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Biomedical subjects

D R Hadden

Publications and source records attributed to D R Hadden.

At least 109 records · Page 6Linked to original sources
PubMed1989

MEN 2A: update on the Northern Ireland and Australian family.

The Northern Ireland/Australian family with multiple endocrine neoplasia type 2A (MEN 2A) originally described in 1987 is presented with a revised and enlarged pedigree. Four members of the first generation studied have died. A seventh member of the second generation studied has developed medullary thyroid carcinoma and has progressed to surgery. None of the third generation members studied has shown any conclusive abnormality in metabolic screening tests. Each member of the third and fourth generations has had genetic counseling and (if appropriate) DNA analysis with gene probes close to the MEN 2A gene locus on chromosome 10. All members of this highly penetrant family have remained asymptomatic for their disease.

Adult↗
PubMed1989

Poikilothermia in a 68-year-old female. A risk factor for accidental hypothermia, or hyperthermia.

A 68-year-old woman presented in wintertime in a cold climate with ataxia and numbness in her legs and was found to be profoundly hypothermic in hospital. No endocrine or neurological cause for hypothermia could be distinguished. Physiological investigation, including a sympathetic release test, exposure to gradually increasing environmental temperatures and prolonged exposure to a high temperature suggested she was at that time regulating her core temperature around a set value which was several degrees lower than normal. Metabolic rate was 42 per cent below the value predicted from standard tables. Further measurements over a one-month period in a warm climate suggested a poikilothermic temperature control mechanism, with a possible risk of environmental hyperthermia. No pathological basis for this disorder has yet been identified, but it is suggested that a small localized hypothalamic vascular event has occurred.

Aged↗
PubMed1989

The Northern Ireland experience of growth hormone therapy for short stature.

In 1967 the first patient in Northern Ireland commenced growth hormone treatment for short stature. By the end of December 1988 a total of 89 patients had been treated. Thirty-two had idiopathic isolated growth hormone deficiency, an incidence of 1.5 new cases per year (in a population of 1.5 million with approximately 30,000 births per year). Since 1967 the mean age at starting treatment has fallen from 18 years to 10 years and the height standard deviation score has fallen from -4.7 +/- 0.6 to -3.4 +/- 0.3. The group with classical growth hormone deficiency (maximum GH less than 7 mU/l during insulin-induced hypoglycaemia) had a greater increase in height velocity over the first year of treatment, 3.8 +/- 0.4 cm, than those with a partial deficiency (maximum growth hormone 7.1 - 20 mU/l), 1.9 +/- 0.4 cm. All pre-pubertal children responded with a rise in the height velocity standard deviation score from -1.8 +/- 0.3 before treatment to +3.5 +/- 0.4 over the first year of treatment. 58% of the adult males and 25% of adult females have attained an adult height within the normal range (3rd centile or above). There have been three deaths, one each from Fanconi's aplastic anaemia which predated growth hormone treatment, an accidental fire injury and a relapsing craniopharyngioma. There have been no deaths from Creutzfeldt-Jakob disease. Growth hormone therapy is safe and effective, but continues to be commenced late in terms both of age and height standard deviation score.

Adolescent↗
PubMed1988

Natural history of pancreatic islet B-cell function in type 2 diabetes mellitus studied over six years by homeostasis model assessment.

Islet B-cell function and insulin sensitivity were estimated with the aid of a mathematical model from repeated fasting plasma glucose and insulin measurements over a 6 year period in 131 patients with type 2 diabetes mellitus who could be managed satisfactorily on dietary therapy alone. They presented between the ages of 40 and 69 years, and were studied before and after one year of treatment, and then at regular intervals from 12 until 72 months later. A method of averaging the individual trends by means of a linear model regression technique was used to assess the progression of their diabetes. Dietary management over the first 12 months resulted in weight loss from 118% to 106% average body weight, and improved insulin sensitivity from 26% to 40% of normal (p less than 0.001). From 12 to 72 months, the fasting plasma glucose rose at a mean rate of 0.23 mmol/l per year (p less than 0.001) despite a rate of weight loss of 0.2% average body weight per year (p less than 0.01). The estimated islet B-cell function, expressed as a percentage of normal, decreased significantly (p less than 0.05) at a rate of 1.5% per year, with no statistically significant change in insulin sensitivity. Extrapolation suggests the reduction in B-cell function predated the departure of fasting plasma glucose from the normal range.

Adult↗
PubMed1988

Renal artery stenosis in hypertensive diabetic patients.

The prevalence of secondary forms of hypertension in diabetes is unknown. One hundred and five of 465 patients randomly selected from a diabetic clinic population were found to be hypertensive. Hypertensive patients aged less than 70 years were screened for renal artery stenosis using intravenous digital subtraction angiography. Two angiograms were technically unsatisfactory. All 18 insulin-dependent patients successfully screened had normal renal arteriograms. Five of 24 non-insulin-dependent patients had unilateral renal artery stenosis but functional tests did not clearly suggest that renal artery stenosis was causing the hypertension in these cases. No patient was referred for surgery or angioplasty. We conclude that renal artery stenosis is common in hypertensive non-insulin-dependent diabetics but may not, in many cases, be the cause of the hypertension. The criteria for investigating diabetic hypertensives for renal artery stenosis should be no different from those used in the general hypertensive population.

Adult↗
PubMed1987

Three months energy restricted diet does not reduce peripheral insulin resistance in newly diagnosed non insulin dependent diabetics.

Sixteen newly diagnosed non insulin dependent diabetic patients were treated for 3 months with an individual energy restricted diet. The effect on weight, hyperglycaemia and insulin response to oral glucose was measured in all subjects, and in 7, peripheral insulin resistance was estimated using a hyperinsulinaemic glucose clamp at two insulin infusion rates (40 and 400 mU m-2 X min-1). After diet, fasting plasma glucose fell from 12.0 +/- 0.7 mmol/l (mean +/- SEM) to 7.4 +/- 0.5 mmol/l (P less than 0.001) and weight fell from 92.9 +/- 4.2 kg to 85.0 +/- 3.1 kg (P less than 0.001). The plasma insulin response to oral glucose was unchanged after diet therapy. Insulin induced glucose disposal (M) was also unaffected by diet at insulin infusion rates of 40 mU m-2 X min-1 (12.5 +/- 1.5 mumol X kg-1 X min-1 vs 15.7 +/- 1.6 mumol X kg-1 X min-1) and 400 mU m-2 X min-1 (49.5 +/- 2.7 mumol X kg-1 X min-1 vs 55.1 +/- 2.5 mumol X kg-1 X min-1). These results show that 3 months reduction of energy consumption with weight loss in newly diagnosed non insulin dependent diabetics improves B-cell responsiveness to glucose but has no effect on liver glucose output or on peripheral insulin action.

Adult↗
PubMed1987

Clinical experience with ketoconazole as a therapy for patients with Cushing's syndrome.

Six consecutive patients with Cushing's disease were treated with the broad spectrum antifungal drug ketoconazole. Urinary cortisol levels rapidly fell to within the normal range in five of the six patients. Acute hypoadrenalism occurred in one patient, and nausea and pyrexia in three. Our experience with hepatotoxicity was different from that reported by others in that reversible hepatotoxicity was demonstrated in three patients within 7 to 12 days of treatment. Further work is required before ketoconazole can be recommended as a standard primary therapy for patients with Cushing's syndrome. Continuing vigilance for both hypoadrenalism and hepatotoxicity is essential in any patient being treated with this drug either for hypercortisolism or for other reasons.

Adult↗
PubMed1987

Is centralized hospital care necessary for all insulin-dependent pregnant diabetics?

A retrospective population study in Northern Ireland examined the benefits of centralized care in insulin-dependent diabetic pregnancies. In the 5 years 1979-1983, there were 139, 250 deliveries in Northern Ireland and of these 221 pregnancies occurred in 187 insulin-dependent diabetic patients; 100 were managed entirely in peripheral maternity units, 61 were referred from a peripheral unit to the Royal Maternity Hospital, Belfast and 60 were managed entirely in this central referral hospital. The patients referred from the periphery had the worst past obstetric history with a combined perinatal mortality rate of 200 per 1000. During the study period the perinatal mortality rate was 107 for the referred pregnancies, 33 for those managed entirely in the peripheral units and 18 for those managed at the Royal Maternity Hospital. If those pregnancies terminated for fetal abnormality, and deaths beyond the perinatal period are included, the figures for total fetal loss were 15.5%, 5.5% and 7.1% respectively. Overall the major congenital malformation rate was 7.5%, and for the respective groups 6.5%, 3.0% and 13.0%. For the general population during the same period the perinatal mortality rate was 1.4% and the major congenital malformation rate was 2.5%. Thus it is suggested that only peripheral hospitals which can offer combined antenatal/endocrine care and with a neonatal intensive care unit should undertake the management of the pregnant diabetic.

Adult↗
PubMed1987

United Kingdom multicentre clinical trial of somatrem.

In a multicentre clinical trial 54 children aged 4.0 to 17.3 years, who had growth hormone deficiency that had not previously been treated, were given biosynthetic methionyl growth hormone (somatrem) 4 units three times a week by subcutaneous or intramuscular injection for one year. Height was measured every three months for at least one year before and during treatment. Forty two patients responded to treatment with an increase in growth of greater than 1.5 cm/year. The remaining 12 who grew more slowly were less obviously short and had a higher pretreatment growth than those who responded. The three who responded and the one who did not had undergone therapeutic spinal irradiation before starting the drug. If a whole year's pretreatment growth rate of less than 5 cm/year had been used as a diagnostic criterion the prediction of those who responded would have slightly improved. About two thirds of the patients developed antibodies against growth hormone and Escherichia coli protein; these were, however, of low and fluctuating titre and binding capacity, and did not influence the response to treatment. No adverse side effects were encountered. We conclude that somatrem is a safe and effective alternative to pituitary growth hormone.

Adolescent↗
PubMed1987

A comparison of the pharmacokinetics of human protamine sodium insulin with human isophane insulin following subcutaneous injection in normal subjects.

The pharmacokinetics of human protamine sodium insulin 0.6 mg% were compared with those of human isophane zinc insulin using the glucose clamp technique. The insulin preparations were administered subcutaneously at a dose of 0.5 U/kg in 7 normal subjects; a placebo injection served as control. Plasma insulin and C-peptide concentrations were then measured over 24 hours. After correction of the results to allow for endogenous insulin secretion the two insulin preparations gave similar values throughout the study except that protamine sodium insulin achieved an earlier peak in plasma insulin concentration (90 minutes) compared to isophane (120 minutes). When measured by an index of the dextrose infusion rate required to maintain euglycaemia the two insulin preparations gave similar values for the first 16 hours, maximum values being obtained during the fourth hour after administration. Using this index isophane zinc insulin gave higher values during the 17th, 19th and 21st hours following administration suggesting it may have a slightly more prolonged action than protamine sodium insulin.

Adult↗
PubMed1987

Insulin infusion and serum potassium in normal subjects.

Two groups of healthy males of normal body mass index underwent hyperinsulinaemic glucose clamp procedures during studies of insulin resistance. Insulin was infused for 2 consecutive 100 minute periods at 40 and 400 mU.m-2.min-1, plasma glucose being maintained by 20% dextrose infusion via a Biostator. One group received 20 mmol/l potassium chloride in the dextrose infusate, calculated to replace the extracellular potassium deficit due to the action of insulin on potassium flux. Despite this, serum potassium fell equally in both groups in response to each level of insulin infusion.

Adult↗
PubMed1986

Neuroendocrine tumors. A European view.

A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger-Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively.

Apudoma↗
PubMed1986

Diabetes in pregnancy 1985.

The art of obstetrics is not a subject which is often discussed in the pages of Diabetologia. However, as the care of the diabetic mother and her offspring is rightly an interdisciplinary responsibility between obstetrician, diabetologist and neonatologist, it is important that each has a close understanding of the various problems. Dr. M.I. Drury (Dublin), speaking as an internist, raises a question on the optimum time and method of delivery of the baby; this has more than purely obstetrical implications. Drs. L. Mølsted-Pedersen (Copenhagen) and C. Kühl (Copenhagen and Klampenborg), obstetrician and internist from the longest-established joint obstetric/diabetic service in the world, present a Scandinavian view on the management of pregnancy. Both centres have distinguished records in the management of diabetic pregnancy. The different viewpoints in Denmark and in Ireland are clear - in Copenhagen, therapeutic abortion is practiced in a pregnancy at risk of severe congenital malformation; in Dublin it is not. Dr. Drury quotes a perinatal loss of 13 of 285 pregnancies (4.5%) in the past 5 years, but does not include the recognised spontaneous abortions which, on his overall figures, are about 10% of conceptions. Dr. Mølsted-Pedersen reports a perinatal loss of 3 of 201 infants (1.5%), excluding 17 spontaneous and 9 induced abortions. If these 9 aborted pregnancies, which were performed due to a risk of severe congenital malformation, were included as fatalities, the Copenhagen figure would be 12 of 210 (5.5%). Of course, we do not know if all those 9 fetuses were affected. The spontaneous abortion rate was 17 of 223 (8.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗