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Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

At least 181 records · Page 10Linked to original sources

Midline granuloma and Wegener's granulomatosis: clinical & therapeutic considerations.

Midline granuloma (MG), limited Wegener's granulomatosis (LWG), and generalized Wegener's granulomatosis (WG) have been viewed by some investigators as representing an interrelated disease spectrum. Others believe that MG and WG are two distinct clinicopathologic entities. A series of cases is presented suggesting that therapy of MG should be individualized. Treatment may include corticosteroids, high-dose irradiation, and/or immunosuppressive drugs. LWG may be treated initially with corticosteroids alone, but lack of response requires the addition of an immunosuppressive agent. WG should be treated with an immunosuppressive drug and, at times, corticosteroids as well. None of the cases of MG described in this report progressed to WG. This may be interpreted as supporting the contention that MG and WG are separate diseases. Alternatively, aggressive treatment of MG with irradiation or immunosuppressives may prevent its transition to more generalized disease.

Adrenal Cortex Hormones↗

Selective suppression of autoantibody responses in NZB/NZW mice treated with long-term cyclophosphamide.

Autoimmune responses were assayed in 80 cyclophosphamide-treated and control NZB/NZW mice over a period of 1 year. Fluctuation between positive and negative immunofluorescent heterogeneous ANA tests and daily alterations of ANA titers were detected in young mice of both sexes. Although high-dose cyclophosphamide therapy (8 mg/kg/day) failed to prevent the spontaneous appearance of ANA, titered ANA values were partially suppressed in high-dose treated mice. This study permitted sequential comparisons between ANA titers and anti-DNA as useful indices of cyclophosphamide-induced suppression of autoimmune disease. ANA titers were relatively resistant to cyclophosphamide therapy. Antibodies directed specifically against DNA were suppressed mice receiving high-dose cyclophosphamide. In treated animals, decreased anti-DNA levels were associated with protection from severe glomerulonephritis and renal vasculitis. Treatment with low-dose cyclophosphamide (1 mg/kg/day) appeared paradoxically to stimulate autoantibody production and renal disease/vasculitis.

Animals↗

Mixed connective tissue disease in siblings.

Mixed connective tissue disease (MCTD) was diagnosed in a brother and sister, and 18 additional family members spanning three generations were studied to detect evidence of autoimmune disease. Symptoms or signs of MCTD without complete expression of the disease were found in 8 relatives of the original cases. Antibodies to ribonucleoprotein and high-titer antinuclear antibodies were found only in the affected siblings. Tests for rheumatoid factor were positive in 9 of 17 relatives of the patients; the titers ranged from 1:160 to 1:2560. The brother and sister with MCTD had an identical HLA genotype--11,12/2,12. The same genotype was inherited by 3 of their siblings, who had impressive rheumatic complaints. This report emphasizes the association between inflammatory connective tissue disease and a specific HLA type within a single kindred.

Adult↗

Opportunities for pharmacists as managers: perceptions of senior executives in the pharmaceutical industry.

OBJECTIVE: To determine how senior-level executives in the pharmaceutical industry perceive pharmacists as managers in their industry. DESIGN: Mailed survey. Senior executive officers of 72 companies who were members of the Pharmaceutical Research and Manufacturers' Association indicated in which of 47 different areas an entry-level pharmacy degree would be beneficial for management positions. RESULTS: 40 responses (56%) were received after a follow-up mailing. The areas chosen most frequently were product development and quality control in pharmaceutics (88%), formulation (88%), drug information (88%), quality assurance (85%), pharmaceutics in research (83%), and product management (83%). The 25% of respondents who had a pharmacy background chose more areas where a pharmacy degree would be beneficial (t = 6.87, df = 38, p < .05) than did nonpharmacists. CONCLUSION: To the extent that senior executives represent the current culture and the future direction of the pharmaceutical industry, pharmacists have a variety of career opportunities within pharmaceutical companies.

Administrative Personnel↗

The in vitro efficacy of a quaternary ammonia disinfectant and/or ethylenediaminetetraacetic acid-tris against commercial broiler hatchery isolates of Pseudomonas aeruginosa.

Studies have indicated variations in the degree of efficacy of certain commercial disinfectants used in poultry production facilities. We used an adequate method of in vitro testing to compare the efficacy of disinfectants while testing them in conditions similar to those of the poultry facilities. BioSentry 904, ethylenediaminetetracetic acid (EDTA)-Tris, and a combination of the two were tested by this method against five field isolates of Pseudomonas aeruginosa at 10(3), 10(6), and 10(9) colony-forming units (CFU)/ml. At the 10(9) CFU/ml concentration, most compounds failed to achieve a total kill with a contact time of 15 min. When tested at bacterial concentrations of 10(3) CFU/ml, the combination of EDTA-Tris mixed at a 1:1 ratio with BioSentry 904 killed the bacteria upon initial contact (< or = 0.05 min). This disinfectant mixture exhibited antagonistic, indifferent, or synergetic effects when exposed to different bacterial isolates at a concentration of 10(6) CFU/ml.

Animals↗

Characterization of Pseudomonas aeruginosa isolates associated with mortality in broiler chicks.

In mid-2000, a broiler chicken company in Alabama experienced high early mortality rates in chicks from two different hatcheries. Five isolates of Pseudomonas aeruginosa, obtained from these contaminated hatcheries and resulting broiler chicks with omphalitis, were selected to determine virulence of the bacteria. One-day-old specific-pathogen-free white leghorn chicks were placed into positive pressure isolation units (10 chicks per unit); feed and water were provided ad libitum. The five isolates of P. aeruginosa (1 x 10(1) or 1 x 10(1) colony-forming units/bird) were used to challenge two replicates of 10 chicks via yolk sac inoculation. Two control groups were injected with 0.1 ml of phosphate-buffered saline, and two groups received no treatment. Mortality was recorded daily, and the chicks that died were necropsied and liver and yolk sacs were cultured. After 14 days, the remaining chickens were euthanatized and necropsied. Bacterial isolates retrieved from liver and yolk sacs were identified by the API 20 NE typing system to confirm that they were the same as the challenge isolate. Virulence varied greatly among the isolates, resulting in mortality rates from 0 to 90%. The challenge isolates produced different and often distinctive postmortem lesion patterns. Antibiotic sensitivity tests showed that all five isolates were resistant to sulfisoxazole, ceftiofur, penicillin, lincomycin, bacitracin, oxytetracycline, erythromycin, naladixic acid, and tetracycline. The isolates varied in sensitivity to other antibiotics, but all isolates were sensitive to gentamicin.

Alabama↗

Effect of BioSentry 904 and ethylenediaminetetraacetic acid-tris disinfecting during incubation of chicken eggs on microbial levels and productivity of poultry.

Proper sanitation practices and the use of efficacious disinfectants in a hatchery have an effect on chick quality. Aerosol bacterial counts, egg moisture loss, hatchability, chick quality, and broiler productivity were evaluated when egg surfaces were contaminated by immersion of each egg into a broth medium containing a field isolate of Pseudomonas aeruginosa and incubated with exposure to one of three disinfectant treatments administered by fine spray: distilled water, BioSentry 904 (904), and a 1:1 ratio of 904 and ethylenediaminetetraacetic acid (EDTA)-Tris. The aerosol bacteria levels were statistically greater on day 21 of incubation in the group treated with distilled water than in those receiving disinfectants. Overall hatch of fertile eggs and egg moisture loss were comparable among all three treatments. At 1 day of age, the chicks incubated with 904 had a statistically lower yolk sac contamination rate than those incubated with 904+EDTA-Tris or distilled water. The 2-wk mortality rates, body weights, feed conversion ratios, yolk sac weights, and yolk sac contamination rates were all similar among the three treatments.

Animals↗

Are the current bioequivalence standards sufficient for the acceptance of narrow therapeutic index drugs? Utilization of a computer simulated warfarin bioequivalence model.

PURPOSE: The purpose of this computer simulation was to determine the likelihood of two bioequivalent (vs. reference) generic warfarin formulations (with varying bioavailability) passing current bioequivalence criteria against each other at varying bioavailability. Methods. A bioequivalence simulation program generated 100 warfarin bioequivalence (BE) studies with 24 patients/study. The reference formulation (R) was assigned a bioavailability of 90%. In these simulations the first generic (G(1)) had a bioavailability that was incrementally decreased from 90%. The second generic (G(2)) had a bioavailability that was incrementally increased from 90%. The bioequivalence testing was performed initially as G(1 )vs. R, then G(2) vs. R, and finally G(2) vs. G(1). The tests were performed according to current criteria for therapeutic index drugs. RESULTS: 5400 BE studies with a total of 129,600 subjects and 2,462,400 sampling times were simulated. When G(1) vs. R was compared, fewer than 80% of studies passed when the relative AUC(0-t )ratios were 88% or less. When G(2) vs. R were compared, fewer than 80% of studies passed when the relative AUC(0-t )ratios were 113% or greater. When Generic 2 and Generic 1 were compared fewer than 80% of studies passed when the relative AUC(0-t) ratios deviated from the reference by 7% or more. DISCUSSION Despite limitations this simulation indicates that two bioequivalent (vs. reference) generic warfarin products may not be bioequivalent to each other. Alternative methods of assessing bioequivalence are needed when more than one generic of narrow therapeutic index drug exists on the market.

Anticoagulants↗

Death at dinner.

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Adolescent↗

Effect of low-dose cimetidine on theophylline metabolism.

The effect of low doses of cimetidine on theophylline clearance and metabolism was studied. In a randomized, crossover study, 10 healthy men received oxtriphylline alone or with cimetidine. Oxtriphylline 200 mg (equivalent to theophylline 135 mg) was given orally every eight hours for 10 doses. Cimetidine 300 mg was given orally at bedtime for four days, beginning the same day as oxtriphylline treatment. At least 10 days separated study periods. In each study period, blood samples for plasma theophylline determinations were drawn 24 hours before the last dose of oxtriphylline, at the time of the last dose, and periodically up to 32 hours after the last dose. A 24-hour urine collection for quantification of theophylline and metabolite excretion was started at the time of the last oxtriphylline dose. Plasma theophylline clearance decreased significantly by a mean of 12.2% during cimetidine treatment. Area under the curve showed a significant mean increase of 17.4%. Increases in clearance and area under the curve values occurred in 9 of 10 subjects. In 6 of 10 subjects who had increases in theophylline trough concentrations, the mean increase was 28.2%; when all 10 subjects were considered, however, the mean increase was 10.3%, which was not significant. No significant differences in the urinary recoveries of theophylline or its metabolites were noted between study periods. Because of the decreases in theophylline clearance produced by low doses of cimetidine in this study, clinicians should monitor for potential theophylline toxicity in patients who receive these drugs concomitantly.

Adult↗