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Biomedical subjects

E Williams

Publications and source records attributed to E Williams.

At least 145 records · Page 8Linked to original sources

Valproate-mediated disturbances of hemostasis: relationship to dose and plasma concentration.

Valproic acid (VPA) may cause impaired platelet function, thrombocytopenia and, occasionally, severe bleeding. Controversy exists both as to the mechanism of this alteration in hemostasis and as to whether these adverse effects are either dose-related or idiosyncratic. Previous investigations have focused primarily on pediatric patients who commonly were receiving multiple anticonvulsant medications. We evaluated a cohort of 27 adult patients with epilepsy who were receiving VPA monotherapy and compared them with age-matched controls to determine whether a correlation exists between platelet count, function, bleeding time, levels of von Willebrand's factor antigen, and VPA dose or plasma concentration. VPA patients had significantly lower platelet counts and longer bleeding times than did controls (p < 0.05). Platelet count was inversely correlated to VPA dose and both free and total VPA concentration (p < 0.01). There was no significant difference in levels of von Willebrand's factor antigen between patients and controls. We assessed platelet aggregation by measurement of whole-blood platelet aggregation and release with agonists including adenosine diphosphate, thrombin, collagen, arachidonic acid, and ristocetin. VPA patients had significant decreases in platelet aggregation values compared with controls. There were significant differences in collagen, arachidonic acid, and adenosine diphosphate release and aggregation between groups that correlated to both VPA dose (p < 0.01) and concentration (p < 0.05). Prolongation of bleeding time was significantly correlated to both VPA dose and concentration. Our data suggest a significant relationship between impaired platelet function and both VPA dose and plasma concentration.

Adult↗

Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study.

OBJECTIVE: To study the effects of a low dose of omega-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We performed a randomized, prospective, double-blind, controlled study of a low dose of omega-3 fatty acids (2.5 g/day) in 20 ambulatory subjects with NIDDM. Subjects ingested five 1-g fish oil capsules each containing 0.5 g omega-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period. RESULTS: Nine subjects completed the study in each group. Both groups exhibited moderate control of glucose levels; modest elevations in baseline total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels; and normal blood pressure values. In the fish oil group, plasma omega-3 fatty acid levels increased significantly. Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil. No difference was observed in collagen-induced production of thromboxane A2 (TXA2, measured as the stable derivative TXB2), or in adenosine-5'-diphosphate- (ADP) induced platelet aggregation or TXA2 generation. Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil. Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure (sBP) by 8 mmHg compared with safflower oil. Fish oil caused a significant but small increase in HbA1c (0.56%) and total cholesterol (20 mg/dl) but had no effect on fasting glucose, high-density lipoprotein cholesterol, or LDL-cholesterol levels. CONCLUSIONS: Small doses of fish oil inhibit platelet aggregation and TXA2 production, reduce upright sBP and TG levels, and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM. Small quantities of omega-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients.

Adult↗

The use of failure mode effect and criticality analysis in a medication error subcommittee.

Failure Mode Effect and Criticality Analysis (FMECA) is the systematic assessment of a process or product that enables one to determine the location and mechanism of potential failures. It has been used by engineers, particularly in the aerospace industry, to identify and prioritize potential failures during product development when there is a lack of data but an abundance of expertise. The Institute for Safe Medication Practices has recommended its use in analyzing the medication administration process in hospitals and in drug product development in the pharamceutical industry. A medication error subcommittee adopted and modified FMECA to identify and prioritize significant failure modes in its specific medication administration process. Based on this analysis, the subcommittee implemented solutions to four of the five highest ranked failure modes. FMECA provided a method for a multidisciplinary group to address the most important medication error concerns based upon the expertise of the group members. It also facilitated consensus building in a group with varied perceptions.

Accident Prevention↗

Muscarinic receptors mediate attenuation of extracellular acetylcholine levels in rat cerebral cortex after cholinesterase inhibition.

Muscarinic autoregulation of extracellular acetylcholine levels was investigated by microdialysis in the cerebral cortex of freely moving rats under basal conditions as well as following systemic administration of a reversible cholinesterase inhibitor. Atropine (2.2 mg/kg s.c. or 0.2 microM via the dialysis probe) did not affect basal extracellular acetylcholine levels in the cerebral cortex. However, it did potentiate the elevation of extracellular acetylcholine levels produced by a dose of systemic heptylphysostigmine which inhibited 25% of cortical and 40% of plasma cholinesterase activity. These observations suggest that the extracellular concentration of acetylcholine following moderate acetylcholinesterase inhibition is regulated through muscarinic receptors.

Acetylcholine↗

Intestinal absorption in patients with rheumatoid arthritis treated with methotrexate.

Twelve patients with rheumatoid arthritis treated for at least 12 months with methotrexate and 11 matched rheumatoid arthritis controls underwent a standard d-xylose absorption test. No patients had any pre-existing clinical of biochemical evidence of malabsorption. No significant difference was observed in the 1 hour plasma d-xylose estimation between methotrexate treated patients and controls. The 2 to 5 hour urinary excretion ratio, however, was significantly lower in the methotrexate-treated group compared with controls indicating a minor degree of malabsorption. Six of the methotrexate treated patients and 5 of the controls underwent endoscopic duodenal biopsy but neither group demonstrated any significant histological changes. In conclusion, methotrexate therapy in patients with rheumatoid arthritis produces mild intestinal malabsorption.

Aged↗

Paternal involvement, maternal employment, and adolescents' academic achievement: an 11-year follow-up.

An 11-year follow-up study explored the effects of paternal involvement in child rearing and maternal employment in prior years on grades and educational expectations of a group of white, middle-class adolescents from intact families. Past maternal employment was found to be a more powerful predictor of children's academic performance and expectations than was amount of father involvement. Part-time maternal employment appeared to be optimal for children's academic expectations.

Adolescent↗

Screening in or out of the new reproductive options: who decides and why.

A lively controversy exists among infertility specialists about the value and necessity of screening candidates for inclusion into infertility programs. Advocates of screening argue that there is both a child advocacy and community welfare responsibility to evaluate prospective candidates (and donors) for the new assisted reproductive techniques. Opponents of screening argue that screening is costly and superfluous, since the majority of applicants are highly motivated and well-adjusted individuals who have the 'right' to pursue parenthood, if they choose. A pilot survey was undertaken to determine whether infertility programs currently have explicit policies regarding suspension or refusal of treatment on psychological grounds and to determine what would (or should) constitute grounds for denial of infertility treatment. A Treatment Refusal Questionnaire was mailed to all members of the Psychological Special Interest Group of the American Fertility Society. Forty-two responded (response rate of 47%). Results revealed that the majority of respondents did not have a formal policy regarding suspension or refusal of treatment, although they did have informal criteria. Four criteria were significantly endorsed as constituting 'red flags' for treatment rejection: substance abuse, physical abuse, severe marital strife, and coercion of one spouse by another. Furthermore, treatment decisions were modified by the type of intervention sought, so that for example, more stringent criteria were operative if clients sought ovum donation than if they sought ovulation induction. These and other findings are presented and discussed.

Adult↗

Clustering of adverse drug events: analysis of risk factors for cerebellar toxicity with high-dose cytarabine.

BACKGROUND: Cerebellar toxicity is a severe, therapy-limiting adverse reaction of cytarabine given in high doses. The Food and Drug Administration received a report of an increased frequency of cerebellar toxicity at the University of Wisconsin Hospital and Clinics after a switch from the product (Cytosar-U) manufactured by The Upjohn Co., Kalamazoo, Mich., to the generic form made by Quad Pharmaceuticals, Inc., Indianapolis, Ind. PURPOSE: To compare the incidence of cerebellar toxicity in Quad-treated patients with Upjohn-treated patients, a record-based cohort study was conducted at the University of Wisconsin Hospital and Clinics between January 1986 and August 1989. METHODS: The incidence of cerebellar toxicity was studied in 63 leukemia patients according to the manufacturer of the product received (34 Upjohn only, 25 Quad only, and four both manufacturers). The relative risk of cerebellar toxicity was adjusted for other known risk factors. RESULTS: Patients in the manufacturer-defined treatment groups did not differ significantly with respect to age, sex, type of leukemia, disease stage, calculated creatinine clearance, presence of abnormal liver function tests, or total dose received. The crude relative risk of cerebellar toxicity comparing the Quad product with the Upjohn product was 5.0 (95% confidence interval = 1.8-13.7). Adjustment for potential confounders did not alter the association. Other risk factors for cerebellar toxicity, independent of manufacturer, were age greater than 50 years, type of leukemia, disease stage, total dose greater than or equal to 20 g/m2, abnormal pretreatment liver function, and reduced creatinine clearance. CONCLUSION: This study found a significantly higher incidence of cerebellar toxicity with high-dose cytarabine manufactured by Quad Pharmaceuticals when compared with the incidence of cerebellar toxicity with the Upjohn product. Further research at independent institutions would be necessary to allow generalization of this finding. In addition, our findings suggest that a dose reduction in high-dose cytarabine therapy may be indicated for patients with reduced glomerular filtration rates.

Adolescent↗

An experimental test of three methods of alcohol risk reduction with young adults.

This study tested 3 forms of alcohol risk reduction programming for young adults. Volunteers were randomly assigned to receive a 6-week class and discussion group, a 6-unit self-help manual, or a single 1-hr feedback and advice session with professional staff. Results reveal significant reductions in self-reported drinking at the end of the intervention phase and maintenance of drinking changes throughout a 2-year follow-up period. Comparable drinking reductions were rated across treatments; however, noncompliance with the self-help reading program suggested limited utility. Treatment response was related to subject age, as subjects showed increased drinking during the year they reached legal drinking status. The efficacy of brief motivational interventions and client matching in prevention programs is discussed.

Accidents, Traffic↗

Culture of bovine pulmonary artery endothelial cells on Gelfoam blocks.

Conventional methods of endothelial cell culture on monolayers and beads require enzymatic digestion, traumatic scraping, or centrifugation to transfer cells to other experimental systems. Gelfoam, a porous gelatin block, not only supports the growth of bovine pulmonary artery endothelial cells but also allows the rapid transfer of cell-laden blocks from one experimental system to another with minimal intervention. This property has been shown to be especially useful for the rapid fixation of endothelial cells for microscopy using standard histologic methods. Histology confirmed that the trabecular nature of the substrate allows endothelial cells to line the interstices of the sponge matrix and grow in a configuration that simulates the appearance of the endothelium in small vessels and capillaries. The inoculation of 1 x 10(5) endothelial cells on 7.5 mg Gelfoam (24 x 8 x 2 mm blocks) was enhanced by fibroblast growth factor and resulted in cell attachment by day 2 with a cell doubling time of 1.7 days. In addition, endothelial cells completely infiltrated 1, 5 and 7.5 mg Gelfoam blocks, as verified by histology. Assays to quantify cell number and protein were easily performed. To facilitate cell counting, the Gelfoam matrix was rapidly removed by the addition of 0.05 mg/ml collagenase, a concentration that interfered minimally with the assay for cellular protein concentration. The data demonstrate that Gelfoam is a suitable support growth matrix for the in vitro culture of bovine pulmonary artery endothelial cells.

Animals↗

Smoking prevalence and attitudes of Gwynedd Health Authority staff towards passive smoking and the Authority's non-smoking policy.

In 1989, a postal survey was undertaken to investigate the smoking prevalence and attitudes of Gwynedd Health Authority employees towards the Authority's non-smoking policy, passive smoking and other related issues. The results show a smoking prevalence rate of 22% for those participating in the survey, with over half of all smokers expressing a wish to stop. Although the rate was similar for males and females, it was marginally higher amongst nursing staff and young employees. Smoking prevalence was highest among the ancillary staff, and lowest among the medical and dental professions. Most employees were in broad agreement with the Authority's non-smoking policy, and a majority thought it about right or favoured extending it. Most non-smokers and ex-smokers believed passive smoking to be a health hazard, with an increased number rating it anti-social. Attitudes towards these issues were similar for males and females, with marked differences between the groups employed in different areas of the service. Younger employees were more aware of the dangers of passive smoking, but less sympathetic towards the policy than the older ones. The findings of this study highlight the differences between smokers and non-smokers on all smoking issues. The implications for health education and the Authority's non-smoking policies are discussed.

Attitude of Health Personnel↗

Immunohistochemistry of lymphocyte B-cell lymphoma of the prostate gland.

A case of small lymphocytic B-cell lymphoma occurring in the prostate gland of a 68-year-old man is reported. These tumours are rarely encountered in surgical specimens, and may be confused with an undifferentiated carcinoma. Differentiation is readily made, using immunohistochemical techniques.

Aged↗