ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.614436.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE It has been demonstrated that β‐endorphin reduces CRH production and hypoglycaemia‐induced ACTH secretion in the rat. We aimed to determine whether supraphysiological levels of β‐endorphin inhibit the ACTH and CRH response to insulin‐induced hypoglycaemia in human subjects.DESIGN Plasma glucose, prolactin, cortisol, ACTH, CRH and AVP were measured at intervals over a 3‐hour period. Intravenous β‐endorphin 5 mg/50 ml or an equal volume of normal saline was infused between 30 and 90 minutes, with soluble insulin 0.15 units/kg administered i.v. at 60 minutes in a cross‐over design.SUBJECTS Six healthy male volunteers aged 20–35 years.MEASUREMENTS Prolactin was measured by a fluoroimmunometric assay, ACTH, CRH and AVP by radioimmunoassay, and cortisol was measured by enzyme‐linked immunosorbent assay. Haemodynamic measurements were recorded prior to each blood sample. Results are expressed as mean ± standard error of the mean.RESULTS β‐Endorphin resulted in a significant decrease in baseline cortisol (P < 0.05) but not ACTH. Plasma glucose (P < 0.001) and CRH (P < 0.05) and PRL (P < 0.05) increased significantly during β‐endorphin compared to normal saline. After insulin administration, glucose reached a similar nadir during β‐endorphin and normal saline (2.1 ± 0.1  and 1.9 ± 0.15 mmol/l, respectively) but the fall in plasma glucose was delayed during β‐endorphin (P < 0.01 by ANOVA). This resulted in a significantly altered time‐course for the ACTH and cortisol responses (P < 0.05 for each), but no difference overall in the magnitude of the response. In contrast, neither the timing nor the magnitude of the CRH and AVP responses were affected. Prolactin also reached a similar peak value after the administration of insulin, while the haemodynamic responses to hypoglycaemia were not significantly altered during β‐endorphin.CONCLUSIONS While β‐endorphin has been shown to be inhibitory to basal ACTH and cortisol secretion in humans, we note a significant increase in plasma CRH in response to β‐endorphin, which may be arising from a peripheral source. Intravenous β‐endorphin increases plasma glucose and delays the onset of hypoglycaemia following insulin but does not result in significant inhibition of the ACTH and cortisol response. This may reflect the poor penetration of β‐endorphin into the central nervous system, although a hypothalamic effect of β‐endorphin is implied by the increased PRL. The significantly delayed time course in ACTH and cortisol secretion noted during β‐endorphin is not explained by a later response of either CRH or AVP. Although peripheral levels of these hormones may be a relatively insensitive

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.630452.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Down's syndrome (DS) is the commonest single cause of severe mental retardation in children. It can be diagnosed antenatally by chorionic villus sampling (CVS) or amniocentesis followed by karyotyping. At one time the sole indication for these invasive procedures was maternal age: typically women above age 35. However, this led to the detection of only some 30% of cases of DS at best. In the past ten years a series of biochemical and other abnormalities have been noted in Down's pregnancies and these form the basis for new screening programmes. The most familiar of the biochemical abnormalities are elevated levels of maternal serum human chorionic gonadotrophin (hCG), and reduced levels of α‐fetoprotein (AFP) and oestriol (E3). Changes are also noted in a number of other fetoplacental products. The underlying mechanism of these changes is unknown: suggestions include the possibility that a Down's syndrome pregnancy is relatively ‘immature’, or that there is a fetal–placental i

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00640.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

BACKGROUND AND OBJECTIVE Prenatal maternal serum screening for Down's syndrome has become an important and established part of modern antenatal care. Previously it has been reported that non‐specific immunoreactive inhibin may be useful in this context. Using a novel assay we have evaluated dimeric inhibin A as a possible second trimester marker of Down's syndrome.METHODS From 1992–1993 records, stored sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were identified and retrieved for analysis. These sera had been prospectively collected at 15, 16 and 17 weeks gestation.SUBJECTS Records revealed 21 women who had had a Down's syndrome pregnancy and who also had serum available for analysis. Sera from 150 chromosomally normal controls, matched for gestation and duration of storage, were also retrievedMEASUREMENTS Dimeric inhibin A was measured using a recently developed two‐site enzyme‐linked immunoassay. This employs a capture anti inhibin βA‐subunit monoclonal antibody, covalently bound to a microtitre plate and a second anti inhibin α‐subunit antibody conjugated to alkaline phosphatase, allowing detection.RESULTS The mean (95% CI) maternal serum dimeric inhibin A in the samples from control pregnancies was 237 (201.5–273.4) ng/l, 266.9 (235.4–298.5) ng/l and 207.2 (178.5–235.9) ng/l at 15, 16 and 17 weeks gestation respectively. Expressing the results from the Down's samples as multiples of the normal median (MoM), the median (95% CI) MoM was 2.6 (2.25–3.57), significantly higher than the controls (P < 0.0001, Mann–WhitneyU‐test). In the sample set tested, for a given false positive rate of 5.3% inhibin A alone afforded a detection rate of 62%, detecting cases previously undetected by routine screening.CONCLUSIONS Dimeric inhibin A appears to be a promising new marker for the prenatal detection of Down's syndrome. Further prospective evaluation and assessment with other

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.544368.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE  Sex‐hormone binding globulin (SHBG) is a liver derived protein whose concentration has been shown to be affected by a number of factors. The aim of the present study was to investigate the possible effect of increased basal GH concentrations on serum concentrations of SHBG, testosterone and thyroid hormones.DESIGNS Recombinant human growth hormone (rhGH) was given as a continuous subcutaneous infusion in a low dose (0.02 U/kg/day) over a period of 14 days in an open study.PATIENTS Eight middle‐aged (42–59 years) overweight (body mass index 26.1–33.8 kg/m2) but otherwise healthy men were studied.MEASUREMENTS Blood samples were obtained after an over‐night fast before and after 2, 7 and 14 days of treatment. Serum was separated and stored at −20°C until assay.RESULTS Serum GH concentrations increased to a steady level of 2–4 mU/l. Serum SHBG concentration decreased between 2 and 7 days of treatment and serum testosterone concentration changed in parallel. There was no change in the ratio between serum SHBG and serum testosterone. Serum T4 and free T4 concentrations decreased, and that of T3 increased as a result of continuous GH infusion. Simple correlations between changes in SHBG concentrations and other hormonal changes showed positive significant correlations between changes of SHBG and of testosterone.CONCLUSIONS Low dose continuously infused GH resulted in a parallel decrease in serum SHBG and testosterone concentrations. Thyroid hormone concentrations were affected in a similar way to that previously demonstrated follow

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.635457.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Disordered water balance causes substantial morbidity in a subset of schizophrenics and is the consequence of unexplained defects in the regulation of fluid intake and antidiuretic function. We aimed to determine whether oropharyngeal regulation of water balance is altered in these patients.DESIGN A 2‐hour infusion of 3% saline, followed 35 minute later by an oral water load (10 ml/kg over 3 minutes).PATIENTS Age and sex‐matched polydipsic schizophrenics with (n= 5) and without (n= 8) hyponatraemia; non‐polydipsic schizophrenics (n= 6); and normal controls (n= 13).MEASUREMENTS Plasma osmolality, sodium, AVP, and reported desire for water (expressed in cups), determined prior to, and for 30 minutes following, the water load.RESULTS Plasma osmolality and sodium were consistently lower in the hyponatraemics (P<0.01). Significant changes did not occur until 20 and 25 minutes, respectively, after oral water loading, and were similar across the four groups. AVP levels were consistently lower in the two polydipsic groups (P<0.001), fell within 5 minutes after drinking and then levelled off. Neither the acute fall nor the overall pattern of the responses differed across groups. Subjective desire for water also decreased within 5 minutes of drinking, and also to a similar extent, in the four groups. Subsequent levels remained suppressed in the non‐polydipsic groups, but rebounded toward baseline in the two polydipsic groups. Thus the overall patterns differed (P<0.05). At the end of the study, ad lib intake correlated significantly with reported desire for water (r= 0.51,P<0.002).CONCLUSIONS The oropharyngeal regulation of water intake is disrupted in polydipsic schizophrenics with and without hyponatraemia. In contrast, the oropharyngeal regulation of AVP secretion appears preserved in the hyponatraemic subset. Previously observed elevations in plasma AVP in this subset are thus unlikely to be related to defects in oroph

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.641463.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE There is evidence to suggest that the release of neurohypophyseal hormones may be influenced by the circulating concentrations of gonadal steroids.We therefore monitored this relationship in women undergoing prophylactic bilateral oophorectomy at the time of hysterectomy with subsequent hormone replacement therapy and compared it with that in women undergoing hysterectomy with conservation of ovariesDESIGN Patients were randomly allocated to receive either transdermal oestradiol patches, 0.05 mg/day, or subdermal implants containing either 50 mg oestradiol or 50 mg oestradiol with 100 mg testosterone. Blood samples for determination of plasma hormone concentrations, electrolytes and osmolality were obtained immediately before and after surgery and then at two‐monthly intervals for 8 months and finally at 12 months.MEASUREMENTS Free oestradiol, vasopressin and oxytocin were measured by radioimmunoassay.RESULTS Vasopressin concentrations were found to fall after surgery in oophorectomized women, but not in those with ovaries. There were no changes in fluid balance to account for the reduced plasma vasopressin concentrations. During treatment oestradiol appeared to enhance and testosterone to suppress vasopressin release. Oophorectomy had no significant effect on plasma oxytocin concentrations, but in the groups receiving oestradiol implants concentrations fell significantly at 8 and 12 months compared with the value at 6 days.CONCLUSION The observed changes in plasma vasopressin concentrations were consistent with the observations in experimental animals and provide evidence that vasopressin release in the human is influenced

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.633455.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare cause of diabetes insipidus, in which AVP serum levels are insufficient. AVP is synthesized along with neurophysin‐II (NPII) as an AVP‐NPII precursor polypeptide in the hypothalamus. After proteolytic cleavage during axonal transport, AVP and NPII are reassembled and stored loosely bound to each other in the posterior pituitary until both are released into the circulation. In this study, we investigated the genetic basis of ADNDI in a German kindred with 10 affected members spanning three generations.DESIGN Genomic DNA was isolated from peripheral blood leucocytes. The entire coding region of the AVP‐NPII gene of one of the affected persons was amplified by polymerase chain reaction (PCR) and subjected to nucleotide sequence analysis. Sequencing results were confirmed by restriction enzyme analysis of PCR products.PATIENTS Six affected and two unaffected members of a family with ADNDI and 54 unrelated healthy control subjects were studied.RESULTS The index patient was found by direct sequencing to be heterozygous for a G to T transversion at nucleotide position 1884 (exon 2) of the AVP‐NPII gene. This mutation introduced a new recognition site for the restriction enzyme Ava II, which was used to test for the presence of the mutation in other family members and in control subjects. The mutation was detected in all family members with ADNDI, but was not found in unaffected family members or in control subjects. The mutation encodes a valine in place of the normal glycine at amino acid 65 of NPII, which is known to be highly conserved during evolution.CONCLUSIONS In this family, the autosomal dominant neurohypophyseal diabetes insipidus phenotype cosegregates with a point mutation in a region of the AVP‐neurophysin‐II gene which codes for the carboxy‐terminal domain of neurophysin‐II. Although the altered amino acid is not directly involved in AVP binding, the mutation might lead to conformational changes that impair the dimerization of neurophysin‐II molecules. This could in turn affect the AVP binding affinity of neurophysin‐II or might interfere with the transport of the AVP‐neurophysin‐II precursor in the AVP‐

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.628449.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The effects of human immunodeficiency virus (HIV) infection on thyroid function have been reported in only a few studies with discrepant results. The aim of this study was to assess the relation between nutritional status and thyroid function in HIV infected patients.DESIGN Prospective, cross‐sectional study.SETTING A 500‐bed teaching and referral hospital serving a population of 450 000.PATIENTS Seventy‐five consecutive HIV infected patients between 21 and 40 years of age (mean 31.8 ± 0.9 years).MEASUREMENTS Nutritional status was evaluated using the body mass index (BMI), triceps skinfold thickness (TSF), mid‐arm muscle circumference (MAMC), and serum albumin concentration (SA). Hormone assays for serum T4, free thyroxine index (FTI), T3, reverse triiodothyronine (rT3), thyroxine‐binding globulin (TBG), TSH and simultaneous CD4 lymphocyte counts were determined in all patients.RESULTS Clinical stage was significantly related to nutritional status (P = 0.0001 for BMI,P = 0.0002 MAMC). The more poorly nourished groups had low mean serum T3 and rT3 levels, particularly for muscular (P = 0.0001 for T3 andP = 0.0076 for rT3) and visceral (P = 0.00001 for T3 andP = 0.0021 for rT3) protein compartments. Multivariate analysis showed that two factors, SA and MAMC, correlated significantly and independently with serum T3 and rT3.CONCLUSIONS A close relation exists between serum thyroid hormone levels and nutritional status in HIV infected patients. These patients are probably euthyroid and the abnormal findings in the thyroid function

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.623445.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Abnormal glucose metabolism with impaired glucose tolerance has been documented in patients with thyrotoxicosis but the pathogenesis is not fully understood. Therefore, the aim of the present study was to study the β‐cell function and the meal induced oxidative glucose and lipid metabolism in patients with thyrotoxicosis.DESIGN  After an overnight fast the impact of hyperthyroidism on standard mixed meal induced glucose oxidation, lipid oxidation and β‐cell function was studied.PATIENTS  Nine untreated patients with Graves’ disease were compared to 9 age and weight matched healthy controls.MEASUREMENTS  Glucose and lipid oxidation were studied by indirect calorimetry before and after the meal. The insulin secretion rate was calculated by the ‘combined model’ approach, after which the insulin secretion rates and the ambient glucose levels were cross‐correlated. The slope of these regression lines was used as a measure of β‐cell sensitivity to glucose and denotes the insulin secretory capacity. β‐Cell function was further evaluated by measurement of proinsulin and its conversion intermediates. Glucoregulatory hormones were also measured. The findings were correlated to the thyroid hormone levels.RESULTS  Fasting blood glucose and post‐prandial glucose response were increased in patients (P < 0.01). The hyperthyroid patients displayed a ‘dual’β‐cell defect: (a) inability to increase the insulin response appropriately to hyperglycaemia and (b) increased proinsulin levels both in the fasting state and in response to a meal. Indirect calorimetry showed increased lipid oxidation in the fasting state and at the end of the meal (P < 0.01).No difference in glucose oxidation was demonstrated in the fasting state but the post‐prandial glucose oxidation was enhanced in the patients (P < 0.01). The adrenaline response was normal, whereas the noradrenaline response was impaired or absent in the patients. The thyroid hormone levels were significantly correlated to fasting levels of blood glucose, insulin, free fatty acids and lipid oxidation, but not to fasting C‐peptide, glucose oxidation or catecholamines.CONCLUSIONS  Untreated Graves’ disease was associated with glucose intolerance due to quantitative as well as qualitative β‐cell defects. The lipid oxidation was increased in the fasting state and at the end of the meal; after the meal the increase in glucose oxidation was more pronounced in the patients. Thyroid hormones thus increased the oxidation but not by an increase in catecholamine

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.636458.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY