PubMed HealthSearch

Biomedical subjects

D Hamilton

Publications and source records attributed to D Hamilton.

At least 55 records · Page 3Linked to original sources

Metabolic dependence of glycolytic enzyme binding in rat and sheep heart.

Perfused rat hearts show a markedly increased binding of phosphofructokinase and fructose-bisphosphate aldolase as a consequence of ischaemia, but little change in binding of pyruvate kinase, lactate dehydrogenase or glyceraldehyde-3-phosphate dehydrogenase. After 10 min ischaemia over one quarter of the phosphofructokinase and three quarters of the aldolase are bound. The effect of anoxia is less well marked in its influence on binding with only aldolase showing a significant increase in binding. These results suggest that one factor involved in the increased binding during ischaemia is the fall in pH of the heart. Binding studies with isolated myofibrils confirm that the affinity and stoichiometry of aldolase binding are considerably increased as the pH is lowered over a range comparable to that which occurs in ischaemic heart. The low level of binding of glyceraldehyde-3-phosphate dehydrogenase in perfused rat hearts correlates with the relatively low affinity of this enzyme for binding to rat or rabbit cardiac myofibrils. There are species differences in the enzyme binding response to ischaemia. Sheep hearts show rapid and large increases in the binding of glyceraldehyde-3-phosphate dehydrogenase in addition to changes in aldolase and phosphofructokinase binding. The greater binding of glyceraldehyde-3-phosphate dehydrogenase reflects the greater affinity of sheep cardiac myofibrils. It is suggested that the altered metabolic demands of ischaemia are satisfied by changes in glycolytic enzyme organisation as the enzymes shift from the soluble to the particulate phase of cardiac muscle.

Animals

Predictors of success in a cohort of medical students.

Secondary school results were compared with personality test scores as predictors of achievement in medical school in a study of a cohort of students, using simple correlation and multiple linear regression. The cohort of 151 students completed 28 courses in the 6 years. We have previously reported that the scores obtained could be reduced to five independent factors: 'physical science'; 'biological science'; 'paraclinical science'; 'basic clinical science'; and 'clinical science'. Both secondary school scores and personality test scores correlated with medical school achievement factors, but school scores correlated best with 'physical' and 'biological' science. Considering secondary school scores, English was the best predictor of 'clinical science', physics was the best predictor of 'basic clinical science' and scores obtained in physics and languages were better predictors of medical school 'biological science' than was school biology. Personality factors were better predictors of 'biological', 'paraclinical' and 'clinical science' than secondary school scores and the combined secondary school score (CSS) was the best predictor of 'physical science' and of 'overall achievement'. We conclude that incorporation of personality measurement with school academic achievement could be of value in selection procedures for applicants for medical school.

Achievement

Converting-enzyme inhibition and 1-sarcosine-8-isoleucine-angiotensin II: effects on renal function in the dehydrated sheep.

The effect of a converting-enzyme inhibitor (captopril) was studied in nine conscious dehydrated Merino ewes. Captopril (4 mg I.V. over 40 min) caused significant decreases in mean arterial blood pressure (M.A.B.P.), renal vascular resistance (R.V.R.) and filtration fraction, and increases in urine flow (V), sodium excretion, glomerular filtration rate (G.F.R.), renal plasma flow, solute clearance (Cosm), solute-free water reabsorption (TC, H2O) and plasma renin activity (P.R.A.). None of these effects was observed when captopril was similarly administered to sheep pretreated with angiotensin II (AII) receptor blocker, 1-sarcosine-8-isoleucine-AII (sarileucin). It is concluded that the effects of captopril were probably not due to bradykinin potentiation but rather to decreased levels of circulating AII. The effect of sarileucin itself was complex. It effectively blocked the pressor response to administered AII, but it also had an AII-like effect indicated by a rise in R.V.R., and decreases in V, G.F.R., Cosm and TC, H2O. This apparent mixture of AII agonist and antagonist properties probably accounts for the absence of any change in M.A.B.P. or P.R.A. during sarileucin administration.

1-Sarcosine-8-Isoleucine Angiotensin II

Non-gastrin secretogogue in ulcerogenic tumors of the pancreas.

In 18 patients with hypersecretion of acid, severe ulcer diathesis, and pancreatic islet cell tumor or hyperplasia, 14 had hypergastrinemia and 4 had normal plasma gastrin concentration. The neoplasms contained several gut peptides beside gastrin. The immunoreactive gastrin in the tumor extracts measured less than 7 ng/g, less than the amount previously reported. The extracts of each patient's tumor also contained a secretogogue other than gastrin that stimulated gastric acid secretion in rats. In addition, the plasma extracts of 2 patients also contained a secretogogue that stimulated acid secretion. After surgical resection of a recurrent metastatic tumor in 1 patient, basal acid secretion decreased from 13.9 to less than 1 meq/h, and the bioactivity of the plasma disappeared. These observations suggest the existence of a secretogogue that appears to be a protein in the pancreatic tumors of some patients with severe ulcer diathesis and hypersecretion.

Adenoma

Pergolide for the treatment of pituitary tumors secreting prolactin or growth hormone.

We gave pergolide mesylate, a new long-acting ergot derivative with dopaminergic properties, to 47 patients with hypersecretion of prolactin or growth hormone. Single doses produced long-lasting reductions of serum prolactin levels; after 24 hours, the values remained depressed at a mean of 28.8 per cent of the base-line value. Among 41 patients (22 women and 19 men) with hyperprolactinemia who took pergolide for three months or more, prolactin levels fell to normal in 37 and remained slightly elevated in 2. In the two patients in whom the levels fell to only 38 to 52 per cent of base line, treatment was regarded as a failure. The level of growth hormone fell to a mean of 52.8 per cent of base line in patients with acromegaly who were taking 100 micrograms of pergolide per day. Among patients for whom adequate CT scans were available, definite tumor shrinkage occurred in 10 of 13 with macroadenomas and definite or probable shrinkage in 5 of 9 with microadenomas. Menses returned in 76 per cent of treated women and testosterone levels rose in 10 of 14 men. We conclude that pergolide reduces hypersecretion and shrinks most prolactin-secreting macroadenomas. In some patients long-term pergolide therapy may be superior to surgery and x-ray treatment.

Acromegaly

Naloxone eye drops reverse the miosis in runners--implications for an endogenous opiate test.

Naloxone 0.16% ophthalmic drops or placebo drops were self-administered to one eye by 13 runners 250 times in a double-blind fashion over three weeks of various intensities and durations of running. An increasing incidence of miosis after running and ipsilateral mydriasis after the naloxone eye drops were administered was noted to correlate with increased run durations. During 34 runs of over 30 minutes duration, 20 subject runs (59%) developed miosis in both eyes and mydriasis in the eye treated with naloxone, but none of 10 subject runs over 30 minutes (9 of which showed miosis) developed mydriasis after placebo drop administration. Calculations (means, SEM) of pupil sizes in various run durations revealed an increased occurrence of miosis which was reversed with naloxone in over 30 minute runs at a significance level greater than 0.005 (single tailed "t" test). It is suggested that exercise generated endogenous opiates cause pupillary miosis, and that ophthalmic naloxone to one eye can block this exercise pupillary effect resulting in ipsilateral mydriasis. Suggestions are given for a simple "Naloxone Anisocoria Test" for the presence or absence of elevated endogenous opiates.

Adolescent

Myotonic dystrophy: HLA antigens and mitogen stimulated lymphocyte responses of a black American family.

A Black American family of four generations with 29 members was studied. Six family members spanning two generations were affected with myotonic dystrophy. HLA A, B, C and DR antigen specificities were determined for each family member using local typing trays. Twelve HLA haplotypes were identified in the family. No significant association was found between the disease and any HLA antigenic type or haplotype. This finding suggests that the involvement of the major histocompatibility complex in the etiology of myotonic dystrophy is unlikely. The cellular responses to twenty-eight family members and 20 unrelated Black Americans to phytohemagglutinin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM), each in three concentrations, were tested with mononuclear cells prepared from peripheral blood. There was a significant difference in responses of the affected family members as compared to the unaffected family members and the unrelated Black Americans. The PHA and PWM responses of the unaffected family members are not significantly different from those of the unrelated Black American controls; however, the Con A responses of the unaffected family members are significantly higher than those of the control group at the lowest Con A dosage. The possible systemic defects of cytoskeletal structures of the affected family members are discussed.

Black People

Bethanechol or cimetidine in the treatment of symptomatic reflux esophagitis: a double-blind control study.

We conducted a double-blind study to compare the effectiveness of oral bethanechol chloride or cimetidine in treating reflux esophagitis to evaluate the drugs' effects on the symptoms of esophagitis and its verification by endoscopy. Forty-three patients were treated with either 300 mg of cimetidine or 25 mg of bethanechol chloride, each administered four times a day for six weeks. In addition to this drug treatment, the patients all received conventional medical therapy. Patients who were treated with either of the two drugs experienced a decrease in symptoms and less severe endoscopic lesions. While cimetidine treatment resulted in complete endoscopic healing in 15 of 22 patients, bethanechol treatment resulted in the same healing in 11 of 21 patients. During therapy, neither endoscopic lesions or symptoms worsened. Our study indicated that either cimetidine or bethanechol is an effective drug in treating reflux esophagitis. The effects of the two drugs can be favorably compared.

Administration, Oral

Successful tumour immunotherapy with cimetidine in mice.

Cimetidine significantly slowed metastatic development and prolonged survival in tumour-bearing mice, in association with inactivation of suppressor cells. Pharmacological blockade of the suppressor cell system may represent a new strategy for successful immunotherapy of human neoplasia.

Animals