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Biomedical subjects

A J Barnes

Publications and source records attributed to A J Barnes.

At least 37 records · Page 2Linked to original sources
PubMed1981

Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.

Gastrointestinal Hormones↗
PubMed1981

The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.

The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.

Adult↗
PubMed1981

Filterability and vascular disease--I. Red cell filterability in diabetes mellitus: its relation to other methods of measuring deformability and to blood viscosity.

Erythrocyte deformability, blood viscosity and other rheological variables were measured in 30 diabetics and 28 normal control subjects. Measurements of red cell rheology were made simultaneously by filtration of whole blood, centrifugation and viscometry of packed red cells. The diabetics showed a significant reduction of erythrocyte deformability measured by filtration, an increase in flexibility measured by centrifugation and values similar to normals for viscometry of packed red cells. Plasma viscosity but not whole blood viscosity (shear rates 23 and 230 s-1) was increased in the diabetics. Erythrocyte flexibility as measured by centrifugation was significantly related to blood viscosity and plasma fibrinogen and glucose in the diabetics, however, neither filtration nor viscometry of packed red cells correlated with other rheological variables. It seems likely that multiple rheological abnormalities are present in diabetes mellitus. Conclusions about erythrocyte rheology in particular will depend critically on the methodology used.

Adult↗
PubMed1981

Diabetes mellitus: its effect on the flow properties of blood.

In a group of long-standing diabetics low shear blood viscosity was increased compared with matched non-diabetic controls, being highest in patients with vascular and microvascular complications. Plasma viscosity was also elevated in the diabetics. Conclusions about erythrocyte deformability depended critically on the methodology used. With filtration, red cell deformability was impaired in the diabetic, with centrifugation, diabetic cells were more deformable whilst there was no differences between diabetic and normal red cells by the method of viscometry of packed red cells. The effect of poor metabolic control on blood rheology was investigated in patients recovering from diabetic ketoacidosis and in newly diagnosed maturity onset diabetics being treated at the clinic with diet alone. In both groups, the initially high levels of blood viscosity fell toward normal with improved metabolic control. It is concluded that multiple rheological abnormalities are present in diabetics and appear to be influenced by the metabolic state of the patient. The relationships between these complex changes and the development of microangiopathy remain to be elucidated.

Blood Viscosity↗
PubMed1980

Neural and hormonal peptides in rectal biopsy specimens from patients with Chagas' disease and chronic autonomic failure.

The neural and hormonal peptide content of rectal biopsy specimens from 10 patients with chronic autonomic failure, 10 patients with chronic gastrointestinal Chagas' disease, and 13 controls was studied with radioimmunoassay and immunocytochemistry. In the patients with Chagas' disease the mean concentrations of rectal vasoactive intestinal polypeptide, enteroglucagon, substance P, and somatostatin were all less than half of those in controls and in patients with chronic autonomic failure. Immunocytochemistry revealed a considerable reduction in the number and immunostaining of the peptide-containing cells and nerves. Concentrations of regulatory peptides in the rectum are thus reduced in association with intrinsic but not extrinsic autonomic neuropathy.

Autonomic Nervous System↗
PubMed1980

Hormonal and metabolic rhythms in Cushing's syndrome.

Hormone and metabolite profiles were investigated over a 12-hr period in six patients with Cushing's syndrome, ten age- and sex-matched normal controls, and six moderately obese subjects matched for weight with the patient group. Mean diurnal plasma cortisol levels were 563 +/- 74 nmole/liter in the patients, 275 +/- 22 nmole/liter in normal controls and 241 +/- 32 nmole/liter in obese subjects, with total loss of diurnal changes in Cushing's syndrome. Fasting blood glucose concentration was similar in all groups although mild hyperglycemia occurred after meals in the Cushing's patients compared with normal and obese subjects (mean 12-hr blood glucose: Cushing's 6.31 +/- 0.39 mmole/liter; normal controls, 5.32 +/- 0.14 mmole/liter, p < 0.01; obese subjects, 5.41 +/- 0.18 mmole/liter, p < 0.05) despite marked hyperinsulinemia (mean 12-hr serum insulin: Cushing's 57.3 +/- 18.2 mU/liter; normal controls, 19.7 +/- 2.5 mU/liter, p < 0.02; obese subjects, 18.1 +/- 4.0 mU/liter, p < 0.05). Concentrations of the gluconeogenic precursors lactate, pyruvate, and alanine were raised in Cushing's syndrome, particularly postprandially. Plasma nonesterified fatty acids (NEFA), blood glycerol, and blood ketone body concentrations were comparable in all three groups although the normal diurnal variation in circulating NEFA and ketone body levels was lost in Cushing's syndrome. Serum triglyceride (TG) concentrations were grossly elevated in the Cushing's patients (mean 12-hr serum TG: Cushing's 3.51 +/- 1.23 mmole/liter; normal controls 0.89 +/- 0.19 mmole/liter, p < 0.02; obese subjects, 0.93 +/- 0.23 mmole/liter, p < 0.05) and correlated positively with serum insulin levels. Plasma glucagon concentrations were raised in Cushing's syndrome (mean 12-hr plasma glucagon: Cushing's 23.2 +/- 3.7 pmole/liter; normal controls 12.3 +/- 1.5 pmole/liter p < 0.01; obese subjects 12.2 +/0 2.0 pmole/liter, p < 0.02) and correlated positively with the serum cortisol but not with blood alanine, suggesting that some stimulatory factor other than alanine was responsible. The metabolic effects of chronic glucocorticoid excess thus may not be explained on the basis of obesity alone. Compensatory hyperinsulinemia limits the disturbance of carbohydrate and lipid metabolism in Cushing's syndrome but may be important in production of the hypertriglyceridemia observed.

Adolescent↗
PubMed1980

Effects of pancreatic polypeptide on motilin and circulating metabolites in man.

Pancreatic polypeptide was infused intravenously in healthy fasting subjects at 1 pmol kg-1 (n = 7) and 4 pmol kg-1 min-1 (n = 10) producing plasma PP concentrations of 223 +/- 37 pmol/l (mean +/- SEM) and 891 +/- 64 pmol/l respectively. These levels are similar to and four-fold higher than those seen after a normal mixed breakfast in healthy young adults. In a separate study five healthy subjects ingested a small breakfast during infusion of PP on different days at 1 pmol kg-1 min-1 and 2 pmol kg-1 min-1 respectively. PP at 1 pmol kg-1 min-1 caused a marked reduction in fasting plasma motilin concentrations to 20% of the basal level (p less than 0.001). There were, however, no significant changes in plasma concentrations of insulin, glucagon, gastrin, secretin, enteroglucagon, gastric inhibitory peptide or neurotensin. Despite previous reports possibly implicating PP in metabolism, there were no significant effects on blood levels of glucose, alanine lactate, 3-hydroxybutyrate, glycerol or non-esterified fatty acids, either in the fasting state or after the ingestion of food. Although it seems unlikely that PP is a major hormonal regulator of intermediary metabolism in man, its ability to suppress motilin at physiological concentrations suggests the possibility of an indirect influence on digestive motor function.

Adult↗
PubMed1980

Response of plasma pancreatic and gastrointestinal hormones and growth hormone to oral and intravenous glucose and insulin hypoglycaemia in Chagas's disease.

Plasma hormonal responses to insulin hypoglycaemia and to oral and intravenous glucose were investigated in chagasic patients with severe bowel disease and compared with controls matched for age, sex, weight, and race. After intravenous insulin, plasma concentrations of pancreatic glucagon and pancreatic polypeptide (PP) were reduced in the patients with Chagas's disease. These subjects also showed a subnormal rise in plasma insulin after oral glucose. Other hormone responses did not differ significantly from those in the normal controls. These results are compatible with partial denervation of the pancreatic alpha, beta, and PP cells in patients with chronic gastrointestinal Chagas's disease.

Adolescent↗
PubMed1979

Suppression of pancreatic endocrine tumour secretion by long-acting somatostatin analogue.

A new long-acting octapeptide analogue of somatostatin, Des AA1,2,4,5,12,13 D Try8 somatostatin, has been tested in 8 patients with pancreatic endocrine tumours. The analogue given subcutaneously suppressed the tumour-derived hormones in patients with insulinomas, glucagonomas, and gastrinomas for up to 24 h. The prolonged action appeared to be the result of slow release from the injection site. No side-effects were observed. Studies of long-term administration of this new peptide are now warranted.

Adult↗
PubMed1979

Hypotrypsinaemia in diabetes mellitus.

Plasma trypsin concentrations were measured in 403 fasting diabetics and 106 healthy controls. Basal trypsin concentrations in the normal subjects were 88 +/- 6 ng/ml (mean +/- S.E.M.). Mean plasma trypsin concentrations in diabetics treated with diet alone (n = 74) were 45 +/- 2 ng/ml, while in a group of young (less than 35 years, n = 88) insulin-dependent diabetics, they were very low at 29 +/- 2 ng/ml and these levels were inversely related to insulin dosage. The findings may help in the understanding of the pathophysiological changes in the exocrine pancreas in the diabetic state and may also shed some light on the physiological interrelationship between the endocrine and exocrine pancreas.

Adolescent↗
PubMed1979

Acromegaly and narcolepsy.

7 of 372 acromegalic patients had troublesome episodes of paroxysmal daytime sleep. Although 3 patients had complete remission of symptoms within a few days of pituitary implantation of isotopes, the cause of this increased frequency of narcolepsy among acromegalic patients is not known.

Acromegaly↗
PubMed1979

Autoimmunity in diabetics induced by hormonal contaminants of insulin.

Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immunocytochemical testing showed that antibody-positive diabetic plasma reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity and naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment.

Adolescent↗
PubMed1979

Cushing's syndrome due to adrenocortical carcinoma - a comphrensive clinical and biochemical study of patients treated by surgery and chemotherapy.

Four post-menopausal women had Cushing's syndrome due to adrenal cortical carcinomas. Comprehensive analyses of blood and urinary steroids showed that although the steroid profiles differed between patients, the pattern in each patient remained almost constant as the disease progressed, or remitted due to therapy. Elevations of serum testosterone and oestradiol were commensurate with the extent of virilisation, and the urinary output of aldosterone was associated with the severity of hypertension. A new finding was that all had substantially increased urinary free deoxycorticosterone. Complete surgical removal of the primary tumours was impossible but when most of the tumour tissue was removed, full clinical and biochemical remissions were obtained for a short time in 2 patients. One patient obtained a clinical and biochemical remission from op'DDD. In another patient the drug caused reduction both in blood pressure and in urinary aldosterone excretion, but there were unpleasant side effects. A third patient could not tolerate op'DDD. Metyrapone therapy produced neither clinical nor biochemical improvement in 3 patients. The mean duration of survival was 17 months after the first symptoms and 10 months from the date of operation. Despite advances in drug therapy, adrenal cortical carcinoma remains a lethal disease. Biochemical screening of multiple steroids offers a means of early diagnosis and disease monitoring. Extensive surgical removal of the tumour offers the best chance of a clinical and biochemical remission.

17-Ketosteroids↗
PubMed1978

Importance of pituitary hormones in aetiology of diabetic ketoacidosis.

The role of pituitary hormones in the aetiology of diabetic ketoacidosis was examined by withdrawing insulin from five pituitary-ablated diabetics for a 12-hour period. The rise in blood glucose and ketone-body concentrations was markedly retarded in these patients when compared with five matched juvenile-type diabetic controls with normal pituitary function. When cortisol replacement in the pituitary-ablated patients was increased to reproduce the high plasma concentrations found in severe ketoacidosis, blood ketones and glucose were increased but were still significantly lower than in the control diabetics. It is concluded that pituitary hormones may be important in the development of diabetic ketoacidosis.

Adult↗
PubMed1978

Hormonal regulation of ketone-body metabolism in man.

The main hormones involved in ketone-body metabolism are the anabolic hormone insulin and the primarily catabolic hormones, glucagon, cortisol, catecholamines and growth hormone. These hormones may regulate ketone-body metabolism at three sites: adipose tissue, by regulating fatty acid supply to the liver; the liver itself, by determining the relative activities of the re-esterification and fatty acid oxidation pathways; and the periphery, by influencing the rate of extrahepatic utilization of ketone bodies. The first two are quantitatively the most important. Insulin acts on all three regulatory sites. In adipose tissue lipolysis is inhibited and re-esterification enhanced with consequent decrease of fatty acid release. Both these processes are extremely insulin-sensitive. In the liver insulin increases fatty acid synthesis and esterification. At the same time malonyl-CoA formation is increased, which inhibits the acylcarnitine transferase system and thus decreases the transport of fatty acids into mitochondria and hence fatty acid oxidation and ketogenesis. Insulin also has a small stimulatory effect on extrahepatic ketone-body utilization. The effects of glucagon depend on whether insulin is present. In normal man glucagon stimulates insulin secretion and the predominant effect is that of insulin, i.e. decreased ketogenesis. In insulin deficiency glucagon has a mild stimulatory effect on lipolysis, increasing fatty acid supply to the liver. The main effects of glucagon are, however, on the liver. It activates the carnitine acyltransferase system through inhibition of malonyl-CoA synthesis. Fatty acid oxidation is increased and ketogenesis enhanced. The overall effect on the liver depends on the relative amounts of insulin and glucagon present. Studies with somatostatin show that glucagon can increase ketogenesis acutely when insulin secretion is inhibited in normal man, but the effects are short-lived. Cortisol has similar effects to glucagon. In the presence of insulin there is a small increase in fatty acid mobilization from adipose tissue, secondary to impaired glucose entry, and perhaps a small effect on lipolysis itself. This fatty acid is, however, directed to triacylglycerol in the liver. In insulin deficiency, again demonstrated by somatostatin infusion, the incoming fatty acidstone-body formation. The mechanism remains obscure. Catecholamines, in contrast, have their most potent effects on adipose tissue, stimulating lipolysis and fatty acid release even in the presence of insulin. They thus act mainly by enhancing precursor supply and have only minor effects on liver and no effect on peripheral utilization. Growth hormone, like glucagon, has little effect in the presence of insulin, but can enhance ketogenesis in insulin deficiency, although again the mechanism is unknown. Thus in normally fed man the effects of insulin will be overriding and little ketogenesis occurs because of limited fatty acid availability in the liver...

Adipose Tissue↗
PubMed1977

Is hyperviscosity a treatable component of diabetic microcirculatory disease?

Blood viscosity at low shear-rates was significantly higher in sixty-four patients with longstanding diabetes than in sixty-one matched non-diabetic controls. This increase was most striking in patients with either proliferative retinopathy or nephropathy, although it was present to a lesser extent in diabetic patients with evidence of myocardial or peripheral ischaemia. Erythrocyte deformability was lower in the fourteen diabetic patients with the most extensive microangiopathy than in twenty-two diabetics with slight or no complications or in controls. Hyperviscosity and reduced erythrocyte deformability may well be important and potentially treatable factors in the aetiology or progression of microcirculatory disease is diabetes.

Adult↗