Search PubMed⌕ Search

Biomedical subjects

D Maclean

Publications and source records attributed to D Maclean.

At least 73 records · Page 4Linked to original sources

Chenodeoxycholic acid therapy for hypertriglyceridaemia in men.

1 Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and thereafter monthly for a further 6 months on clofibrate 2 g daily. 2 The mean serum triglyceride level fell by 36% after dietary treatment alone (P less than 0.05) and by 47% from initial values on diet plus chenodeoxycholic acid (P less than 0.01). In the nine patients who proceeded to clofibrate therapy there was a rise in triglyceride levels on placebo capsules to the level achieved by diet alone, and a further fall on diet plus clofibrate of 47% of initial values (P less than 0.05). 3 Chenodeoxycholic acid therapy is effective in the management of hypertriglyceridaemia not completely cured by dietary measures, and may be as efficacious as clofibrate.

Adult↗

Long-term preservation of ischemic myocardium after experimental coronary artery occlusion.

The results of experiments with indirect methods have suggested that various interventions reduce infarct size after coronary artery occlusion. To determine and quantify directly both the short- and long-term effects of several interventions on myocardial salvage without relying on indirect methods, the left coronary artery was occluded in 880 rats; they were then given either no treatment or one of the following interventions: (a) hyaluronidase, an enzyme that hydrolyzes interstitial glycoproteins, 1,500 National Formulary (NF) U/kg i.v. 5 min and 24 h after occlusion; (b) cobra venom factor, a protein that depletes the third component of complement, 20 U/kg i.v. 5 min after occlusion; (c) a glucocorticoid: hydrocortisone, 50 mg/kg i.v. 5 min after occlusion; or the five-fold more potent methylprednisolone (MP): (i) 50 mg/kg i.v. 5 min after occlusion or (ii) 50 mg/kg i.v. 5 min after occlusion followed by 50 mg/kg i.m. 3, 6, and 24 h after occlusion; or (d) reserpine, an agent that depletes the heart of catecholamines, 0.5 mg/kg i.m. once on each of the 3 days before occlusion. The animals were sacrificed either 2 days after occlusion, i.e., at the time of peak necrosis, or after 3 wk, i.e., after the infarct was completely healed. The amount of preserved myocardium was then assessed by two independent techniques: planimetric measurement of serial histologic sections and creatine kinase activity of the whole left ventricle. The amount of normal myocardium preserved at 21 days postocclusion was significantly increased, by 22.3+/-7.8% (P < 0.025) after the administration of hyaluronidase, by 25.3+/-5.8% (P < 0.005) after cobra venom factor, by 14.5+/-6.9% (P < 0.05) after hydrocortisone, by 20.8+/-8.2% (P < 0.025) after the single dose of MP, by 20.9+/-3.9% (P < 0.001) after the four doses of MP, and by 10.2+/-3.7% (P < 0.05) as a result of pretreatment with reserpine. The four doses of MP significantly thinned the infarct-by 25.6+/-2.9% (P < 0.001)-and although ventricular rupture did not occur, the intervention caused distension of the left ventricle as a result of stretching of the infarcted tissue during scar formation. Thus, myocardium acutely jeopardized by ischemia can be preserved on a long-term basis.

Animals↗

Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution.

Surgical occlusion of the left coronary artery of the rat is a relatively simple, economical technique for producing experimental myocardial infarction (MI). Histologic study of 1- to 21-day-old MI in rats showed that following a mild and brief acute inflammatory response at the margins of the necrotic myocardium, there is chronic inflammation, vascular and collagenous proliferation, and resorption of necrostic tissue which progresses until scar formation is complete, usually by 21 days. From Day 1 to Day 21 the volume of infarcted myocardium decreases from 45.9 +/- 5.9% (mean +/- SEM) to 26.1 +/- 3.2% of the left ventricle and infarct thickness decreases from 1.30 +/- 0.06 mm to 0.47 +/- 0.02 mm. Concomitantly, the percent of the surface area of the left ventricle which is infarcted decreases insignificantly from 55.7 +/- 7.2% to 48.3 +/- 4.2%, indicating that the decrease in volume of the infarcted tissue occurs primarily as a result of thinning of the MI. This study provides qualitative and quantitative information on the natural history of MI in rats, which should be useful as a baseline for future studies.

Animals↗

Hyaluronidase-induced reductions in myocardial infarct size.

The size of myocardial infarctions following coronary artery occlusion in the rat was determined directly by measurement of creatine phosphokinase activity in homogenized whole left ventricles and by planimetric measurement of the area of the infarctions in histologic sections of serial slices of the left ventricles. Hyaluronidase was shown to produce significant reductions in expected infarct size both 48 hours and 3 weeks after occlusion without impairing fibrosis during the healing phase. Thus, the amount of myocardial necrosis that follows a coronary artery occlusion has been shown directly to be amenable to reduction with a pharmacological intervention.

Animals↗

Deep vein thrombosis after femoropopliteal bypass grafting with observations on the incidence of complications following the use of dextran 70.

Radiological thrombosis was demonstrated on six occasions in the leg veins in 66 patients following the placement of 71 femoropopliteal bypass grafts. All patients received dextran 70 as prophylaxis postoperatively. The incidence was similar for grafts with the lower anastomosis either above or below the knee joint. No predisposing factors to venous thrombosis were apparent other than blood dyscrasias. A further group of patients who had arterial reconstructive procedures were examined to determine the incidence of the complications of bleeding and heart failure which might be attributed to the routine use of dextran 70. The incidence of complications in this larger group indicates that the routine use of dextran 70 is not a significant factor in their occurrence in the postoperative period.

Dextrans↗

Pulmonary oedema during treatment of acute water intoxication.

Acute water intoxication with deepening coma and uncontrolled epileptiform seizures in a 25-year-old previously fit male schizophrenic was treated with hypertonic (2 N) saline and a 20% mannitol solution. This improved his neurological state but precipitated severe pulmonary oedema. Intravenous frusemide increased his urinary output sufficiently to clear the pulmonary oedema. In acute water intoxication the use of hypertonic solutions may thus precipitate left heart failure by expanding the intra-pulmonary blood volume beyond the capacity of even a healthy left ventricle to compensate. Simple water restriction will produce a slower but perhaps safer improvement.

Acute Disease↗

Acute pancreatitis and diabetic ketoacidosis in accidental hypothermia and hypothermic myxoedema.

Serial serum amylase and blood glucose levels were measured in 68 hypothermic (rectal temperature 35 degrees C or less) patients, including 15 who had hypothermic myxoedema (serum protein bound iodine 3.5 mug/100 ml or less). Raised amylase levels were found in 34 patients and probably reflected a mild acute pancreatitis. The high amylase levels correlated with low arterial PO(2) levels and significantly with high arterial PCO(2) levels and the base deficit but not with the severity or duration of the hypothermia. The acute pancreatitis does not explain why hypothermic patients with myxoedema have a poorer prognosis than those who are euthyroid. The pancreatitis occasionally contributed to the development, sometimes delayed, of diabetic ketoacidosis, blood glucose levels of over 120 mg/100 ml being found in 20 patients. There was a significant correlation between the raised serum amylase levels and the hyperglycaemia. Hypoglycaemia, sometimes profound, was found in 12 patients.

Acute Disease↗