concentrations determined experimentally to provide a pharmacokinetic-pharmacodynamic (PK-PD) model. The EC50 for piperacillin alone averaged 5.66 +/- 0.29 micrograms/ml. The EC50 for all doses of piperacillin combined with 0.5 g of tazobactam were dose-dependent and averaged 1.70 +/- 0.56, 3.95 +/- 1.02, and 6.14 +/- 1.24 micrograms/ml for PIP 2, 4, and 8 g, respectively. By increasing the dose of TZB in combination with a fixed dose of PIP, a decreased EC50 was observed. CONCLUSIONS: The PK-PD model allowed a detailed evaluation of the dosing regimens investigated. The results suggested that for these combinations, 3 times a day administration is as effective as 4 times a day. Pharmacodynamic activity of the combinations can be prolonged by sufficiently high inhibitor concentrations.

Colony-Forming Units Assay↗
PubMed1996

A cDNA encoding the calcitonin gene-related peptide type 1 receptor.

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity. We report here the cloning of a complementary DNA (cDNA) encoding a human CGRP1 receptor, which shares significant peptide sequence homology with the human calcitonin receptor, a member of the G-protein-coupled receptor superfamily. Northern blot analysis revealed that the messenger RNA for this receptor is predominantly expressed in the lung and heart. In situ studies showed specific localization of the receptor mRNA to alveolar cells in the lung and to cardiac myocytes in the heart. Stable expression of the cDNA in human embryonic kidney 293 (HEK 293) cells produced specific, high affinity binding sites for CGRP that displayed pharmacological and functional properties very similar to native human CGRP1 receptor. Exposure of these cells to CGRP resulted in a 60-fold increase in cAMP production, which was inhibited in a competitive manner by the CGRP1 receptor antagonist, CGRP-(8-37).

Adrenomedullin↗
PubMed1994

Multicenter in vitro comparative study of fluoroquinolones after four years of widespread clinical use.

In vitro activities of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, and seven other oral antimicrobials including amoxicillin-clavulanic acid (A/C), oxacillin, cefaclor, cefixime, cefuroxime, erythromycin, and trimethoprim-sulfamethoxazole (T/S) were evaluated against 1708 fresh bacterial isolates from four hospital laboratories approximately 4 years after the introduction of ciprofloxacin. T/S and ofloxacin had the lowest MIC90s and greatest percentage of susceptible strains overall, followed by the other three quinolones. Quinolones were the most active drugs tested against Gram-negative bacteria, with little variation in the activity among the four compounds against most species. Quinolone resistance was detected to some degree in the majority of Gram-negative species tested, with Pseudomonas, Acinetobacter, Xanthomonas, and Providencia demonstrating the highest percentage of resistant strains. Ofloxacin and ciprofloxacin were relatively more active against Gram-positive bacteria than were fleroxacin and lomefloxacin, but T/S and A/C had more susceptible strains than any of the quinolones. Oxacillin-resistant staphylococci, enterococci, and streptococci exhibited the least quinolone susceptibility. This study showed that while resistance is developing among several previously susceptible bacterial species, quinolones remain important alternatives for the oral treatment of many types of infections. Actions to prevent or limit resistance will be important to maintain the viability of the quinolones as therapeutic agents in both hospital and community environments.

Anti-Bacterial Agents↗
PubMed1990

Buffered charcoal-yeast extract medium for the isolation of brucellae.

A patient with chronic osteomyelitis caused by Brucella abortus had negative agglutination titers. Because of a superimposed staphylococcal infection that resulted in the overgrowth of this organism on nonselective media, brucellae were isolated only on a selective buffered charcoal-yeast extract (BCYE) agar. Sixteen strains of various Brucella species were inoculated on BCYE agar; selective BCYE agar with polymyxin, anisomycin, and cefamandole; and brucella blood agar. The growth and recovery rates on the three media tested were comparable for 14 strains. BCYE agar with polymyxin, anisomycin, and cefamandole may be useful as a selective medium for the isolation of brucellae.

Adult↗
PubMed1986

Recurrent varicella-zoster infection after acyclovir therapy in immunocompromised patients.

Varicella-zoster virus (VZV) infection is a late complication of bone marrow transplantation in almost half of the long-term survivors. We have reported the clinical relapse of VZV infection in two marrow transplant recipients treated with standard regimens of acyclovir, a new antiviral agent with activity against VZV. Since most VZV infections occur after discharge from a transplant center, primary care physicians must be alert to the possibility of relapse of VZV infection after acyclovir therapy.

Acyclovir↗
PubMed1984

Identification and characterization of the alc gene product of bacteriophage T4.

Bacteriophage T4 infection rapidly and almost completely inhibits transcription of host and other phage DNAs. Two processes have been implicated to date in this inhibition: (1) ADP ribosylation of the alpha subunits of the RNA polymerase, involving gpalt (which is injected with the phage DNA) and, later, gpmod; and (2) the action of the T4 alc/unf gene product, synthesized immediately after infection. The latter unfolds the host genome and also blocks transcription of cytosine-containing DNA. Here, we describe the identification on two-dimensional polyacrylamide gels of gpalc/unf, the more precise mapping of the gene and the identification and analysis of the appropriate DNA sequence from an Unf+ alc mutant.

Amino Acid Sequence↗