Serum cholesterol concentration before and after streptokinase in acute myocardial infarction.

OBJECTIVE: To determine if serum cholesterol concentration should be measured before or after streptokinase therapy within the first 24 h of myocardial infarction. DESIGN: Prospective study of patients receiving streptokinase therapy for acute myocardial infarction (AMI). SETTING: Coronary care unit of a district general hospital. SUBJECTS: Thirty-one patients (26 men aged 38-74 years, mean 60 years) admitted with a definite diagnosis of myocardial infarction. INTERVENTION: Streptokinase therapy given intravenously at a mean of 5 h (range 1.5-15 h) after the onset of chest pain. MAIN OUTCOME MEASURES: Serum cholesterol concentration just prior to, and 11.5 h (range 4-20.5 h) after streptokinase administration. RESULTS: There was a significant mean fall of 0.4 mmol l-1 (P = 0.002, 95% CI = 0.2-0.6) in serum cholesterol concentration from a pre-streptokinase concentration of 7.0 (range 5.3-9.9) to a post-streptokinase concentration of 6.6 (range 4.9-9.9). In the patients who showed a fall in cholesterol concentration, the magnitude of fall correlated with the baseline cholesterol concentration (r = 0.66, P < 0.01) but not with peak cardiac enzyme activities (r = 0.05, P > 0.2 for aspartate aminotransferase; r = 0.10, P > 0.2 for lactate dehydrogenase), time from onset of chest pain to post-streptokinase measurement (r = 0.27, P > 0.2) or time from streptokinase administration to post-streptokinase measurement (r = 0.01, P > 0.2). CONCLUSION: Serum cholesterol concentration may be underestimated when measured after streptokinase therapy, particularly when the true basal value is high. Further management of this risk factor may be based more accurately on its measurement before than after streptokinase therapy within the first 24 h of AMI.

Fatal paracetamol poisoning in an epileptic.

Treatment nomograms are used in paracetamol poisoning for indicating when antidotes should be given to prevent hepatic or renal damage. We report a fatal case of paracetamol poisoning in an epileptic taking phenytoin, in whom no antidotal treatment was given because it was not indicated.

Pituitary-adrenal response to stimulation of the limbic system and lateral hypothalamus in the rhesus monkey (Macacca mulatta).

Various sites within the limbic system, frontal lobe and lateral hypothalamus of the rhesus monkey brain were electrically stimulated using chronically implanted electrodes. Increases in plasma cortisol was observed after stimulation of the lateral hypothalamic area, basolateral amygdala, pyriform cortex, hippocampus, certain sites in the cingulate gyrus and orbital part of the frontal lobe. Inactive sites included the caudate nucleus, putamen and white matter in the frontal lobe.

Role of central and peripheral mechanisms in the action of alpha-methyldopa on blood pressure and renin secretion.

The mechanism by which alpha-methyldopa lowers arterial pressure and suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were prevented by adjusting a suprarenal aortic clamp. After intravenous alpha-methyldopa (100 mg/kg) mean arterial pressure (MAP) decreased form 127+/-3 to a mean minimum of 107+/-4 mm Hg (P less than .01) and plasma renin activity (PRA) decreased from 20.6+/-4.8 to 10.9+/-1.7 ng/ml/3 hr (P less than .05). Blockade of peripheral dopa decarboxylase with intravenous carbidopa (20 mg/kg) significantly attenuated the hypotensive action of intravenous alpha-methyldopa but MAP still decreased from 145+/-6 to 130+/-5 mm Hg(P less than .001). Intravenous carbidopa completely abolished the fall in PRA produced by intravenous alpha-methyldopa (16.8+/-2.8 to 16.9+/-2.1 ng/ml/3 hr.) Intraventricular carbidopa (3 microng/kg/min) did not block the hypotensive (135+/-8 to 113+/-7 mm Hg, P less than .01) or renin-lowering effect (24.3+/-5 to 13.4+/-3.2 ng/ml/3 hr, P less than .01) of intravenous alpha-methyldopa (0.5 mg/kg decreased MAP from 118 +/- 5 to 104 +/- 5 mm Hg (P less than 0.001) but had no effect on PRA (23.4+/-6 TO 19.4+/-7 NG/ML/3 hr.) Intraventricular alpha-methylnorepinephrine (2 microng/kg) also decreased MAP from 127+/-5 to 112+/-3mm Hg (P less than .006) but again failed to significantly alter PRA (36.1+/-11.8 to 37.2+/-15 ng/ml/3 hr). These results indicate that there is both a central and peripheral component to the antihypertensive effect of alpha-methyldopa in the dog and that the suppression of renin secretion results from a peripheral action of the drug.

Effect of adrenergic blockade and dexamethasone on the aldosterone response to brain stimulation in the rhesus monkey.

The increase in aldosterone and plasma renin activity (PRA) observed after stimulation of extrahypothalamic sites within the brain of the rhesus monkey was prevented by the prior administration of the beta-adrenergic blocking agent propranolol. alpha-Adrenergic blockade by phentolamine had no inhibiting effect. Propranolol only partially reduced the response of aldosterone to lateral hypothalamic stimulation in spite of inhibition of PRA; a partial reduction in aldosterone was also obtained from this site after dexamethasone treatment without any effect on PRA. It was concluded that the increase in aldosterone observed after extra-hypothalamic stimulation was mediated mainly through the renin-angiotensin mechanism whereas in the case of the hypothalamus, release of ACTH was also a contributory factor.

Effect of brain stimulation on aldosterone secretion in the rhesus monkey (Macaca Mulatta).

The lateral hypothalamus, and various sites within the limbic system and frontal lobe of the rhesus monkey brain were electrically stimulated using chronically implanted electrodes. A considerble increase in plasma aldosterone levels was observed after stimulation of the lateral hypothalamic area, certain localized sites in the cingulate area, and lower medial parts of the frontal lobe. Inactive sites included most of the amygdala, hippocampus, and basal ganglia, together with other areas within the frontal lobe and cingulate gyrus. Stimulation of all active areas was followed by an increase in plasma renin activity. Plasma cortisol also increased considerably after hypothalamic stimulation but in the case of extra-hypothalamic sites the cortisol response was much less.

Pulmonary oedema in meningococcal meningitis.

Two cases of meningococcal meningitis complicated by pulmonary oedema are described. The pulmonary arterial wedge pressure was raised in the one case studied. Profound sympathetic over-activity may be the cause of the pulmonary oedema occurring in this situation. If this is so, adrenergic blockade would appear to be a rational approach to therapy.

Pituitary hormone response to brain stimulation in man.

Plasma cortisol, GH and LH responses to electrical stimulation of the orbital part of the frontal lobe and the cingulate area of the brain were studied in patients undergoing limbic leucotomy. In six out of 15 patients the plasma cortisol levels increased by 5-7--18-0 mug/100 ml after orbito-frontal stimulation whereas plasma GH values did not rise during this period. Plasma LH levels remained unchanged. No definite hormone responses could be attributed to stimulation of the cingulate area. It appears that the orbito-frontal area of the brain is concerned with augmenting the release of ACTH but not that of GH or LH.

Report of a family with inherited medullary carcinoma of the thyroid and phaeochromocytoma.

A family in which several members have medullary carcinoma and phaeochromocytoma is described. Four of the 5 patients in this family who had a phaeochromocytoma have died; in one of these the medullary carcinoma may have contributed to death but in general the thyroid cancers were slow growing. In our experience successful diagnosis and treatment of the phaeochromocytomas have presented the greatest challenge. The welfare of future generations with this syndrome would seem to depend upon regular clinical and biochemical surveillance of the individuals and expeditious diagnosis and treatment of their tumours, particularly the phaeochromocytomas.

Hypothalamic-pituitary function in anorexia nervosa.

Hypothalamic-pituitary function was studied in 4 patients with anorexia nervosa of different degree of severity before and after refeeding. Gonadotrophin secretion was low in all subjects and improved in two after a prolonged period of feeding. In one subject there was a failure of pituitary gonadotrophin secretion after the administration of hypothalamic gonadotrophin-releasing hormone but the response was restored to normal after treatment. Thyroid function was reduced in one patient only but returned to normal after intravenous therapy for 6 days. Growth hormone and cortisol levels were elevated in all patients, and in one severe case the growth hormone values were extremely high. There was also a disturbance of the hypothalamic control of growth hormone and pituitary-adrenal function, which returned to normal after refeeding. One patient with severe hypothermia was resistant to the administration of a pyrogen, but developed a normal febrile response after treatment.

One year's experience in a Ministry of Health dialysis centre.

A 10-bed dialysis unit, opened at the London Hospital in 1968, admitted 37 patients during its first year of operation. The aims of the unit were to prepare patients for renal transplantation and to provide instruction for dialysis treatment at home. A total of 2,012 days were spent in hospital, the average intervals between admission, the first dialysis, and discharge being 23.8 and 20 days, respectively. The overall number of readmissions was 1.5 per patient. These figures, together with the increasing number of patients accepted for such treatment, indicate the considerable number of supporting hospital beds, as well as medical and technical staff, required to maintain a dialysis unit.

Rate of disappearance of endogenous insulin from the circulation after removal of insulinomas.

In two patients with insulinomas a rapid rate of disappearance of insulin from the circulation was found after the tumours had been removed. In a third case the rate of disappearance was slower but the insulin was not immunologically identical to normal human insulin standards, as it was in the other two cases.