Pharmacological studies on cephacetrile in human volunteers.
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Adult↗
Biomedical subjects
R Wise
Publications and source records attributed to R Wise.
Clinical trial of a unique hydrocortisone containing topical aerosol in a variety of dermatologic disorders.
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Administration, Topical↗
Laterality differences in the perception of pressure.
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Adolescent↗
Enumeration of phagocytosed Staphylococcus aureus inside cells of the mouse macrophage cell line J774 by bioluminescence, fluorescence and viable counting techniques.
In order to quantify intracellular Staphylococcus aureus within a macrophage-like cell line by a bioluminescence technique, the mouse cell line J774 and opsonized Staphylococcus aureus were incubated together to allow phagocytosis to occur. Experiments using UV microscopy and fluorescent stained S. aureus were performed to determine an estimate of the mean intracellular bacterial numbers. For enumeration of intracellular bacteria by a bioluminescence technique, extracellular bacteria were removed by washing, the macrophages lysed mechanically and osmotically and treated with apyrase to remove somatic ATP. Bacterial cells were washed and the intracellular ATP measured by firefly luciferase bioluminescence in a luminometer. This new method of enumerating intracellular bacteria was compared to the conventional method of viable counts and found to correlate (r = 0.78). The bioluminescence assay developed was found to be a relatively rapid alternative method to the techniques currently used to enumerate intracellular bacteria and could prove advantageous in studies of intracellular killing and effects of antimicrobial agents on intracellular pathogens.
Animals↗
Ceftibuten: a new orally absorbed cephalosporin. In vitro activity against strains from the United Kingdom.
The in vitro activity of ceftibuten was studied in 572 bacterial strains and was compared with the activity of other orally administered beta-lactams. Ceftibuten displayed high activity against the Enterobacteriaceae, generally being 16-fold more active than cefuroxime, cefaclor, cephalexin, or amoxicillin-clavulanic acid. Its activity was comparable to cefixime. There was little ceftibuten or cefixime activity against staphylococci (MIC90s greater than or equal to 64 micrograms/ml) and reduced activity against Streptococcus pneumoniae (MIC90, 16 micrograms/ml). Haemophilus influenzae and Neisseria spp. were highly susceptible to ceftibuten and cefixime. The protein binding of ceftibuten was 77%, and the primary target site was PBP 3. A high degree of stability to beta-lactamase hydrolysis was observed.
Administration, Oral↗
15O positron emission tomographic scanning in predominantly never-treated acute schizophrenic patients.
Positron emission tomography with oxygen-15 was used to compare regional cerebral blood flow and the regional cerebral metabolic rate of oxygen in a group of predominantly never-treated, acute schizophrenic patients and in matched controls. The results of this study did not support the hypothesis that schizophrenics have reduced frontal blood flow and/or metabolism; and only equivocal support was obtained for the hypothesis that metabolism within the basal ganglia is reduced in schizophrenics. However, support was obtained for the hypothesis that an abnormality in hemisphere laterality may underlie schizophrenic illness.
Acute Disease↗
Activity, stability, and pharmacology of the epimers of moxalactam.
By an agar-dilution procedure, the minimal inhibitory concentrations of R, S, and R + S epimers of moxalactam were determined for 23 commonly isolated organisms. Generally the R epimer was twice as active as the S epimer; however, against Pseudomonas aeruginosa the two were equally active. The stability of the epimers and of the R + S mixture in saline and serum was studied by high-pressure liquid chromatography. Each epimer was stable at -20 C. The interconversion half-life in serum at 37 C, 22 C, and 4 C was 1.5, 4.8, and 13 hr, respectively, for R and 1.5, 11, and 43 hr for S. In buffer both epimers were more stable. In buffered saline the final mixture of R:S was 50:50, if one started with either the R or the S epimer. In serum, however, the R:S ratio of the mixture at equilibrium was 45:55. In patients with normal renal function the ratio of R:S in serum at 2 hr was 0.69 and at 8 hr, 0.55. In patients with severe renal failure the R:S ratio at 2 hr was approximately 0.9 and at 6 hr, 0.85. Probably, in renal failure, time is sufficient for re-equilibration of the epimeric mixture, and hence there is little alteration in the R:S ratio with time.
Bacteria↗
Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime.
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Biotransformation↗
Methods for evaluating the penetration of beta-lactam antibiotics into tissues.
Methods for the study of tissue penetration by beta-lactam antibiotics have been critiqued and compared. Mathematical models may be useful in assessments of the influence of lipid solubility and protein binding on tissue penetration. In vitro models may be used for evaluation of the probable pharmacokinetic properties of beta-lactams but are of greater use in studies of the interaction between antimicrobial concentrations and the kinetics of bacterial killing. Numerous animal models have been used. Fibrin clots, intraperitoneal cages, and soft tissue models all tend to yield limited information on tissue penetration as they often have no pathophysiologic counterpart in humans. Three types of studies in humans--tissue homogenates, body fluids, and experimental fluids--all entail certain advantages and problems. Tissue homogenates are often contaminated with body fluids, such as urine and bile. The usefulness of drug assays in ascitic or pleural fluid is limited by the depot effect. Studies of experimental fluids (e.g., fluid from blisters induced chemically or by suction) may have some clinical relevance and yield consistent results.
Animals↗
Evaluation of a genus-specific monoclonal antibody in an amplified enzyme-linked immunoassay in the detection of Chlamydia in urine samples from men.
In this study, the authors used amplified enzyme-linked immunoassay (IDEIA Chlamydia test) on urine samples of 623 male patients attending a sexually transmitted disease clinic. They compared the results with routine urethral cell culture isolation, which showed a sensitivity and specificity of 72.6% and 98.6%, respectively. The sensitivity was significantly higher (79.7%) in patients with clinical evidence of urethritis as compared with those without such evidence (59%). The use of first-catch, early-morning urine may improve the sensitivity of the test.
Antibodies, Monoclonal↗
Characteristics of Norplant users.
OBJECTIVE: To determine whether a profile can be developed to indicate which clients are the best candidates for Norplant by describing the characteristics of clients who use this contraceptive for 5 years and those who have it removed early. DESIGN: A descriptive study of data collected from a convenience sample. SELLING: A state-supported university hospital's obstetric and gynecology outpatient clinic serving primarily indigent clients in the southern United States. PARTICIPANTS: Women (N = 256), primarily with low incomes, being seen for removal of Norplant contraceptive capsules. Of these, 166 women had completed the recommended 5 years. MAIN OUTCOME MEASURES: Characteristics of the clients who retained the contraceptive for the recommended 5 years and characteristics of clients who came for early removal. RESULTS: Clients who retained the contraceptive for 5 years differed from those who did not on only three characteristics: race, age, and parity. No significant differences were found in education or marital status. CONCLUSIONS: No clear profile of successful Norplant users emerged. Instead, thorough counseling of each individual is essential to the client's completion of 5 years with Norplant. Advantages and disadvantages must be explained and the client's tolerance of possible side effects must be assessed, thereby helping the client to make an informed choice.
Adolescent↗
No evidence for transhemispheric diaschisis after human cerebral infarction.
Forty-four studies of regional cerebral blood flow (rCBF), fractional oxygen extraction (rOER) and oxygen consumption (rCMRO2) were made on twenty-five patients with recent internal carotid artery territory infarcts. The purpose was to study flow-metabolism relationships in the contralateral hemispheres, and to investigate whether contralateral rCMRO2 was depressed as a result of the recent infarcts. Two groups of controls were included for comparison--seventeen normal volunteers, and ten patients with proven extracranial cerebrovascular disease but without evidence of cerebral infarction. The results demonstrated that: contralateral hemispheric rCMRO2 was less variable than regional oxygen availability (the product of rCBF and arterial oxygen content). This was due, in part, to the effect of individual variations in PaCO2 on rCBF, but other uncontrolled factors, such as intracranial pressure, may have had influences. As a result, rCMRO2 did not correlate with rCBF; mean rCMRO2 in the contralateral hemispheres was 12% lower than normal (a significant difference), but was not different from the value found in patients with extracranial vascular disease in whom there was no evidence of infarction or ischemia; contralateral rCMRO2 did not correlate with the size of the infarct in the opposite hemisphere. It is concluded that rCMRO2 cannot be inferred from rCBF measurements in uncontrolled human studies (as frequently done in the past), and that depression of contralateral rCMRO2 may have preceded infarction in the opposite hemisphere, a consequence of the previous influences of diseases that predispose to stroke.
Adult↗
The clinical relevance of protein binding and tissue concentrations in antimicrobial therapy.
The relevance of protein binding, molecular size and lipophilicity to tissue penetration of antimicrobials is discussed, and the clinical relevance of tissue penetration of these agents is assessed. In order to assess the relevance of any factor on the clinical outcome of a group of infections it is necessary to obtain some form of dose response; i.e. the dose has to be (intentionally or otherwise) titrated down until negative responses are seen. Information on clinical failures tends not to be reported, hence useful data are difficult to obtain. The relevance of protein binding to the microbiological activity of a drug is important and the use of some highly bound agents in readily assessable diseases is illustrated with a few examples: the poor efficacy of fusidic acid in gonorrhoea, when high failure rates are found with doses of 2g; ceftriaxone in gonorrhoea, at doses (25mg) with which one would expect cures, is associated with significant failures; the failure of cefoperazone in serious illness can be related to the degree of protein binding. The degree of tissue penetration (protein binding apart) is related to clinical efficacy in urinary tract infections (where ample evidence is available), chest infections (where the data are somewhat fewer but probably convincing) and meningitis where experimental data are firm but clinical information less readily available.
Anti-Bacterial Agents↗
A review of the mechanisms of action and resistance of antimicrobial agents.
Over the past 60 years, the introduction of new antibiotics has been matched by the development of new mechanisms of resistance by the bacteria. Current antibiotics act at a variety of sites within the target bacteria, including the cross-linking enzymes in the cell wall (beta-lactams), various ribosomal enzymes (macrolides, tetracyclines and aminoglycosides), nucleic acid polymerases (quinolones and rifampin) and folate synthesis (sulphas and trimethoprim). Four major mechanisms of resistance have been shown. Target site alterations, such as changes to the penicillin-binding protein, are common. Inactivation of antimicrobials, as by penicillinases or the new carbapenemases, is often seen. Some bacteria such as Pseudomonas aeruginosa can produce alterations in cell wall permeability that deny access to antimicrobials during the course of therapy. Finally, newly described efflux mechanisms pump the antimicrobial out of the cell before it can reach its target site.
Anti-Bacterial Agents↗
The relentless problem of antimicrobial resistance.
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Drug Resistance, Microbial↗
[The postantibiotic effect of azithromycin on respiratory pathogens].
We assessed the post-antibiotic effect (PAE) of azithromycin against 3 strains of Streptococcus pneumoniae 2 strains of Haemophilus influenzae and 2 strains of Moraxella catarrhalis. The strains were exposed for 2 hours to a concentration of 0.5 mg/l. A stationary phase inoculum of 1 x 10(6)-5 x 10(6) CFU/ml in IsoSensitest Broth with 5% lysed horse blood and 20 mg/l NAD was used and shaken for the duration of the experiment. Antibiotic was neutralised by dilution 1:1000 into pre-warmed medium. [table: see text] In conclusion, even at such low concentration as achieved in serum, azithromycin has a PAE against the respiratory pathogens studied. In our opinion this could allow the use of azithromycin, in the usual regimen even in bacteremic respiratory infections.
Anti-Bacterial Agents↗
Beyond the exchange--the future of B2B.
Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important.
Commerce↗