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Biomedical subjects

D Perry-Keene

Publications and source records attributed to D Perry-Keene.

7 recordsLinked to original sources

The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults.

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. Patients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 +/- 1 yr (+/- SEM; range 17-67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 +/- 0.27 (range -8.8 +3.82; n = 78) to +1.08 +/- 2.87 (range -7.21 to +6.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment [17.6% and 68.9% with subnormal (< 2 SD) or normal (+/- 2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or dual energy x-ray absorptiometry (DEXA; P < 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or deuterium dilution (P = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional reaction as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.

Adult

Predictive diagnosis of multiple endocrine neoplasia (MEN 1) in four Australian kindreds.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is a tumour predisposition syndrome that usually manifests in the first four decades of life. It has an autosomal dominant mode of inheritance which means that any new member of a MEN1 kindred has roughly a 50% chance of developing the disorder during their lifetime. The localisation of the MEN1 gene to a small region of chromosome band 11q13 has led to the development of DNA-based predictive diagnosis for this disease. AIMS: To establish a polymerase chain reaction (PCR)-based system, using simple tandem repeat polymorphisms (STRPs), to predict gene carriers in four Australian MEN 1 kindreds. METHODS: Six STRP markers flanking the MEN1 region of chromosome band 11q13 were used to screen individuals for a common haplotype in order to determine carrier status. RESULTS: The accuracy of prediction was calculated to be > 95% in informative individuals. CONCLUSIONS: DNA-based presymptomatic detection of affected members of MEN 1 kindreds could facilitate their care and reduce the inconvenience and expense of repeated testing of unaffected members. However, due to occasional recombination events or uninformativeness of markers in certain individuals, carrier status cannot always be predicted.

Adult

Screening for thyroid malignancy: the role of fine-needle biopsy.

Cytological examination of the aspirate of fine-needle biopsy is becoming more widely accepted as a screening test for malignancy in thyroid nodules. However, it tends to be used in addition to, rather than instead of, more traditional methods. In this five-year prospective evaluation we performed fine-needle biopsy in 618 euthyroid patients with nodular thyroid enlargement, 86% of whom also underwent radionuclide scans and 55% of whom underwent ultrasound scans. In 19% of patients fine-needle biopsy yielded insufficient material for diagnosis, and in 14% of patients normal follicular cells were found (which indicated that the clinical lesion was not sampled). To date, a histological diagnosis has been obtained in 258 (42%) patients, 44 of whom had malignancies. The results of the radionuclide and ultrasound scans did not alter the odds in favour of the detection of malignancy. The cytological diagnosis of malignancy was falsely-positive in two patients and falsely-negative in four patients (three cases of which probably were sampling errors). If, in addition to overtly-malignant cells, atypical Hürthle cells and follicular neoplasms were considered to be potentially malignant, fine-needle biopsy alone had a sensitivity of 87% and a specificity of 72%. This good accuracy would be reduced by sampling failures, but a policy of operating on all patients with potentially-malignant cells, or on those in whom satisfactory aspirates could not be obtained, would yield high rates of the diagnosis of malignancy and would reduce the number of operations. Our data indicate that the most-appropriate method of screening thyroid nodules for malignancy is fine-needle biopsy without pertechnetate scanning or ultrasound examinations.

Australia

Phaeochromocytoma in Queensland--1970-83.

A statewide survey was conducted in Queensland to record all cases of phaeochromocytoma between the years of 1970 and 1983 inclusive. There were 46 cases giving an incidence of 1.55/million population per year. Twenty-nine patients (63%) were successfully treated while 10 patients (22%) died of the tumour effects. Seven cases (15%) were found incidentally at autopsy, though at least one showed diagnostic clinical features before death. Five patients (11%) had extra adrenal phaeochromocytoma, five patients (11%) had multiple tumours, four patients (9%) had multiple endocrine neoplasia and three patients (7%) had clinically malignant tumours. Of 13 patients suffering a major adrenergic crisis only six survived. Five patients with unsuspected phaeochromocytoma suffered crisis under anaesthesia and only one survived. Only one of the patients dying of benign phaeochromocytoma had adequate ante mortem adrenergic blockade. Of all patients in the series 35% were not diagnosed in life.

Adolescent

Chronic diphenylhydantoin therapy does not reduce plasma 25-hydroxy-vitamin D.

A randomized controlled study was performed to investigate the effect of 2 years' monitored diphenylhydantoin (DPH) therapy on plasma 25-hydroxyvitamin D (25-OHD) in non-epileptic, non-institutionalized subjects. Mean +/- SEM plasma 25-OHD of 18 DPH-treated subjects at the end of 2 years' drug treatment was 59 +/- 8 nmol/l (23.6 +/- 3.2 ng/ml), which was not decreased compared to that of eighteen control subjects (54 +/- 8 nmol/l, 21.6 +/- 3.2 ng/ml). In addition, mean plasma 25-OHD had not changed 1 month after ceasing DPH. The treated group had a higher mean serum alkaline phosphatase (SAP) during DPH treatment, attributable to hepatic enzyme induction. It is concluded that therapeutic doses of DPH without other anticonvulsants do not have a clinically significant effect on plasma 25-OHD.

Adult

Thyroid hormone levels and protein binding in patients on long-term diphenylhydantoin treatment.

The effect of long-term diphenylhydantoin (DPH) treatment on thyroid hormone concentrations and protein binding was determined in a randomized controlled trial. As has been demonstrated previously, total thyroxine (T4) concentrations were significantly depressed in patients on DPH. There was no significant effect on indirect indices of protein binding of thyroid hormones, and the free thyroxine index (FTI) was also significantly depressed. Triiodothyronine (T3) and thyrotrophin (TSH) concentrations were either unaffected, or only very slightly affected by DPH. Significant effects on the FTI were still apparent 4 weeks after discontinuing treatment. It is concluded that the depression of total T4 levels observed in vivo is not due solely to diminished protein binding, but may instead be largely explained by reports suggesting enhanced degradation of T4 following DPH therapy.

Adult