S. S. Nussey

The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas

OBJECTIVES We assessed the long‐term efficacy and toxicity of conservative surgery and radiotherapy in the control of pituitary adenomas.

Automated detection of diabetic retinopathy in digital retinal images: a tool for diabetic retinopathy screening

Aims  To develop a system to detect automatically features of diabetic retinopathy in colour digital retinal images and to evaluate its potential in diabetic retinopathy screening.

Polycystic ovaries and associated metabolic abnormalities in Indian subcontinent Asian women

To determine the prevalence of polycystic ovaries (PCO) in Asian women living in England who are of Indian subcontinent origin or ancestry and to investigate the relationship between the presence of PCO and/or non‐insulin dependent diabetes mellitus (NIDDM) and insulin sensitivity and other metabolic parameters.

Synthesis of NG, NG Dimethylarginine by Human Endothelial Cells

Endothelial cells synthesise nitric oxide from L-arginine and this process can be inhibited by NG, NG dimethylarginine (asymmetric dimethylarginine; ADMA), a constituent of plasma and urine. In the present study cultures of human umbilical vein endothelial cells have been shown to release ADMA. Over 7 days 5.1 ± 2.8; μg ADMA was produced by 107 cells (n = 8). These results suggest the presence of a metabolic pathway that may regulate NO synthesis within the endothelium.

Bone mineralization after treatment of growth hormone deficiency in survivors of childhood malignancy.

Having noted symptomatic osteoporotic vertebral collapse in young adult survivors of childhood malignancy, bone mineral density (BMD) was examined at three sites by dual‐energy X‐ray absorptiometry in 64 patients treated in childhood for intracranial malignancy (group 1; n = 21) or acute leukaemia (group 2; n = 43). Patients in group 1 were selected for growth hormone deficiency (GHD) by auxological and biochemical criteria before the end of puberty (Tanner stage V). Seven patients (six men; mean (± SEM) age at study, 28.0 ± 2.9 years; mean age at diagnosis, 8.7 ± 1.5 years) in this group had been treated with human pituitary growth hormone (GH) for 1–12 years; and 14 patients (nine men; mean age at study, 26.8 ± 1.0 years; mean age at diagnosis, 10.7 ± 1.4 years) had not received GH. Bone densities in group 1 were normal in the GH‐treated patients at the femoral neck (98.4 ± 3.8% of control), lumbar spine (100.4 ± 6.1% of control) and Wards triangle (101.0 ± 6.1% of control) but markedly reduced in the untreated group (femoral neck, 81.2 ± 2.6% of control (p= 0.002); lumbar spine, 79.1 ± 4.1% of control (p= 0.04); Wards triangle, 80.1 ± 3.6% of control (p= 0.01)). The majority of patients in group 2 had been treated for acute lymphoblastic leukaemia (ALL) and were in three subgroups. Fifteen (ten men; mean age at study, 22.1 ± 0.8 years; mean age at diagnosis, 5.7 ± 0.8 years) had no auxological evidence of GHD, ten (six men; mean age at study, 18.8 ± 0.7 years; mean age at diagnosis, 6.6 ± 1.2 years) received GH therapy for a mean of 2.6 years (range, 0.5–5.0 years), while 14 patients (three men; mean age at study, 20.9 ± 0.4 years; mean age at diagnosis, 5.1 ± 0.8 years) had GHD but did not receive GH. A small group of four patients (three men; mean age at study, 23.2 ± 2.1 years; mean age at diagnosis, 8.0 ± 2.3 years) who had been treated for acute myeloid leukaemia (AML) in childhood was also studied. The patients with AML had normal bone densities at all three sites (femoral neck, 106 ± 6.1% of control; lumbar spine, 96.5 ± 3.0% of control; Wards triangle, 110.8 ± 9.3% of control), as did the patients with ALL who did not have GHD (femoral neck, 102.3 ± 2.9% of control; lumbar spine, 98.6 ± 1.7% of control; Wards triangle, 108.3 ± 3.2% of control). The patients with ALL and GHD not treated with GH had markedly reduced BMD at all three sites (femoral neck, 90.5 ± 2.6% of control; lumbar spine, 88.4 ± 2.5% of control; Wards triangle, 94.5 ± 3.7% of control), but those treated with GH had a BMD no different from control (femoral neck, 100.6 ± 3.3% of control; lumbar spine, 95.7 ± 4.6% of control; Wards triangle, 106.2 ± 4.9% of control). It is concluded that GHD during childhood and adolescence predisposes to osteopenia.

Cytotoxic effects of amiodarone and desethylamiodarone on human thyrocytes

Since recent in vivo evidence suggests that the benzofuran antiarrhythmic drug amiodarone has a direct toxic effect on the human thyroid gland, we have investigated the effects of both amiodarone and its metabolite desethylamiodarone on a novel immortalized functional human thyrocyte line (SGHTL-34 cells). Desethylamiodarone markedly reduced cell number as assessed from both DNA and protein content. Few cells were left after 24 hr exposure to 12.5 micrograms/ml; the concentration producing death of 50% of cells (EC50) was 6.8 +/- 1.1 micrograms/ml (mean +/- SE, N = 15). Amiodarone was much less potent, producing a maximum decrease in cell number of approximately 25% at concentrations up to 50 micrograms/ml. The effect of desethylamiodarone was seen within 24 hr of culture. T3 in concentrations up to 0.75 micrograms/ml had no effect on the action of amiodarone or desethylamiodarone on SGHTL-34 cells. Light microscopy demonstrated vacuolation of SGHTL-34 cells after 4-day culture with either the drug or its metabolite. Studies using primary cultures of human retroorbital fibroblasts demonstrated that the greater cytotoxicity of desethylamiodarone was not confined to thyrocytes. When SGHTL-34 cells were incubated with 2.5 micrograms/ml desethylamiodarone for 4 days, 71.7 +/- 0.9% was taken up by the cells; there was no detectable conversion to amiodarone. Incubation of thyrocytes with 50 micrograms/ml amiodarone for 4 days resulted in the uptake of 80.1 +/- 2.1% by the cells. In addition, 5.0 +/- 0.1% of the amiodarone was converted to material with the same retention time as desethylamiodarone standard; of this material, 72.9 +/- 2.8% was taken up by the cells. We conclude that desethylamiodarone, at concentrations near those found in the plasma of patients on long-term amiodarone therapy, exerts a direct cytotoxic effect on human thyroid cells in short-term culture. This effect may play a role in the aetiology of clinical thyroid disease during amiodarone therapy. We suggest that, since the effect is not restricted to thyrocytes, desethylamiodarone may play a role in the aetiology of amiodarone toxicity which occurs clinically in many tissues.

RESPONSES OF PLASMA OXYTOCIN AND ARGININE VASOPRESSIN TO NAUSEA INDUCED BY APOMORPHINE AND IPECACUANHA

Apomorphine, a centrally‐acting emetic, was administered subcutaneously (50 /μg/kg) to nine normal subjects (four male, five female; aged 22‐36 years) and four patients with idiopathic diabetes insipidus (DI) (one male, three female; aged 24‐49 years). In the normal subjects this stimulus caused nausea (and vomiting in seven of nine) with a latency of 9‐5 ± 0‐9 min which was followed by a large increase in plasma arginine vasopressin (AVP) concentration (from 0‐9 ± 0‐2 pmol/1 to 249 ± 104 pmol/1 at 15 min after the onset of symptoms; mean ± SEM, P<001). There was a small but significant increase in plasma oxytocin (OXT) concentration (from 1‐6 ± 0‐4 pmol/1 to 6‐2 ± 3‐4 pmol/1; P<005). Mean arterial pressure (MAP) fell slightly (from 87±1‐9 mm Hg to 71±4‐4 mm Hg; P < 005) 15 min after the onset of nausea; there was no change in blood haematocrit or plasma osmolality and sodium concentration. In the DI patients apomorphine produced nausea (with vomiting in three of four) with a latency of 100±1 ‐4 min but failed to cause an increase in either plasma AVP or OXT. In the DI patients the fall in MAP did not reach statistical significance (83 ± 4 mm Hg to 71 ± 11 mm Hg); there was also no change in haematocrit, osmolality or sodium concentration. Ipecacuanha, an emetic with both peripheral and central actions, was administered orally to seven normal subjects (three male, four female; aged 22‐36 years) six of whom also underwent apomorphine tests. Nausea followed with a latency of 16‐9 ± 3‐2 min (with vomiting in five of seven). However, despite producing symptoms considered by the subjects to be as severe as those caused by apomorphine there was no increase in plasma AVP or OXT. In contrast to apomorphine, ipecacuanha produced a significant increase in MAP (from 82 ± 2 mm Hg to 11101+7 mm Hg; P<0‐05) and pulse rate (62 ± 3 min‐1 to 76 ± 4 mm‐1; P<0‐05); there was no change in haematocrit, osmolality or sodium concentration.

The role of oxytocin: present concepts

(Received 11 October 1990; returned for revision 21 December 1990; finally revised 10 January 1991; accepted 10 January 1991) indeed involved in human parturition. The onset of labour is associated with only a slight to moderate increase in the levels of oxytocin in the blood but as labour progresses there is a further increase, probably related to distension of the genital tract (Ferguson reflex). Even the reports that patients with diabetes insipidus and no detectable circulating oxytocin can proceed to normal labour can be reconciled with the

Insulin resistance and endothelial dysfunction in the brothers of Indian subcontinent Asian women with polycystic ovaries

background  Ultrasonographic appearances of polycystic ovaries (PCO) are found in 50% of South London Indian subcontinent Asians, a population at high risk of coronary disease and type 2 diabetes (DM). PCO is a familial condition but the genetics remain to be clarified. At present, the only characteristic documented in male family members is premature male pattern balding before the age of 30 years. Our aim was to quantify insulin resistance and endothelial cell function in the brothers of Indian subcontinent Asian women with PCO and/or a family history of type 2 DM.

THE EFFECT OF OXYTOCIN INFUSION ON ADENOHYPOPHYSEAL FUNCTION IN MAN

The responses of the adenohypophyseal hormones adrenocorticotrophin (ACTH), growth hormone (GH), thyroid stimulating hormone (TSH), prolactin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) to sub‐maximal doses of hypothalamic releasing factors were studied in six lean male volunteers (age 23‐35 years) with and without infusions of oxytocin (OXT). OXT infusion (mean plasma concentration 133.6±2.6 pmol/1) completely inhibited the plasma ACTH responses to corticotrophin releasing hormone (CRH) (saline, peak increment ACTH 1.61±0.75 pmol/l; OXT, peak increment ACTH — 0.04±0.28 pmol/l; P < 0.05). OXT infusion had no significant effect on the GH response to growth hormone releasing hormone (GHRH), the TSH and prolactin responses to thyrotrophin releasing hormone (thyroliberin, TRH) or the LH and FSH responses to gonadotrophin releasing hormone (luteoliberin, GnRH). The data support a role for OXT in the modulation of ACTH secretion in man.