Search

To assess whether the introduction of a management of raised glucose clinical decision tool could improve assessment of patients with hyperglycaemia by non-specialist physicians, leading to early discharge and improved quality of inpatient care.

Specific problems in patients with insulin-dependent diabetes mellitus (IDDM) and GH deficiency are hypoglycaemic attacks, increased insulin sensitivity and loss of energy. These problems may be related to GH deficiency.

The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-2H2]glucose (0-480 min) and in random order either IGF-I 20 micrograms kg-1 h-1 (43.7 pmol kg-1 min-1 or insulin 0.5 mU kg-1 min-1 (3.4 pmol kg-1 min-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 +/- 0.13 at baseline (150-180 min) to 0.35 +/- 0.26 mg kg-1 min-1 (P < 0.01) at 360 min, and glucose utilization rate (Rd) increased from 1.79 +/- 0.28 to 4.17 +/- 0.84 mg kg-1 min-1 (P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output +l37.3% +/- 9% (P < 0.01), heart rate +13% +/- 2% (P < 0.01) and stroke volume +21% +/- 7% (P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 +/- 0.13 to 0.34 +/- 0.33 mg kg-1 min-1 (P < 0.01) and FFA from 0.546 mmol l-1 to 0.198 mmol l-1 (P < 0.01), glucose Rd increased from 1.89 +/- 0.18 to 5.41 +/- 1.47 mg kg-1 min-1 (P < 0.01) and there were no significant changes in the cardiovascular variables.

To assess whether the introduction of a management of raised glucose clinical decision tool could improve assessment of patients with hyperglycaemia by non-specialist physicians, leading to early discharge and improved quality of inpatient care.Participants were adults aged 18 years or over presenting to the Medical Assessment Unit with a capillary blood glucose level11.1 mmol/l. Phase 1 of the study (phase 1) evaluated current clinical practice and potential impact of the clinical decision tool. Phase 2 evaluated the effectiveness of the management of raised glucose tool in clinical practice. Primary outcome measures were inpatient length of stay and same-calendar-day discharges. Secondary outcome measures were diabetes specialist input, patient assessment, intravenous insulin infusion use and patient satisfaction.Implementation of the management of raised glucose clinical decision tool allowed safe, same-calendar-day discharges of 40% of patients with hyperglycaemia as their primary reason for attendance. Median length of stay was lower in the phase 1 than in phase 2 (1.0 vs. 3.5 days, P0.01). Early discharge did not result in an increase in readmissions. There was improvement in hyperglycaemia assessment for all patients (P0.01), a reduction in the use of intravenous insulin infusions (P0.01) and high level of patient satisfaction.The management of raised glucose clinical decision tool resulted in a significant increase in the number of same-calendar-day discharges and reduction in hospital length of stay without adverse impact on readmission rates. Additionally, the tool was associated with improvements in inpatient diabetes care and patient satisfaction.

Adult patients with growth hormone deficiency are thought to be at higher risk of mortality from cardiovascular disease. We therefore investigated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of lipids, lipoproteins and cholesterol precursors in adult growth hormone deficient patients.Double-blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month).Eighteen patients with severe growth hormone deficiency.Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months.In the rhGH treated group there was a significant fall in serum cholesterol (P0.01) (6.44 +/- 0.49 to 5.71 +/- 0.48 mmol/l), LDL cholesterol (P0.02) (4.29 +/- 0.49 to 3.62 +/- 0.44 mmol/l), LDL cholesterol/HDL cholesterol ratio (P0.02) (3.99 +/- 0.62 to 3.26 +/- 0.39), apolipoprotein B (P0.01 (1.30 +/- 0.11 to 1.15 +/- 0.11 g/l) and mevalonic acid (P0.05) (13.4 +/- 10.96 to 6.21 +/- 1.91 micrograms/l). There were no significant changes in triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulin was inversely correlated with the fall in cholesterol (P0.05), LDL cholesterol (P0.01) and apolipoprotein B (P0.01). There were no significant changes in any of the measured variables in the placebo group.We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up-regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.

There is evidence that the hormonal control of hepatic IGF-I production is mediated by GH and insulin. To elucidate the role of these hormones further we administered s.c. or i.p. insulin (at 2·5 and 5·0 IU/day) and/or GH (0·8 IU/day) to rats made diabetic with streptozotocin 16 days previously. Hepatic IGF-I production was then assessed by quantifying hepatic IGF-I mRNA levels by autoradiography of Northern blots. Diabetes resulted in a fivefold reduction in hepatic IGF-I mRNA levels (optical density (OD) of the 0·7–1·1 kb band: controls, 1·3±0·09; diabetics, 0·28±0·08; PPPP

Carbamazepine (CBZ) is a widely used antiepileptic drug (AED). Recently, a chewable tablet (Tegretol chewtabs) has been formulated. This open substitution study was designed to compare the two formulations with respect to efficacy and tolerability in patients with intractable epilepsy. Thirty patients (24 males, 6 females, mean age 46 years, range 28-83) were studied. Duration of epilepsy was 21-68 years (median 34 years). Four patients were taking CBZ monotherapy, 17, 6 and 3 patients were respectively taking CBZ plus 1, 2 and 3 additional AEDs. Upon entry to study, patients were switched to an equivalent dose of chewtabs and subsequently evaluated at 2, 4, 8 and 12 weeks. Two patients did not complete the study. On entry, the mean 14 day seizure rate was 2.5. On chewtabs mean 14 day rates were 2.4, 2.2, 2.4 and 2.7 after 2, 4, 8 and 12 weeks of treatment respectively. On entry the mean steady state trough serum CBZ concentration was 35 mumols/l compared to 32, 31, 32 and 34 mumols/l after 2, 4, 8 and 12 weeks respectively. Nineteen patients were classified showing good or excellent tolerability, 7 satisfactory and 2 fair. In conclusion, chewtabs were essentially equivalent to the conventional formulation in efficacy and tolerability. After 12 weeks treatment, 19 patients preferred the chewable formulation.

The treatment of diabetes was revolutionised shortly after the turn of the twentieth century by the extraction and purification of insulin. Methods to protract (i.e. prolong) the action of insulin were developed in the 1930s; little changed in the technology of insulin protraction until the turn of this century when, with renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, technology advanced again. Two new long-acting insulin analogues have come to the market; some may be familiar with insulin glargine, which has been widely used for some years now. This review attempts to describe the novel method of protraction that insulin detemir (launched last summer) employs by albumin binding, to discuss the possible therapeutic benefits of this method of protraction and to describe the findings of studies comparing insulin detemir with other currently available long-acting insulin preparations. The intention of this article is not to review all of the currently available long-acting insulin analogues.

Growth hormone (GH) is known to be required for physical well-being. Although it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD).A double-blind, placebo-controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH-deficient adults, where nine continued with GH replacement.GH-treated adults (10 men, 11 women), all with severe GHD (peak GH7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years).Semi-structured interviews were given at baseline and end-point plus questionnaires that included a new hormone-deficiency specific, individualized, QoL questionnaire (HDQoL), the General Well-being Index (GWBI), the Well-being Questionnaire (W-BQ12), the Short-Form 36 health status questionnaire (SF-36), the Nottingham Health Profile (NHP) and the General Health Questionnaire (GHQ).Three months after baseline the serum total IGF-I of placebo-treated patients fell from normal, age-related levels (mean 26.6 +/- 13.2 nmol/l) to levels indicative of severe GHD (11.6 +/- 6.6 nmol/l) (P0.001). Psychological symptoms of GH withdrawal, reported in interviews at end-point by placebo-treated patients, included decreased energy, and increased tiredness, pain, irritability and depression. Patients who believed they knew which treatment they had received correctly identified the treatment (GH or placebo) at end-point (chi2=11.25, P0.01). Significant between-treatment-group differences in change scores were found for SF-36 General Health (P0.01), W-BQ12 Energy (P0.01) and HDQoL do physically (P0.05), indicating reduced general health, reduced energy and greater perceived impact of hormone deficiency on physical capabilities in the placebo-treated group at end-point relative to GH-treated patients.Withdrawal of GH treatment from adults with severe GH deficiency has detrimental psychological effects.

To evaluate the psychometric properties of two health status measures for adults with growth hormone deficiency (GHD): Nottingham Health Profile (NHP) and Short-Form Health Survey (SF-36).(1) A cross-sectional survey of adults with treated or untreated GHD to assess reliability and validity of the questionnaires. (2) A randomized, placebo-controlled study of 3 months' GH withdrawal from GH-treated adults to assess the sensitivity of the questionnaires to change.(1) A cross-sectional survey of 157 patients with severe GHD (peak GH10 mU/l on provocative testing), mean age 48.9 years (range 23-70 years), who had either received GH replacement therapy for at least 6 months immediately prior to the study or had not received GH treatment in the previous 6 months. (2) GH treatment was withdrawn from 12 of 21 GH-treated adults, all with severe GHD (peak GH7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years).The NHP and SF-36 were used once in the cross-sectional survey, but twice in the GH-withdrawal study, at baseline and end-point (after 3 months).(1) Cross-sectional survey. Both questionnaires had high internal consistency reliability with subscale Cronbach's alphas of0.73 (NHP) and0.78 (SF-36). Calculation of an NHP Total Score, occasionally reported in the literature, was shown to be inadvisable. Overall, patients with GHD were found to have significantly worse perceived functioning than the UK general population in SF-36 subscales of General Health, Bodily Pain, Social Functioning, Physical Functioning, Role-Emotional, Role-Physical, and Vitality. Although neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations with duration of GH treatment (P0.01) for GH-treated patients in SF-36 Mental Health (r = 0.29, N = 87) and SF-36 Vitality (r = 0.33, N = 88), indicating improvement with increasing treatment duration. The SF-36 was also more sensitive than the NHP to sex differences: men had significantly better health status compared with women (P0.05) in all SF-36 subscales but Mental Health, but only in one NHP subscale (Physical Mobility). (2) GH-withdrawal study. Significant between-group differences in change were found in SF-36 General Health [t(17) = 2.76, P = 0.013, two-tailed] and SF-36 Mental Health [t(17) = 2.41, P = 0.027, two-tailed]: patients withdrawn from GH reported reduced general health and mental health at end-point. The NHP found no significant change.The SF-36 is a better measure than the NHP of health status of people with GH deficiency because of its greater discriminatory power, with ability to detect lesser degrees of disability. It also has superior sensitivity to some subgroup differences and superior sensitivity to change compared with the NHP. The SF-36 is highly acceptable to respondents, and has very good internal consistency reliability. The SF-36 is recommended to measure the health status of adults with GH deficiency.

Specific problems in patients with insulin-dependent diabetes mellitus (IDDM) and GH deficiency are hypoglycaemic attacks, increased insulin sensitivity and loss of energy. These problems may be related to GH deficiency.GH replacement was initiated in five patients with type 1 diabetes mellitus and GH deficiency for 6 months [four males and one female, mean age 41.6 +/- 3.8 years, mean +/- standard error of the mean (SEM); body mass index (BMI) 22.3 +/- 1.2 kg/m2].Body composition (bioimpedance), metabolic control [haemoglobin A1C (HbA1C)], insulin requirement and frequency of hypoglycaemia were measured, and quality of life was assessed using validated questionnaires. Monthly eye photographs were taken.IGF-I concentrations were below the age-adjusted range at baseline and increased significantly following GH replacement therapy [analysis of variance (ANOVA), P0.05]. Diabetes control as assessed by HbA1C remained stable (8.2 +/- 0.2 vs. 8.0 +/- 0.4), but needed a 1.75-fold increase in insulin dose/day. Lean body mass tended to increase (P = 0.07) and body fat mass decreased significantly (P0.01). Number of severe hypoglycaemic (3 mmol/l) attacks decreased significantly (P0.04) and quality of life assessed by validated questionnaires improved significantly in all patients [Psychological and General Well-Being Schedule (PGWBS), P0.04; Nottingham Health Profile (NHP), P0.05]. Monthly eye photographs revealed no changes in the retina in any patients.GH replacement therapy has a beneficial effect at the dose used. It restores body composition and decreases frequency and severity of hypoglycaemic episodes, thus improving quality of life. Long-term trials are needed to determine the safety of GH replacement therapy in these patients.

Patients with adult GH-deficiency are thought to have an increased risk of cardiovascular disease. Sialic acid (SA) concentrations have been proposed as a marker of atherosclerotic disease probably related to an inflammatory response of the arterial wall. SA as a marker of cardiovascular disease in adult GH-deficiency and its relation to changes in fasting lipid profile and hormone concentrations have not yet been investigated.We performed a randomised, double-blind placebo-controlled study in 18 patients with adult GH-deficiency before and after 3 months GH replacement therapy (0.036 U/kg/d; GH-treated group: 6 females, 3 males; age: 47.3 +/- 5.4 years., mean +/- SEM; placebo-group: 5 females, 4 males; mean age 50.2 +/- 4.7). In addition, SA concentrations were measured in 18 sex and age matched healthy control subjects.Blood samples were obtained after an overnight fast. Serum SA, triglycerides and cholesterol were measured using enzymatic methods. Lipoprotein classes were separated by ultracentrifugation. Insulin and IGF-I were determined by radioimmunoassay, HbA1C was measured by anion exchange liquid chromatography.SA concentrations of the patients with adult GH-deficiency were not significantly different compared to the control group (GH-deficient group: 2.29 +/- 0.02 mmol/l, mean +/- SEM vs. control group: 2.09 +/- 0.13 mmol/l, P = 0.25). Before GH replacement therapy SA concentrations correlated positively with the patients age (r = 0.45; P0.04) and fasting insulin concentrations (r = 0.5; P0.03) but not with fasting lipid profile. GH replacement therapy significantly increased IGF-I (GH: + 27 +/- 2.6 vs. placebo: + 1.0 +/- 0.8 nmol/l, P0.001) and fasting insulin concentrations (GH: + 71.9 +/- 8.0 vs. placebo: + 19.6 +/- 22.6 pmol/l, P0.04) compared to placebo therapy. SA concentrations (GH: - 0.41 +/- 0.15 vs. placebo: - 0.01 +/- 0.12 mmol/l, P0.05), total cholesterol (GH: - 0.71 +/- 0.16 vs. placebo: 0.23 +/- 0.21 mmol/l, P0.003) and LDL-cholesterol (- 0.71 +/- 0.14 vs. placebo: - 0.12 +/- 0.21 mmol/l P0.04) significantly decreased after GH replacement therapy compared to placebo therapy. No significant correlation between changes in SA concentrations and changes in lipid profile were observed following GH replacement therapy.These results suggest that, firstly, GH replacement therapy may have a beneficial effect on the pathogenesis of atherosclerosis despite the increase in insulin concentrations, a surrogate marker of insulin resistance, secondly, the proposed beneficial effect of GH on the atherosclerotic process is likely to be multifactorial and cannot only be explained by changes in lipid profile and finally, SA might be a useful marker for the process of atherosclerotic disease in interventional studies.

Insulin-like growth factor-I (IGF-I) has both insulin-like and anabolic actions but unlike insulin, IGF-I circulates bound to a number of specific binding proteins that regulate its availability and activity. Patients with type 1 diabetes mellitus have low levels of circulating IGF-I despite increased growth hormone (GH) secretion, and are a group that may benefit from rhIGF-I therapy. Understanding the relationship between IGF-I and its binding proteins is necessary to appreciate the actions of exogenously administered rhIGF-I. Therefore, we examined the effects of 19 days' subcutaneous administration of rhIGF-I (50 micrograms/kg BID) on the levels of IGF-I, IGF-II and the IGF-binding proteins (IGFBPs), as well as the daily dose of insulin necessary to maintain glycaemic control in patients with type 1 diabetes mellitus.This was an open study, and the patients were studied initially while resident (days 1-5) in the hospital and thereafter (days 6-24) as outpatients. Serum was collected at baseline and at intervals throughout the study for the measurement of total IGF-I, IGF-II, IGFBP-1, -2, -3, free insulin and growth hormone (GH). Daily insulin doses and glucometer readings were recorded throughout the study. The changes in each of these variables were examined. The subjects were six adults (35.3 +/- 4.0 years, mean +/- SE), with type 1 diabetes, and all had reasonable glycaemic control (HbA1c 7.2 +/- 0.5%).rhIGF-I administration increased circulating total IGF-I over two-fold (15.3 +/- 1.9 vs. 33.7 +/- 5.4 nmol/l, mean +/- SEM, P0.01, day 1 vs. day 20) and decreased plasma IGF-II concentration (85.0 +/- 4.7 vs. 50.6 +/- 4.7 nmol/l, P0.01, day 1 vs. day 20). The dose of insulin required for adequate glycaemic control decreased significantly during rhIGF-I therapy (46 +/- 7 vs. 31 +/- 8 U/day, P0.05, day -1 vs. day 19), as did the fasting free insulin concentration (8.4 +/- 1.5 vs. 5.0 +/- 0.8 mU/l, P0.05, baseline vs. day 5). IGFBP-2 concentration increased (388 +/- 115 vs. 758 +/- 219 micrograms/l, P0.05, day 1 vs. day 20), but IGFBP-1 and IGFBP-3 were unchanged during rhIGF-I treatment. Mean nocturnal GH concentration decreased (12.7 +/- 3.3 vs. 3.8 +/- 0.9 mU/l, P = 0.05) after 4 days' rhIGF-I therapy.Twice daily rhIGF-I therapy in adults with type 1 diabetes resulted in an increase in circulating IGF-I with a reciprocal decrease in IGF-II, and a marked elevation of IGFBP-2 concentration. The levels of IGFBP-1 and -3 were not dramatically changed despite a reduction in the concentration of serum free insulin, and a large decrease in the requirement for insulin. The mechanisms behind these changes remains unclear but alterations in circulating levels of of IGFBPs may alter IGF-I bioactivity. If rhIGF-I is to have an application in the management of adults with type 1 diabetes, further work is necessary to determine the metabolic consequences of the alterations seen in the IGFs and their binding proteins following rhIGF-I administration.

Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P0.01). The total cholesterol concentration (P0.02), the low density lipoprotein cholesterol concentration (P0.02), and the VLDL cholesterol/VLDL apoB ratio (P0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.

Houssay was the first to observe that hypophysectomy reduced the hyperglycaemia of diabetes (1) in animals. Following these observations the metabolic properties of pituitary extracts were studied in detail (2). Young was the first to show that the diabetogenic factor in the pituitary co-extracted with the growth promoting activity (3) and subsequently short term and long term GH administration was shown to induce transient or permanent diabetes respectively (4,5). Following the full characterisation and identification of growth hormone (GH) a number of studies were performed that demonstrated profound effects on glucose metabolism. Acromegaly “natures” experiment of GH excess is associated with a spectrum of impaired glucose tolerance and diabetes (6). Mintz elegantly demonstrated the diabetogenic effects of endogenous GH in a study in which glucose tolerance was measured after insulin induced hypoglycaemic GH release. (7). Glucose levels were much higher in the presence of elevated GH. When high doses of GH are administered to normal subjects the insulin antagonistic effect is seen after a lag of 3-4 hours (8,9). Although the mechanisms are poorly understood GH appears to reduce the sensitivity to insulin at both the liver and peripheral tissues (fat and muscle) (10, 11, 12, 13). GH increases lipolysis and FFA release and this has been proposed as a possible mechanism for the reduced-insulin sensitivity. FFA delivery to the liver promotes gluconeogenesis and increased availability of FFA in the periphery competes with glucose as an oxidative substrate (14). There is also some evidence to suggest that GH has a direct effect on the pancreatic islets leading to increased insulin secretion (15).

Total body water (TBW) is reduced in adult GH deficiency (GHD) largely due to a reduction of extracellular water. It is unknown whether total blood volume (TBV) contributes to the reduced extracellular water in GHD. GH and insulin-like growth factor I (IGF-I) have been demonstrated to stimulate erythropoiesis in vitro, in animal models, and in growing children. Whether GH has a regulatory effect on red cell mass (RCM) in adults is not known. We analyzed body composition by bioelectrical impedance and used standard radionuclide dilution methods to measure RCM and plasma volume (PV) along with measuring full blood count, ferritin, vitamin B12, red cell folate, IGF-I, IGF-binding protein-3, and erythropoietin in 13 adult patients with GHD as part of a 3-month, double blind, placebo-controlled trial of GH (0.036 U/kg.day). TBW and lean body mass significantly increased by 2.5 +/- 0.53 kg (mean +/- SEM; P0.004) and 3.4 +/- 0.73 kg (P0.004), respectively, and fat mass significantly decreased by 2.4 +/- 0.32 kg (P0.001) in the GH-treated group. The baseline RCM of all patients with GHD was lower than the predicted normal values (1635 +/- 108 vs. 1850 +/- 104 mL; P0.002). GH significantly increased RCM, PV, and TBV by 183 +/- 43 (P0.006), 350 +/- 117 (P0.03), and 515 +/- 109 (P0.004) mL, respectively. The red cell count increased by 0.36 +/- 0.116 x 10(12)/L (P0.03) with a decrease in ferritin levels by 39.1 +/- 4.84 micrograms/L (P0.001) after GH treatment. Serum IGF-I and IGF-binding protein-3 concentrations increased by 3.0 +/- 0.43 (P0.001) and 1.3 +/- 0.15 (P0.001) SD, respectively, but the erythropoietin concentration was unchanged after GH treatment. No significant changes in body composition or blood volume were recorded in the placebo group. Significant positive correlations could be established between changes in TBW and TBV, lean body mass and TBV (r = 0.78; P0.04 and r = 0.77; P0.04, respectively), and a significant negative correlation existed between changes in fat mass and changes in TBV in the GH-treated group (r = -0.95; P0.02). We conclude that 1) erythropoiesis is impaired in GHD; 2) GH stimulates erythropoiesis in adult GHD; and 3) GH increases PV and TBV, which may contribute to the increased exercise performance seen in these patients.

Cushing's syndrome is characterized by central obesity and muscle wasting. As GH is anabolic, it may be able to counteract the loss of body protein. To evaluate the potential therapeutic use of GH preoperatively, eight patients with Cushing's syndrome received sc injections of recombinant human GH (0.07 U/kg.day) for 7 days. Whole body leucine and glucose turnover were measured after an infusion of [1-13C]leucine and [6,6-2H2]glucose before (day 0) and after 2 and 7 days of GH treatment. Compared with the value on day 0, there was a significant increase on days 2 and 7 in insulin (P0.005 and P0.001), C peptide (P0.01 and P0.005), insulin-like growth factor I (P0.001), and glucose concentrations (P0.01 and P0.005) and a decrease in the leucine concentration (P0.005). There was no significant change in glucose production rate, glucose MCR, leucine production rate (a measure of protein degradation), or nonoxidative leucine disappearance rate (a measure of protein synthesis). The leucine MCR was increased after 7 days (P0.05), and the clearance of leucine into protein (nonoxidative leucine disappearance rate/leucine concentration) was increased (P0.05) after 2 and 7 days of GH treatment. This is consistent with GH stimulating the availability of amino acid transporters. GH may, therefore, have a therapeutic role in the preoperative treatment of Cushing's syndrome.

Despite early evidence from studies performed soon after its discovery, the role of human growth hormone (GH) in metabolic processes during adulthood has, until recently, been largely ignored. The importance of GH in the regulation of body composition in the adult is clearly demonstrated by the abnormalities seen in "nature's experiments', i.e. acromegaly and GH deficiency. Body composition has been shown to change favourably following successful treatment of acromegaly. Formal replacement studies in adult GH-deficient patients, made possible by the recent advent of recombinant GH, have also shown dramatic changes in body composition, with increases in lean body mass and reductions in fat mass towards normality and associated improvements in physical performance. Thus, adult GH deficiency, like acromegaly, has become widely accepted as a distinct clinical entity warranting treatment.

Rats were maintained in chambers and breathed air (control, n=8) or an atmosphere containing 10% oxygen (hypoxic, n=10) for 35 days. On completion of the experiment the hypoxic animals weighed less than the controls (hypoxic, 290 ± 11.7g; control, 339 ± 19.2g; means ± S.E.M., p

Two populations of Fijian Melanesians over 40 years of age were compared. The first population was located in a remote rural area and the other in an urban environment. There was no significant difference between the two populations in age, height and diastolic blood pressure. Highly significant differences were observed in mean weight, body mass index, prevalence of impaired glucose tolerance, prevalence of diabetes, mean glycosolated haemoglobin, mean systolic blood pressure, fasting cholesterol, immunological albumin, immunological transferrin, and Al and B apolipoproteins. The higher value was associated with urban living. Thus urban living is associated with obesity, impaired glucose tolerance, diabetes, higher systolic blood pressure, higher levels of fasting lipids and increased risk factors for cardiovascular disease.

Two populations of Fijian Melanesians over 40 years of age were compared. The first population was located in a remote rural area and the other in an urban environment. There was no significant difference between the two populations in age, height and diastolic blood pressure. Highly significant differences were observed in mean weight, body mass index, prevalence of impaired glucose tolerance, prevalence of diabetes, mean glycosolated haemoglobin, mean systolic blood pressure, fasting cholesterol, immunological albumin, immunological transferrin, and A1 and B apolipoproteins. The higher value was associated with urban living. Thus urban living is associated with obesity, impaired glucose tolerance, diabetes, higher systolic blood pressure, higher levels of fasting lipids and increased risk factors for cardiovascular disease.

The frequency and sequelae of head injury in epileptic seizures were assessed. Two hundred and fifty five resident patients with chronic long term epilepsy (165M, 90F) of average age 54 years were studied for a year and 43 patients in a short term assessment unit (22M, 21F) of average age 26 years were studied for a month. A total of 27,934 seizures were recorded, of which 12,626 (45.2%) were associated with falls. There were 766 significant head injuries. Four hundred and twenty two required simple dressing and observation, and 341 required sutures (average number of sutures 4.5). There was one confirmed skull fracture, one confirmed extradural haemorrhage and one confirmed subdural haemorrhage. Thus 2.7% of all seizures resulted in a head injury (6.1% of seizures associated with falling). Simple dressing was required in 1.5%; 1.2% required sutures. Only one in every 9311 seizures (one in every 4208 seizures associated with falls) resulted in skull fracture, extradural or subdural haemorrhage. Minor seizure related head injury is therefore relatively common, while severe head injury is rare.

Summary We report the case of a 7 year old girl who developed central hypoventilation following pertussis and who was treated by negative pressure ventilation using a new portable tank respirator. We believe this is the first reported case of central hypoventilation following pertussis successfully treated by intermittent negative pressure ventilation.