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Biomedical subjects

G Davidson

Publications and source records attributed to G Davidson.

At least 73 records · Page 4Linked to original sources

Familial visceral myopathy associated with a mitochondrial myopathy.

A 27 year old man with intestinal pseudo-obstruction who developed parenteral nutrition induced hyperlipidaemia and who also had ophthalmoplegia and an undifferentiated myopathy is described. Histological examination of biopsy specimens and molecular analysis show that this patient had both familial visceral myopathy and a mitochondrial myopathy, suggesting that a mitochondrial DNA mutation is the molecular lesion in familial visceral myopathy.

Adult↗

Safe working practices and HIV infection: knowledge, attitudes, perception of risk, and policy in hospital.

OBJECTIVES--To assess the knowledge, attitudes, and perceptions of risk of occupational HIV transmission in hospital in relation to existing guidelines. DESIGN--Cross sectional anonymous questionnaire survey of all occupational groups. SETTING--One large inner city teaching hospital. SUBJECTS--All 1530 staff working in the hospital in October 1991 and 22 managers. MAIN MEASURES--Knowledge of safe working practices and hospital guidelines; attitudes towards patients with AIDS; perception of risk of occupational transmission of HIV; availability of guidelines. RESULTS--The response rate in the questionnaire survey was 63% (958/1530). Although staff across all occupational groups knew of the potential risk of infection from needlestick injury (98%, 904/922), significantly more non-clinical staff (ambulance, catering, and domestic staff) than clinical staff (doctors, nurses, and paramedics) thought HIV could be transmitted by giving blood (38%, 153/404 v 12%, 40/346; chi 2 = 66.1 p < 0.001); one in ten clinical staff believed this. Except for midwives, half of staff in most occupational groups and 19% (17/91) of doctors and 22% (28/125) of nurses thought gloves should be worn in all contacts with people with AIDS. Most staff (62%, 593/958), including 38% (36/94) of doctors and 52% (67/128) of nurses thought patients should be routinely tested on admission, 17% of doctors and 19% of nurses thought they should be isolated in hospital. One in three staff perceived themselves at risk of HIV. Midwives, nurses, and theatre technicians were most aware of guidelines for safe working compared with only half of doctors, ambulance, and paramedical staff and no incinerator staff. CONCLUSIONS--Policy guidelines for safe working practices for patients with HIV infection and AIDS need to be disseminated across all occupational groups to reduce negative staff attitudes, improve knowledge of occupational transmission, establish an appropriate perception of risk, and create a supportive and caring hospital environment for people with HIV. IMPLICATIONS--Managers need to disseminate policy guidelines and information to all staff on an ongoing basis.

Acquired Immunodeficiency Syndrome↗

Destructive spondyloarthropathy in a patient on continuous ambulatory peritoneal dialysis for 13 years.

Since 1984 there have been reports of a destructive spondyloarthropathy occurring in patients on long-term hemodialysis. The primary abnormality appears to be an accumulation of beta 2-microglobulin, which is not adequately removed by dialysis, and forms amyloid deposits in articular and periarticular tissues. We report a case of this disease in a patient treated only by peritoneal dialysis. While this form of treatment may delay the development of arthropathy, as compared to hemodialysis, it does not prevent it. An increasing incidence of this disorder may be expected, since increasing numbers of patients have been on long-term peritoneal dialysis.

Aged↗

Candoxatril, an orally active neutral endopeptidase inhibitor, raises plasma atrial natriuretic factor and is natriuretic in essential hypertension.

OBJECTIVE: Candoxatril (UK79,300) is an orally available inhibitor of the neutral endopeptidase (E.C.3.4.24.11) which degrades atrial natriuretic factor (ANF). This study was designed to establish initial safety and efficacy data in essential hypertension for this novel class of drug. DESIGN: A prospective, double-blind, placebo-controlled, single-dose comparison of candoxatril with placebo in a crossover manner. Three doses of candoxatril (10, 50 and 200 mg) were used, with four subjects at each dose level. SETTING: The Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow, UK (a hospital clinical research unit). PATIENTS: Twelve patients with untreated essential hypertension. Diastolic blood pressure was greater than 95 mmHg on three separate occasions before entry to the study. INTERVENTION: Candoxatril or matching placebo was administered orally in the fasting state. Serial measurements of urinary volume and electrolyte excretion were taken (on each hour, urine volume was replaced with an equivalent volume of water by mouth). Blood pressure and heart rate were recorded for 12 h after drug administration and serial blood samples were taken for measurement of plasma ANF and neurohormone concentrations. MAIN OUTCOME MEASURES: Urine volume and electrolyte concentration; blood pressure; heart rate; plasma atrial natriuretic factor. RESULTS: Plasma ANF concentrations rose significantly in all patients within 2 h of candoxatril administration compared with placebo although peak and integrated ANF levels were similar at all three doses. A significant natriuresis was only seen after 200 mg candoxatril, with a greater cumulative urine sodium excretion over 12 h compared with placebo; this was associated with a greater diuresis over 12 h compared with placebo. After a single oral dose of candoxatril, blood pressure and heart rate remained unchanged. CONCLUSIONS: Candoxatril in a single dose caused no adverse effects in essential hypertension. The drug caused a rise in basal ANF levels at all doses, but natriuresis was only seen with the highest dose used. No change in blood pressure was recorded after acute dosing, and the results of chronic studies with this compound are awaited. Oral inhibitors of ANF degradation may have therapeutic potential in cardiovascular disorders.

Administration, Oral↗

Lesions of the tunica media in traumatic rupture of vertebral arteries: histologic and biochemical studies.

Discontinuous non-circumferential lesions of tunica media were observed in four cases of traumatic rupture of the vertebral artery. We hypothesize that these lesions were due to mechanical disruption of smooth muscle cells and the liberation of catabolic enzymes with subsequent degradation of the arterial media. To test this hypothesis, healthy vertebral arteries were incubated with crude extracts of bovine smooth muscle cytosol in attempt to reproduce the histological changes of the arterial media in traumatized vertebral arteries. We observed cytosol-induced degradation of tunica media, characterized by pallor of staining with the Masson's Trichrome method, which was due to catabolic enzyme activity that was effectively inhibited by heat inactivation of the cytosol. The cytosol-induced tinctorial changes were similar to the lesions of the tunica media in naturally-occurring cases of traumatic vertebral artery rupture. We conclude that although vertebral arteries can be ruptured by physical distortion alone, associated lesions of the tunica media are due to in situ trauma-associated release of heat-labile catabolic enzymes.

Adult↗

On-site occupational health nursing services: estimating the net savings: Part I.

1. The following question can be successfully answered with a well developed quantitative assessment model: Is more money likely to be saved from the services of an on-site occupational health nursing program than is expended in providing these services? 2. The focus of this evaluation should be restricted to the net cost savings from the direct substitution of on-site for off-site provision of occupational health nursing services by such programs. 3. The evaluation model requires estimates of five separate factors for each occupational health nursing service provided by such programs that directly substitute for its off-site provision.

Health Education↗

On-site occupational health nursing services: estimating the net savings: Part II.

1. A primary management use of this quantitative assessment model is to estimate the overall net cost savings from operating an entire on-site occupational health nursing program. 2. Another management use of this model is to estimate the net cost savings contributed by individual occupational health nursing services included in the on-site program. 3. The exclusive focus of the model on the net cost savings arising from the direct substitution of on-site for off-site occupational health nursing services can be extended with the application of a break even analysis. 4. A sensitivity analysis can be applied to factors of the model to help overcome the effects of substantial uncertainty concerning their estimates.

Cost Savings↗

Ultrastructure of melatonin-responsive cells in the ovine pars tuberalis.

Functional receptors for melatonin have been localized and characterized on the pars tuberalis (PT) of a number of mammalian species, but the cell-type responsive to melatonin is unknown. The ultrastructure of the ovine pars tuberalis has been examined and these findings correlated with the functional response of the gland to melatonin. This study revealed that two secretory cell types predominate in the ovine PT, which differ in the abundance of dense-core granules. The most abundant of the cells are either agranular or very sparsely granulated and represent 90% of the total population, with the remaining 10% being composed of cells with abundant dense-core vesicles. Few follicular cells were observed. This ratio of secretory cell-types persisted in primary culture, with the two types non-separable by Percoll gradient centrifugation. Using forskolin, as a non-specific stimulant of adenylate cyclase, melatonin was shown to inhibit the formation of cyclic AMP by 80-90% in cells both before and after Percoll centrifugation. The results demonstrate that the agranular secretory cells of the ovine pars tuberalis are the melatonin responsive cell-type of this gland.

Animals↗

Low-grade astrocytoma of the tectal region as an unusual cause of knee pain: case report.

A 12-year-old boy was investigated for knee pain and contractures, and was found to have an intraspinal tumor of a lumbar nerve root and a tumor in the tectal region, both low-grade astrocytomas. We postulated that the tectal region astrocytoma metastasized to the lumbar intraspinal region. After surgery, the child underwent focal irradiation to the posterior fossa supplemented by craniospinal irradiation and a boost dose to the region of the lumbar spinal tumor. A low-grade astrocytoma rarely presents as spinal metastasis. This case may represent the first of a primary tectal low-grade astrocytoma manifesting as a symptomatic spinal mass.

Astrocytoma↗

Intracellular signalling in the ovine pars tuberalis: an investigation using aluminium fluoride and melatonin.

The effect of aluminium fluoride (AlF4-) has been studied on inositol phosphate accumulation, calcium mobilization, cyclic AMP production and [2-125I]iodomelatonin binding in ovine pars tuberalis cells. These cells have high-affinity receptors for, and respond to, melatonin through inhibition of forskolin-stimulated adenylate cyclase. In the presence of 10 mM LiCl, AlF4- stimulated the net accumulation of inositol monophosphate and inositol bisphosphate. Consistent with these findings, AlF4- increased intracellular calcium; although this response was attenuated in calcium-depleted medium, indicating that the calcium response comprises both intracellular and extracellular components. Melatonin was ineffective on either basal or AlF4(-)-stimulated turnover of inositol phosphates. In concordance with the inositol phosphate response, melatonin had no effect on either the AlF4(-)-stimulated or the basal calcium levels. AlF4- blocked the increase in cyclic AMP stimulation by 1 microM forskolin, being as effective as melatonin, achieving approximately 90% inhibition. AlF4- also attenuated the binding of [2-125I]iodomelatonin to ovine pars tuberalis membranes by 15%. At the concentration used, these results are consistent with the interpretation that AlF4- activates many G protein-mediated responses, and thus imply that the inhibitory pathway for cyclic AMP predominates over the stimulatory arm, whereas there can only be a stimulatory pathway linked to phosphoinositide metabolism in ovine pars tuberalis cells.

Aluminum↗

The atriopeptidase inhibitor UK 69,578 increases atrial natriuretic factor and causes a natriuresis in normal humans.

The endopeptidase EC 3.4.24.11 (atriopeptidase) degrades atrial natriuretic factor (ANF). Intravenous administration of UK 69,578 (0.025 to 10.0 mg/kg), a new specific atriopeptidase inhibitor, in 16 normal volunteers produced a two- to three-fold rise in endogenous ANF. Peak levels were reached within 2 h declining to control values by 8 h. The rise in ANF was associated with an increase in urine volume and mean urinary sodium excretion rose from 64.9 mmoles/8 h after placebo to 116.1 mmoles/8 h after 10 mg/kg UK 69,578. Despite the natriuresis, plasma active renin concentration was suppressed for up to 8 h. We conclude that inhibition of the endopeptidase EC 3.4.24.11 in humans elevates endogenous ANF and causes a natriuresis and may offer a novel therapeutic approach to the treatment of hypertension and cardiac failure.

Adult↗

A comparison of calcium pentagastrin and TRH tests in screening for medullary carcinoma of the thyroid in MEN IIA.

Intravenous injections of calcium gluconate and pentagastrin (CPG) or TRH were compared as secretagogues for calcitonin (CT) in screening for medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type IIA (MEN IIA). Administration of CPG resulted in a prompt increase in plasma CT in all five patients with MTC studied, one of whom had a normal baseline value (peak 412-371,000 ng/l, 636-4847% above basal). TRH produced a rise in plasma CT levels only in MTC patients with elevated basal values; the magnitude of increase was less than that observed with CPG (peak 168-17,200 ng/l, 113-180% above basal). CT levels did not rise above 300 ng/l with either test in four unaffected first-degree relatives of MEN IIA patients, three subjects with sporadic unilateral phaeochromocytomas and five controls with essential hypertension. CPG remains the CT secretagogue of choice in screening for MTC in MEN II A.

Adult↗

Monte Carlo simulation of HIV infection in an intravenous drug user community.

Intravenous drug users are crucial to the understanding and control of human immunodeficiency virus (HIV) transmission. We have developed a population-based simulation of a community of intravenous drug users. This model was implemented using Monte Carlo techniques, which permit great flexibility in creating realistic social structures, to describe the needle-sharing network of drug users. We present the baseline behavior of this model in a generic community and demonstrate the model's utility for assessing public health interventions. Our early results demonstrate the powerful effects of social networks on HIV transmission and the importance of prevalence levels in assessing the effectiveness of interventions in the drug-injecting community.

Equipment Contamination↗