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Biomedical subjects

P Sharp

Publications and source records attributed to P Sharp.

At least 19 recordsLinked to original sources

99mTc-nanocolloid scintigraphy for assessing osteomyelitis in diabetic neuropathic feet.

Distinguishing osteomyelitis from neuropathic osteoarthropathy in diabetic feet is a common and difficult clinical problem with no highly accurate discriminatory investigation. This study assesses the novel use of marrow scintigraphy and compares it with magnetic resonance imaging (MRI) for the diagnosis of osteomyelitis in neuropathic osteoarthropathic diabetic feet. Nine diabetic patients with chronic foot ulcers were prospectively assessed independently using 99mTc-nanocolloid scintigraphy and MRI. Those patients showing features of osteomyelitis underwent percutaneous bone biopsy or surgical ray excision for histological confirmation. Other patients were followed up clinically for a minimum of 6 months to exclude osteomyelitis. Marrow scintigraphy, in agreement with MRI, demonstrated all four cases of biopsy proven osteomyelitis and excluded three cases with neuropathic osteoarthropathy alone. One case of suspected osteomyelitis of the ankle on marrow scintigraphy, but not MRI, was not confirmed clinically. One case of suspected osteomyelitis on both imaging modalities was shown on biopsy to demonstrate changes of avascular necrosis but not osteomyelitis. In this study 99mTc-nanocolloid scintigraphy shows a sensitivity of 100% and specificity of 60%. An important false positive result is seen with avascular necrosis, both on marrow scintigraphy and on MRI. Although larger studies are needed to evaluate this technique, 99mTc-nanocolloid marrow scintigraphy may be an alternative to MRI for assessing diabetic feet for osteomyelitis.

Adult

First-trimester diagnosis of Smith-Lemli-Opitz syndrome.

We report here the prenatal diagnosis of Smith-Lemli-Opitz (SLO) syndrome in the first trimester by direct measurement of 7-dehydrocholesterol (7-DHC) in a chorionic villus (CV) biopsy. The proband was diagnosed clinically at birth and the diagnosis was confirmed biochemically by demonstrating elevated 7-DHC in plasma. The family pursued prenatal diagnosis in their fourth, fifth, and sixth pregnancies. The fourth pregnancy spontaneously miscarried at 9 weeks' gestation. Analysis in both direct and cultured curetting tissue (identified as similar to CV tissue) showed an abnormal tissue neutral sterol pattern with an elevated 7-DHC concentration. The fifth pregnancy also miscarried spontaneously at 9 weeks but no tissue of unequivocal fetal origin could be identified to allow biochemical investigation. In the sixth pregnancy, ultrasound examination at the time of CV sampling showed a thickened nuchal fold. Direct analysis of the CV sample revealed elevated levels of 7-DHC consistent with the diagnosis of SLO. The pregnancy was terminated and both fetal tissue and cultured fetal cells showed marked increases in 7-DHC, confirming the prenatal diagnosis.

Cells, Cultured

Human mucopolysaccharidosis IIID: clinical, biochemical, morphological and immunohistochemical characteristics.

Mucopolysaccharidosis IIID (MPS IIID) is one of the rarest of the MPS-III syndromes. To date, the clinical manifestations of 10 patients have been reported, the deficient N-acetylglucosamine 6-sulfatase (G6S) enzyme has been purified, and the G6S gene has been cloned, sequenced and localized. However, morphological manifestations of this condition have not been reported and the pathogenesis of the severe neurological deficits remains an enigma. In this paper we describe and correlate the clinical, biochemical and pathological observations for 2 cases of MPS IIID. We used monoclonal antibodies against heparan sulfate (HS) and GM2-ganglioside, thin layer chromatography, mass spectrometry, and morphological techniques to demonstrate the nature and the distribution of the uncatabolized substrates. The majority of the cells in various tissues showed morphological changes expected with lysosomal storage of HS. The central nervous system (CNS) was most severely affected because of the secondary storage of GM2 and GM3 gangliosides in addition to the primary accumulation of HS. The extent as well as the distribution of the diverse storage materials varied within and among different neurons as observed in MPS-III A, B, and C syndromes. This study supports the hypothesis that the neurological dysfunction and neurodegeneration common to the Sanfilippo syndromes is, in part, due to the secondary metabolic perturbations induced by HS accumulation.

Adolescent

Effectiveness of health education to increase screening for cervical cancer among eastern-band Cherokee Indian women in North Carolina.

BACKGROUND: The North Carolina Native American Cervical Cancer Prevention Project was a 5-year, National Cancer Institute-funded trial of health education designed to increase screening for cervical cancer among Native-American women in North Carolina. PURPOSE: This study was conducted to evaluate the effectiveness of this education program in the Eastern-Band Cherokee target population. METHODS: Cherokee tribal lands were mapped and all households (N = 2223) were listed to ensure maximum coverage of the eligible population (women, aged 18 years and older, who were enrolled tribal members). Eligible women were identified by the use of a brief questionnaire administered to an adult member of the household. Of the 1279 households with eligible women, 1020 (79.8%) agreed to participate. The intervention was an individualized health education program delivered by female Cherokee lay health educators. The participants were randomly assigned to receive or not to receive the intervention (i.e., to program and control groups, respectively) by use of the Solomon Four-Group design. Data were collected in face-to-face interviews conducted in the participant's home. Of the 996 women who were ultimately enrolled, 540 were randomly assigned to receive a pretest (preintervention) interview that involved administration of a 96-item questionnaire designed to collect data on knowledge, intentions, and behaviors related to cervical cancer; of these 540 women, 263 were randomly assigned to receive the education program. The remaining 456 women did not receive the pretest, but 218 were randomly assigned to receive the education program. Six months after receiving the education program, the women in all four groups were administered a post-test that was identical to the pretest. Logistic regression was used to assess the effects of the pretest and the educational program. All P values resulted from two-sided statistical tests. RESULTS: Eight hundred and fifteen (81.8%) of the 996 participants completed the post-test interview. The remaining 181 women who were lost to follow-up were evenly distributed among the four study groups. At the post-test, 282 (73.2%) of the 385 women who received the education program reported having had a Pap smear following the intervention, compared with 275 (64%) of the 430 control subjects. Women who received the education program were more likely to answer all knowledge items correctly on the post-test (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.08-4.39) and to report having obtained a Pap smear in the past year (OR = 2.06, 95% CI = 1.14-3.72) than women in the control groups. CONCLUSION: Women who received the education program exhibited a greater knowledge about cervical cancer prevention and were more likely to have reported having had a Pap smear within the past year than women who did not receive the program.

Adult

Relative fasting hypoinsulinaemia and ultrasonically measured early arterial disease in type 2 diabetes. The SENDCAP Study Group, St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study.

Macrovasular disease is the most important cause of morbidity and mortality in Type 2 (non-insulin-dependent) diabetes. Dyslipidaemia and hyperinsulinaemia have been proposed as aetiological factors. This paper describes the interrelationships between fasting serum insulin, serum lipids, and the extent of ultrasonically measured early arterial disease in Type 2 diabetic subjects screened for entry into a prospective study set up to ascertain whether improving serum lipids can alter the progress of arterial disease in Type 2 diabetes. Measurements were made of the initima media thickness (IMT) in the carotid artery, and an arterial ultrasound score (AUS) based on appearances of both carotid and femoral arteries was calculated for 192 established Type 2 diabetic subjects, males and females, mean age 51 (range 35-66) years, median duration of diabetes 3.5 years, with no known cardiovascular disease. Multiple regression analysis showed that carotid IMT increased with age and was inversely related to serum insulin (variance accounted for, R2, = 8.8%, p = 0.0002). AUS increased with age and was related inversely to serum insulin, or to C-peptide when this was substituted in the model. In addition to age and serum insulin, AUS was positively associated with non-HDL cholesterol and negatively with HDL 3 cholesterol (R2 = 26%, p = 0.0001). Early thickening and damage to the arterial wall in Type 2 diabetes may be related to relative fasting hypoinsulinaemia.

Adult

The development of the hypothalamic-pituitary-gonadal axis in juvenile great tits.

The development of the hypolamic-pituitary-gonadal axis in free-living nestling great tits (Parus major) was studied from the day of hatching until about 40 days of age. The hypothalamic content of GnRH was low during the entire nestling period, although a significant increase was noted between 6 and 9 days of age. Thereafter there was no further increase. The pituitary content of LH was low in 1- to 6-day-old nestlings, but increased significantly at 9 days of age; this increase was only temporary, and levels decreased in 12-day-old nestlings. Injections of chicken GnRH increased plasma levels of LH in newly hatched great tits. The high plasma levels of LH in newly hatched great tits of both sexes decreased to basal by 9 days of age. Circulating levels of testosterone and estradiol showed more or less the same pattern as LH. Both steroids showed very high levels in newly hatched birds of both sexes. Testosterone levels were down to basal in 3-day-old nestlings, and estradiol levels were basal in 2-day-old nestlings. The only sex difference was observed in 1- and 2-day-old nestlings. During this period males had significantly higher plasma levels of testosterone than females. Gonads showed a more or less linear growth during the entire nestling period, and did not increase further after fledging. Histological and ultrastructural examinations of the testis showed that mature Leydig cells appeared for the first time in 6-day-old birds and become common in 9-day-old nestlings. The development of the seminiferous tubules, the interstitial tissue, and the tunica albuginea reached a "plateau" when the nestlings had reached an age of 9 days. At no age had the germinal epithelium developed beyond the stage of spermatogonia. GnRH treatment did not change male testosterone or female estradiol levels until the nestlings were 9 days of age. The response decreased in older nestlings. Castration of 9-day-old male nestlings showed that neither was there a negative feedback of testosterone on LH in older nestlings.

Aging

Exposure of wild waterfowl to Mycoplasma anatis.

We developed an ELISA procedure to assess the presence of M. anatis-specific serum antibody in ducks. Sera from exposed and unexposed Pekin ducks (Anas platyrhynchos) were used to standardize the ELISA and to establish reference ranges to classify ELISA results as exposed or not exposed. We conducted serological surveys of female waterfowl in the central and eastern United States between 1988 and 1992 to assess the frequency of exposure in wild waterfowl. Adult breeding mallards (Anas platyrhynchos), wintering mallards, and black ducks (Anas rubripes) had high prevalences of exposure to M. anatis (25% to > 80%). In comparison, none of the breeding adult canvasbacks (Aythya valisineria) had serum antibody levels indicating exposure. Approximately 50% of the juvenile mallards and black ducks were exposed to M. anatis by 8 months of age, indicating high transmission rates among wild birds.

Animals

Widespread anatomical projections of the serotonergic modulatory neuron, CB1, in Aplysia.

Although sensitization-related changes in the neural circuitry of withdrawal reflexes in Aplysia are well studied, relatively few studies address the organization of the modulatory components of sensitization. In particular, it is not known whether individual modulatory loci can simultaneously influence multiple reflex circuits. There is, however, evidence that a single modulatory transmitter, serotonin, plays a pivotal role in facilitating different reflex circuits during sensitization. Furthermore, it is known that activation of a pair of serotonergic neurons, the CB1s, produces heterosynaptic facilitation of the sensorimotor connections of one of these reflex circuits. These data together raise the possibility that the CB1s may produce sensitizing changes in the neural elements of multiple reflex systems simultaneously. In the present study, we utilized immunocytochemistry and intracellular labeling to obtain anatomical evidence of CB1's possible role in modulating multiple reflex circuits. We found that two distinct neurons satisfy previously published physiological criteria for CB1. One of these, CB1, is immunoreactive to serotonin. The second cell, here named CB2, has a different neuroanatomy and is not serotonin immunoreactive. Focusing on CB1, we found (1) profuse fine processes given off by its axons in the posterior neuropil of the cerebral ganglion, (2) extensive branching and fine processes in the pleural ganglion, and (3) a branch of CB1 that projects into the pedal ganglion. These three observations are consistent with the hypothesis that, in addition to its already established role in modulating the siphon withdrawal circuit, CB1 may also modulate synaptic connections between (1) the sensory and motor neurons of the tentacle withdrawal reflex (2) the sensory neurons and interneurons of the tail and tail-elicited siphon withdrawal reflex, and (3) the sensory and motor neurons of the tail withdrawal reflex. These observations support further physiological investigations of a possible global role of CB1 in modulating the tail and tentacle withdrawal reflexes.

Animals

Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults.

OBJECTIVES: The physiological role of growth hormone in adult life has recently attracted increased interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH in a large number of hypopituitary adults. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH daily dose was 0.04 (0.02-0.05) IU/kg s.c. PATIENTS: Forty GH deficient hypopituitary patients (19 M, 21 F; aged 19-67 years) on conventional replacement therapy were studied. MEASUREMENTS: Serum insulin like growth factor I (IGF-I), skinfold thickness, total body potassium, total body water (TBW), exercise tolerance and muscle strength, and well-being. RESULTS: During the 6-month double blind phase, two GH treated patients withdrew because of adverse events. Lean body mass (LBM) increased and percentage body fat (%BF) decreased on GH but not on placebo (P) (LBM: (GH: from 48.5 +/- 9.6 to 49.6 +/- 9.5 kg; P: from 50.9 +/- 9.2 to 50.1 +/- 9.0 kg, P < 0.05 GH vs P) and %BF (GH: from 34.7 +/- 11.4 to 34.2 +/- 10.7; P: from 37.4 +/- 7.6 to 38.7 +/- 8.1, P < 0.05 GH vs P)). TBW increased on GH (P < 0.01) but not on P. No change was observed in waist-to-hip ratio or in muscle strength. During longer-term follow-up combining the double blind and open phase components of the study, 34, 27 and 11 patients received GH for 6, 12 and 18 months respectively. Patients dropped out because of adverse events or lack of perceived benefit. Skinfold thicknesses decreased significantly at 6 and 12 months and the waist circumference at 6 months. Waist-to-hip ratio decreased significantly on GH at 12 months. LBM increased on GH treatment from 49.6 +/- 9.1 to 51.6 +/- 9.4 kg (P < 0.0006), 51.9 +/- 8.9 kg (P < 0.07) and 53.1 +/- 10.5 kg (P < 0.0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37.2 +/- 10.7 to 34.7 +/- 10.1 (P < 0.005), 35.1 +/- 12.8 (NS) and 34.5 +/- 8.6 (P < 0.04) at 6,12 and 18 months respectively. TBW also increased at 6 and 12 months of GH treatment. Exercise time increased significantly at 6, 12 and 18 months of GH treatment. Muscle strength in selected muscle groups increased significantly at 6, 12 or 18 months of GH treatment. Randomization resulted in the placebo group having a greater GHQ score (higher morbidity) than the GH group before therapy. Over the controlled phase, GHQ scores improved on placebo but not on GH and CPRS score was unchanged in either group. In the open phase, the GHQ score did not change on GH therapy but CPRS score improved at 6 and 12 months. CONCLUSIONS: Growth hormone replacement therapy in adults for 6 months increased lean body mass, total body water and exercise tolerance, and decreased body fat. Growth hormone replacement for longer than 6 months maintains the advantageous effects seen in shorter-term studies and may have additional effects on body fat distribution, muscle strength and psychological well-being.

Adult

Cellular mechanisms underlying the increased duodenal iron absorption in rats in response to phenylhydrazine-induced haemolytic anaemia.

Haemolytic anaemia induced by phenylhydrazine (PZ) promotes iron absorption across rat small intestine. This present study investigates the role of the brush border potential difference (Vm) and mucosal reducing activity in the response. In addition, quantitative autoradiography was used to assess PZ-induced changes in the villus localization of brush border iron uptake. Iron transfer from duodenum to blood was increased significantly 5 days after treatment with PZ. Autoradiography showed that most brush border iron uptake occurred at the upper villus region and the maximal rate was increased fourfold by PZ. Duodenal villus length was increased in PZ-treated rats. PZ treatment did not influence mucosal reducing activity but Vm, measured using duodenal sheets, increased from -50 to -57 mV (P < 0.001) and this was due to a reduced brush border sodium permeability. Thus, an expanded absorptive surface and an enhanced electrical driving force for iron uptake across the duodenal brush border are important adaptations for increased iron absorption in PZ-induced haemolytic anaemia.

Anemia, Hemolytic

The effects of short and long-term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance.

The effects of replacement with biosynthetic human GH on carbohydrate tolerance and lipid metabolism were studied in 40 hypopituitary adults during a randomized double blind, placebo-controlled trial for 6 months, followed by a 12-month open trial. The daily GH dose was 0.04 +/- 0.01 IU/kg. Fasting plasma glucose, serum fructosamine, plasmid lipids, lipoproteins, and plasma C-peptide concentrations were measured, and an oral glucose tolerance test was performed every 6 months. There was no change in fasting triglyceride levels at any stage of the study. There was no significant change in fasting total or LDL cholesterol, total HDL cholesterol, high density lipoprotein2 (HDL2) cholesterol, HDL3 cholesterol, apoprotein-A1, or apoprotein-B during GH or placebo treatment in the placebo-controlled 6-months study. In the open phase of the trial, total and low density lipoprotein cholesterol showed a sustained downward trend during GH therapy. Compared to the pretreatment level, the HDL cholesterol concentration was significantly higher at 18 months. Cholesterol subfractions HDL2 and HDL3 and apoprotein-A1 and -B were not different from the pretreatment levels. The total/HDL cholesterol ratio decreased significantly at 12 and 18 months. During the controlled phase, fasting plasma glucose was similar during GH and placebo administration, but fasting insulin and C-peptide increased during GH therapy, but not during placebo treatment. The mean area under the curve (AUC) for glucose increased by a small, but significant, extent over the 6 months of GH treatment and was higher at 6 months than during placebo treatment. The AUC for insulin also increased during GH treatment. During the open trial, the fasting plasma glucose level increased at 6 and 12 months, and the fasting plasma insulin level increased at 6, 12, and 18 months of GH treatment. The plasma glucose AUC during the oral glucose tolerance test was significantly higher at 6 months, and the plasma insulin AUC was significantly higher at 6, 12, and 18 months of GH therapy. In conclusion, GH therapy has some metabolic effects that are considered beneficial and others that are less desirable.

Adult

Effects of Mycoplasma anatis and cold stress on hatching success and growth of mallard ducklings.

We inoculated game-farm mallard (Anas platyrhynchos) eggs and 1-day-old birds with Mycoplasma anatis to determine its effect on hatching success and growth rates of ducklings. Inoculations of eggs reduced hatching success, hatchling size, and duckling growth rates, compared to controls. Intratracheal inoculations of 1-day-old birds did not affect growth rates. Hatchlings and 1-day-old ducklings grew much slower for the first 7 to 10 days when raised at 17 to 19 C, compared to controls raised at 30 to 35 C. The effect of cold stress on growth was greater than the effect of M. anatis infection; we found no synergistic effects between cold stress and M. anatis infection.

Animals

The occurrence of mycoplasmas in selected wild North American waterfowl.

We determined the prevalence of mycoplasma infection in breeding mallard (Anas platyrhynchos) and canvasback (Aythya valisineria) hens and their broods from the central United States (1988 to 1990); and wintering American black duck (Anas rubripes) and mallard hens from the eastern United States (1990 to 1993). Mycoplasmas were isolated by culturing tracheal swabs from 656 live birds and tissue samples from 112 dead waterfowl. Nine (18%) of 51 mycoplasma isolates were identified as Mycoplasma anatis; M. anatis was recovered from four mallards, a black duck, and a gadwall (Anas strepera) duckling. Nineteen (37%) of 51 mycoplasma isolates were identified as Mycoplasma cloacale; these isolates were obtained from mallard, canvasback, and black duck adults, and from a mallard duckling. Additional unspeciated mycoplasmas were isolated from mallards, black ducks, and one canvasback.

Animals

Development of a cervical cancer education program for native American women in North Carolina.

The North Carolina Native American Cervical Cancer Prevention Project is a five-year, NCI-funded public health education program. The project was developed to address the problem of excess mortality from cervical cancer among Native American women by increasing screening and follow-up of abnormal cervical smears. This paper describes the process of developing and implementing the intervention, an individualized health education program. Development of the intervention was guided by the health belief model, social learning theory, self efficacy theory, and PRECEDE, a planning model. Community analysis revealed that the target populations had limited awareness of cervical cancer as a specific type of cancer, and had an experientially-based pessimistic outlook regarding survival with cancer. Steps in developing the cervical-cancer prevention program included 1) development of objectives, 2) selection of strategies and development of cervical cancer education materials, 3) pretesting and revision, and 4) implementation, monitoring, and further revision. Native American lay health educators were recruited and trained to deliver the program. The experience of developing and implementing the individualized health education program suggests that the design of health education programs for Native Americans should begin with examination of basic assumptions regarding the nature of health and illness in the target population. The unique cultures and the diversity of Native American populations are critical factors in the development of health education programs for them.

Adolescent

Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil.

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.

Adolescent

Pitfalls in the prenatal diagnosis of peroxisomal beta-oxidation defects by chorionic villus sampling.

Variability in the level of expression of very long chain fatty acids (VLCFAs) is documented in cultured chorionic villus (CV) cells derived from two fetuses, one at risk for an unusual peroxisomal fatty acid beta-oxidation defect, and the other at risk for the X-linked form of adrenoleucodystrophy (ALD). Cells from early subcultures of chorionic cells from both cases gave normal values for VLCFA ratios. The results for the fetus at risk for the beta-oxidation defect were interpreted to indicate that the fetus was not affected; however, at birth, the infant was clinically and biochemically affected. In the case of the fetus at risk for X-linked ALD, although VLCFAs were normal in subculture 1, the levels of these fatty acids increased dramatically in subculture 3, suggesting an abnormal fetus. Termination of the pregnancy and subsequent biochemical and morphological follow-up confirmed that the fetus was indeed affected by ALD.

Adrenal Cortex

The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism.

OBJECTIVE: The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with biosynthetic human GH in hypopituitary adults on aspects of calcium homeostasis, bone metabolism and bone mineral mass. PATIENTS: Forty hypopituitary adults (21 females and 19 males; aged 19-67 years). DESIGN: A prospective randomized double-blind placebo-controlled trial lasting for 6 months. PROTOCOL: Following baseline assessments, GH was given in a daily dose of 0.02-0.05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. MEASUREMENTS: Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. RESULTS: Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I increased significantly on GH treatment (mean +/- SD) (GH: 276 +/- 197 vs P: 88 +/- 50 micrograms/l, P < 0.0001 at 6 months). Plasma calcium increased slightly but significantly in the GH-treated group (2.23 +/- 0.11-2.29 +/- 0.11 mmol/l, P < 0.05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2.29 +/- 0.11; P, 2.26 +/- 0.09 mmol/l). Plasma phosphate increased on GH (GH: 1.02 +/- 0.23-1.32 +/- 0.19; P: 0.99 +/- 0.16-0.96 +/- 0.12 mmol/l over the 6 months of treatment, P < 0.001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104 +/- 32 vs P: 69 +/- 32 U/l, P < 0.01, osteocalcin: GH: 17.2 +/- 8.0 vs P: 5.3 +/- 3.2 micrograms/l, P < 0.001 and P1CP: GH: 207 +/- 152 vs P: 93 +/- 31 micrograms/l, P < 0.01). There was no difference in the intact parathyroid hormone level (GH: 31 +/- 14 vs P: 31 +/- 15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. CONCLUSION: In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.

Adult

Hyperosmolar non-ketotic diabetic coma and rhabdomyolysis.

Rhabdomyolysis is a rare but potentially fatal complication of hyperosmolar states. We report a case of severe hyperosmolar non-ketotic diabetic coma causing rhabdomyolysis in a young man. Despite very high levels of creatine kinase there was no detectable myoglobinuria. Creatine kinase estimation should be a standard investigation in all patients presenting with a hyperosmolar state.

Adult