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Biomedical subjects

E Williams

Publications and source records attributed to E Williams.

At least 19 recordsLinked to original sources

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

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

Thymectomy in myasthenia gravis. The Jamaican experience.

Forty-five patients with myasthenia gravis (MG) were subjected to thymectomy by the median sternotomy technique and were followed up for 4,380 patient months. No operative deaths occurred and 93.3% of the patients benefited from surgery with 28.8% achieving remission. Forty patients (88.5%) showed improvement within one month, and 73% of those who achieved remission did so in the first 2 years. Outcome was not affected by thymic pathology except in one patient who had a thymoma removed. These results confirm the value of thymectomy in the management of MG patients with generalised disease and the efficacy of the simple median sternotomy procedure.

Adolescent

The effects of co-dependence on physicians and nurses.

To evaluate the effect on physicians and nurses of being closely involved with one or more chemical dependent persons, a sample of 67 physicians and 133 nurses with chemical dependent significant others was surveyed. The majority reported that the quality of their work was adversely affected by this association. Reduced ability to concentrate, absenteeism, errors, poor judgment, and patient neglect were reported. Most reported their professional education had not prepared them to recognize and assist people with chemical dependence and half thought their professional education negatively influenced their ability to help. About half had attempted to treat the chemical dependent person(s) themselves, sometimes giving medication and occasionally diverting drugs for this purpose. Most said their self-esteem and self-confidence were damaged by these relationships. Over one-third reported being diagnosed as depressed and 12% had attempted suicide. There were few differences between physicians and nurses on the effects of being in a co-dependent relationship(s), although nurses and women were more likely to have chemically dependent parents. Implications for professional education are identified.

Adult

Mitral valve prolapse and psychiatric complications: a case report.

This case study describes a 9-year-old-girl presenting with symptoms of anxiety and depression who was found to have mitral valve prolapse syndrome. The relationship of mitral valve prolapse and anxiety and depression has been studied and a review of the literature is presented. The family history of heart and psychiatric problems is explored. The importance of the bio-psycho-social approach is stressed as well as the suggestion that mitral valve prolapse be included as part of the differential diagnosis for anxiety.

Anxiety Disorders

Cloning and expression of the carbon monoxide dehydrogenase genes from Pseudomonas thermocarboxydovorans strain C2.

Carbon monoxide dehydrogenase (CODH) from Pseudomonas thermocarboxydovorans strain C2 is composed of three non-identical subunits. A gene library of C2 DNA in lambda vector L47.1 was generated and screened using anti-CODH serum. Western blotting experiments revealed a protein which co-migrated with and had the same immunological reaction as the large subunit of CODH in some of the clones isolated from the library. The coding region was pinpointed to a 4 kb fragment which was subcloned into plasmid. Western blotting experiments showed that all three subunits of CODH were coded for by the subclone. However, no CODH activity was detected.

Aldehyde Oxidoreductases

Secondary prevention with college drinkers: evaluation of an alcohol skills training program.

This study evaluated secondary prevention approaches for young adults (N = 36, mean age 23 years) at risk for alcohol problems. Subjects were randomly assigned to cognitive-behavioral alcohol skills training, a didactic alcohol information program, or assessment only. The skills program included training in blood alcohol level estimation, limit setting, and relapse prevention skills. All subjects maintained daily drinking records during the 8-week intervention and for 1 week at each follow-up. Repeated measures MANOVA found a significant reduction over 1-year follow-up in self-reported alcohol consumption for the total sample. For all drinking measures, the directional findings consistently favored skills training. Despite overall reductions, most subjects continued to report occasional heavy drinking.

Accidents, Traffic

Use of DNA fluorochromes for studying meiosis in the woody species Thryptomene calycina.

The fluorescent DNA probes DAPI and Hoechst 33258 produce superior images to the traditional acetocarmine stain of the small chromosomes of the woody shrub Thryptomene calycina at all stages of microsporocyte meiosis and microspore mitosis. Hoechst 33258 was slightly superior to DAPI because of reduced background fluorescence. Binding with the DNA-specific probes required a fixative containing chloroform to remove autofluorescent materials, a pretreatment with acetic acid and a pH of least 6 during treatment. The nucleoli did not fluoresce after treatment with DAPI or Hoechst 33258. Superior resolution of chromosomes after treatment with the fluorochromes enabled easy determination of the haploid number at metaphase I, metaphase II and at metaphase of the microspore mitosis.

Bisbenzimidazole

Warthin's tumour in Jamaica. Incidence, electron microscopy and immunoenzyme studies.

Warthin's tumour has traditionally had a strong male association, and has been said to be rare in Blacks. Current studies describe a new trend; a rise in females, strongly linked to cigarette smoking. The tumour has eosinophilic epithelial cells packed with distinctive mitochondria, and a lymphoid stroma. Immunological investigations have demonstrated polyclonal B cells, T cells and macrophages. Views differ as to whether B or T cells predominate. Between 1958 and 1989, the Jamaica Cancer Registry recorded 491 benign and malignant salivary gland tumours. There were 18 cases of Warthin's tumour (3.7%), with a male: female ratio of 5:1. The low proportion of females is similar to the trend for female lung cancer in Kingston & St. Andrew. A case of Warthin's tumour was studied by light and electron microscopy and immunoenzyme methods. The epithelial cells contained numerous mitochondria with stacked cristae, as previously described. Similar morphology occurs in oncocytic tumours; riboflavin-deficient rats and mice; rats given non-lethal doses of hypoglycin; dogs treated with annatto extracts; and hibernating or starving frogs. The mitochondrial changes may be an adaptive response. The immunoenzyme studies utilized newly available monoclonal antibodies: UCHL1, L26, 4KB5, MT1 and LN2. The reaction patterns indicate a distribution of B and T cells in a manner expected in a lymph node. The interaction between mitochondrial changes, adaptive metabolic pathways, the immune cells and tobacco raises some interesting questions.

Adenolymphoma

The effect of heptyl-physostigmine, a new cholinesterase inhibitor, on the central cholinergic system of the rat.

Heptyl-physostigmine (Heptyl-Phy; MF-201) is a new carbamate derivative of physostigmine (Phy) with greater lipophilicity and longer inhibitory action on cholinesterase (ChE) activity than the parent compound. Following single dose administration of 5 mg/kg heptyl-Phy i.m., maximal whole brain acetylcholinesterase (AChE) inhibition (82%) if reached at 60 min. Inhibition of plasma BuChE butyrylcholinesterase (BuChE) remains close to the steady state level (60%) between 120 and 360 min. At 360 min, whole brain AChE activity is still 67% inhibited compared to controls. Inhibition of AChE activity displays brain regional differences which are more significant at 360 min. At this time point, AChe activity in cerebellum is only 40% inhibited while frontal cortex and medial septum are still 80% inhibited. Increases in acetylcholine (ACh) levels also show regional differences, however, there is no direct relationship between AChE inhibition and ACh increase. The electrically evoked [3H]ACh release in cortical slices was inhibited only by the highest concentration of heptyl-Phy tested (10(-4) M). At this concentration ChE activity was 97% inhibited in vitro. In conclusion, our results demonstrate that heptyl-Phy compares favorably to other reversible cholinesterase inhibitors (ChEI), particularly to Phy as far as producing a more long-lasting inhibition of AChE and a more prolonged increase of ACh in brain with less severe side effects. Therefore, it represents an interesting candidate for cholinomimetic therapy of Alzheimer disease (AD).

Acetylcholinesterase

Neurosurgical stimulation, impedance monitoring and data acquisition system.

We describe the design of a programmable neurosurgical stimulator with impedance monitoring facilities. The computer is used both to control a stimulator and for the storage of various parameters employed in the process. The stimulator is designed to minimize tissue damage by injecting net zero charge; its output is a current, independent of load resistance. By measuring electrode voltage, the load impedance can be calculated. Software is provided in order to log patient data, and trajectory details with reference to coordinates calculated from other imaging systems such as CAT scanners.

Computer Systems

A prospective study of the reliability and convergent validity of three physical activity measures in a field research trial.

This investigation sought to determine the test-retest reliability and convergent validity of three commonly used physical activity measures. The Stanford Physical Activity Recall, the Caltrac Activity Monitor, and a daily physical activity log were administered to 45 subjects over a 3-week period. The results indicated high levels of test-retest reliability for the Stanford and the daily log; low test-retest reliability was obtained for the Caltrac. Convergent validity was also high between the Stanford and daily log but was low for both of these measures with the Caltrac. These results suggest that the Stanford Physical Activity Recall may be the self-report measure of choice for large studies due to its high reliability and convergent validity with a more time-consuming daily log, as well as its cost- and time-efficiency. Based on the results, it is recommended that the Caltrac activity sensors not be used for field studies of physical activity until the logistical problems of their use in clinical trials are solved.

Adult