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Biomedical subjects

L Wide

Publications and source records attributed to L Wide.

At least 127 records · Page 7Linked to original sources

Increased bone turnover during gonadotropin-releasing hormone superagonist-induced ovulation inhibition.

Superactive stimulatory analogs of GnRH inhibit ovulation in women. This investigation was done to assess bone turnover during GnRH agonist-induced anovulation. Particular interest was directed to the effects of smoking, since smokers have an increased risk of osteoporosis. Fasting serum calcium, phosphate, PTH, and bone Gla-protein (osteocalcin) levels, as well as urinary calcium, cAMP, and hydroxyproline excretion and the renal tubular threshold for phosphate were determined before and after 6 months of GnRH superagonist contraceptive treatment in 47 women, 22 of whom smoked more than 10 cigarettes daily. Before treatment the women who smoked had significantly higher serum phosphate concentrations and lower serum PTH concentrations than the women who did not smoke. Fasting serum calcium and the urinary calcium to creatinine ratio increased after treatment in all women, especially in the nonsmokers. The nonsmokers also had more pronounced increases in serum phosphate and osteocalcin concentrations. A decrease in serum PTH during treatment was confined to the nonsmokers. These results suggest increased bone resorption and turnover during GnRH agonist-induced anovulation and indicate that smoking habits should be taken into account in the evaluation of bone disease.

Adult↗

Evidence for diverse structural variations of the forms of human FSH within and between pituitaries.

The biological activity of FSH in vitro (B-vitro) was compared with its radioimmunological (RIA) activity in 38 pituitary extracts from men and women. The B-vitro method was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10-day-old rats. The mean B-vitro/RIA ratios for FSH of men and young and elderly women were almost identical. The mean values of median charge of the forms of FSH differed significantly between the three groups of human adults. The B-vitro/RIA ratio of different forms of FSH, separated by electrophoresis of 14 individual pituitary extracts, was higher for less negatively charged than for more negatively charged forms. Some forms of FSH with the same charge and separated from different pituitary extracts, e.g. from a young and an elderly woman, had significantly different B-vitro/RIA ratios. This ratio, thus, was not related to the charge per se of the hormone. However, the relation between the B-vitro/RIA ratio and the charge of FSH was similar for individual pituitary extracts when charge was expressed in relation to median charge. The results suggest that different molecular structural variations of FSH are involved in the polymorphisms observed within and between individual pituitaries. In human adults, the variation of FSH between the pituitaries mainly affects the metabolic clearance rate (MCR) of the hormone, whereas the variation within the individual pituitary affects both the MCR of the hormone and its biological effect at the target cell.

Adolescent↗

Some qualitative differences of hCG in serum from early and late pregnancies and trophoblastic diseases.

Twenty-four sera were obtained from women in the first and third trimester of pregnancy, women with gestational choriocarcinoma, and men with testicular hCG-producing tumours. The hCG-activity was measured by an in vivo bioassay (B) based upon the increase in mouse uterine weight. The sera were also analysed by three immunoassays (I), one for hCG, one for alpha-hCG subunits, and one for beta-subunits. All sera were also subjected to electrophoresis in 0.17% agarose suspension in 0.075 mol/l sodium veronal buffer at pH 8.6, and median charge, expressed as median mobility, was estimated for hCG. The metabolic clearance rate (MCR) of hCG in serum in early and late pregnancy and from one patient with choriocarcinoma was measured in mice. The B/I ratio was lower and the forms of hCG were less negatively charged in late pregnancy compared with early pregnancy. The lower B/I ratio might be due to the higher MCR of hCG in the test animal in the in vivo bioassay. The B/I ratio in choriocarcinoma was higher than in early pregnancy. However, the median charge of hCG was almost identical in these two groups. The most negatively charged forms of hCG were found in the men with testicular tumours. The four groups: early pregnancy, late pregnancy, gestational choriocarcinoma, and testicular tumours could be differentiated by measuring the median charge and the B/I ratio of hCG in serum. The production, later in pregnancy, of forms of hCG which disappear faster from the circulation might partially explain the lower hCG concentration in serum at this stage of gestation.

Animals↗

Cytotoxic treatment in patients with malignant carcinoid tumors. Response to streptozocin--alone or in combination with 5-FU.

Thirty-one patients with malignant carcinoid tumors were treated with streptozocin--alone (n = 7) or in combination with FU (n = 24). The responses to treatment were followed by the determination of tumor markers, urinary 5-HIAA, serum PP, HCG-alpha and -beta subunits, as well as determination of the size of liver metastases on computerized tomography or ultrasonography. Three patients (9.7%) showed objective responses with a mean remission time of 2.7 months. Eighteen patients (58%) showed stable disease, whereas ten patients (32.3%) showed progressive disease directly from the start of therapy. A good correlation was found between the changes in tumor markers and tumor size, although the changes occurred earlier in the markers than in the size. Estimated median survival from the time of histologically verified carcinoid tumor was 41 months and from start of therapy 22 months. Our data indicate that combination treatment with streptozocin and 5-fluorouracil is of little value for patients with malignant carcinoid tumors.

Adult↗

Transsphenoidal therapeutic puncture of a cystic pituitary adenoma.

Transsphenoidal diagnostic puncture of skull base tumours has been a routine procedure in Uppsala for a decade. Bromocriptine is the treatment of choice for patients with prolactin secreting pituitary adenomas. Here we report on a patient with a pituitary adenoma who instead developed an increase in tumour size after bromocriptine treatment. Magnetic resonance imaging showed the tumor to be cystic. A transsphenoidal puncture was used therapeutically instead of surgery with excellent result.

Adenoma↗

Optimal discrimination of mild hyperparathyroidism with total serum calcium, ionized calcium and parathyroid hormone measurements.

The serum concentrations of calcium, albumin and parathyroid hormone (PTH) and the plasma levels of ionized calcium were determined in 124 healthy subjects, 89 patients with primary hyperparathyroidism (HPT), 23 of whom had the syndrome of multiple endocrine neoplasia type 1 (MEN-1) and 43 patients who had hypercalcaemia of other causes than HPT (non-HPT), in most cases due to widespread malignancies. The total serum calcium was corrected for the serum albumin concentration (CaM). Healthy females over the age of 50 had higher CaM, than younger females and the women of all ages also had, higher serum PTH levels than males. For all study groups both the intra- and inter-diurnal variations were small for all the studied variables. Discriminant function and optimal discriminatory limits were calculated with the help of computer programs. A consideration of all the individuals in the discriminant analysis, revealed that measurements of CaM alone separated most HPT patients both from the healthy subjects and from the non-HPT patients. However, when only those who had borderline values (defined as CaM between 2.45 and 2.75 mmol/l) were included it turned out that measurements of ionized calcium markedly improved the delineation of mild HPT from the healthy subjects and that, in addition, PTH measurements helped to exclude those with non-HPT hypercalcaemia. The optimal discriminatory levels of serum calcium were calculated as the levels which caused the minimum loss in terms of misclassification when attention was paid to the relative importance of false positive to false negative classifications and to the prevalence of HPT. The optimal discriminatory level for serum calcium for a weighting ratio between false positive to false negative of 1:1, and a prevalence of HPT of 1%, was calculated to be 2.68 mmol/l and for a prevalence of 50% 2.56 mmol/l. In the latter situation a weighting ratio of 10:1 for false positive to false negative gave a level of 2.63 mmol/l while a weighting ratio of 1:10 corresponded to an optimal discriminatory level of 2.47 mmol/l.

Adolescent↗

Treatment of malignant endocrine pancreatic tumors with human leukocyte interferon.

Twelve patients with malignant endocrine pancreatic tumors refractory to cytotoxic treatment were treated with human leukocyte interferon im at daily doses of 3 X 10(6)-6 X 10(6) IU. Ten of 12 patients showed an objective response with a mean duration of 15.2 months, median, 11 months (range, 2-36+). All ten patients had a decrease in tumor markers and an objective reduction in tumor size was also noted in four. Improvement of clinical manifestations was seen in all cases with an objective response. Adverse effects, including influenza-like syndrome, reduction of blood cells, and chemical signs of liver dysfunction occurred, but were reversible or could be circumvented by dose reduction. One patient developed hypothyreosis on an autoimmune basis; another patient developed liver steatosis. Although the number of patients is small, the results are promising. Interferon therapy seems to be as potent as cytotoxic treatment but with far less side effects. This study indicates that further trials with interferon in patients with less advanced stages of malignant endocrine pancreatic tumor should be performed.

Adult↗

Relationships between calcium metabolic indices and blood pressure in patients with essential hypertension as compared with a healthy population.

Relations between indices of mineral metabolism and blood pressure were examined in 182 subjects, comprising 58 patients with essential hypertension (EHT) and 124 healthy subjects attending a general health survey. Multivariate techniques of statistical analysis were employed to test the hypothesis of different relationships between blood pressure and calcium metabolism within the subpopulations and to eliminate confounding effects of age, sex and obesity. Plasma ionized calcium was inversely related and the urinary calcium excretion positively related to blood pressure in the total group. This was not significantly different between the groups. Serum parathyroid hormone (PTH) was, however, related to diastolic blood pressure only in the EHT group. The EHT patients had significantly lower plasma levels of ionized calcium, significantly higher levels of PTH and significantly greater excretion of calcium in the urine than the healthy subjects. The results of this investigation support the hypothesis that among patients with EHT the renal tubular reabsorption of calcium is impaired resulting in a reduction of plasma ionized calcium and thereby stimulation of PTH. The findings of linear relationships suggests the possibility of a direct association between calcium metabolism and the regulation of blood pressure.

Adult↗

Treatment of malignant endocrine pancreatic tumours with human leucocyte interferon.

22 patients with advanced malignant endocrine pancreatic tumours were treated with human leucocyte interferon 3-6 X 10(6) IU per day. Objective responses (more than 50% reduction in tumour markers or tumour size) were seen in 7/7 with watery diarrhoea/hypokalaemia/achlorhydria syndrome, 3/4 with the Zollinger-Ellison syndrome, 6/9 with "non-functioning" tumours, and 1 with a mixed tumour mainly producing somatostatin. The median duration of response was 8.5 months, and all responders improved clinically. Adverse effects seemed more tolerable than those of cytotoxic treatment.

Clinical Trials as Topic↗

Aspects of thyroid function during use of Norplant implants.

Plasma thyroxin (T4), triiodothyronine (T3), T3-uptake and thyroid stimulating hormone (TSH) were measured in 18 women using Norplant implants or Norplant-2 implants for six months. Free T4-index and free T3-index were also calculated. All women had used non-hormonal contraceptives before insertion of the implants. T4 decreased and T3-uptake increased, indicating a lower level of thyroid binding proteins during treatment. Free T4-index remained unchanged, indicating that the free concentration of thyroxin was unaltered. All women were euthyroid and TSH was unchanged. It is concluded that treatment with Norplant implants does not result in a change in thyroid function.

Adult↗

Serum electrolytes and parathyroid hormone concentrations in acute myocardial infarction.

Serum concentrations of calcium, magnesium, potassium and phosphate can be lowered experimentally by adrenaline, which also can stimulate the secretion of parathyroid hormone (PTH). In order to evaluate the possible clinical importance of these mechanisms serial blood samples were drawn during the first three hospital days in 26 patients with acute myocardial infarction (AMI), a condition known to increase plasma catecholamine levels. During the study period there were no consistent significant changes of the serum electrolytes. The serum PTH levels, however, were significantly raised in the AMI patients already on admission and did not normalize during the observation time. The PTH concentrations were unexplained by infarct size, concomitant diseases or medication. These findings suggest that PTH could be an independent risk factor for AMI.

Calcium↗

Indices of mineral metabolism in relation to blood pressure in a sample of a healthy population.

Indices of mineral metabolism in blood and urine were analysed in relation to blood pressure in 97 healthy subjects aged 16-82 years. In a multivariate analysis, after allowing for the effects of sex, body mass index (BMI) and age, there was an inverse relationship between plasma level of ionized calcium and mean blood pressure (MBP) (beta = -50.0 mmHg/mmol/l P-ionized calcium, p = 0.0005). In univariate analyses MBP also showed statistically significant inverse relationships with plasma ionized calcium, serum phosphate and renal threshold concentration of phosphate; positive relationships to MBP were found for fasting urinary excretion of calcium and cyclic adenosine monophosphate. However, when examined multivariately, only the relation between MBP and plasma ionized calcium persisted. This study supports previous findings of an inverse relationship between blood pressure and serum ionized calcium and extends the observations to the physiological range. It is further evident from this study that BMI and age should be taken into account in analyses of the relationship between blood pressure and mineral metabolism.

Adolescent↗

Prolonged low-intensity exercise raises the serum parathyroid hormone levels.

Twelve healthy males performed 5 h exercise on a bicycle ergometer at a constant work load of approximately 50% of their maximum capacity. The serum concentrations of parathyroid hormone (PTH) increased after the first hour and were continuously elevated throughout the exercise period. The rise in PTH was 5-7% above pre-exercise levels, corresponding to 20-30% of the maximal increase obtained by the same assay during prolonged hypocalcaemia. The probable cause for the rise in PTH was that the plasma ionized calcium tended to be lowered during exercise. Since the total serum calcium concentrations were raised (by 3-5%) during exercise the reduction of the free, ionized, fraction was presumably largely due to increased complex-binding although an outward transport from plasma was not excluded. The serum concentrations of magnesium were gradually reduced during exercise while those of phosphate and potassium were raised throughout, probably as a result of leakage from the working muscle.

Adult↗

TRH tests with analyses of TSH, prolactin, and GH responses in subtypes of patients with major depressive disorders.

TRH tests were performed on 131 patients with RDC diagnoses of major depressive disorders to study altered endocrine control mechanisms in subtypes of depression. The TSH response to TRH was measured in all patients. In more than a third of the sample the prolactin (PRL) and growth hormone (GH) responses were also analysed. There were no differences between bipolar, primary unipolar and secondary unipolar patients in means of any endocrine variable. However, the expected positive correlation between baseline TSH and delta TSH was absent in the secondary unipolar group, indicating a dysregulation of pituitary TRH receptor sensitivity in this depressive subtype. Only delta TSH was dependent on depressive state, being lower in currently ill primary unipolar patients only. Patients with melancholic features (endogeneity scores high) had blunted TSH responses. Weight loss was connected with TSH blunting in all depressive subtypes. Among patients with blunted delta TSH (less than 5 mU/l) there was no relationship between degree of weight loss and delta TSH. Further, examination of partial correlation coefficients suggests weight loss of affect delta TSH by virtue of its being part of the melancholic syndrome. A significant correlation between blunted delta TSH and nonsuppression of cortisol in the DST was found only among primary unipolar patients, arguing for some independence of the TRH test and the DST in mirroring disturbed endocrine controls in depression.

Adolescent↗

Alteration in density, morphology and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism.

Dispersed parathyroid cells from normal human and bovine glands and from 10 patients with primary (7 adenomas, 3 hyperplasias) and 4 patients with uraemic hyperparathyroidism (HPT) have been investigated with respect to density, morphology and parathyroid hormone (PTH) release. Percoll density gradients enabled an efficient isolation of viable parathyroid cells which generally banded between 1.035-1.090 g/ml. The average density was significantly higher in cells from the normal than the abnormal glands. The pathological glands contained large chief cells, oxyphil and transitional oxyphil cells and, in one case, water-clear cells which were enriched in fractions with densities below 1.055 g/ml. Measurements of cell diameters revealed an increased proportion of enlarged cells in the preparation of abnormal glands. Nuclear diameters were similar in the normal human glands, adenomas and hyperplasias, but the variability was greater among the adenomas. In comparison to normal bovine parathyroid cells, PTH release of cells from the pathological human glands was reduced and abnormally insensitive to extracellular calcium. The oxyphil and water-clear cells secreted similar amounts of PTH as the chief cells of the abnormal glands. The disturbed PTH release in secondary HPT seemed to be confined mainly to cells within nodules of the hyperplastic glands. The results show that the disturbed hormone regulation in HPT is related to morphological changes of the cells and that buoyant density gradients can be used to accumulate the abnormal cells.

Adenoma↗

Stimulation of parathyroid hormone secretion by EDTA infusion--a test for the differential diagnosis of hypercalcaemia.

A constant EDTA infusion of 24 mg/kg/h during 60-120 min was given to 26 patients with primary hyperparathyroidism (HPT), 8 patients with hypercalcaemia of other origin and 10 healthy control subjects. PTH and ionized calcium concentrations were measured at 5-10 min intervals. In all three groups the infusion caused a linear decrease in plasma ionized calcium. In both the HPT patients and the healthy subjects there was a prompt increase in the serum levels of parathyroid hormone (PTH) until a plateau was reached. The PTH response of the HPT patients appeared already within the hypercalcaemic range and the plateau value was attained at higher levels of PTH and ionized calcium than in the healthy subjects. The enhanced response distinguished half of the HPT patients with basal PTH values within the reference range from the healthy controls. The patients with nonhyperparathyroid hypercalcaemia displayed no increase in PTH values until the ionized calcium concentration was reduced far into or below the reference range. Thus the EDTA infusion permitted a complete differentiation between HPT and other causes of hypercalcaemia. In most cases an infusion over 30 min was sufficient for this purpose.

Adult↗

The regulation of metabolic clearance rate of human FSH in mice by variation of the molecular structure of the hormone.

The relationship between charge on human FSH (hFSH) molecules and their metabolic clearance rate (MCR) was investigated. The median charge of the hFSH molecules was expressed as their median mobility at electrophoresis in 0.075 M sodium veronal buffer, pH 8.6. MCR was estimated after single iv injection in mice of unfractionated and fractionated extracts of human pituitaries. There was a highly significant (P less than 0.001) correlation between charge and MCR both for forms of FSH present within the individual pituitary and for FSH in different pituitaries. After the iv injection there was a gradual change to a more negative median charge of hFSH in plasma. This was explained by the more rapid clearance of the less negatively charged forms of hFSH and thus selective survival of different forms in the circulation. This is a most likely explanation for the differences in median charge between FSH in pituitaries and in sera of men and women of corresponding age. The results suggest that MCR of human FSH is controlled by a gonadal-pituitary feed-back mechanism which involves changes in the structure of the FSH produced by the pituitary. It is suggested that charge is one factor involved in the regulation of the survival of FSH in the circulation and that this is of physiological importance for the control of the ovarian function during the menstrual cycle.

Adolescent↗