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Biomedical subjects

D R Cullen

Publications and source records attributed to D R Cullen.

At least 37 records · Page 2Linked to original sources
PubMed1989

Hepatic microsomal enzyme induction and adrenal crisis due to o,p'DDD therapy for metastatic adrenocortical carcinoma.

Two cases are described in which metastatic adrenocortical carcinoma associated with Cushing's syndrome was treated with mitotane (o,p'DDD). The first patient had initially been treated by bilateral adrenalectomy and, whilst responding to mitotane biochemically and by remission of metastases, experienced repeated episodes of adrenal crisis requiring a substantial increase in steroid therapy. The second patient failed to respond to the drug, but evidence of hepatic enzyme induction was noted during its administration. It is suggested that hepatic microsomal enzyme induction can occur in association with treatment with mitotane and that this can lead to an increased destruction of exogenous steroid with clinical consequences.

Addison Disease↗
PubMed1988

Does adding fibre to a low energy, high carbohydrate, low fat diet confer any benefit to the management of newly diagnosed overweight type II diabetics?

The effect of supplementing a low energy (roughly 5.0 MJ), high carbohydrate (180 g), low fat (roughly 25 g) diet with 10-15 g of either cereal fibre or guar gum was investigated in 24 newly diagnosed overweight non-insulin-dependent (type II) diabetics. The patients were divided into three treatment groups: one received a low fibre control diet throughout the study period of 20 weeks and the other received two supplements of cereal fibre and guar gum in a crossover manner. The nutrient content of the diets was kept constant throughout. Though patients taking the low fibre diet showed a smaller reduction in fasting plasma glucose concentrations over the first eight weeks than patients taking a high fibre diet, this difference was not evident at the end of 20 weeks; reductions in weight and glycated haemoglobin values were similar for each dietary regimen throughout the trial. There was little evidence that supplementing a low energy, high carbohydrate diet with fibre confers any therapeutic benefit to type II diabetics and no evidence that taking fibre as viscous polysaccharides is any more beneficial to overweight diabetics than taking a similar fibre supplement as cereal. On the contrary, guar gum caused more abdominal discomfort and flatulence than the other diets.

Blood Glucose↗
PubMed1986

Amino acid profiles in early diabetic and non-diabetic pregnancy.

Plasma amino acid concentrations were measured in six insulin-dependent diabetic women and seven non-diabetic women in early pregnancy while fasting and one hour after a standard meal. Fasting plasma levels of total amino acids and individual amino acids were similar in the two groups, excepting isoleucine, which was raised in the diabetics. One hour post-prandially total amino acid concentrations were similar in the two groups; however, mean concentrations of total branched chain amino acids and mean concentration of the individual amino acids, serine, valine, isoleucine, leucine and tyrosine were elevated in the diabetics. Amino acids are important in early islet development and in insulin secretion from fetal pancreas in vitro. The elevated post-prandial amino acid levels found in pregnant diabetics in early pregnancy may contribute to fetal islet hypertrophy and hyperinsulinaemia.

Adult↗
PubMed1985

Glycosylated haemoglobin in normal pregnancy: a longitudinal study with two independent methods.

Twenty-one women completed a longitudinal study of glycosylated haemoglobin in normal pregnancy. Glycosylated haemoglobin levels were measured using two independent techniques (ion-exchange column and colorimetric). Concurrent serial oral glucose tolerance tests (75-g glucose load) and erythrocyte indices were obtained. Changes in mean glycosylated haemoglobin were similar with both techniques with a nadir at 17 weeks, a peak at delivery (p less than 0.002 versus 17 weeks) and a fall post-partum. Glycosylated haemoglobin levels in abnormal pregnancies, e.g. diabetic, should be interpreted in the knowledge of these physiological changes.

Adolescent↗
PubMed1985

Adrenal scintigraphy with 75Se selenonorcholestenol: a review.

We have reviewed 58 patients on whom adrenal scintigraphy has been performed using 75Se selenonorcholestenol. For 15 patients whose adrenal function was biochemically normal, the upper limit of normal of the 7 day adrenal uptake test was 0.45%, considerably higher than the generally accepted value of 0.3%. There is evidence from this group of patients that stress and obesity might account for uptakes in the range 0.3-0.45%. The sensitivity of the uptake test is poor, with 7 out of 23 patients with Cushing's syndrome having uptakes within the normal range. Scintigraphy of such patients may still be useful in differentiating between unilateral and bilateral adrenal involvement.

Adrenal Cortex↗
PubMed1982

Diurnal variations in blood intermediary metabolites in mild gestational diabetic patients and the effect of a carbohydrate-restricted diet.

Twenty-four hour metabolic profiles were performed in the third trimester of pregnancy in seven non-diabetic women (group A) and in two groups of mild gestational diabetics, at diagnosis (group B, seven patients) and after treatment with a 150-g carbohydrate diet (group C, seven patients). Mean 24-h blood metabolite levels (+/- SD) in groups A, B and C were: glucose: 4.65 +/- 0.82, 5.35 +/- 3.06 and 5.40 +/- 1.7 mmol/l; alanine: 1.05 +/- 0.18, 1.14 +/- 0.42 and 0.78 +/- 0.22 mmol/l; alanine: 0.31 +/- 0.03, 0.31 +/- 0.10 and 0.27 +/-0.07 mmol/l; ketone bodies: 0.11 +/- 0.04, 0.19 +/- 0.05 and 0.26 +/- 0.15 mmol/l. Glucose levels were not significantly different between the groups. Ketone body levels were elevated in the diabetics prior to treatment (p less than 0.01) and rose higher on diet. Lactate levels were reduced on the diet (0.05 less than p less than 0.10). Abnormalities in the concentrations of total blood ketone body levels in gestational diabetics may be detrimental to fetal development and therapy should be designed to minimise changes in intermediary metabolites.

Alanine↗
PubMed1981

The effect of continuous subcutaneous insulin infusion and conventional insulin regimes on 24-hour variations of blood glucose and intermediary metabolites in the third trimester of diabetic pregnancy.

Twenty-four hour metabolic profiles were performed in the third trimester of pregnancy in seven diabetic women; first when optimally controlled using conventional insulin regimes and subsequently when controlled with continuous subcutaneous insulin infusion. Seven non-diabetic women also studied. Mean +/- SD 24 h metabolite levels in the diabetics before and during continuous subcutaneous insulin infusion and in the controls were respectively: glucose-5.8 +/- 1.2;5.0 +/- 0.9;4.7 +/- 0.8 mmol/l; total ketone bodies -0.2 +/- 0.06; 0.15 +/- 0.05; 0.11 +/- 0.04 mmol/l; lactate - 0.90 +/- 0.33;0.90 +/- 0.24; 1.05 +/- 0.18 mmol/L; alanine - 0.29 +/- 0.06; 0.30 +/- 0.06; 0.31 +/- 0.03 mmol/l. Total ketone body levels were significantly elevated (p less than 0.05) on conventional therapy but not on continuous subcutaneous insulin infusion compared with controls. Variations in metabolites over 24 h, as measured by mean standard deviations, were increased for glucose (p less than 0.001) and for total ketone bodies (p less than 0.05) on the conventional regimes we employed compared with controls. On continuous subcutaneous insulin infusion variations of blood glucose were not affected whereas variations in total ketone bodies were no different from controls. The best possible maternal metabolic control is necessary for normal foetal development and continuous subcutaneous insulin infusion provides a method of achieving this.

Adult↗
PubMed1981

Rapid changes in somatomedin activity during insulin-induced hypoglycemia: possible release of an inhibitory factor.

Somatomedin activity was determined by bioassay during insulin-induced hypoglycemia in 24 patients with a variety of pituitary disorders. Initial somatomedin levels appeared to depend primarily on the state of GH secretion and were unaffected by abnormal PRL secretion. During the test, somatomedin activity fell to a minimum after 45 to 60 min and subsequently returned to initial values in those patients whose GH levels rose in response to insulin hypoglycemia, but not in patients lacking a GH response. Heat treatment of the plasma abolished the change in somatomedin activity in the majority of patients, and it is likely that the apparent fall in somatomedin was due to the presence of a heat-labile inhibitor of somatomedin action on cartilage.

Drug Stability↗
PubMed1980

Subcutaneous continuous insulin infusion and control of blood glucose concentration in diabetics in third trimester of pregnancy.

The effect of subcutaneous continuous insulin infusion on the control of blood glucose concentrations was assessed in eight pregnant diabetics in the third trimester. Twenty-four-hour glucose profiles were obtained after strict inpatient control on conventional insulin regimens and after the start of the continuous infusion, which was maintained for 5-55 days. Mean 24-hour glucose concentrations (6.2 mmol/l on conventional regimen, 5.9 mmol/l on continuous infusion; 111.6 and 106.2 mg/100 ml respectively) and mean fasting concentrations (5.3 v 6.2 mmol/l; 95.4 v 111.6 mg/100 ml) were not significantly changed by continuous infusion. Diurnal variations in glucose concentration tended to be smaller on continuous infusion: standard deviation from mean 24-hour glucose concentration was reduced from 2.5 to 2.0 mmol/l (from 45 to 36 mg/100 ml), maximum excursion from 8.4 to 7.4 mmol/l (151.2 to 133.2 mg/100 ml), and M value from 16 to 14. Subcutaneous continuous insulin infusion may be useful in limiting diurnal variations of blood glucose concentrations and warrants further investigation since such an action may be beneficial in the management of pregnant diabetics, in whom the best possible control of blood glucose concentrations is sought for the good of the fetus.

Adult↗
PubMed1979

Coagulation abnormalities in diabetic coma before and 24 hours after treatment.

A coagulation screen consisting of measurement of the prothrombin time, thrombin time, kaolin caphalin clotting time, platelet count, plasma fibrinogen level, fibrin degradation products and ethanol gelation test was performed on 24 patients with impairment of consciousness due to acute diabetic metabolic decompensation at the start of treatment and 24 hours later. 22 out of 24 patients showed at least one coagulation abnormality on admission of which the commonest were a prolonged prothrombin time, shortened kaolin cephalin clotting.time and raised plasma fibrinogen level. After 24 hours of treatment these values were more normal but 20 out of 22 patients still displayed some abnormality. 15 patients had two or more coagulation abnormalities on admission including 3 patients with haematological abnormalities suggestive of disseminated intravascular coagulation. This group was older and had higher blood ureas than those with fewer abnormalities, but plasma glucose, sodium, potassium and bicarbonate levels were similar in both groups of patients. All 5 patients with hyperosmolar non-ketotic coma and all 3 patients who died without recovering consciousness had two or more coagulation abnormalities on admission.

Adolescent↗
PubMed1979

Primary hypothyroidism preceding thyrotoxicosis: a report of 2 cases and a review of the literature.

Two cases are reported in whom primary hypothyroidism preceded thyrotoxic Graves' disease. The hypothesis is advanced that this sequence of events was mediated by spontaneous changes in the patient's autoimmune reactions to thyroid. In particular, it may reflect a spontaneous alteration in the balance between blocking antibodies reactive at or near the TSH receptor or cytotoxic thyroid autoimmune mechanisms on the one hand, and thyroid stimulating autoantibodies on the other.

Antibodies↗
PubMed1978

Glucose-induced insulin secretion in patients with parathyroid disorders.

Glucose-induced insulin secretion was studied in ten patients with primary hyperparathyroidism and two with idiopathic hypoparathyroidism both before and after treatment. In each individual, insulin secretion during an intravenous glucose tolerance test was greater when the plasma calcium was higher. No consistent change in insulin secretion with plasma calcium concentration was observed during an oral glucose tolerance test. These findings could be explained by the suggestion that insulin secretion provoked by orally administered glucose is enhanced by gut hormones which may stimulate insulin secretion by a mechanism independent of extracellular calcium.

Calcium↗
PubMed1976

Gastric emptying of solid meals in diabetics.

The gastric emptying rate of an isotopically labelled solid meal was compared in 29 insulin-dependent well-controlled diabetics and 18 normal controls. The diabetics were assessed for evidence of autonomic neuropathy. No significant difference in gastric emptying rate was found between controls and diabetics with or without autonomic neuropathy. Only three diabetics had greatly delayed gastric emptying, but in one of these the test had given a normal result on an earlier occasion.

Adult↗
PubMed1976

The 14C-glycocholate test in diabetic diarrhoea.

Twenty-four insulin-dependent diabetics, including seven with diabetic diarrhoea, were studied by means of the 14C-glycocholate (14C-GCA) test and various tests for autonomic dysfunction. The breath component of het test was abnormal in four of the seven patients with diarrhoea and one of the other diabetics. Three patients with diarrhoea and a positive breath test result responded to antibiotics, whereas two with diarrhoea and a negative test result did not. High faecal 14C, suggesting bile acid malabsorption, was found in only one patient with diarrhoea and he had previously failed to respond to cholestyramine. These results suggest that bacterial overgrowth in the small intestine does occur in some but not all patients with diabetic diarrhoea and that the 14C-GCA test can predict the response to antibiotics. All the patients with diabetic diarrhoea had good evidence of autonomic dysfunction.

Anti-Bacterial Agents↗
PubMed1976

Pituitary function in patients receiving intermittent cytotoxic and corticosteroid therapy for malignant lymphoma.

Diurnal variation in plasma-cortisol was studied immediately before and after intermittent steroid therapy in seven patients receiving monthly courses of quadruple chemotherapy for Hodgkin's or non-Hodgkins lymphoma over a period of 6 months. The serum-thyroid-stimulating-hormone (T.S.H.) response to intravenous T.S.H.-releasing factor was also measured before and during the first course and before the second and fourth courses. The morning plasma-cortisol concentration fell significantly over 6 months when measured immediately before the start of each course. The mean evening cortisol concentration also fell over this period. In most patients the T.S.H. response showed a downward trend during treatment, although in two patients the response returned to normal whilst they were still undergoing therapy.

Adult↗
PubMed1976

The association between serum triglycerides and gamma glutamyl transpeptidase activity in diabetes mellitus.

A study conducted on 228 diabetic patients has shown a significant positive association between serum gamma-glutamyl transpeptidase (GGT) and triglyceride levels. Both fall with treatment, the most marked reduction occurring in patients on insulin. We suggest that the association between serum GGT and triglyceride levels and also the higher incidence of raised GGT and triglyceride levels in new diabetics may reflect hepatic microsomal enzyme induction of the rate-limiting enzymes of triglyceride synthesis. Serum GGT does not seem to correlate with hepatomegaly in diabetes mellitus.

Adolescent↗
PubMed1971

Hypothalamic-pituitary-adrenal function in patients treated with long-term depot tetracosactrin.

Four patients treated with depot tetracosactrin for 10 to 18 months maintained normal hypothalamic-pituitary-adrenal function assessed by the nyctohemeral variation of plasma corticosteroids and by the responses of plasma corticosteroids to insulin-induced hypoglycaemia, lysine-vasopressin, and depot tetracosactrin. The pituitary component of the response was analysed by measuring plasma immunoreactive ACTH levels. Three patients showed a nyctohemeral ACTH rhythm and normal ACTH responses to insulin-induced hypoglycaemia. Consistently undetectable morning plasma ACTH levels were found in the fourth patient, who also showed an unusually delayed rise in both ACTH and corticosteroid levels in response to insulin-induced hypoglycaemia, though the peak values attained were normal.The lack of suppression of hypothalamic-pituitary-adrenal function together with the good clinical response in these four patients suggests that treatment with depot tetracosactrin should be considered when long-term corticosteroid therapy is required.

Adolescent↗