Biomedical subjects
Publications and source records attributed to J Williamson.
Arthrobacter simplex dehydrogenated withaferin A to 4-dehydrowithaferin A but it was not able to dehydrogenate this substrate in position 27. 27-Dehydrowithaferin A was prepared chemically using pyridinium chlorochromate. Whereas 4-dehydrowithaferin A surpassed in its effect on leukemic (388 cells the original compound and all its derivates synthesized so far, 27-dehydrowithaferin A was biologically inactive.
1. A mitochondrion-associated antigen to primary biliary cirrhosis (PBC) in man has been shown by solid-phase radioimmunoassay and immunoautoradiography to occur in several parasitic protozoa (Trypanosoma, Plasmodium and Eimeria spp.) and in the helminths Ascaridia galli and Nippostrongylus brasiliensis. 2. Stercorarian trypanosomes and T. brucei procyclics, with more highly-developed mitochondria, appear to contain more PBC antigen than the salivarian trypomastigote, in accordance with the known mitochondrial association of the antigen. 3. Trypanosoma lewisi and A. galli gave consistently high reactivity for PBC antigen, the antigen of the former being localized predominantly to the microsomal fraction.
Thirteen premenopausal women with uterine fibroids were treated for a maximum of 6 months with a long-acting agonist of luteinizing hormone-releasing hormone (LH-RH), goserelin (Zoladex depot, ICI Pharmaceuticals, Macclesfield, UK) 3.6 mg, administered subcutaneously every 28 days. A 55% reduction (range, 38% to 84%) in uterine volume assessed by ultrasound was obtained. The greatest reduction (30%) was apparent within the first treatment cycle regardless of whether treatment was started in the early follicular or the luteal phase. Fibroid regression was inversely correlated with urinary estrogen concentration. Treatment was well tolerated and only one subject withdrew from the study before its scheduled completion. Following cessation of therapy, ovulatory menstruation returned within 3 months in the majority of the subjects, but this was accompanied by a rapid regrowth of the fibroids. This medical approach to the management of fibroids merits further investigation but as yet cannot be regarded as an alternative to surgery.
In an effort to discern the amount of renal damage incurred by antegrade percutaneous nephrostomy and nephrostomy tract dilation, we studied the long-term effect of acutely created 24F and 36F percutaneous nephrostomy tracts on 12 pig kidneys. Half of the nephrostomy tracts were dilated using a semi-rigid 24F fascial dilating system (Amplatz design) and half were dilated using a 36F balloon dilation system. Animals were killed at six weeks and the nephrostomy tract was dissected, fixed in formalin, and microscopic cross-sections were stained with Masson's trichrome stain for collagen prior to morphometry using computerized planimetry. In this study, renal damage from the nephrostomy tract averaged 0.15% of the total renal cortical surface. Balloon dilation to 36F incurred no more significant damage than fascial dilation to 24F.
An investigation into the nature of fumes produced during thermal welding of plasticized PVC sheeting has been carried out with the objective of determining if the known carcinogen vinyl chloride monomer (VCM) is formed and to assess the level of exposure to the operator. The results show that the atmospheric concentrations of VCM are well below accepted occupational exposure limits. This finding is consistent with reports in the technical literature which suggest that VCM is produced during thermal degradation of PVC only at temperatures considerably higher than those encountered during plastic welding.
Assessment prior to a move to residential care has been carried out by the Departments of Geriatric Medicine in the Lothian Region for many years. Results have been reviewed over 7 years in one Department; 688 people were assessed; 7% were placed in alternative accommodation as a result of the assessment and a further 15% were offered specialist advice. The workload was 50 assessments per 10,000 population over 65 years per year. Of these, 58% were already known to the geriatrician and 23% were seen as part of the normal work of the department. It was concluded that the benefits of assessment make the extra work involved well worth while.
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Pharmacy departments play a role in helping to design and implement a pain management program in community hospitals. The history, documentation of need, and benefits of the program are presented. Protocol guidelines for the intravenous infusion of morphine are outlined, and specific job functions of the nurse and pharmacist members of the pain management team are defined. In addition, the results of a pain management study are reported, which describe the efficacy of the treatment protocol in 22 patients.
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Microorganisms known to hydroxylate alkaloids, amino acids, and aromatic substrates were examined for their potential to hydroxylate 17 beta-estradiol and estrone. Thin-layer chromatography of fermentation extracts revealed a wide range of steroid products. Aspergillus alliaceus (UI 315) was the only culture capable of producing good yields of catechol estrogens with 17 beta-estradiol. The organism also transformed estrone but not to catechol products. Analytical experiments with high-performance liquid chromatography revealed that A. alliaceus formed 4- and 2-hydroxyestradiol with yields of 45 and 16%, respectively. A preparative-scale incubation was conducted in 2 liters of medium containing 1 g of 17 beta-estradiol as substrate. 4-Hydroxyestradiol was isolated and identified by proton nuclear magnetic resonance and high-resolution mass spectrometry. Ascorbic acid was added to microbial reaction mixtures as an antioxidant to prevent the decomposition of unstable catechol estrogen metabolites. The microbial transformation of 17 beta-estradiol by A. alliaceus provides an efficient one-step method for the preparation of catechol estrogens.
Forty six normal volunteers were randomly assigned in double-blind fashion to once daily orally administered nadolol 10, 20, 40, or 80 mg for five days. Significant and dose related intraocular pressure (IOP) reductions (range 20-40%) were demonstrated both at three hours and 24 hours post dosing (p less than 0.001, all dosages). The reductions in IOP were dose related (p less than 0.05). One subject (in the 10 mg group) failed to show a significant intraocular pressure reduction. Significant reductions in blood pressure and heart rate also were recorded at all dose levels (with the exception of diastolic pressure in the 10 mg group), though considerably less in degree than IOP reductions. Two subjects (20 mg and 80 mg groups) experienced known side effects of beta blocker therapy necessitating termination of the drug, and four others experienced mild side effects but had no difficulty completing the study. The results have prompted further investigation of the usefulness of low doses of oral nadolol as therapy in chronic simple glaucoma patients.
This open study of beta blockers in chronic simple glaucoma compared the efficacy of once daily (o.d.) oral nadolol therapy with twice daily (b.d.) topical timolol therapy. Sixty eight patients were randomly assigned to starting doses of either 20, 40, or 80 mg of nadolol o.d. (51 patients) or 0.25% timolol b.d. (17 patients) and were seen at weekly intervals for a four-week (short-term) period. Upward dosage titration (80 mg o.d. maximum, nadolol and 0.5% b.d. maximum, timolol) was permitted if, at any visit, the intraocular pressure (IOP) in either eye was greater than 21 mmHg. At the end of 4 weeks the IOPs of a comparable number of patients were controlled (IOP less than 22 mmHg) with 20 mg nadolol o.d. and 0.25% timolol b.d. The 40 mg and 80 mg o.d. nadolol regimens were comparable with each other, superior to the 20 mg regimen, and (at least) equivalent to 0.5% timolol. The absolute degree of IOP reduction achieved with oral nadolol was equivalent to that with topical timolol. Alterations in blood pressure and heart rate were predictably greater with the orally administered beta blocker. Long-term therapy (up to 24 months) in 28 nadolol patients and 5 timolol patients indicates no more likelihood of tolerance with nadolol therapy. Patient withdrawals from the study due to adverse reactions occurred with nadolol but not timolol. Since oral nadolol administered once daily is as efficacious as b.d. topical timolol, it can be recommended as first-line therapy for certain subsets of the glaucoma clinic population.
Of 95 new cases of parkinsonism referred to a department of geriatric medicine, 48 (51%) were associated with prescribed drugs. Clinical features in drug-induced and idiopathic cases were very similar, including the proportion with typical tremor. 25% of patients with drug-induced parkinsonism (DIP) could not walk when first seen and 45% required hospital admission (for a median stay of 23 days, range 5-101). The clinical features of DIP resolved permanently in two-thirds of cases in a mean of 7 weeks but with a range of 1 to 36 weeks. 5 cases of DIP initially resolved but idiopathic parkinsonism developed after an interval of 3 to 18 months. Perhaps some old people have low striatal dopamine levels and a small neuroleptic effect tips them into overt parkinsonism or unmasks latent idiopathic disease. The commonest offending drug was prochlorperazine (21 cases). In no case did this drug seem to be indicated.
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