Biomedical subjects

D E Price

Publications and source records attributed to D E Price.

At least 37 records · Page 2Linked to original sources

PubMed1992

A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF-oma, hypercalcitoninaemia and intractable peptic ulceration.

A 42-year-old woman with a family history of multiple endocrine neoplasia type 1 (MEN 1) presented with symptomatic hypoglycaemia and peptic ulceration. Investigation revealed an insulinoma, hyperparathyroidism, hypercalcitoninaemia with a positive pentagastrin stimulation test, acromegaly due to a GRF-oma, hyperprolactinaemia and normal serum gastrin levels. Five pancreatic tumours were removed at laparotomy and immunostaining was positive for insulin, calcitonin, somatostatin and glucagon. Post-operatively she developed elevated serum gastrin levels and gross peptic ulceration, despite H2-blockers, and died of gastro-intestinal haemorrhage suggesting that removal of the somatostatinoma may have allowed increased gastrin secretion from a gastrinoma. This case emphasizes the importance of measuring a wide variety of tumour marker peptides in MEN 1 and suggests that caution is required in interpretation of the pentagastrin stimulation test in such cases. Patients with MEN 1 and known peptic ulceration may require perioperative omeprazole treatment even if serum gastrin levels are normal.

Adenoma↗

PubMed1992

Diabetic neuropathic cachexia associated with malabsorption.

Diabetic neuropathic cachexia is characterized by neuropathic pain and severe weight loss of unknown aetiology. We describe four patients with diabetic neuropathic cachexia who were found to have malabsorption. Four diabetic patients presented with neuropathic pain, anorexia, depression and weight loss of 16 (range 10-21) kg. None complained of diarrhoea. There were three males and one female, median age 54 (46-67) years. A butterfat test showed a serum turbidity difference of 9 (6-10) light scattering units (normal greater than 60 units). The median serum xylose was low and there was delayed urinary xylose excretion. Urinary indicans, small bowel histology, liver function tests, and thyroid and renal function were normal. Ultrasound scans of liver, gall bladder and pancreas, and endoscopic retrograde cholangiopancreatogram were normal. The patients were treated with pancreatic supplements and a high calorie diet. Three have completely recovered and the other patient is improving. Thus these cases of diabetic neuropathic cachexia appeared to be associated with malabsorption which may be due to pancreatic dysfunction. It is suggested that the management of diabetic neuropathic cachexia should include the investigation and treatment of malabsorption.

Aged↗

PubMed1992

Growth of children before onset of diabetes.

OBJECTIVE: To examine the growth of children before the onset of diabetes. RESEARCH DESIGN AND METHODS: Heights before diagnosis, expressed as SDS, of each diabetic child identified from the diabetes register and of two age- and sex-matched control subjects were obtained from records of routine examinations performed at 3.5, 6, 11, and 13 yr. The heights of their siblings, with control subjects, also were obtained. RESULTS: Diabetic children were considerably taller than control subjects before diagnosis (0-1 yr before diagnosis SDS 0.82 +/- 0.26 vs. 0.16 +/- 0.14, P less than 0.05, n = 24; 1-2 yr before diagnosis SDS 1.02 +/- 0.17 vs. 0.16 +/- 0.14, P less than 0.001, n = 30; 2-3 yr before diagnosis SDS 0.97 +/- 0.23 vs. 0.04 +/- 0.20, P less than 0.005, n = 16). At more than 3 yr before diagnosis, the diabetic children were not significantly taller than control subjects (SDS 0.8 +/- 0.2 vs. 0.27 +/- 0.13, respectively; n = 33). The siblings of the diabetic children were no taller than control subjects. CONCLUSIONS: Diabetic children, but not their siblings, were taller than control subjects before diagnosis, suggesting growth-inducing metabolic changes may precede the onset of clinical diabetes by at least 3 yr.

Adolescent↗

PubMed1991

Changes in circulating thyroid hormone levels and systolic time intervals in acute hypothyroidism.

OBJECTIVE: We have previously reported that, in thyrotoxic patients treated with carbimazole, serum T4 and T3 levels are the first parameters to return to normal, followed by the systolic time interval (STI, a marker of thyroid function at tissue level) and then the serum TSH. The aim of this study was to compare the rate of change of thyroid hormones, TSH and STI in treated hypothyroid patients after the sudden withdrawal of thyroxine. DESIGN AND PATIENTS: Serum T4, T3 (free and total) and TSH were measured in 12 patients taking thyroxine for primary hypothyroidism; seven were biochemically euthyroid and five were over-replaced, as defined by an elevated free T4 and a sub-normal TSH. Thyroxine was withdrawn and the measurements repeated three times a week until the STI rose above the euthyroid range (0.26-0.32). RESULTS: After stopping thyroxine, the serum TSH and STI left the normal range, in advance of the free T4 and T3, after 9.5 +/- 0.95 and 12.2 +/- 1.5 days respectively (mean +/- SEM). The TSH was the first parameter to leave the euthyroid range in all subjects except one in whom the serum TSH was fully suppressed (less than 0.05 mU/l) initially. In the euthyroid group the TSH and STI increased rapidly after stopping thyroxine (time to leave euthyroid range 7.4 +/- 0.8 and 9.4 +/- 0.7 days respectively). In contrast, in the over-replaced group serum TSH and STI became elevated after 12.4 +/- 1.0 days (P less than 0.005 vs euthyroid group) and 16.0 +/- 2.7 days (P less than 0.05 vs euthyroid group) respectively. There was no delay in the fall in serum T4 or T3 in the over-replaced group when compared with the euthyroid group. CONCLUSIONS: In the evolution of primary hypothyroidism, markers of thyroid function at a tissue level (TSH and STI) become abnormal in advance of thyroid hormones. After stopping thyroxine therapy in treated hypothyroid patients, there is a delayed rise in STI and serum TSH levels in subjects with a subnormal TSH level, as compared with those with a normal TSH on treatment. This suggests mild tissue thyrotoxicosis in these individuals.

Acute Disease↗

PubMed1991

The management of impotence in diabetic men by vacuum tumescence therapy.

The treatment of impotence in diabetic men with vacuum tumescence therapy was studied in a specialist clinic. Of 54 diabetic men referred with impotence, seven declined treatment, three chose self-injection with papaverine, and 44 chose vacuum therapy. Patients underwent autonomic function testing (heart rate response to respiration), measurement of penile blood flow (duplex Doppler scanning), and estimation of serum prolactin and testosterone levels. After 2 months, 33 men (75%) were able to have satisfactory intercourse using vacuum therapy. Three others could produce a satisfactory erection with vacuum therapy but their partners found it unacceptable. Eight men (18%) were unable to have satisfactory intercourse; six of these were later treated by self-injection. The median frequency of use of vacuum therapy was 5.5 (1-26) times a month. Outcome was independent of penile blood flow, autonomic function or endocrine status. Impotent diabetic men should be given counselling and offered a choice of the available treatments. Vacuum tumescence therapy is an effective and simple treatment which requires little investigation.

Diabetes Mellitus↗

PubMed1991

Birthweight of babies born to mothers with type 1 diabetes: is it related to blood glucose control in the first trimester?

A retrospective study of 133 pregnancies in women with Type 1 diabetes was performed, and the 116 which progressed beyond 28 weeks were further analysed. Despite good maternal blood glucose control (mean (+/- SE) HbA1 levels 8.6 +/- 0.2% at the end of the first trimester; 6.9 +/- 0.2% at delivery; normal range 4.0-8.5%), 38% of babies had birthweights above the 90th centile and operative intervention occurred in 77 deliveries (66%). There was no significant correlation between birthweight and HbA1 level at any stage of pregnancy, but mothers with babies above the 90th centile for weight had a higher HbA1 at the end of the first trimester than mothers with babies below the 90th centile (9.3 +/- 0.5 vs 7.9 +/- 0.2%, p less than 0.05). In contrast there was no difference in the HbA1 levels at delivery (7.0 +/- 0.3 vs 6.8 +/- 0.2%). The perinatal mortality rate was 17.7 per 1000 births. The results confirm that in Type 1 diabetes large babies are common despite good blood glucose control, and suggest that maternal blood glucose control in the first trimester may be an important determinant of birthweight.

Birth Weight↗

PubMed1991

Effect of aldose reductase inhibition on resistance to ischemic conduction block in diabetic subjects.

OBJECTIVE: To study the effect of aldose reductase inhibition with ponalrestat on resistance to ischemic conduction block (RICB) in diabetic subjects. RESEARCH DESIGN AND METHODS: Twenty-one healthy diabetic subjects without neuropathy were studied. Subjects were randomized to take either a double-blind trial of 600 mg ponalrestat or placebo once daily for 6 wk. The median nerve action potential (MNAP) and conduction velocity (NCV), before and after 20 min of forearm ischemia, were measured at the start and finish of the study. RESULTS: RICB (MNAP remaining after ischemia) decreased from 39.5 to 29.4% in the ponalrestat-treated group (P less than 0.05) and increased from 48.1 +/- 10.2 to 49.5 +/- 6.5% in the placebo-treated group. MNAP and NCV were unchanged in both groups. CONCLUSIONS: Aldose reductase inhibition with ponalrestat partly reverses RICB in diabetes, perhaps by improving nerve hypoxia or reducing nerve energy substrates.

Aldehyde Reductase↗

PubMed1989

The effect of aldose reductase inhibition on erythrocyte polyols and galactitol accumulation in diabetic patients.

Erythrocyte sorbitol level has previously been used as a measure of the efficacy of aldose reductase inhibitors, but its value is limited by fluctuations related to variations in blood glucose concentration. The aim of the study was to compare sorbitol content with the ability to accumulate galactitol during ex vivo incubation with galactose, of erythrocytes taken from diabetic patients following administration of a single 600 mg dose of the aldose reductase inhibitor, ponalrestat. Twelve patients were studied in a placebo-controlled crossover trial. Blood glucose levels were not statistically different during the placebo and ponalrestat treatment periods except at 1 h after the dose was taken (10.6 +/- 6.7 vs 7.7 +/- 4.6 mmol l-1 (+/- SD), p less than 0.05). Ponalrestat reduced erythrocyte sorbitol concentrations compared with placebo at 3, 5 and 7 h (0.82 +/- 0.36, 0.69 +/- 0.23, and 0.83 +/- 0.35 mg l-1 vs 1.79 +/- 0.67, 1.68 +/- 0.65, and 1.57 +/- 0.59 mg l-1 respectively, p less than 0.005) and 24 h post-dose (1.57 + 0.45 vs 2.01 + 0.73 mg l-1, p less than 0.05). Ponalrestat also reduced erythrocyte galactitol accumulation at 3, 5 and 24 h post-dose from 5.53 +/- 2.41, 5.43 +/- 1.89, and 5.42 +/- 1.96 mg l-1 2-h-1 to 1.47 +/- 0.30, 1.76 +/- 0.41, and 4.12 +/- 0.72 mg l-1 2-h-1 respectively, p less than 0.01. Galactitol accumulation rate appeared to be a less variable parameter than erythrocyte sorbitol and was not influenced by fluctuations in blood glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

PubMed1989

Resistance to ischaemic conduction failure in chronic hypoxaemia and diabetes.

Median nerve function was studied in twelve diabetic subjects, six subjects with chronic hypoxaemia and ten control subjects. Resistance to ischaemic conduction failure (RICF), a characteristic electrophysiological feature of diabetic neuropathy, was assessed by measuring the decline in median nerve action potential amplitude at minute intervals for up to 20 minutes while the arm was rendered ischaemic. Initial nerve conduction velocity and action potential amplitude was similar in all three groups. Following the onset of ischaemia the time to a 50% reduction in action potential amplitude was prolonged in both diabetic subjects and hypoxaemic subjects compared with controls. After 20 minutes of ischaemia no control subject had persisting nerve function, while function remained in 5 (80%) of hypoxaemic subjects and 10 (83%) of diabetic subjects. The time to a 50% reduction in action potential amplitude during ischaemia correlated with the blood oxygen saturation among the hypoxic subjects and haemoglobin Alc among diabetic subjects. These results are consistent with the hypothesis that hypoxia has a role in the pathogenesis of resistance to ischaemic conduction failure in diabetes.

Adult↗

PubMed1988

Effect of aldose reductase inhibition on nerve conduction velocity and resistance to ischemic conduction block in experimental diabetes.

The relationships between nerve polyol levels and both nerve conduction velocity (NCV) and resistance to ischemic conduction block (RICB) in streptozocin-induced diabetic rats were examined in two studies. In the first study, sciatic NCV and RICB of the tail nerve, assessed by measuring the time to disappearance of the nerve action potential after the tail was rendered ischemic, were measured in nondiabetic rats, untreated diabetic rats, and diabetic rats given Statil, an aldose reductase inhibitor (ARI). Sciatic NCV was lower in the untreated diabetic animals than in control animals (P less than .05), and RICB of the tail nerve was greater (P less than .001). Treatment with the ARI completely prevented the slowing of NCV but had no significant effect on the increase in RICB. In the second study, similar groups of rats were treated with either ARI, insulin, or myo-inositol. Sciatic NCV was lower in the untreated diabetic rats than in the nondiabetic rats (P less than .001). In diabetic rats treated with the ARI and in those treated with insulin, NCV was greater than in the untreated diabetic rats (P less than .05 and P less than .001, respectively) and was not significantly different from the nondiabetic rats. NCV in the myo-inositol-treated rats was not significantly different from that in the untreated diabetic rats. RICB was assessed by measuring the decline in sciatic nerve action potential amplitude at minute intervals after death.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1987

The relationship between peripheral nerve resistance to ischaemia and diabetic control.

The cause of the abnormal resistance to ischaemia of peripheral nerve function in diabetes is unknown. Median nerve function was more resistant to ischaemia in diabetic patients than in control subjects. In diabetic patients the degree of resistance to ischaemia correlated closely with HbAlc but not with the coincident blood glucose level, the duration of diabetes, the vibration perception threshold at the thumb or the initial median nerve action potential amplitude. Thus in diabetes the resistance of peripheral nerve function to ischaemia is dependent on medium term metabolic control and is not directly related to the presence or absence of neuropathy.

Action Potentials↗

PubMed1986

The effect of low-dose phenobarbitone on three indices of hepatic microsomal enzyme induction.

The effects of low-dose phenobarbitone on three indices of hepatic enzyme induction were studied. Eight healthy volunteers took phenobarbitone 7.5 mg daily for 4 weeks followed by 15 mg daily for 4 weeks; five subjects took 30 mg daily for a further 2 weeks. Phenobarbitone 15 mg daily produced a significant rise in antipyrine clearance (P less than 0.05). Phenobarbitone 30 mg daily produced a further rise, but probably because of the reduced numbers of subjects, this did not achieve significance (P = 0.06). Urinary 6-beta-hydroxycortisol and D-glucaric acid levels did not change significantly and remained within the range seen in subjects not taking enzyme-inducing drugs. We conclude that phenobarbitone 7.5 mg daily produces little (if any) enzyme induction whereas 15 mg, or more, may have the potential to produce drug interactions through enzyme induction.

Adult↗

PubMed1984