ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02276.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02277.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE We wished to assess the effect of changes In the plasma concentration of 1,25‐dihydroxyvitamin D on the plasma elimination half‐time for 25‐hydroxyvitamin D In man.DESIGN The turnover of 25‐hydroxyvltamin D in plasma was Investigated after intravenous doses of the radioac‐tively labelled metabolite had been given to a group of patients (n= 17) with disorders of bone and mineral metabolism before and after oral treatment with calcium or 1,25‐dihydroxyvitamin D.PATIENTS Seven patients with post‐menopausal osteoporosis, five with hypoparathyroidlsm, three with hypo‐phosphataemic osteomalacia, one with renal osteodystro‐phy and one patient with coeliac disease were studied.MEASUREMENTS Intravenous injections of3H‐labelled 25‐hydroxyvitamin D were given and plasma elimination half‐time assessed over periods of 4–14 days during which frequent measurements of plasma calcium, phosphate, parathyroid hormone, 25‐hydroxyvltamln D and 1,25‐dihydroxyvitamin D were made. Changes in the plasma elimination half‐time for3H‐25‐hydroxyvltamin D before and after treatment with calcium and 1,25‐dlhydroxyvitamin D were evaluated by non‐parametric statistical analysis.RESULTS The elimination half‐time for3H‐25‐hydroxyvita‐min D in plasma was significantly shortened by raising the circulating concentration of 1,25‐dihydroxyvitamin D. Conversely, in a patient with intestinal malabsorption of calcium, the metabolic clearance of3H‐25‐hydroxyvitamln D was prolonged when the concentration of 1,25‐dlhydroxy‐vitamln D In plasma was decreased by suppressing secondary hyperparathyroldism with large calcium supplements. In the longer‐term studies (n= 10) there was a highly significant Inverse relation (r= 0.88,P<0.001) between the change in the plasma concentration of 1,25‐dlhydroxyvitamin D and the Induced change in the elimination half‐time of3H‐25‐hydroxyvitamin D. There was also a significant correlation (r= 0.66,p<0.0025) between the observed fall in the plasma concentration of unlabelled 25‐hydroxyvitamin D and the predicted fall calculated from the measured value for the half‐time of the3H‐labelled metabolite. In acute studies in patients with post‐menopausal osteoporosis (n= 7), enhanced metabolic Inactlvatlon of3H‐25‐hydroxyvitamln D was detectable within 24 hours of oral administration of 1,25‐dihydroxyvitamin D.CONCLUSIONS The effect of 1,25‐dlhydrhyvltamln D on the catabolism of 25‐hydroxyvltamin D can contribute to the development of vitamin D deficiency in many clinical disorders. When the natural supply of vitamin D is limited by sunlight deprivation, a sustained Increase in the plasma concentration of 1,25‐dihydroxyvitamin D due to primary

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02278.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE To assess whether hypercalcaemia due to primary hyperparathyroidism is associated with significant cardiac arrhythmias.DESIGN AND PARTICIPANTS The prevalence of cardiac arrhythmias and conduction disturbances was evaluated by 12‐lead ECG and 24‐hour long‐term ECG during presurgical hypercalcaemia and after post‐surgical normalization of serum calcium values in 20 patients with primary hyperparathyroidism.RESULTS After surgery, mean±SD calcium levels decreased from 2.85±0.1 to 2.40±0.1 mmol/l (P<0.001). There was a significant increase in QT‐intervals (0.36±0.05 vs 0.39 ± 0.05) and QTc‐intervals (0.38 ± 0.04 vs 0.42±0.03) after surgery (P<0.01). Long‐term ECG showed no change in the minimal heart rate 47 ± 8 vs 48 ± 7 beats/min or in the longest RR interval 1.6 ± 0.5 vs 1.6 ± 0.5 s (PNS). There was no difference in the prevalence of supraventricular or ventricular arrhythmias. No episode of high‐grade AV‐block was observed before surgery. Circadian heart rate rhythm did not change between investigations.CONCLUSIONS It is concluded that moderate hypercalcaemia, in spite of causing a shortening of the repolarization phase (QT‐interval), has no clinically significan

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02279.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVES We wished to determine whether women with multinodular goitre and spontaneous subclinical hyperthyroidism have decreased bone density.DESIGN AND SUBJECTS Bone density was measured at the distal and proximal forearm. Data were expressed as Z‐scores relative to the mean values out of 125 control subjects matched for age and menopause. The Z‐scores of 23 women with subclinical hyperthyroid goitre (TSH<0.1 mU/l and normal values for FT4 and total T3) and of 54 women with euthyroid goitre were compared.MEASUREMENTS Bone density was measured by single photon absorptiometry. TSH was measured by IRMA, FT4 by RIA.RESULTS Relative to the euthyroid goitre subjects the mean±SEM Z‐scores of both the distal and proximal forearm density were lower (‐ 0.69±0.17 vs ‐ 0.1 ± 0.18,P<0.05 and ‐0.5±0.18 vs 0.07±0.18,P<0.05, respectively). Median (range) FT4 in the subclinical hyperthyroid goitre subjects was significantly higher than euthyroid goitre subjects (15.6 (11–23.2) pmol/l vs 11.9 (8.3–18.3) pmol/l,P<0.001) although still within the normal range. FT4 correlated inversely with Z‐scores of both distal and proximal forearm bone density in the subjects with subclinical hyperthyroidism (r= ‐0.42,P<0.05 andr= ‐0.43,P<0.05, respectively), but not in the euthyroid goitre subjects.CONCLUSION These findings indicate that women with untreated multinodular goitre and subclinical hyperthyroidism have reduced b

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02280.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE To study the changes in unbound T3 concentration in the first trimester of pregnancy.DESIGN We measured serum unbound T3 concentration before and after termination of pregnancy.PATIENTS Twenty‐six clinically euthyrold women.MEASUREMENTS We used one non‐analogue assay (Sciavo) and three analogue assays (Amersham, Becton Dickinson and Diagnostic Products Corporation).RESULTS Regression analysis did not show any significant agreement between the analogue and non‐analogue assays. After termination of pregnancy, unbound T3 concentration as measured by Sciavo and Amersham assays did not change whereas unbound T3 concentration increased and decreased as measured by Becton Dickinson and Diagnostic Products assays respectively. Changes were not directly related to albumin or thyroid binding globulin.CONCLUSION We believe unbound T3 concentrations as measured by the analogue assays used in this study are due to a balance of errors and cannot be used to determine true physiological changes in preg

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02281.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline.DESIGN AND PATIENTS Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2–3 years in 15 healthy women aged 45–54 years. Nine remained premenopausal and six became post‐menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 postmenopausal women, aged 45–54 years, who were participating in a double‐blind study.MEASUREMENTS Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion.RESULTS Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post‐menopausal values were 30–50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean ± SEM: urinary pyridinoline (premenopausal) = 29 ± 2vsurinary pyridinoline (post‐menopausal) = 38 ± 6,P<0.05; urinary deoxypyridinoline (premenopausal) = 8 ± 1vsurinary deoxypyridinoline (post‐menopausal) = 12 ± 1,P<0.05). Three months of post‐menopausal hormone replacement therapy decreased (P<0.001) both to premenopausal levels.CONCLUSION Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hor

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02282.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE To determine how the second messenger adenosine‐3′,5′‐monophosphate (cyclic AMP) is able to mediate divergent actions of FSH and LH on granulosa cell growth and differentiation in human ovaries.DESIGN Human granulosa cells were cultured for 96 hours in serum‐free medium 199 containing increasing doses of either FSH, LH or dibutyryl cyclic AMP. Extra and intra‐cellular cyclic AMP levels were determined by radioimmunoassay. Tritiated thymidine uptake and cell number were measured as indices of cell growth, and spent medium was assayed for steroids (oestradiol and progesterone) to reflect differentiation.PATIENTS ‘Mature’ granulosa cells were aspirated from preovulatory follicles in the ovaries of clomiphene‐stimulated patients undergoing laparoscoplc sterilization; ‘lutelnized’ granulosa cells were aspirated from periovulatory follicles in the ovaries of gonadotrophin‐stimulated in‐vitro fertilization patients.RESULTS LH consistently inhibited, whereas FSH maintained or stimulated, basal granulosa cell numbers. Steroidogenesis was dose‐dependently increased by both gonadotrophins, with LH having the significantly greater effect over the entire dose‐response range (1–100 μg/1). LH also induced significantly more cyclic AMP production than FSH, both intra and extra‐cellularly, providing a basis for differential post‐receptor signalling via a common second messenger. Addition of dibutyryl cyclic AMP, at low concentrations (10–250 μmol/1) to the cultured cells in the absence of gonadotrophins mimicked FSH effects with stimulation/maintenance of cell numbers and moderate steroidogenesls. High concentrations of dibutyryl cyclic AMP (500–1000 μmol/1) caused a significant inhibition of cell numbers together with maximal steroidogenesis, simulating LH action.CONCLUSIONS These results suggest that granulosa cell maturation in the follicular phase of the menstrual cycle (controlled by FSH) is associated with a low cyclic AMP tone that favours cell growth and expression of aromatase activity in the developing preovulatory follicle. During the early luteal phase (dominated by LH), the intracellular cycle AMP tone increases to allow maximal progesterone production and inhibition of cell growth in the corpus luteum. Thereby one second messenger can mediate divergent gonadotrophic effects on granuiosa cell gro

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02283.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE The purpose of this study was to determine whether glucocorticoids can block the induction of HLA‐DR antigen expression by interferon gamma in human fibroblasts in culture.DESIGN AND PATIENTS Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids.MEASUREMENTS Cultures were analysed for HLA‐DR expression using quantitative immunoblotting and indirect immunofluorescence.RESULTS Glucocorticoids could block HLA‐DR induction in a dose‐dependent manner. At 10‐8 mol/1, the steroids dexamethasone and RU 28362 inhibited expression by 70% (P<0.004) and 56% (P<0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10‐5mol/1, RU 38486 blocked virtually the entire glucocorticoid effect.CONCLUSIONS These results suggest that glucocorticoids can regulate HLA‐DR induction by interferon gamma at physiological concentrations, an action which is stereospecific and mediated through the glucocorti

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02284.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE We wished to examine and characterize the prolactin pulsatile secretory pattern In both normal and agonadal males in order to assess whether there was any concordance with LH secretion.DESIGN Patients were sampled every 5 minutes for 12 hours.PATIENTS We studied five normal and four agonadal men, the latter group before and on testosterone enanthate (TE) (200 mg l.m. every 15 days) treatment.MEASUREMENTS Prolactin and luteinizing hormone plasma levels were determined using commercial RIA systems. Pulse detection was performed using the DETECT program and the degree of concordance between luteinizing hormone and prolactin was established computing the specific concordance Index.RESULTS We demonstrated the presence of a frequent PRL secretory pattern in normal men (22.8±1.8 peaks/12h; mean±SEM) and in agonadal patients, both in basal conditions and during testosterone treatment (20.5±2.8 and 18±1.6 peaks/12h, respectively). The testosterone treatment in agonadal men significantly reduced luteinlzing hormone pulse frequency (baseline: 27.5±2, testosterone administration: 18.1±3 peaks/12h,P<0.01) but did not affect pulsatile prolactin release. Using a 10 and 15 minute sampling protocol, we observed that prolactin pulse frequency significantly decreased (P<0.01) and was similar to the frequencies estimated In previous reports. When lutelnizing hormone and prolactin time series were studied to evaluate the possible presence of a specific concordance (SC) between the secretory events of the two hormones, no significant degree of concomitancy was observed neither using the specific concordance index or the cross‐correlation analysis.CONCLUSONS This report demonstrates (a) the presence of frequent pulsatile release of prolactin in both controls and agonadal patients (baseline and on testosterone enanthate), (b) the use of an appropriate sampling Interval (5 minutes) to unmask the prolactin pulsatile release, (c) that in men, lutelnizing hormone secretory events are not temporally linked to prolactin secretion, and (d) that androgens, even if reducing luteinlzing hormone pulse frequency in agonadal patients, do not significantly affect prolactin pulsatile secretion, suggesting that testosterone and its metabolites do not affect lactotroph a

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02285.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY