Simvastatin use in children.
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Biomedical subjects
Publications and source records attributed to M Thomson.
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Soluble rat tail tendon collagen produced respiratory distress, agitation, convulsions and finally death in rabbits when infused intravenously (i.v.) in lethal doses. Similar observations were noted when a lethal dose of arachidonic acid (unsaturated essential fatty acid) was infused. These agents caused thrombocytopenia, indicative of in vivo platelet aggregation, hypotension and increased levels of thromboxane (TX) B2 (a stable metabolite of TXA2) in the plasma. Histopathological examination of lung, heart and liver tissue indicated that the lungs and livers of treated animals were adversely affected, while heart tissues appeared to be normal. Histopathological examination of lung and liver tissues of animals pretreated with garlic, then treated with a lethal dose of collagen or arachidonic acid showed a significant reduction in the damage observed compared to animals not pretreated with garlic.
OBJECTIVE: To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN: Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING: Edinburgh, Scotland. SUBJECTS: 107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION: The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES: Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS: Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION: Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes.
High levels of platelet activating factor (PAF) activity were demonstrated by platelet aggregation and serotonin release assays to be present in fright induced epidermal secretions of the Arabian Gulf catfish, Arius bilineatus (Valenciennes, 1840). The PAF activity was purified by thin-layer chromatography. Mass spectral analysis combined with chemical and enzymatic modification of the purified PAF and inhibitor studies indicated that PAF activity was due to the presence of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine (AGEPC) molecules. The total AGEPC concentration in the epidermal secretions based on PAF assays was 8 x 10(8) M, well above the threshold level for platelet activation which is near 5 x 10(-11) M. Thus, stimulated epidermal secretory cells of Arius bilineatus supply platelet activating molecules at physiologically high concentrations to sites of injury.
Different preparations of soluble collagen, from rabbit skin, rat skin, rat tail tendon and guinea-pig skin, produced respiratory distress, agitation, convulsions and finally death when infused intravenously in lethal doses. Analysis of plasma enzyme levels indicated significant increases in total, cardiac and hepatic lactate dehydrogenase, suggesting that damage to the liver occurred as a result of collagen infusion. Histopathological examination of lungs, livers and hearts of collagen-treated rabbits confirmed that damage had occurred to the lungs and livers of these animals, while heart tissues appeared to be normal. The source of collagen did not appear to influence its toxicity at the tissue level.
Plasma cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin and corticotrophin releasing hormone or factor (CRF) all rise progressively as pregnancy advances, and fall postnatally. The placenta produces large amounts of CRF in the third trimester and this is released into the maternal circulation. Present evidence suggests that it stimulates the maternal pituitary to produce ACTH while desensitizing the maternal pituitary to further stimulation with CRF. Maternal control of ACTH production is retained, allowing a persistent response to stress and a diurnal rhythm, perhaps through the secretion of vasopressin. The placenta also produces pro-opiomelanocortin peptides; however, the nature of the fragments produced from the precursor differs from that formed in the anterior pituitary of the mother and the role of these fragments in the control of maternal adrenal function is unclear. These changes in the hypothalamo-pituitary-adrenal axis during pregnancy are associated with loss of the normal suppression of cortisol by dexamethasone and elevated basal levels of cortisol with preservation of a diurnal rhythm, features also found in some patients with endogenous depression. Several studies have suggested a relationship between alterations in maternal concentrations of cortisol and beta-endorphin and the development of postnatal mood disturbances.
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After a substantial increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the Cardiothoracic Surgical Unit at St. Vincent's Hospital, Sydney, a prospective study was undertaken in early 1986 to ascertain the carrier status of all patients entering the Unit. Of 84 patients, 27.4% were found to carry MRSA and the perineum was the major site of carriage, with 69.6% of MRSA positive cases carrying the organism in this site. As a result of these findings, the period of perioperative antibiotic cover was shortened, whole-body washing of patients with a 1% triclosan preparation was instituted and routine postoperative perineal swabs were taken. During the 18 months after implementation of these policies, a highly significant reduction in the number of MRSA carriers and infections was observed. The monitoring of perineal colonization proved to be a useful marker for increases in MRSA in the Unit.
Three new proteins with cardiac stimulatory and haemolytic activity, designated tenebrosins-A, -B and -C, have been purified from the Australian sea anemone Actinia tenebrosa. These proteins are basic (pI greater than or equal to 9.4), have mol. wt of about 20,000, and have very similar amino acid compositions and N-terminal amino acid sequences. None of the proteins contains cysteine or cystine residues. On isolated, spontaneously beating guinea pig atria they exhibit at 1-2 nM strong positive inotropic and slight to moderate chronotropic effects. In some cases a transient negative inotropic effect occurs prior to onset of the positive inotropic response. The proteins are also haemolytic, producing 50% haemolysis of guinea pig erythrocytes at concentrations similar to those showing positive inotropic effects.
Rabbits were given collagen and arachidonic acid intravenously. Blood pressure, platelet counts, plasma thromboxane-B2 (TXB2) and plasma 6-keto-prostaglandin F1 alpha, (6-keto-PGF1 alpha) were determined. Both thrombogenic agents, upon infusion of a lethal dose, caused thrombocytopenia, indicative of in vivo platelet aggregation and hypotension. These changes were associated with an increase in plasma levels of TXB2 and 6-keto-PGF1 alpha measured by radioimmunoassay (RIA). Pretreatment of rabbits with an aqueous extract of garlic (500 mgkg) provided protection from thrombocytopenia and hypotension. Thromboxane-B2 synthesis was significantly reduced in animals pretreated with garlic and then injected with a lethal dose of either collagen or arachidonic acid. The amount of TXB2 synthesized in these animals was not sufficient to induce thrombocytopenia or hypotension. All animals pretreated with garlic were well protected against the effects of collagen or arachidonate infusion, and no apparent symptoms were observed in these animals. These observations indicate that garlic may be beneficial in the prevention of thrombosis.
Nutrient intakes in four areas of the UK were compared, 7-d weighed intake data were obtained for representative community samples of middle-aged men in Caerphilly (South Wales), Northern Ireland, Edinburgh and Bristol (Speedwell). Intakes of energy were higher in Edinburgh than in the other three areas, but following allowance for this, differences in nutrient intakes were very small. The exceptions were P/S ratio and alcohol consumption. The P/S ratio for Northern Ireland (0.38) was considerably higher than that for the other areas (0.30 to 0.32). The proportion of heavy drinkers was higher in Edinburgh (15 per cent) than in other areas (5-9 per cent) and the proportion of abstainers was highest in Northern Ireland (38 per cent). Differences in nutrient intakes did not parallel the differences in ischaemic heart disease (IHD) mortality rates between the areas.
The safety and efficacy of lisinopril in the treatment of mild to moderate essential hypertension was evaluated by Belgian general practitioners in patients whose hypertensive condition remained uncontrolled by previous treatment and/or in whom the prior drug regimen was not tolerated. In this 8-week study, 3060 eligible patients were initially treated with 20 mg lisinopril once daily; this dose was increased to 40 mg if diastolic blood pressure (DBP) was greater than 90 mm Hg after 4 weeks. Lisinopril monotherapy in the 1902 patients completing the trial resulted in marked reductions of systolic (SBP) and DBP from 172.5/102.4 mm Hg at baseline to 147.4/86.6 mm Hg by week 8. More than 90% of patients achieved a DBP less than 95 mm Hg. The decrease in blood pressure was similar in patients older and younger than 65 year of age. Only about 20% of patients required an increase in their daily intake of lisinopril to 40 mg. Treatment was well tolerated and the profile of adverse events was similar to the pattern found with other nonsulfydryl angiotensin converting enzyme inhibitors. Tolerance in the elderly was similar to that experience by hypertensives under 65 years of age. Thus, lisinopril at 20 or 40 mg once daily proved both well tolerated and effective in reducing blood pressure in patients with mild to moderate essential hypertension.
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