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Biomedical subjects

L Wide

Publications and source records attributed to L Wide.

At least 73 records · Page 4Linked to original sources
PubMed1991

Physiological response to phlebotomies for autologous transfusion at elective hip-joint surgery.

In order to study the physiological response to phlebotomies for autotransfusion, an autotransfusion program was designed for 10 patients undergoing hip-joint replacement surgery for arthrosis. 4 phlebotomies of 450 ml each were performed within 12 days. Blood samples were taken immediately before phlebotomy for blood hemoglobin (Hb), serum erythropoietin (Epo), reticulocyte count (ret) and erythrocyte 2,3-diphosphoglycerate (DPG). All 4 phlebotomies could be performed in 9/10 patients, and only 1 patient had significant symptoms (fatigue). The operation was performed 2 weeks after the last phlebotomy. None of the patients had recovered the initial Hb level at operation (24.8 +/- 9 per liter lower than initially), and they were all even more anemic after the operation (36.8 +/- 16.9 g/l lower than initially). Serum Epo increased from 13.6 +/- 7.2 IU to 30.6 +/- 12.2 (SD) IU per liter, and reticulocyte counts increased to a maximum of 3.68 +/- 1.69%. DPG increased in all patients except the one who had significant fatigue. It is concluded that the patients tolerated the phlebotomy program well but that a significant anemia developed. The compensatory increase in erythropoietin and reticulocyte count, adequate for this degree of anemia, was small compared to the increase seen at more severe anemia, indicating that there may be a role for pharmacological stimulation of erythropoiesis in blood predeposit programs.

Adult↗
PubMed1991

Treatment of myelodysplastic syndromes with recombinant human erythropoietin.

12 patients with myelodysplastic syndromes were treated with recombinant human erythropoietin (r-epo). 5 patients had stable anemia, 78-92 g/l, and 7 were transfusion-dependent. In 11 patients, r-epo was given intravenously three times a week, with dose escalation after 4 and 8 wk if hemoglobin did not increase more than 15 g/l. The doses were 600, 1500 and 3000 U/kg bodyweight/wk. The 12th patient was treated subcutaneously with a dose of 560 U/kg/wk. 3 patients showed a significant response with an increase in hemoglobin of greater than or equal to 15 g/l. 2 of these had stable anemia before treatment and increased in hemoglobin from 87 to 116 g/l and from 80 to 99 g/l, respectively. The 3rd patient was transfusion-dependent and rose to a stable hemoglobin level between 76 and 80 g/l without transfusions. 2 patients showed a reduction of their transfusion need. Mean initial serum erythropoietin in the responding group was 366 U/l compared to 1049 among the non-responders (p = 0.367). Response was observed in 5/7 patients without bone marrow sideroblasts and in 0/5 patients with sideroblasts (p = 0.027). Erythropoietin seems to be an effective and well-tolerated treatment for a certain proportion of patients with MDS. A larger patient material might provide a model for predicting responses.

Adult↗
PubMed1991

Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds.

A total of 80 individuals in 4 kindreds with multiple endocrine neoplasia type 1 (MEN 1) have been subjected to repeated biochemical screening during a 10-yr period with the principal aim being to analyze characteristics of the developing pancreatic lesion. Age at presentation of the MEN 1 trait averaged 18 yr in 7 previously unaffected individuals, and this effect of the screening procedure represented a lowering by almost 2 decades. Pancreatic endocrine involvement was recognized at a mean age of 25 yr and constituted the presenting lesion in a majority of the patients. A standardized meal test and basal values of serum pancreatic polypeptide, insulin, proinsulin, and gastrin were the most efficient markers for the pancreatic lesion and preceded signs of pancreatic tumors upon radiological examinations by a mean of 3.5 yr. A 75% penetrance of the islet cell disease and 90% for primary hyperparathyroidism within the affected individuals equalled the prevalences reported in autopsy studies. Two of the kindreds showed signs of intrafamilial homogeneity with respect to the profile of peptide excess (P less than 0.05) and considerable discrepancy in the malignant potential of the pancreatic lesions. The results of early detection and surgical intervention of the pancreatic tumors in MEN 1 suggested an impact on morbidity, while any effect on the mortality of these individuals remains to be clarified.

Adult↗
PubMed1991

Values of intact serum parathyroid hormone in different stages of renal insufficiency.

Intact serum parathyroid hormone (PTH) values were determined in 136 patients consulting the out-patient clinic for renal medicine and in 36 patients on maintenance hemodialysis in order to reveal the extent of parathyroid involvement in different stages of renal insufficiency. Elevated PTH values were found in 53 of the conservatively treated patients and in all but 4 of those on hemodialysis. Serum creatinine values and the duration of uremia correlated significantly to serum PTH, and multivariate analyses revealed that these variables were of dominating importance in determining the extent of PTH elevation. The negative relationship between PTH and plasma ionized calcium indicated maintained calcium regulation of hormone release from the parathyroid, although a relative secretory autonomy seemed to develop in parallel with the functional renal impairment. It is concluded that measurements of intact serum PTH values can demonstrate parathyroid hypersecretion in early renal insufficiency and constitutes a useful tool in the management of patients with renal disease.

Adolescent↗
PubMed1991

Disturbance of basal and stimulated serum levels of intact parathyroid hormone in primary hyperparathyroidism.

In patients with primary hyperparathyroidism, measurements were made of basal and stimulated levels of intact parathyroid hormone (PTH). The basal PTH values were elevated in all but six of 89 patients and provided clear separation towards normal individuals (n = 75) and patients with hypercalcemia of other origin (n = 34). The PTH value correlated with the serum calcium concentration in hyperparathyroidism and with the weight of excised parathyroid adenomas but not with that of chief cell hyperplasias. A constant ethylenediaminetetraacetic acid infusion during 60 minutes of induced essentially linear reductions of plasma-ionized calcium concentrations, averaging 0.02 mmol/L/10 minutes, which were associated with swift, curvilinear, elevations of PTH levels that reached a plateau after 10 to 20 minutes. The increment in serum PTH level correlated with the basal PTH value both in patients with hyperparathyroidism and controls. However, in proportion to the much greater glandular mass in the patients with hyperparathyroidism, the secretion of PTH was relatively reduced. The findings support the value of the intact PTH assay in the differential diagnosis of hypercalcemia and show that PTH secretion in vivo is extremely sensitive to hypocalcemic stimulation, that the pathological parathyroid tissue in hyperparathyroidism is characterized by a reduction of hormone release per unit weight, and that the hormone secretion in hyperparathyroidism operates closer to its maximal capacity than under normal circumstances.

Adult↗
PubMed1990

Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors.

A prospective study was performed on 84 patients with neuroendocrine pancreatic tumors. Fifty-nine (70%) had malignant tumors and received causal medical treatment. Streptozotocin in combination with 5-fluorouracil or doxorubicin was used as first-line treatment and produced overall objective responses in 20 of 44 (45%) patients with a median duration of response of 27.5 months. Thirty-two patients who failed on chemotherapy subsequently received interferon treatment and 20 (63%) responded objectively with a median duration of 20.5 months. Octreotide, third-line treatment in 14 patients, produced objective responses in four patients (28%) (median duration of response, 16 months). The median survival from diagnosis in malignant cases was 6.7 years. Even if none of the current medical therapies are curative for patients with malignant endocrine pancreatic tumors, a prolonged survival would be observed during the last decade. Since the age at diagnosis has not been dramatically reduced despite improvements in diagnostic methods, the prolonged survival might be attributed to causal medical treatment.

Adolescent↗
PubMed1990

Calcium metabolic indices, vascular retinopathy, and plasma renin activity in essential hypertension.

The interplays between calcium metabolic indices, retinal vascular status, plasma renin activity and blood pressure were examined in 67 patients with untreated essential hypertension. There was an inverse relationship between plasma ionized calcium and blood pressure (P = .002), whereas albumin-modified total serum calcium was directly related to blood pressure (P = .02). The plasma cyclic AMP level (P = .05) and the 24 h urinary excretion of cyclic AMP (P = .03) were also positively associated with blood pressure. Patients with vascular retinopathy had lower plasma ionized calcium concentrations (P = .01) and higher 24 h urinary cyclic AMP excretions (P = .05) than those without such changes, even when the differences in blood pressure, age, sex and body mass index were taken into account in analyses of covariance. Plasma renin activity did not interfere with the relationships between calcium metabolic indices and blood pressure, nor were there any associations between the renin status and the calcium metabolic indices. These findings suggest that a low concentration of plasma ionized calcium is an independent risk factor for vascular disease.

Adult↗
PubMed1990

Molecular charge heterogeneity of human serum erythropoietin.

The charge heterogeneity of human serum erythropoietin (S-Epo) was studied in 89 serum specimens from 78 subjects by zone electrophoresis in 0.17% agarose suspension at pH 8.6. The electrophoretic elution profiles of S-Epo were determined with a radioimmunoassay for Epo. The number of Epo peaks indicated that at least 20-30 different forms of Epo were present in a single serum specimen. The median charge of Epo, estimated as its median electrophoretic mobility, was determined for each serum specimen. This median charge was measured in 10 healthy adults, 46 patients with anaemia, six patients with secondary polycythaemia, one patient with polycythaemia vera treated by phlebotomy, and six healthy newborn infants (cord sera). Forty-four of the patients with anaemia had a median charge of S-Epo within the reference range for healthy adults, while all the patients with polycythaemia and the newborn infants had less negatively charged forms of S-Epo. In nine patients in whom the S-Epo level had a circadian rhythm, the forms of S-Epo in the evening were less negative than those in the morning. The median charge of recombinant preparations was much less negative than that of S-Epo in healthy individuals, while that of the 2nd International Reference Preparation was more negative than in any of the 78 subjects analysed. A significant change to less negatively charged S-Epo forms was observed 24 h after a subcutaneous injection of recombinant Epo in one patient, who before the injection had a normal median charge and concentration of S-Epo. In conclusion, Epo exhibits a considerable charge heterogeneity in individual serum specimens, the forms of S-Epo in the morning may differ from those in the evening, those in adults differ from those in newborn infants, and those in patients with anaemia differ from those in polycythaemia. The results also suggest that the methods used in this study may be useful for detecting the presence of injected recombinant Epo in the blood in persons with a normal endogenous Epo production.

Adult↗
PubMed1990

Impaired secretion of parathyroid hormone in patients with rheumatoid arthritis: relationship to inflammatory activity.

Hypocalcaemic tests, employing infusion of EDTA over 1 h, were performed in 22 patients with rheumatoid arthritis (RA) and 14 healthy controls. The basal levels of calcium and parathyroid hormone (PTH) were not significantly different in the two groups. The RA patients displayed a markedly impaired PTH response during infusion of EDTA compared with the controls although the reduction of plasma ionized calcium was similar. The PTH response was furthermore significantly, inversely, related to the inflammatory activity measured as sedimentation rate (r = 0.65; P less than 0.01), i.e. the more pronounced the inflammation, the less the capacity to secrete PTH. Since secretion of PTH is related to the intracellular calcium concentration of the parathyroid cells, these findings are in line with previous observations of a higher intracellular calcium content in inflammatory disease. They also support the earlier indications of reduced bone turnover in inflammatory arthritides. An insufficient parathyroid function could be one factor contributing to bone disease in these conditions.

Acute-Phase Reaction↗
PubMed1990

Neuroendocrine pancreatic tumours: clinical presentation, biochemical and histopathological findings in 84 patients.

A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 35 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominal symptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.

Adenoma, Islet Cell↗
PubMed1990

Effects of prolonged adrenaline infusion and of mental stress on plasma minerals and parathyroid hormone.

The role of the sympatho-adrenal system for the secretion of PTH in humans is not established. Previous studies on the effects of adrenaline on plasma mineral homeostasis have focused on injections or short-term infusions of adrenaline, and conflicting results concerning calcium and parathyroid hormone (PTH) responses have been reported. We therefore infused adrenaline or placebo continuously for 3 h to 10 healthy volunteers and studied several plasma minerals, as well as PTH levels. Venous plasma adrenaline concentrations increased to the upper physiological range (5 nmol l-1) during adrenaline infusion. Another nine volunteers were exposed for 25 min to mental stress (a colour word conflict test; CWT), which causes marked circulatory changes and raises plasma catecholamine concentrations. Plasma ionized and total calcium, and magnesium concentrations were slowly and gradually reduced during infusion of adrenaline, but there was only a small increase in PTH. Plasma potassium was decreased by adrenaline within 30 min and thereafter did not change further during infusion. There was a marked but transient increase in the plasma free fatty acids concentration, which were not related to the reduction of the calcium or magnesium levels. The adrenaline-induced decrements in calcium, magnesium and potassium, and increases in heart rates persisted 30 min after the infusion, despite a rapid decrease in plasma adrenaline concentrations within 5 min of termination of the infusion. Plasma phosphate concentrations were lowered during the first 90 min of adrenaline infusion, but after 3 h they had returned to baseline despite continued infusion. CWT induced small increments of the plasma ionized calcium and PTH concentrations. Plasma potassium levels were raised despite increases in plasma adrenaline at the beginning of the stress test, while phosphate values were reduced at the end of the test. Thus, long-lasting elevations of circulating adrenaline lower plasma ionized and total calcium, phosphate, magnesium and potassium, but the time courses for these changes differed markedly. Despite the reduction of plasma ionized calcium there was only little increase in PTH and thus no indication that sustained elevations of circulating adrenaline stimulates the secretion of PTH in vivo in humans. Responses to acute mental stress and adrenaline infusion differed qualitatively, indicating that adrenaline responses to stress are of minor importance in this respect.

Adult↗
PubMed1990

Effects on serum parathyroid hormone of intravenous treatment with alphacalcidol in patients on chronic hemodialysis.

Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D. Intravenous administration of alphacalcidol, a synthetic analogue which is metabolized to calcitriol, was given during 12 weeks to 51 patients on chronic hemodialysis in doses between 1 and 4 micrograms/dialysis session. The treatment caused a modest rise, by 0.25 mmol/l, in serum calcium but a 60% reduction of intact serum PTH concentrations. Most patients acquired normal PTH values and hypercalcemia was easily avoided by dose adjustments. There was a significant reduction in serum PTH within the 1st week before the serum calcium concentrations were increased, but after that time the induced suppression of PTH was correlated to the induced rise in serum calcium. These observations are compatible with the view that calcitriol exerts both a direct inhibition of PTH release and increases the gland's sensitivity to calcium. The major implication of the study is that intravenous treatment with alphacalcidol is of great clinical value since it is easy to administer and provides suppression of hypersecretion of PTH with few side effects.

Aluminum↗
PubMed1990

Change in electrophoretic mobility of human follicle-stimulating hormone in serum after administration of gonadotropin-releasing hormone.

The median electrophoretic mobility of FSH in serum (S-FSH) was determined in 14 girls, aged 9-14 yr, with Turner's syndrome before and after iv administration of GnRH. The basal S-FSH level varied almost 100-fold between patients. Less negatively charged forms of FSH appeared in serum in all patients after GnRH stimulation. The aim of the study was to determine if the change in electrophoretic mobility of S-FSH after GnRH treatment was related to the basal S-FSH level, the absolute or relative increase in the S-FSH level after GnRH, or the electrophoretic mobility of S-FSH present in the basal state. A highly significant (r = 0.94; P less than 0.001) correlation was found between the relative increase in S-FSH 60 min after GnRH treatment and the decrease in electrophoretic mobility. A selective survival of different forms of FSH in the circulation is proposed as the most likely explanation for the appearance in serum of the less negatively charged forms of FSH after GnRH stimulation.

Adolescent↗
PubMed1990

Platelet and plasma catecholamines in relation to plasma minerals and parathyroid hormone following acute myocardial infarction.

Epinephrine has been shown to lower the plasma concentrations of several minerals and elevate those of parathyroid hormone (PTH). In order to evaluate the possible clinical importance of such experimental observations, 34 patients with acute myocardial infarction (AMI) were studied with daily determinations of plasma catecholamines, minerals, and PTH during the first week after AMI and at follow-up one month later. In addition, platelet catecholamines were determined as they fluctuate more slowly than plasma catecholamines. After infarction initial platelet epinephrine and norepinephrine levels were higher (p less than 0.05 for both) in nonsurvivors than survivors during a one year follow-up. Results suggested that activation of the sympathoadrenal system influences calcium homeostasis following AMI, but that the impact of sympathoadrenal activation on mineral metabolism is of minor clinical significance in the average AMI patient. High platelet catecholamine levels may predict a poor outcome after AMI.

Adrenal Medulla↗
PubMed1990

Characterization of dimeric forms of human pituitary growth hormone by bioassay, radioreceptor assay, and radioimmunoassay.

Seven highly purified dimeric forms of human pituitary growth hormone, composed of the monomeric forms 20 K hGH, 22 K hGH and 24 K hGH linked together by noncovalent or covalent bonds, have been characterized by an in vitro bioassay (the Nb2 assay), a radioreceptor assay and a radioimmunoassay. Considerable differences in the ability to displace labelled recombinant hGH were observed in the radioreceptor assay. The seven dimeric forms varied over a range between 22 K hGH (most effective) and 20 K hGH. The three covalently-linked dimeric forms had nearly identical affinity constants. The mitogenic action of all but one of the hGH dimers in the Nb2 assay was in the same mutual order as the receptor binding activity in the radioreceptor assay. In the RIA, all dose-response curves were parallel except for those obtained with 20 K hGH and with the dimeric form (20 K-20 K)hGH. In this assay, dimeric variants of the constituents 22 K hGH and 24 K hGH were approximately twice as active as 22 K hGH on a molar basis, suggesting about the same affinity between the antibodies and each of the monomeric forms. Determination of the amino acid compositions of the dimeric forms provided support for their content of monomeric constituents as established earlier by electrophoretic analysis.

Amino Acids↗
PubMed1989

Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: development of neutralizing interferon antibodies and possible loss of antitumor activity.

Twenty patients with malignant carcinoid tumors were treated for 6 months with recombinant interferon alfa-2b (IFN alpha-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a greater than 50% reduction of tumor markers (urinary 5-hydroxyindoleacetic acid or plasma neuropeptide K), showing objective tumor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers and size. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%) had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN alpha-2b. Two of these patients initially showed an objective response, which lasted until IFN antibodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibodies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid autoantibodies. IFN alpha-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these patients.

Aged↗
PubMed1989

Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study.

Patients with essential hypertension, in particular those with low plasma renin activity (PRA), are reported to have lowered plasma-ionized calcium and elevated parathyroid hormone levels. In this study 1 microgram alphacalcidol (1 alpha-hydroxy-vitamin D3) was given in a double-blind, placebo-controlled fashion over four months to 39 subjects with mild to moderate hypertension. There was a significant rise in PRA in the treatment group when compared to placebo (P less than .05), but the mean blood pressure response was similar in the two groups. When the treatment group was divided according to pretreatment PRA it was, however, seen that subjects with low PRA displayed a reduction in diastolic blood pressure, whereas those with high PRA raised their blood pressure compared to placebo. Also subjects with low pretreatment values for plasma-ionized calcium and high levels of parathyroid hormone showed a reduction in diastolic blood pressure. This study supports the idea of a relationship between calcium metabolism and the renin-aldosterone system in essential hypertension and describes a beneficial effect of vitamin D supplementation on blood pressure in low-renin hypertension.

Blood Pressure↗