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Biomedical subjects

M Ryan

Publications and source records attributed to M Ryan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection.

Antimony potassium tartrate (APT) is a complex salt that until recently was used worldwide as an antischistosomal drug. Treatment was efficacious only if APT was administered intravenously to humans at a near lethal total dose of 36 mg/kg. Because unconfirmed epidemiologic studies suggested there might be an association between APT treatment and bladder cancer, we initiated prechronic toxicity studies with the drug to select a route of administration and doses in the event that chronic studies of APT were needed. The toxicity and concentration of tissue antimony levels were compared in 14-d studies with F344 rats and B6C3F1 mice administered APT in the drinking water or by ip injection to determine the most appropriate route for longer term studies. Drinking water doses estimated by water consumption were 0, 16, 28, 59, 94 and 168 mg/kg in rats and 0, 59, 98, 174, 273, and 407 mg/kg in mice. APT was poorly absorbed and relatively nontoxic orally, whereas ip administration of the drug caused mortality, body weight decrements, and lesions in the liver and kidney at doses about one order of magnitude below those in drinking water. Because of these data and the dose-related accumulation of antimony in the target organs, an ip dose regimen was selected for subsequent studies. Both sexes of F344 rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, and 24 mg/kg doses of APT every other day for 90 d by ip injection. There were no clinical signs of toxicity nor gross or microscopic lesions in mice that could be attributed to toxicity of APT, although elevated concentrations of antimony were detected in the liver and spleen of mice. Rats were more sensitive than mice to the toxic effects of APT, exhibiting dose-related mortality, body weight decrements, and hepatotoxicity. The concentrations of antimony measured in liver, blood, kidney, spleen, and heart of rats were proportional to dose, but there were no biochemical changes indicative of toxicity except in the liver. Hepatocellular degeneration and necrosis occurred in association with dose-related elevations in activities of the liver-specific serum enzymes sorbitol dehydrogenase and alanine aminotransferase. By alternating the site of abdominal injection and the days of treatment, mesenteric inflammation at the site of administration was minimized in the rats and mice, indicating that the ip route would be suitable for chronic studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1991

Magnetic resonance imaging in the assessment of rheumatoid arthritis--a comparison with plain film radiographs.

Conventional radiography lacks sensitivity in early rheumatoid disease. MRI with its advantages of soft tissue discrimination and multiplanar imaging facility might detect earlier disease. This study compares the MR images and conventional radiographs of 11 rheumatoid patients' wrists and carpi. In all cases, erosions were more extensive and numerous on the MR images compared to plain radiographs. MR is useful in detecting early aggressive disease and in monitoring the response to treatments.

Adult↗
PubMed1991

Risk information for public consumption: print media coverage of two risky situations.

This study examines (1) the extent to which newspaper and magazine coverage of two risky situations included the kinds of cognitive information about risks that would help readers make risk judgments and (2) the extent to which the scientific sophistication of the audience would influence such inclusion. The two situations were a nuclear power plant accident that released a small amount of radioactive steam into the atmosphere and a report in the New England Journal of Medicine about a potential relationship between coffee consumption and pancreatic cancer. Stories about each topic in trade magazines, popular science magazines, general magazines, and both prestige and more typical daily newspapers were examined to determine the nature and extent of risk information included. The analysis found more detailed risk information in these stories than has been found in past studies, but it also suggested that sophistication of audience was not a good predictor of the presence/absence of such information. The most pronounced differences in communication strategies were found instead between topics, not across types of media. Closer examination of individual stories suggests that the variance may be attributable to differences in the way stories about the two incidents were framed by journalists.

Accidents↗
PubMed1991

Heparin as a therapy for atherosclerosis: preliminary observations on the intrapulmonary administration of low-dose heparin in the morning versus evening gauged by its effect on blood variables.

Reports on clinical trials with subcutaneous and intrapulmonary administration of low-dose heparin suggest that it may be an attractive therapeutic modality for the treatment of coronary artery disease because of unprecedented reduction in mortality of treated subjects. As a preliminary to a clinical trial with low-dose intrapulmonary heparin, a pilot study was conducted on three subjects. It compares overall circadian responses of 37 blood variables following intrapulmonary administration of heparin (10,500-18,800 U) in the morning (0800 h) and in the evening (2000 h). After each of these times, blood samples, mostly at 3 h intervals for the ensuing 27 h, were analyzed for heparin, APTT, TT, functional fibrinogen, CBC, enzymes, lipids, electrolytes, and hormones. Each time series was analyzed for circadian rhythm by the least-squares fit of a 24 h cosine and circadian mesors were compared by the Bingham test of rhythm parameters. Following heparin in the evening, but not in the morning, a statistically significant increase in circulating heparin levels, as well as directional increases in APTT and TT and decreases in fibrinogen, were observed in all three subjects. Same direction changes in several other variables were also observed. It is concluded that inhalation of heparin in low-dose levels results in variable circadian effects on blood parameters measured, ranging from no changes in their levels to minimal within normal range changes, and that these effects are dependent upon the timing of dose administration. It is suggested that the timed self-administration of low-dose heparin by inhalation be seriously considered for long-term clinical trials in the treatment and prevention of atherosclerosis.

Administration, Inhalation↗
PubMed1991

Lung CT density correlates with measurements of airflow limitation and the diffusing capacity.

We studied 80 subjects (63 M, 17 F; 23-82 yrs) and related lung computerized tomography (CT) density with age, height, spirometry, lung volumes, diffusing capacity and arterial blood gas tensions. These subjects demonstrated a wide range of physiological impairment (forced expiratory volume in one second (FEV1) 8-116% predicted; diffusing capacity (Kco) 15-139% predicted; arterial oxygen tension (Pao2) 38-91 mmHg). They ranged from normal subjects to patients with chronic respiratory failure. Lung density was derived from CT density histograms measured as both mean Emergency Medical Information (EMI) number (EMI scale: 0 = water, -500 = air, EMI number of normal lung tissue range approximately -200 to -450) and the lowest 5th percentile EMI number, the latter value being more likely to represent the density of lung parenchyma. Lung CT density correlated most strongly with airflow obstruction (EMI 5th percentile versus FEV1/forced vital capacity (FVC) % predicted, r = 0.73, p less than 0.001) and diffusing capacity (EMI 5th percentile versus Kco, r = 0.77, p less than 0.001). This suggests that reduction in lung density, which reflects loss of the surface area of the distal airspaces, is a major index of respiratory function in patients with smoking related chronic obstructive pulmonary disease (COPD). These data provide no indication of other factors such as small and large airways disease, and loss of elastic recoil, which may contribute to airflow limitation, or disruption of the pulmonary vascular bed which may also affect CT lung density.

Adult↗
PubMed1990

Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers.

A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose-related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.

Adult↗
PubMed1990

Scottish general practitioners' attitudes and knowledge in respect of prescribing costs.

The government's proposal to introduce drug budgets will compel general practitioners to consider the financial consequences of prescribing. A survey was carried out of general practitioner principals in Grampian and a sample elsewhere in Scotland to examine their attitudes towards considering costs when prescribing and assess the accuracy of their knowledge of drug costs. Most general practitioners agreed that costs should be borne in mind when choosing medicines but their knowledge of drug costs was often inaccurate. Only one third of estimates were correct to within 25% of the actual cost, and there was a tendency to overstate the cost of cheap drugs and understate the cost of expensive ones. Some general practitioners were not aware of the relative prices of competing products or proprietary products and generic equivalents. The findings highlight the importance of providing general practitioners with readily accessible and up to date information on drug costs if prescribing budgets are to work.

Attitude of Health Personnel↗
PubMed1990

Expression of HLA ABC and DR antigens in thyroid neoplasia and correlation with mononuclear leukocyte infiltration.

The rejection of tumor cells by the immune system depends on the production of tumor-associated antigens and the expression of HLA antigens on these cells. We therefore studied the expression of HLA ABC and DR antigens in malignant and benign thyroid disorders and correlated it with the types and extent of mononuclear cell infiltration. In the normal thyroid, HLA ABC expression was weak and focal, while it was diffusely present in benign disorders and in most but not all malignancies. HLA DR antigens, while absent or infrequently expressed in normal thyroid, were strongly but often focally expressed in all cases of autoimmune thyroid disease (AITD), as well as in most cases of malignant tumors and benign epithelium surrounding these tumors, and colloid nodule disease. There was a T cell predominance in all disorders, and the CD4+/CD8+ ratio was greater than 1 in most benign and malignant specimens. There was a direct correlation between the high expression of HLA antigens and dense inflammatory infiltration in AITD but not in most tumor specimens. Lack of such correlation suggests that the expression of HLA antigens is an autonomous event in tumors, independent of cellular infiltrate.

Antibodies, Monoclonal↗
PubMed1990

Surface immunoglobulin-positive T lymphocytes in HIV-1 infection: relationship to CD4+ lymphocyte depletion.

T lymphocytes bound to autologous immunoglobulin (surface Ig + T cells) and serum antibodies that bind to allogeneic lymphocytes have been detected in HIV-1-infected individuals, but their significance in the immunopathogenesis of HIV-1 infection is uncertain. We tested peripheral blood from HIV-1-infected individuals to determine if surface Ig+ T cells are specific for HIV-1 infection and are associated with CD4+ lymphocyte depletion. The majority of HIV-1-infected individuals contained substantial numbers of circulating surface Ig+ T cells. The presence of such cells was restricted to seropositive individuals and not related to risk factors associated with the acquisition of HIV-1 infection. Autologous immunoglobulin was detected on both CD4+ and CD8+ cells in all patients tested. Most individuals with surface Ig+ T lymphocytes also had serum anti-T-lymphocyte antibodies. The presence of surface Ig+ T lymphocytes correlated significantly with lower absolute CD4+ lymphocyte counts only in asymptomatic, HIV-1-infected individuals.

Antigens, CD↗
PubMed1990

The effect of diclofenac and nefopam on postoperative dental pain.

Eighty-two outpatients who received general anaesthesia for surgical removal of maxillary or mandibular third molars were given either diclofenac 75 mg or nefopam 20 mg intramuscularly for postoperative pain control. They and the control group were also allowed oral paracetamol as required. The results showed that there was no significant pain relief from these single intramuscular injections.

Adult↗
PubMed1990

Movement of the femoral head after Salter osteotomy for acetabular dysplasia.

A Salter innominate osteotomy is used to treat acetabular dysplasia, but reports of its effects on the position of the femoral head are few and conflicting. Lateral shift would increase the resultant forces acting on the joint and be detrimental. We studied 15 Salter innominate osteotomies and demonstrated that a correctly performed osteotomy does not significantly alter the distance from the centre of the femoral head to the midline of the body. Stereophotogrammetry was used in three patients to delineate the axis of rotation of the distal acetabular fragment and determine the locus of movement of the centre of the femoral head about it. Our results explain why the Salter osteotomy does not lateralise the femoral head.

Acetabulum↗