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Biomedical subjects

D Owens

Publications and source records attributed to D Owens.

At least 19 recordsLinked to original sources

Alterations in cellular cholesterol metabolism following administration of 6-hydroxydopamine to rabbits.

1. The role of adrenergic mechanisms in the regulation of cholesterol metabolism was investigated by studying the effects of 6-hydroxydopamine (6-OHDA) on serum cholesterol levels and on the activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-O-acyl-transferase (ACAT) in the livers and intestines, and cholesterol 7 alpha-hydroxylase in the livers of male New Zealand White rabbits. 2. Total serum cholesterol levels were significantly reduced (P less than 0.01) in 6-OHDA-treated animals. This was reflected in the very low density lipoprotein, low density lipoprotein and high density lipoprotein fractions. The reduction in lipoprotein cholesterol levels reflected reduced cholesterol proportions in the lipoprotein fractions. 3. The 6-OHDA-treated animals also had significantly lower activities of intestinal (P less than 0.001) and hepatic (P less than 0.01) HMGCoA reductase. The specific activities of intestinal ACAT, hepatic ACAT and cholesterol 7 alpha-hydroxylase were comparable in both groups. 4. In contrast to the results observed in vivo, 6-OHDA did not have any in vitro effect on cholesterol biosynthesis in cultured human leucocytes. 5. This latter finding suggests that the effects of 6-OHDA on cellular cholesterol biosynthesis in vivo are indirect, possibly resulting from the known toxic effect of this drug in sympathetic nerve terminals, and imply a potential role for the sympathetic nervous system in the regulation of cellular cholesterol biosynthesis in vivo.

Animals

Horner's syndrome in severe tetanus.

A 66 year old man was admitted with a left Horner's syndrome, and trismus due to tetanus. Three days later he had respiratory arrests, classical tetanic spasms and was ventilated. He had associated severe autonomic dysfunction, tachyarrhythmias, hypotension, sweating and constipation. There was complete resolution of the left Horner's syndrome with recovery from tetanus.

Aged

Factors related to the presentation of patients with thick primary melanomas.

OBJECTIVE: To identify any characteristics of patients that are associated with presentation with thick primary melanoma. DESIGN: This was a retrospective survey of the clinical records of 1300 patients attending the Newcastle Melanoma Unit. Characteristics of 131 patients with thick melanomas (defined as 3 mm or greater in thickness) were compared with those of 543 patients with thin melanomas (defined as 0.75 mm or less in thickness). Comparisons were made using contingency table analysis, Wilcoxon rank sum tests, log rank analysis and logistic regression. SETTING: The Newcastle Melanoma Unit is a tertiary referral centre for the treatment of primary melanoma. PATIENTS: We surveyed all 1300 patients attending the Newcastle Melanoma Unit over the years 1981-1990. They represented approximately 90% of the patients in the Hunter region of New South Wales who developed melanoma during this period. Excluded from analysis were 39 patients with occult primary melanomas, 79 with multiple primary melanomas, 51 with primary melanomas of unknown thickness and seven with incomplete records, leaving 1124 patients in the study. MAIN OUTCOME MEASURES: These were selected before the results were known. The hypothesis was generated following analysis of the data. RESULTS: Patients with thick primary melanoma were more likely to be men (68% men and 32% women in the thick melanoma group, compared with 45% and 55% respectively in the thin melanoma group, P less than 0.005) over 60 (75% were over 50 years of age in the thick group versus 33% in the thin melanoma group, P less than 0.001) with nodular melanoma (62%, versus 2% in the thin melanoma group, P less than 0.001) and with melanoma on the head and neck (27%, versus 12% in patients with thin melanoma, P less than 0.005). The time from detection of a change in skin to diagnosis was not longer for those with thick compared to those with thin melanomas. CONCLUSION: The greatest problem of those with thin melanomas. CONCLUSION: The greatest problem of detecting melanoma at an early (surgically curable) stage appears to be in patients over the age of 50 who have nodular melanoma, particularly in the head and neck.

Adolescent

Hypercholesterolaemia: simvastatin and pravastatin alter cholesterol metabolism by different mechanisms.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin, reduced low-density-lipoprotein (LDL) cholesterol in hypercholesterolaemic patients by 40% (P less than 0.001). The reduction in LDL cholesterol was accompanied by a significant decrease in the esterified/free cholesterol ratio of the patients' LDL from 2.51 +/- 0.13 to 2.06 +/- 0.14 (P less than 0.01). This change led to a significant increase (P less than 0.05) in the capacity of the LDL to suppress [14C]acetate incorporation into cholesterol in mononuclear leucocytes. Furthermore, [14C]acetate incorporation into the patients mononuclear leucocytes was significantly lower (P less than 0.02) following drug treatment (117 +/- 22 vs. 162 +/- 29 nmol/mg cell protein). Comparison of simvastatin with another HMG-CoA reductase inhibitor pravastatin, showed similar reduction in LDL cholesterol. Pravastatin treatment however, did not result in a reduction in the LDL esterified/free cholesterol ratio or in the changes in cellular cholesterol synthesis and its regulation by LDL which accompanied simvastatin treatment. The activity of the enzyme acyl-coenzyme A: cholesterol acyltransferase (ACAT) in patients' mononuclear cells remained unchanged after treatment with either drug. Results of the study show that while the drugs are equally effective in lowering LDL cholesterol, simvastatin has additional compositional effects on LDL which increase its capacity to regulate mononuclear leucocyte cholesterologenesis.

Adult

Serum lipoproteins and cholesterol metabolism in two hypercholesterolaemic rabbit models.

Serum lipoproteins and key hepatic and intestinal enzymes regulating cholesterol synthesis, esterification and catabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-o-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase respectively, were compared in two hypercholesterolaemic rabbit models - the cholesterol-fed animal and the hypercholesterolaemic diabetic animal. Hypercholesterolaemia in the cholesterol-fed animals was reflected in the VLDL and LDL fractions, whereas VLDL and HDL2 cholesterol levels were elevated in the diabetic animals. The lipoproteins of the cholesterol-fed animals were enriched with cholesterol but the lipoprotein fractions in the diabetic animals were enriched with triacylglycerol. While hepatic HMGCoA reductase activity was significantly reduced in both groups, the activities of hepatic ACAT and cholesterol 7 alpha-hydroxylase were significantly increased in the cholesterol-fed animals and significantly reduced in the diabetic animals compared with controls. In the intestine, the activity of HMGCoA reductase was increased and ACAT reduced in the diabetic animals. By contrast, in the cholesterol-fed group. HMGCoA reductase activity was lower and ACAT activity was higher in comparison with the control group. These differences in lipoproteins and cellular cholesterol metabolism between the hypercholesterolaemic rabbit models may explain the differences in susceptibility to atherosclerosis, previously reported in these two animal models.

Animals

Physical and emotional stress associated with components of the infertility investigation: perspectives of professionals and patients.

OBJECTIVE: The present study examined patients', nurses', and physicians' perceptions of the physical and emotional difficulty of infertility treatment. DESIGN: A mail survey method was used. PATIENTS, PARTICIPANTS: Participants included 26 patients, 76 nurses, and 71 physicians from infertility clinics in the United States and Canada. MAIN OUTCOME MEASURES: A rating scale measured the physical and emotional difficulty level of 36 components from the infertility investigation. RESULTS: Nurses rated the emotional and physical distress of patients higher than did patients and physicians, whereas patients rated their distress higher than did physicians. Older nurses and physicians inferred lower levels of physical and emotional distress than did their younger counterparts. A greater breadth of experience with infertility treatments was associated with higher ratings of emotional distress by nurses and lower ratings by physicians. CONCLUSIONS: Patients, nurses, and physicians perceive infertility treatment from unique vantage points creating differences in perceptions that have implications for patient care. Factors including era of professional training, stage of life, and changes resulting from advancing technology are viewed as influencing health care professionals' perceptions of infertility distress.

Adult

Ethnic factors in voluntary and compulsory admissions.

Socio-demographic and clinical aspects of compulsory and informal admissions to general adult psychiatry wards over a two-year period are compared. In addition, Afro-Caribbean patients are compared with white UK-born patients. Relative rates of admission are examined. The study confirms other reports of greater than expected compulsory admissions of Afro-Caribbean patients and pays particular attention to the circumstances preceding compulsory entry to hospital and the persons and agencies involved in that process.

Adolescent

Hypertriglyceridaemia and its influence on low density lipoprotein regulation of cellular cholesterol synthesis: a comparison between hypertriglyceridaemic diabetic and non-diabetic patients.

The present investigation was undertaken to examine the relationship between serum triglyceride and composition of lipoprotein. Six groups of patients were examined, three with Type 2 (non-insulin-dependent) diabetes and three without diabetes. The groups were further categorized on the basis of their serum cholesterol and triglyceride levels into normocholesterolaemic (serum cholesterol less than 6.5 mmol l-1) and hypercholesterolaemic (serum cholesterol greater than 6.5 mmol l-1) with and without hypertriglyceridaemia (serum triglyceride greater than or less than 3.5 mmol l-1). Low density lipoprotein (LDL) composition was determined and regulation of cholesterol synthesis by LDL was assessed by measuring its effect on [14C]-acetate incorporation into mononuclear leucocyte cholesterol. LDL from the hypercholesterolaemic diabetic patients had a significantly higher esterified cholesterol content when the patients were normotriglyceridaemic (1.14 +/- 0.04 vs 0.76 +/- 0.04 g g-1; p less than 0.01). The ability of LDL to suppress cholesterol synthesis (percent inhibition) was significantly less using LDL from the normocholesterolaemic diabetic patients or hypercholesterolaemic non-diabetic or diabetic patients compared with LDL from the normocholesterolaemic non-diabetic control subjects (47.4 +/- 3.9%, 39.1 +/- 5.1% and 35.2 +/- 4.1% vs 59.5 +/- 1.2%, p less than 0.01). However, hypertriglyceridaemia had no effect on LDL suppression of cholesterol synthesis. We conclude that hypertriglyceridaemia alters LDL composition but the alteration is not associated with the ability of LDL to regulate cholesterol synthesis.

Acetates

Upper gastrointestinal endoscopy in octogenarians.

A retrospective study of upper gastrointestinal endoscopy (GIE) in 217 octogenarians performed over a two-year period in a district general hospital was carried out. It showed that upper GIE in octogenarians is a safe and easy as in other age groups, and provides more useful information. Patients were referred mainly by the geriatricians for elective endoscopy, reflecting the growing recognition of the value of elective upper GIE in the very elderly. The incidence of peptic ulcer disease as a cause of upper GI bleeding was much less than previously reported. Thirty-nine patients with upper GI haemorrhage had an endoscopy within 24 hours. We believe that this helps to identify patients with a high risk of mortality and those who might benefit from early surgery. Eighty per cent of the patients had one or more associated diseases, but there were no complications from endoscopy. We would like to emphasise that there is no contraindication for upper GIE in very elderly patients.

Aged

Self-poisoning patients discharged from accident and emergency: risk factors and outcome.

In a prospective audit of 1,096 consecutive attendances by deliberate self-poisoning patients at an accident and emergency department (A&E), such patients were discharged directly from A&E on 31% of occasions. Outcome and risk were compared for patients admitted to hospital and discharged directly from A&E. In the following year repetition of self-poisoning occurred in the same proportions of patients admitted to hospital and discharged from A&E (12%, relative risk 1.02). Suicide during the following three years occurred in 1.3% of patients admitted and 1.1% of those discharged (relative risk 1.2). Patients admitted to hospital from A&E were those likely to be at greater risk: they were older, reported more physical ill-health, expressed a threat or left a note more often, and had more frequently experienced psychiatric inpatient care. Thus, nearly one-third of deliberate self-poisoning attenders were discharged from A&E; outcomes were similar despite higher risk among admitted patients, suggesting that brief admission has some benefit.

Adolescent

Cellular cholesterol metabolism in mitogen-stimulated lymphocytes--requirement for de novo synthesis.

The relationship between cholesterol synthesis and uptake in proliferating lymphocytes has been examined. [14C]Acetate incorporation into lymphocytes cultured under lipoprotein-deficient conditions increased initially in response to mitogen, decreased after 24 h, and increased rapidly between 72 and 96 h. Addition of LDL (10 micrograms/ml) to the culture during the 'trough' period caused [14C]acetate incorporation to return rapidly to baseline, while at peak periods LDL suppression of cholesterol synthesis was minimal. Lymphocytes cultured in the presence of the HMG-CoA reductase inhibitor, mevinolin, exhibited a time-dependent increase in their capacity to incorporate [14C]acetate into cholesterol, evident when mevinolin was removed by washing prior to assay. PHA enhanced 125I-labelled LDL receptor-mediated binding by lymphocytes cultured in lipoprotein-deficient medium over a 4 day period and mevinolin augmented the effect. [3H]Thymidine incorporation into mitogen-stimulated lipoprotein-deficient cultures was inhibited up to 75% by mevinolin (1 mumol/l). LDL (2.5-10 micrograms/ml) substantially reversed this inhibition in 72 h cultures, but only partially overcame inhibition in cells cultured for 96 h. Results suggest that endogenous cholesterol synthesis may be obligatory for lymphocyte proliferation after the initial round of cell division.

Acetates

Cellular cholesterol regulation--a defect in the type 2 (non-insulin-dependent) diabetic patient in poor metabolic control.

This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p less than 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.

Apolipoproteins B

Cholesterol metabolism in alloxan-induced diabetic rabbits.

The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated with lipid and lipoprotein levels. Although intestinal HMG-CoA reductase activity was significantly increased (P less than 0.001) in poorly controlled compared with moderately controlled diabetic rabbits, there was a significant reduction in the activities of intestinal ACAT (P less than 0.01), hepatic HMG-CoA reductase (P less than 0.05) and ACAT (P less than 0.001), and phenol 2-monooxygenase (P less than 0.01). The poorly controlled animals were hypercholesterolemic (P less than 0.01), and this was reflected in the very-low-density and high-density lipoprotein fractions. Serum cholesterol levels in the nondiabetic and moderately controlled diabetic groups were similar. This increase in intestinal HMG-CoA reductase activity in the poorly controlled diabetic animals occurred in the absence of hyperphagia. Although abnormalities in cellular cholesterol metabolism could be partly responsible for the alterations in serum cholesterol levels in diabetes, the precise mechanisms underlying these enzymatic changes have yet to be elucidated.

Alloxan