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Biomedical subjects

L Wide

Publications and source records attributed to L Wide.

At least 91 records · Page 5Linked to original sources

Circadian rhythm of erythropoietin in human serum.

When a sensitive radioimmunoassay for erythropoietin in serum (S-Epo), using labelled recombinant hEpo and antiserum to urinary hEpo, was evaluated for clinical use, a large intra-individual variation was observed during a 24 h period. The possibility of a circadian rhythm with a variation during day time which has to be considered for clinical evaluation of the S-Epo level was investigated in 27 hospitalized adult patients. They had various illnesses, but all had a level of S-Epo at 08.00 or 12.00 hours within the reference range of healthy individuals and normal cortisol levels during the 24 h. A well-marked circadian rhythm of S-Epo was found with the lowest mean level at 08.00 hours, a 42% increase at 16.00 hours and a 60% increase to the highest at 20.00 hours. Twelve (44%) of the 27 patients, with S-Epo levels within the reference range (3.3-13.5 IU/l) at 08.00 or 12.00 hours, had levels above this range at 16.00 hours. For clinical evaluation of the S-Epo level, the time of day for collection of the blood specimen has to be taken into consideration. It is recommended that blood specimens are taken in the morning between 07.30 and 12.00 hours. The mechanisms behind the observed circadian rhythm of S-Epo are unknown.

Adult↗

Marked erythropoietin increase before fall in Hb after treatment with cytostatic drugs suggests mechanism other than anaemia for stimulation.

Serum erythropoietin (Epo) was measured in 23 patients before, during and after intensive cytostatic treatment courses for acute leukaemia or before bone marrow transplantation. A marked increase was seen in all patients, starting 1 or 2 d after initiation of treatment. A peak was reached after about 7 d, at levels as high as 1450 IU/l, after which Epo fell rapidly, even in patients who were anaemic at that time. In 13 of the patients there was no fall in Hb level that could explain the increase in Epo. The increase was too large to be explained by an altered Epo metabolism or marrow utilization. Cytostatic drugs cause an increase in Epo production not mediated through anaemia, possibly initiated by a cytostatic effect on the kidneys or by an unknown stimulatory factor, responsive to bone marrow inhibition.

Antineoplastic Agents↗

Serum electrolytes and parathyroid hormone in patients in a coronary care unit.

A prospective study was carried out in 499 patients admitted to a coronary care unit (CCU) in order to evaluate the incidence of clinically significant electrolyte disturbances. Low serum potassium values (less than 3.6 mmol l) occurred in 7% of the CCU patients and low serum magnesium values (less than 0.70 mmol l-1) in 6%. Few patients had low values of both these ions (1.9%). In 49 patients the contents of these electrolytes in muscle biopsies were similar to the values of control subjects and were unrelated to treatment with diuretics. Serum calcium was determined in 444 of the patients and was above the reference range in 11 (2.5%). If we consider their concomitant parathyroid hormone (PTH) values, primary hyperparathyroidism was likely to occur in at least seven patients (1.5%). Patients with acute myocardial infarction (AMI) had mean PTH and electrolyte values similar to those of individuals without this disease. In conclusion, the present study indicates that clinically important disturbances of magnesium, potassium or calcium homeostasis are rare among unselected patients admitted to a CCU.

Adrenergic beta-Antagonists↗

Effects of acute intravenous injection of two growth hormone-releasing hormones (GHRH 1-40 and 1-29) on serum growth hormone and other pituitary hormones in short children with pulsatile growth hormone secretion.

We administered two different growth hormone-releasing hormones (GHRH) to 20 short, prepubertal children who had spontaneous secretion of growth hormone (GH), assessed from 24-hour GH secretion profiles (72 sampling periods of 20 min). We compared one i.v. injection of 1 microgram/kg of GHRH 1-40 with that of GHRH 1-29 regarding serum concentrations of GH, prolactin, luteinizing hormone, follicle-stimulating hormone and IGF-I. The children were allocated to two groups without statistical randomization. Both groups were given both peptides, with at least 1 week in between. The first group started with GHRH 1-40, the other with GHRH 1-29. The peptides both induced an increased serum concentration of GH of the same magnitude: mean maximal peak of 89 +/- 12 mU/l after GHRH 1-40 and 94 +/- 10 mU/l after GHRH 1-29 (n.s.). The mean difference in maximum serum GH concentration in each child after injection was 52 +/- 9 mU/l, range 1-153 mU/l. GHRH 1-29 also induced a short-term, small increase in the concentrations of prolactin (p less than 0.05), luteinizing hormone (p less than 0.01) and follicle-stimulating hormone (p less than 0.05). We conclude that the shorter sequence GHRH 1-29, when given in a dose of 1 microgram/kg, gives a rise in serum concentration of GH similar to that after the native form GHRH 1-40.

Adolescent↗

High frequency of in situ hybridization on thin plastic sections of human placenta with a cDNA probe for beta hCG.

We describe two different techniques with plastic embedding in in situ hybridization histochemistry (ISHH). Their applicability was demonstrated by use of human placenta of the tenth gestational week and a tritium-labeled cDNA probe for the beta-subunit of hCG. In the first method, ISHH was performed on whole pieces of tissue (en bloc ISHH) pretreated with a weak acid solution, embedded in methacrylate, and sectioned at 3 microns for autoradiography. In the second technique, en bloc ISHH was carried out on tissue pre-treated with the weak acid and thereafter with detergent to further facilitate probe penetration. An acrylic resin was used for embedding, and section thickness was reduced to 1 microns. With both techniques, beta hCG cDNA/mRNA hybrids were localized exclusively to the syncytiotrophoblast (ST), in agreement with a previous study using sections of frozen placentas for hybridization to the same probe. However, owing to the higher resolution of the plastic sections the reliability of this localization was greatly increased. The number of autoradiographic grains over the acrylic resin 1-microns sections was found to be considerably higher than that over the methacrylate 3-microns sections. This study showed that treatment of tissue with detergent before en bloc ISHH, with subsequent embedding in acrylic resin and sectioning at 1 microns, gives high resolution in combination with a high signal-to-noise ratio after autoradiography. As the acrylic resin permits cutting of ultrathin sections, the results suggest that the technique may become useful for ISHH studies at the subcellular level.

Autoradiography↗

The effects of octreotide on basal and stimulated hormone levels in patients with carcinoid syndrome.

The carcinoid syndrome, a common feature of small intestinal carcinoid tumors with liver metastases, includes flushing, diarrhea, bronchoconstriction, and right heart failure. The etiology of the carcinoid syndrome is not well understood, but serotonin seems to be involved in the diarrhea, whereas tachykinins may play a role in the flush reaction. In a double blind placebo-controlled study, we studied the effect of octreotide in 20 patients with midgut carcinoid tumors and liver metastases. A sc injection of 50 micrograms octreotide caused a significant (P less than 0.001) decrease in median plasma tachykinins and serum pancreatic polypeptide, GH, and insulin for up to 4 h. Administration of octreotide (50 micrograms, twice daily, sc) caused a 26% decrease in urinary 5-hydroxyindoleacetia acid excretion, but the number of flushing attacks or bowel movements did not change significantly. A typical flush was provoked by pentagastrin, and plasma tachykinin and serotonin levels were measured. The flush reaction was graded on a 10-point visual analog scale. Octreotide (50 micrograms, sc) given 45 min before flush stimulation prevented tachykinin release completely and significantly reduced the median flushing score from 8.5 to 2. Placebo administered in the same way did not prevent tachykinin release after pentagastrin administration. Thus, octreotide prevents pentagastrin-induced flushing and the related hormonal changes in patients with the carcinoid syndrome.

Aged↗

Effects of blood transfusions on some hematological variables in endurance athletes.

Selected hematological variables (blood hemoglobin concentration [Hb], serum (s-) iron, s-bilirubin, s-ferritin, blood lactate, and s-erythropoietin [Epo]) were analyzed before and for 4 wk after autologous blood transfusions. A group of well-trained (8 male and 4 female) former endurance athletes was phlebotomized and 3-4 months later reinfused with the freezer-stored autologous red blood cells (RBC) from 1350 ml of blood. The [Hb] increased significantly (P less than 0.001 for both sexes) from 146.7 +/- 5.31 and 131.7 +/- 11.20 g. l-1 immediately before reinfusion to maximum values of 163.5 +/- 7.47 and 155.9 +/- 11.43 g.l-1 (mean +/- SD) in males and females, respectively, 2 d after reinfusion. S-iron increased transiently 5 h after reinfusion. S-bilirubin remained unchanged throughout the study. S-ferritin increased gradually (P less than 0.02) from 48 +/- 32.91 mmol.l-1 before reinfusion to a maximum of 80.8 +/- 39.52 mmol.l-1 2 wk after reinfusion. S-[Epo] increased transiently (P less than 0.01) from 8.83 +/- 2.51 (mean +/- SD) to 12.36 +/- 5.64 U.l-1, (mean +/- SD) 5 h after reinfusion. Subsequently, there was a significant marked decrease in s-[Epo] to 5.85 +/- 1.32 U.l-1, (mean +/- SD) 1 d after reinfusion (P less than 000.1, as compared to before reinfusion). Thereafter, s-[Epo] remained low throughout the study. Blood lactate was significantly decreased only the first 2 d after reinfusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment with active vitamin D (alphacalcidol) in patients with mild primary hyperparathyroidism.

The parathyroid gland possesses receptors for 1,25-dihydroxyvitamin D3, the active metabolite of the vitamin D system, and in vitro experiments have shown that 1,25-dihydroxyvitamin D3 can inhibit the secretion of PTH. In this study 31 subjects who had displayed persistent mild hypercalcemia for 14 years and presumably had mild primary hyperparathyroidism (HPT) were challenged with 1.0 microgram alphacalcidol (1 alpha-(OH)-vitamin D3) over 6 months in a double-blind, placebo-controlled study. Before initiation of therapy, the hyperparathyroid subjects showed lower serum levels of 1,25-dihydroxyvitamin D in relation to PTH or calcium when compared with age- and sex-matched controls. Treatment induced a slight rise in serum calcium (0.05 mmol/l), but no significant decrease of the PTH levels. Eighteen of the subjects thereafter entered an open study with a higher dose of alphacalcidol (2.0 micrograms) over 1 year. Although this high dose induced a marked rise in serum calcium (0.17 mmol/l), there was only a transient reduction of the PTH levels. Thus, during long-term condition there was an escape from the suppressive action of the elevated calcium concentrations and no evidence of a specific inhibition of PTH secretion by a small oral dose of active vitamin D.

Aged↗

A new pituitary protein 7B2 is increased in patients with high alpha- or beta-hCG.

The presence of 7B2 (a 180 amino acid peptide first extracted from the porcine pituitary) was investigated by a specific radioimmunoassay and gel filtration chromatography in the plasma of three groups of patients known to have increased levels of alpha- and beta-hCG subunits. Plasma 7B2 immunoreactive equivalents (7B2-IE) were increased in postmenopausal women (range 67-143 pmol/l, median: 94 pmol/l, N = 20, P less than 0.05), in patients with Klinefelter's syndrome (range 195-230 pmol/l), median 213 pmol/l, N = 4, P less than 0.01) and in 17 patients with malignant endocrine gastrointestinal tumours (range 66-20,000 pmol/l, N = 32) compared with healthy controls (range 23.6-98.2 pmol/l, median 41.5 pmol/l, N = 40). Tumour tissue from 4 patients with endocrine pancreatic tumours had significantly higher 7B2-IE concentrations than normal pancreatic tissue, with the highest concentration in an insulinoma (449 pmol/g, normal: 28 pmol/g). During therapy almost parallel changes in plasma 7B2 and other hormones were noted and 7B2-IE therefore might be an additional marker for cancers of the APUD system.

Adolescent↗

Follicle-stimulating hormones in anterior pituitary glands from children and adults differ in relation to sex and age.

Follicle-stimulating hormone (FSH) in extracts of the anterior lobe of pituitaries, collected at autopsy from 13 boys, 21 girls, 17 men and 26 women, was measured in terms of biological activity (B) in vitro by the Sertoli cell aromatase bioassay, and in terms of immunological activity (I) by a radioimmunoassay. The highest concentration of FSH in the anterior lobe found by bioassay was in young girls, who had a mean value three to seven times higher than that in young and elderly men and women and nine times higher than that in young boys. The total amount of FSH in the pituitary found by bioassay and immunoassay was very much less in young boys than in all other groups. The B/I ratio of FSH was higher for all the 27 children below 10 years of age than for any of the 43 adults. This difference in B/I ratio of FSH in whole pituitary extracts persisted in fractions after electrophoretic separation. The mean B/I ratio for young girls was 1.26 times higher than that for young boys and 2.25 times higher than that for adults. Young and elderly men and women had almost identical B/I ratios. All extracts were analysed after electrophoresis and the median charge and charge homogeneity of FSH were estimated. The number of different forms of FSH in pituitary extracts from a child was at least 20-30, similar to that in an adult. In girls, the median charge of FSH was similar to that of young women and significantly less negative than in elderly women. The median charge of FSH in boys was more negative than in girls, but less negative than in both young and elderly men. After treatment of pituitary extracts with neuraminidase, the median charge of FSH in infants was significantly more negative than that in adults. This, together with the differences in B/I ratios between children and adults, indicates a change at puberty in the molecular structure of FSH from juvenile to adult forms of the hormone.

Adolescent↗

An association between mineral metabolism and the renin-aldosterone system in human hypertension.

In recent years abnormalities of calcium metabolism have been described in human hypertension. In this study, the relationships between indices of calcium metabolism and the renin-aldosterone system were studied in 39 subjects with untreated essential hypertension. No significant associations were found between the major determinants of calcium metabolism (plasma ionised calcium, parathyroid hormone and 1,25(OH)2-vitamin D) and the renin-aldosterone system. Serum magnesium was, however, positively correlated to plasma renin activity (PRA) (r = 0.38, P less than 0.05) while both 24 h urinary excretion of calcium and cAMP were found to be correlated to both PRA and urinary aldosterone in a positive way (r = 0.39-0.42, P less than 0.01 and r = 0.33-0.57, P less than 0.01, respectively). In this study there was no other evidence of any major influence of the renin-aldosterone status on the calcium balance in human hypertension. The urinary leak of calcium might be determined by the action of the renin-aldosterone system.

Adult↗

Interactions between indices of calcium metabolism and blood pressure during calcium infusion in humans.

Calcium plays a central role in maintaining vascular tone. Recent studies indicate that there are continuous relationships between systemic calcium metabolism and BP, as over the whole range of normal and raised BPs there is an inverse correlation between plasma ionised calcium concentration and BP. Twenty-two subjects with normal or moderately elevated BP participated in the present study, undertaken to investigate the interactions between systemic calcium metabolism and BP during a two-hour constant-rate calcium infusion in the absence and in the presence of concomitant verapamil infusion. During the infusion there was an increase in plasma ionised calcium by 0.40 mmol/l, SBP rose by 14 mmHg, and DBP by 9.7 mmHg. Higher basal plasma ionised calcium and lower basal serum parathyroid hormone concentrations were associated with a more pronounced diastolic pressor response to the calcium infusion. A greater DBP increase was also accompanied by more pronounced parathyroid hormone suppression, determined as cyclic adenosine monophosphate excretion, and greater tissue uptake of calcium during the infusion. Conversely, higher basal BPs were associated with greater tissue calcium uptake during the infusions. This relationship was abolished when verapamil was present. The present findings extend the previous observations of continuous relationships between indices of calcium metabolism and BP and indicate that both a direct effect of the calcium ion and indirect effects, as evidenced by cyclic adenosine monophosphate excretion, affect the BP response to acute hypercalcaemia.

Adult↗

The importance of human chorionic gonadotropin support of the corpus luteum during human gonadotropin therapy in women with anovulatory infertility.

One hundred ten women with anovulatory infertility (World Health Organization [WHO] group I n = 50, WHO group II n = 60) were given 341 treatment courses with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Additional hCG was given as single or repeated injections during the luteal phase in 205 ovulatory cycles. In WHO group I, the incidence of luteal phase defects was lower and the pregnancy rate higher in cycles with extra hCG administration during the luteal phase than in cycles with no extra hCG. In WHO group II, there was no such difference after supplemental hCG. The abortion rate was the same after cycles with or without extra hCG administration. It is suggested that during ovulation induction with hMG/hCG in anovulatory women with no evidence of endogenous estrogen activity, the luteal phase should be supplemented with additional hCG.

Adult↗

Changes in calcium metabolic indices during long-term treatment of patients with essential hypertension.

1. Disturbances of calcium metabolism, mimicking mild, compensated secondary hyperparathyroidism, accompany essential hypertension, but it is not known whether these alterations are primary or only secondary to the elevated blood pressure. 2. Indices of systemic calcium metabolism were followed prospectively during 6 months' treatment with either propranolol, bendroflumethiazide or verapamil in 35 patients with essential hypertension. Multivariate statistical methods were employed to study the effects of blood pressure reduction upon the metabolic indices with adjustment for the effects of the different antihypertensive agents. 3. Propranolol treatment increased the plasma ionized calcium and serum phosphate concentrations, and reduced the serum levels of parathyroid hormone, free fatty acids and glycerol. Neither the total nor the total albumin-modified serum calcium concentration was significantly affected. Thus, presumably the decrease in free fatty acids reduced the calcium complex and the calcium binding to albumin, and consequently increased the plasma ionized calcium, thereby suppressing the secretion of parathyroid hormone. 4. Bendroflumethiazide caused a reduction of the fasting renal calcium excretion to half the pretreatment level, but produced no other significant changes in the various indices of calcium metabolism. 5. During verapamil treatment, the fasting renal excretion of calcium and magnesium increased, whereas the free fatty acids and glycerol concentrations in serum were reduced. These two changes presumably balanced each other, as the plasma ionized calcium and serum parathyroid hormone concentrations were not significantly altered. 6. There were no consistent relationships between the decrease in blood pressure and the changes in the metabolic indices, either in the total sample or within any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hypertension in primary hyperparathyroidism--reduction of blood pressure by long-term treatment with vitamin D (alphacalcidol). A double-blind, placebo-controlled study.

Patients with primary hyperparathyroidism (HPT) often have raised blood pressure but a simple cause-and-effect relationship has not been established. In 33 persons with probable primary HPT and mild hypercalcemia detected in a health survey, diastolic blood pressure (DBP) was significantly higher than among age- and sex-matched, normocalcemic, controls (89.4 +/- 9.8 (SD) v 85.2 +/- 8.9 mm Hg; P less than 0.05). Among the hypercalcemic individuals, DBP was, in a multivariate analysis, inversely related to the serum calcium and plasma-ionized calcium concentrations and to the serum levels of parathyroid hormone. A prospective, placebo-controlled, double-blind, study evaluating the effects of active vitamin D, alphacalcidol, (1 microgram daily) was carried out in the hypercalcemic patients over a six-month period. This treatment caused a slight further increase (0.05 mmol/L) of both serum calcium and plasma-ionized calcium concentrations. At the same time there was a significant reduction of DBP with a mean of 6.7 mm Hg compared with placebo (P less than 0.05). The hypotensive action of the vitamin D compound was inversely related to the pretreatment serum levels of 1,25(OH)2D3 and additive to concomitant, unchanged, antihypertensive medications. The negative correlation between serum calcium and blood pressure is similar to that obtained in normocalcemic individuals and suggests that raised blood pressure, at least in the milder forms of primary HPT, is only independently associated with the disease. Active vitamin D, although it raises serum calcium, can lower blood pressure also in hypercalcemic patients as previously demonstrated in normocalcemic individuals.

Blood Pressure↗

Long-term treatment with a new non-ergot long-acting dopamine agonist, CV 205-502, in women with hyperprolactinaemia.

Twenty-four hyperprolactinaemic women were treated for 6 months with the new, non-ergot, long-acting dopamine agonist, CV 205-502. The treatment resulted in normalization of PRL secretion in 17 of the 24 women at once-daily doses of 0.05 to 0.15 mg of the drug. Sixteen of these women as well as 4 of those who remained hyperprolactinaemic had regular menstrual bleeding. Five of the patients had previously discontinued bromocriptine therapy because of adverse effects but had no problems tolerating CV 205-502. Of three bromocriptine-resistant women, two responded partially while one also remained unresponsive to CV 205-502 treatment. Mild to moderate galactorrhoea was recorded at baseline in 19 of the 24 women. After 6 months' treatment mild galactorrhoea was still present in six patients, four of whom had attained normal PRL levels. Side-effects were mild and transient. CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinaemia.

Adult↗

Effects of thyroid hormones (T4,T3), bromocriptine and Triac on inappropriate TSH hypersecretion.

Inappropriate TSH hypersecretion was diagnosed in a 38-year-old woman (case 1) and in a 38-year-old man (case 2). Both of them had earlier been treated by ablative therapy for hyperthyroidism. The present diagnosis was based on elevated basal serum TSH levels despite elevated serum free thyroid hormone levels. Both of them had exaggerated TSH responses to TRH (peak value 240 mU/l in case 1 and 408 mU/l in case 2). Their albumin and prealbumin levels were normal. The serum TBG level was normal in case 1 but was elevated in case 2. Serum levels of alpha-subunits of TSH, and pituitary CT scans were normal. Despite mild clinical hyperthyroidism, peripheral indices of thyroid hormone action were normal. They had also relatives with apparent resistance to thyroid hormones. In view of the possibility that prolonged pituitary thyrotrophic stimulation is detrimental, various therapeutic approaches to suppress TSH levels were tried. Both T3 and T4 treatments lowered serum TSH levels, but were poorly tolerated. Acute administration of L-dopa or bromocriptine reduced serum TSH levels, but this was not seen during long-term therapy. TRIAC treatment lowered serum TSH levels, and the drug was well tolerated. Serum TSH responses to TRH were not blunted during T3, T4 or TRIAC treatments. Somatostatin also reduced serum TSH levels, but did not potentiate the effect of low dose T3 therapy. Our results suggest that the patients had unbalanced pituitary and peripheral thyroid hormone resistance, predominantly at the pituitary level. Of the drugs studied, TRIAC seemed to be the most suitable therapy.

Adult↗