ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.695517.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.702520.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Secondary hyperparathyroidism may cause bone loss and structural deterioration of bone and may thus be a cause of fracture in the elderly. Vitamin D deficiency, renal impairment and medications are potential causes of hyperparathyroidism and may also directly predispose to fracture. We present the first findings of an ongoing study of hip fracture, vitamin D deficiency and hyperparathyroidism in a large Australian nursing home.DESIGN Descriptive prevalence study.PATIENTS Two hundred and fifty‐one nursing home residents were eligible for inclusion. Informed consent and successful venepuncture were obtained for 99. Residents were of median age 83 years with interquartile range (IR) 77–89 years.MEASUREMENTS 25‐Hydroxyvitamin D (25OHD), intact parathyroid hormone (PTH), creatinine and biochemistry, demographic data and current medications.RESULTS Fifty‐two per cent of 99 subjects had 25OHD below the reference range of 28–165 nmol/l and 96.5% were below the reference range mean. Those with low 25OHD had lower plasma calcium corrected for albumin than those with normal 25OHD (medians 2.34vs2.41mmol/l, 95% confidence interval for the difference between medians (CI) −0.10 to −0.04 mmol/l,P=0.0001) and higher PTH (medians 5.8vs3.9 pmol/l, CI 0.10–2.6pmol/l,P=0.0360). Twenty‐eight per cent of 97 residents had PTH above the upper reference range limit of 6.5 pmol/l. Residents receiving frusemide had higher PTH than other residents (medians 6.95vs3.45 pmol/l, CI 1.9–4.2pmol/l,P<0.0001). In linear modelling, the most important predictor of the natural logarithm of PTH was daily frusemide dose, adjustedR2(Ra2)=31.8%,F=39.3,P<0.001. Creatinine and the reciprocal of 25OHD were other significant predictors with the finalRa2=39.4%,F=17.7,P<0.001.CONCLUSIONS Vitamin D deficiency is a common risk factor for secondary hyperparathyroidism in nursing home residents despite a climate in which vitamin D nutrition is thought to be ample. However, the daily frusemide dose is a more impo

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.701521.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE A number of long‐term research studies are in progress to evaluate the effects of treatment with GH on growth and final height in children with short stature but no demonstrable abnormality of GH secretion. Such treatment is invasive, expensive and carries some risk to the child. An early indication of growth response would allow restriction of treatment to those children most likely to benefit, but anthropometric measurements are relatively subjective, insensitive and imprecise. The aim of this study was to evaluate bone alkaline phosphatase, procollagen Type I C‐terminal propeptide, procollagen Type III N‐terminal propeptide and the cross‐linked carboxyterminal telopeptide of Type I collagen as early biochemical predictors of height velocity response to growth‐promoting treatments in short normal children.DESIGN A prospective intervention study, partially placebo controlled on a double blind basis.PATIENTS Fifty healthy children with familial short stature or constitutional delay in growth and puberty (8 girls, 42 boys, ages 5.5–16.5 years and all either prepubertal (45) or in very early puberty (5 boys) at the start of treatment) were treated with placebo (6), GH alone (32), GH plus oxandrolone (8) or GH plus testosterone (4).MEASUREMENTS Bone alkaline phosphatase and the collagen markers were measured at the start of treatment and 3 months later. Height velocity was calculated at the start of treatment and again after one year.RESULTS Pre‐treatment biochemical marker concentrations did not predict height velocity response after one year. Increments in all markers after 3 months were significantly correlated with height velocity increments after one year of treatment, the highest correlations being observed for bone alkaline phosphatase (r = 0.67,P < 0.0001) and procollagen Type III N‐terminal propeptide (r = 0.57,P < 0.0001). Highly significant correlations (P < 0.0001) were also observed between bone alkaline phosphatase and procollagen Type I C‐terminal propeptide (r = 0.55) and between procollagen Type III N‐terminal propeptide and the cross‐linked carboxyterminal telopeptide of Type I collagen (r = 0.62). Multiple linear regression with stepwise selection of variables identified bone alkaline phosphatase and procollagen Type III N‐terminal propeptide as the only two independent variables that contributed significantly to the prediction of height velocity response after one year (analysis of variance,P < 0.0001). Together they predicted 59% of the variability in height velocity response after a year.CONCLUSIONS The best early predic tors of height velocity response were bone alkaline phosphatase (a protein found in hypertrophic chondrocytes in the epiphyseal growth plate, in calcifying matrix vesicles and in mature osteoblasts) and procollagen Type III N‐terminal propeptide, a marker of interstitial fibril biosynthesis in soft tissues. Using these markers, GH treatment could be

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.706cn527.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE All of the presently used methods for in‐vivo determination of body composition have inherent methodological errors and depend on various assumptions. We have therefore compared several different methods used to measure body fat in adult GH deficiency during GH treatment.DESIGN Comparison of body composition data from a two‐phase trial with an initial placebo‐controlled, double‐blind 6‐month period, followed by open treatment with GH until all patients had received GH for 12 months.PATIENTS Twenty‐five patients with known GH deficiency entered the study. Baseline examinations were complete in 23 patients, and 22 patients (16 males, 6 females) completed all examinations after treatment.MEASUREMENTS Body fat calculated from total body potassium (TBK) by whole‐body40K counting, total body water (TBW) by tritium dilution, total body nitrogen (TBN) by neutron activation, and bioelectric impedance (BIA) measurements were compared to body fat determinations by dual‐energy X‐ray absorptiometry (DEXA) in two‐compartment and multicompartment body composition models.RESULTS At baseline, DEXA fat mass agreed well at group level with measurements based on TBW or TBK alone, in a four‐compartment model based on TBK and TBW, and a multicompartment model based on bone mineral (by DEXA), TBN and TBW. Body fat by BIA agreed less well. After 12 months of GH treatment, body fat decreased by all methods used. This decrease was smaller by DEXA than by the other methods. The four‐compartment model based on TBK and TBW, and TBW alone, showed the best agreement with changes in DEXA fat.CONCLUSION All methods showed a decrease of body fat with GH treatment, but variati

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.690512.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Adults with GH deficiency frequently complain of lack of energy, fatigue, social isol ation and problems with sexual relationships resulting in a low perceived quality of life. Previous studies of quality of life (QOL) in GH deficient adults have involved small numbers of patients and used measures not specifically designed for this patient population. We have devised a health related QOL model specifically designed for use in adults with GH deficiency and to assess the impact of future GH replacement therapy.DESIGN Six measurements were chosen for inclusion in the model. Two were adapted for use after clinical interviews with 12 adult GH deficient patients: the Impact and the Life Fulfilment scales. The others were the Nottingham Health Profile, the Hospital Anxiety and Depression Scale, the Self‐Esteem Scale and the Mental Fatigue Questionnaire. The reliability of the 6 measures was assessed by 2 methods: test re‐test correlation and internal consistency (Cronbach's α). The validity of the Impact and Life Fulfilment scales was assessed by correlation with the other 4 scales.PATIENTS Questionnaires were completed by 32 adults with hypothalamic pituitary disorders and GH deficiency (11 male, mean age 35.1 years), with a stimulated maximum serum GH response less than 10 mU/l (mean 2.96).Two had previously received GH injections in childhood. The questionnaires were also completed by 32 age and sex matched control subjects.RESULTS The 6 scales had test re‐test correlations of 0.70–0.92 indicating reliability over time. The Impact and Life Fulfilment Scales and the Mental Fatigue Questionnaire had Cronbach's α scores of greater than 0.6 indicating their potential for use in clinical trials. The Impact and Life Fulfilment scales correlated significantly with many physical and psychological domains from the other 4 scales indicating these were valid in the assessment of health related QOL in GH deficient adults. Compared to the controls the patients with GH deficiency were significantly psychosocially disadvantaged in terms of depression, self‐esteem, mental fatigue and life fulfilment.CONCLUSION The results of the reliability and validity studies indicate that this health related quality of life model for use with adults with GH deficiency is a potentially valid and reliable tool that could be used to assess the

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.704523.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

BACKGROUND AND OBJECTIVE We have previously reported elevated serum immunoreactive inhibin (INH) levels in patients with ovarian malignancies, particularly granulosa cell and mucinous tumours. The present study was designed to compare INH measurements using a heterologous radioimmunoassay with cross‐reactivity for inhibin α‐subunit derived peptides with measurements obtained using a new ELISA specific for dimeric inhibin‐A. It was hypothesized that granulosa cell tumours may secrete significant quantities of inhibin‐A whereas mucinous tumours were unlikely to do so because of the lack of a relation between INH and FSH measurements in the latter group.DESIGN Serum samples obtained from women found to have ovarian cancer were assayed using the heterologous radioimmunoassay (the Monash assay) and using an ELISA specific for dimeric inhibin (the Groome assay) and the results were compared.PATIENTS Samples for assay were available from 69 normal post‐menopausal control women, 12 patients with mucinous tumours of the ovary, 26 with serous tumours, 7 with granulosa cell tumours and 8 with various other ovarian tumours. Patients were post‐menopausal or had been subjected to bilateral oophorectomy at the time these samples were collected.MEASUREMENTS The Monash and Groome assays were carried out as described previously. The upper limit of normal for post‐menopausal women in the Monash assay was 122 U/l and for the Groome assay was calculated to be 32 ng/l.RESULTS Among the 69 normal subjects, 4 were found to have elevated inhibin levels using the Monash RIA (133–190 U/l) and 4 were found to have elevated levels in the Groome ELISA (45.5–55.3 ng/l). Among 12 patients with mucinous tumours, 10 (83%) had elevated inhibin levels using the Monash assay but only 3 (25%) had elevated levels with the Groome assay (P < 0.005). Among 26 with serous tumours, 15 (58%) had elevated levels in the Monash assay but only 1 (4%) in the Groome assay (P < 0.001). Among 7 samples from patients with granulosa cell tumours, 100% were elevated in the Monash assay and 71% in the Groome assay (NS, non‐significant). In a miscellaneous group of tumours all 8 had elevated levels in the Monash assay and 2 in the Groome assay (P < 0.001).CONCLUSIONS It was concluded that in normal post‐menopausal subjects, INH is generally undetectable or present at low levels, consistent with the loss of ovarian function. The majority of granulosa cell tumours appear to secrete significant amounts of dimeric inhibin‐A, whereas mucinous tumours secrete predominantly other forms of INH, presumably related to the α‐subunit. Serous tumours may also secrete inhibin‐related peptides but not dimeric inhibin‐A. The nature of the inhibin related peptides pro

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.627450.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The third trimester of pregnancy is characterized by a mildly hyperactive hypothalamic–pituitary–adrenal (HPA) axis, possibly driven by elevated circulating levels of corticotrophin releasing hormone (CRH) of placental origin. In‐vitro studies have demonstrated that glucocorticoids and oestrogen stimulate while progesterone inhibits the expression of CRH mRNA and/or protein, suggesting that several potential interactions between the placenta and the HPA axis may exist.DESIGN AND PATIENTS To investigate the detailed pattern of circulating immunoreactive (ir) CRH, ACTH, cortisol, oestradiol and progesterone during the third trimester of pregnancy, plasma samples were drawn serially every 30 minutes from 22 healthy pregnant women (age 32.0 ± 1.1 years, mean ± SE) between the 34th and 36th week of gestation. Ten women had plasma samples drawn between 0800 h and 2000 h (daytime group), and 12 between 2000 h and 0800 h (night‐time group). The hormone concentrations obtained were analysed for pulsatility by the Detect program, for detection of circadian rhythmicity by comparison between the first and second 6‐hour periods within each group by Student'st‐test, and for time‐dependent correlations by cross‐correlation analysis.RESULTS All five hormones were secreted in a pulsatile fashion. There was no apparent circadian rhythm of CRH or oes tradiol secretion, whereas there was a clear circadian rhythm in plasma ACTH, cortisol and progesterone secretion, with the latter in reverse phase (P<0.05). No significant correlations were observed between CRH and ACTH, whereas, as expected, ACTH and cortisol concentrations were strongly correlated with each other over time (r=0.32 and 0.70 at lag time 30 minutes for the daytime and night‐time groups, respectively), with ACTH leading cortisol. A weak positive correlation was observed between CRH and cortisol concentrations for the night‐time group at lag time 0 minute, suggesting that the latter may have a positive effect on the formerin vivoCONCLUSIONS These data suggest that placental CRH, although pulsatile, drives quantitatively the maternal HPA axis in the third trimester of pregnancy in a non‐circadian, non‐pulsatile fashion. The maternal HPA axis is probably driven in a circadian and pulsatile fashion by another major ACTH secretagogue, most likely

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.683505.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Pregnancy induced hypertension has been shown to be associated with a normal or low activity of the maternal circulating renin–angiotensin system (RAS) but little is known of the local RAS in placenta and fetal membranes. The present study attempts to determine, at full term of human preeclamptic pregnancies, the activity of the chorioplacental renin–angiotensin system.PATIENTS AND MEASUREMENTS We analysed the concentrations of active renin, prorenin, angiotensin converting enzyme (ACE) and angiotensin II in homogenates of human placenta and fetal membranes from preeclamptic patients at full term pregnancy. The values of renin, ACE and angiotensin II found in the patients with moderate preeclampsia (gestosis index 0–1) (n = 10) were compared with those of normal pregnant women (n = 8).RESULTS Our experiments showed that in preeclamptic pregnancies, the chorion membrane contained the highest concentrations of active renin (2905 ± 152 pg/g, mean ± SD), prorenin (21 315 ± 2849 pg/g) and ACE (1258 ± 302 U/g) whereas the placenta had more angiotensin II than the chorion and amnion (741 ± 45vs456 ± 40 and 428 ± 64 pg/g, respectively). In the placenta, as in the fetal membranes, no significant difference was found in the levels of active renin, ACE or angiotensin II between hypertensive patients and normal subjects but a slightly lower level of chorionic prorenin (P < 0.05) was observed in pregnancy induced hypertension.CONCLUSION These findings indicate that in moderate preeclampsia (gestosis index 0–1), the activity of the renin–angiotensin sy

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.703525.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Little is known of the hormone environment of the developing early human embryo. We have therefore measured selected steroids in the intrauterine fluids of early pregnancy.DESIGN Measurement of progesterone, 17α‐hydroxyprogesterone, oestradiol‐17β, testoste rone, androstenedione, cortisol and dehydroepiandrosterone sulphate in matched samples of coelomic fluid, amniotic fluid and maternal serum collected before pregnancy termination from 12 women between 8 and 12 weeks gestation.RESULTS Mean concentrations of progesterone, oestradiol‐17β and 17α‐hydroxyprogesterone in coelomic fluid were respectively 20, 6 and 2 times greater than in maternal serum and 8, 13 and 2.6 times those in amniotic fluid. Concentrations of testosterone and androstenedione were highest in maternal serum and lowest in amniotic fluid. Cortisol and dehydroepiandrosterone sulphate were found in intrauterine fluids only at the limit of detection but in normal concentrations in maternal serum.CONCLUSIONS Coelomic fluid contains relatively high concentrations of progesterone, oestradiol‐17β and 17α‐hydroxyprogesterone which may be synthesized locally. Amniotic fluid contains lower concentrations of steroids (other than progesterone) than are found in coelomic fluid or maternal serum. Free diffusion of steroids across the amnion appears limited. This may constitute a mechanism to protect the embryo from unwanted exposure to bio

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.710532.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY