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Biomedical subjects

L Wide

Publications and source records attributed to L Wide.

At least 199 records · Page 11Linked to original sources

Chronic pulsatile low dose GnRH therapy for induction of testosterone production and spermatogenesis in a man with secondary hypogonadotropic hypogonadism.

Prolonged intermittent treatment with low doses of GnRH was given to a 23-yr-old man with secondary hypogonadotropic hypogonadism. The patient had experienced sudden onset of diabetes insipidus followed by progressive decrease of gonadotropins and gonadal function. Modern radiological techniques did not reveal any organic genesis. A small portable computerized infusion pump connected to a sc catheter was used for the 220-day GnRH therapy. One microgram gnRH was administered every 90 min during the first 90 days and 5 micrograms GnRH every 90 min during the following 130 days. During the prolonged GnRH treatment testosterone secretion normalized, libido and potency improved, and ejaculation returned. Spermatogenesis became close to normal and the subject's wife became pregnant after 181 days of treatment. The prolonged treatment with the small infusion pump was well accepted and did not interfere with the patient's daily life activations. Thus, chronic pulsatile low dose GnRH treatment can restore normal pituitary-gonadal function in idiopathic male hypogonadotropic hypogonadism.

Adult↗

Treatment with cimetidine in patients with primary hyperparathyroidism.

Treatment with cimetidine (1000 mg daily in four divided doses) was given for 3--30 weeks to 10 patients with primary hyperparathyroidism (HPT). All patients had hypercalcaemia and raised serum concentrations of parathyroid hormone (PTH). During treatment no consistent effects were noted on neither serum calcium or PTH and normalization did not occur in any case. Hypergastrinaemia was demonstrated in 6 patients and was also unaffected by therapy while in the 4 patients with normal pre-treatment gastrin values a slight increase was seen. This study does not support the view that cimetidine can be of use for the treatment of primary HPT.

Adult↗

Regulation of parathyroid hormone release in primary and secondary hyperparathyroidism - studies in vivo and in vitro.

The effects of calcium on parathyroid hormone (PTH) release were studied in vivo and in vitro in primary hyperparathyroidism (HPT) and in vitro in secondary HPT. In vivo the serum PTH was clearly reduced by intravenous calcium infusion in all the examined patients with primary HPT caused by adenoma. In vitro the release of PTH from dispersed parathyroid cells was likewise suppressed by raising the calcium concentrations in the incubation media, though in all cases a basal release of PTH still persisted even at high calcium concentrations. The degree of suppressibility in vitro varied, but in both primary HPT with adenoma and in secondary HPT it was inversely related to the patients' serum calcium values. These results suggest that the secretion of PTH in patients with primary and secondary HPT is not autonomous either in vivo or in vitro. Furthermore, the non-suppressible basal release of PTH indicates that a major cause for the increased secretion of PTH is the increased number of parenchymal cells. However, the degree of suppressibility of the individual cells rather than the absolute number of cells, seems to be of great importance for the individual serum calcium values in HPT.

Adenoma↗

Gonadotrophic activity of the guinea-pig placenta during pregnancy.

A gonadotrophic substance was extracted from placentae and subplacentae of guinea-pigs. Biological and immunological assays of these tissues obtained on Days 10-63 of pregnancy showed the highest mean concentration of the gonadotrophin on Day 18. Extracts chromatographed on Sephadex G200 had components active in the radioimmunoassay system for hCG, hCG-alpha and hCG-beta subunits. The elution profiles of these extracts were similar to those obtained with human term placentae and purified hCG and its subunits. The guinea-pig placental extracts also cross-reacted with an antiserum to the beta subunit of ovine LH, as did hCG. The biological activity of placental and subplacental extracts and of the hCG standard as neutralized by an anti-hCG serum. There is a strong similarity between hCG and the substance extracted from guinea-pig placentae which may therefore have a luteotrophic function similar to that of hCG.

Animals↗

Evaluation of parathyroid function in patients with hypergastrinaemia and pernicious anaemia.

In order to evaluate the possible causal relationship between raised serum gastrin levels and the development of primary hyperparathyroidism (HPT) which is suggested from experimental studies we evaluated parathyroid function in a group of 32 patients with hypergastrinaemia and pernicious anaemia. The values for serum calcium and parathyroid hormone were determined as well as the fasting urinary excretions of cyclic AMP and calcium. There was no relationship between the serum gastrin levels and any of the other studied parameters and there was no consistent pattern suggesting parathyroid hyperfunction. A retrospective analysis of hospital records from 441 patients operated for primary HPT showed a prevalence of pernicious anaemia of 1.8%. This figure is higher than that found in the unselected age-matched population (0.31%). However, taken together this study does not support the hypothesis that hypergastrinaemia is of particular importance for the pathogenesis of primary HPT.

Adult↗

Rapid regression of pituitary tumours during bromocriptine treatment of women with hyperprolactinaemia.

Four hyperprolactinaemic women with large pituitary adenomas with suprasellar extension were given primary tumour therapy with bromocriptine. The treatment resulted in rapid tumour regression in all the women, as verified by repeated computerized tomography (CT) scans. Pronounced visual field defects were present in three of the four women before treatment. All of them had marked improvement of vision within a few days after the initiation of bromocriptine therapy and they regained normal or nearly normal visual fields during the treatment. The raised serum prolactin concentrations decreased to normal levels in all the women. Thus, medical treatment with bromocriptine can induce rapid tumour regression in patients with hyperprolactinaemia and large pituitary tumours.

Adenoma↗

Long-term intranasal luteinizing hormone-releasing hormone agonist treatment for contraception in women.

Fifty-one female volunteers used a superactive stimulatory luteinizing hormone-releasing hormone (LH-RH) analog for suppression of ovulation for 3 to 12 months. The potent LH-RH agonist D-Ser(TBU)6-EA10-LH-RH was administered intranasally once daily in a dose of 400 or 600 micrograms. No pregnancies occurred during the 283 treatment months. Severe bleeding disturbances were not observed during the long-term treatment. No signs of hyperplastic changes were found in endometrial biopsies. There were no serious side effects. Ovulation promptly returned after cessation of treatment even in women with amenorrhea during treatment periods of 1 year or more. Thus, long-term LH-RH agonist treatment proved to be a safe, effective, and rapidly reversible new method for peptide contraception.

Administration, Intranasal↗

Endometrial patterns in women on chronic luteinizing hormone-releasing hormone agonist treatment for contraception.

Endometrial biopsy specimens were obtained from 12 healthy women under chronic intranasal luteinizing hormone-releasing hormone (LH-RH) agonist treatment for evaluation of the risk of endometrial hyperplasia during long-term inhibition of ovulation. A single daily dose of 400 or 600 microgram of the superactive LH-RH agonist D-Ser(TBU)6-EA10-LH-RH was given for 13 to 55 weeks. Treatment was monitored by clinical examination, basal body temperature (BBT) recordings, and frequently taken venous blood specimens for determination of estradiol and progesterone. Ovulation was inhibited during all but 2 of the 102 treatment cycles. No pregnancy occurred. Six of the women had slight menstrual-like bleeding, and six hac amenorrhea during the treatment period. No dysfunctional uterine bleeding occurred. The dominating histologic picture of the 17 endometrial biopsies, obtained after 78 to 380 days of treatment, was inactive or weak proliferative glands with slightly atrophic stroma. There were no signs of hyperplasia. After discontinuation of treatment ovulatory menstrual cycle rapidly returned.

Administration, Intranasal↗

Serum ferritin in alcoholics and the relation to liver damage, iron state and erythropoietic activity.

Serum ferritin was measured in two groups of alcoholics; one comprised 71 individuals on ambulatory control and with varying current alcohol intake and the other 19 alcoholics followed with serial determinations during two weeks of abstinence Serum ferritin was elevated in 26 subjects in the larger group, and 22 of them had elevated ASAT and ALAT values. Low-grade but significant correlations were found between serum levels of ferritin and serum concentrations of some variables used to detect liver affection (ASAT, ALAT, bilirubin and gamma-GT). Serum ferritin and ASAT declined in a parallel fashion in the 19 patients studied longitudinally, so that the ferritin:ASAT ratio described a straight line. No correlation was found between serum ferritin or the serum ferritin:ASAT ratio and serum iron. Neither was any correlation observed between the magnitude of the changes in serum ferritin and the changes in serum iron, serum transferrin or circulating platelets or reticulocytes observed in the serially followed alcoholics. These data indicate that elevated serum ferritin in alcoholics is associated with the degree of liver affection and not with the degree of erythropoietic activity.

Adult↗

Studies of thyroid hormone and methimazole levels in patients with Graves' disease on a standardized anti-thyroid drug regimen.

The outcome of a standardized carbimazole (CMI) regimen was evaluated in fifty-four patients with Graves' disease. Triiodothyronine (T3) and thyroxine (T4) serum values were determined before and throughout the first 6-8 months of therapy. Before therapy, decreasing T4/T3 ratios were found with increasing T3 levels, reflecting a relative increase in T3 production compared with T4 in thyrotoxicosis. High pretreatment T3 values were comparatively common among patients in whom a fixed CMI dosage had a insufficient effect. T4 levels were less informative in this respect. Serum levels of methimazole (MMI), the active metabolite of CMI, were dose-dependent. A 50% reduction in dosage resulted in a similar decrease in the serum values. For a give dose, the MMI levels differed considerably among individuals. The variation was not related to thyroid hormone values. It appears that the response to the anti-thyroid drug is primarily dependent upon the severity of the disease, Which is clearly reflected in serum T3 levels, rather than individual differences in drug handling. A routine CMI regimen for the treatment of thyrotoxicosis is suggested.

Adolescent↗

Detergent enzymes and occupational safety. Observations on sensitization during Esperase production.

During a 10-year survey of 667 workers producing the detergent enzyme Esperase, derived from an alkolophilic strain of Bacillus licheniformis, 31 were found to have been sensitized. All but one were at the same time sensitized to subtilisins, with which they also had been working. No distinction could be made between symptoms attributed to Esperase and symptoms attributed to enzymes derived from Bacillus subtilis (licheniformis) or other enzymes. Symptoms, when present, were mainly from the lower respiratory tract. Nine sensitized workers were symptom-free. Sensitization was by IgE antibodies and detected by the RAST test. Twenty-one sensitized workers were transferred for precautionary measures or left the company. All 26 sensitized workers, whom it was possible to follow and reinvestigate, were no longer RAST-positive. Ten workers remained in their jobs. No signs of deteriorating lung function or permanent lung damage were found. The study indicated that, when strictly enforced, recommended operating procedures for workers handling hitherto well-known detergent enzymes are sufficient for dealing with Esperase. The data suggest there is no significant risk of consumer sensitization.

Asthma↗

The similarity of chorionic gonadotrophin and its subunits in term placentae from man, apes, old and New World monkeys and a prosimian.

Chorionic gonadotrophin (CG) was estimated, by bioassay and radioimmunoassay (RIA), in placental extracts from 11 ape and monkey species. There was a significant correlation between the results of the two assay systems (r = 0.903, p less than 0.001). The concentration of CG in most primate term placentae was the same as that in the human placenta at term. Extracts from all placentae cross-reacted with antiserum to ovine LH-beta subunit, and those of the chimpanzee and gorilla also had a significant cross-reaction with an antiserum to the carboxyl terminal peptide of the HCG-beta subunit. Primate placentae chromatographed on Sephadex G-200 had components active in the RIA systems for HCG, HCG-alpha HCG-beta subunits. In general, the elution profiles of all ape and monkey placental extracts resemble those made from human term placentae and of purified HCG and its subunits. The shape of the elution patterns from human and non-human material suggests that there was more than one molecular form of CG-alpha subunit activity. A second, more retarded molecular form having beta subunit activity was found in extracts made from human, gorilla, gibbon and rhesus monkey placentae. The similarity between the structure of ape and monkey placental CG with HCG and its subunits implies a function similar to that of HCG in late pregnancy.

Animals↗

HCG, progesterone and 17-beta-estradiol levels during extra-amniotically induced early abortion by a new prostaglandin derivative (Sulprostone).

A new prostaglandin E2 derivative (Sulprostone) was given extra-amniotically to 17 healthy women, who were 7-8 weeks pregnant, in order to assess the plasma profile of HCG, 17 beta-estradiol (E2), and progesterone and to evaluate the effectiveness and overall acceptability of the method in relation to different dose levels. On the lowest dose level (5 micrograms) only 3 of 7 patients aborted within a 3-to 6-day period. At higher dose levels (10 and 15 micrograms, respectively) 9 out of 10 women exhibited clinical evidence of an abortion. In the group who aborted, E2, progesterone, and HCG decreased continuously, whereas in the nonabortion group decreased levels were found 3 and 6 h after administration of the drug, but already after 24 h the values had again increased. Practically all treated women experienced lower abdominal discomfort, 7 (41%) reported the pains being severe. Vomiting and/or diarrhea occurred in 4 patients (24%). Similarly to other hitherto tested prostaglandins in humans, this new analogue exhibits its effect primarily through direct stimulatory effect on the uterine smooth muscle, resulting in subsequent decline in the concentrations of HCG, E2, and progesterone. In the group of successful inductions the decrease of the HCG concentration was close the half-time of HCG, indicating a permanent damage to the placenta. Despite the high success rate at a dose of 10 micrograms or more, the side effects, mainly abdominal cramps. were too severe to make this method feasible for the induction of early abortion when comparing to the available routine procedure of rapid vacuum curettage used on an outpatients basis.

Abortifacient Agents↗

Hypersecretion of an abnormal form of follicle-stimulating hormone associated with suppressed luteinizing hormone secretion in a woman with a pituitary adenoma.

Pituitary tumors producing FSH have hitherto been reported only in males, all of whom have had normal or raised LH levels in serum. This report describes a female with a pituitary adenoma associated with supranormal serum levels of FSH. The FSH was also qualitatively abnormal when compared with FSH in the serum of other postmenopausal women, had a lower apparent molecular weight on gel chromatography, and was less negatively charged, as shown by electrophoresis. The results of LRH tests and suppression tests with ethinyl estradiol indicated autonomy of the FSH-producing adenoma. The FSH level increased concomitant with tumor enlargement and decreased after surgical removal of the pituitary adenoma or pituitary irradiation. The serum level of the glycoprotein alpha-subunit was raised about 100-fold. Any free FSH beta-subunits were not detectable in serum. The abnormal FSH had antigenic sites in common with both the alpha- and beta-subunits of FSH. The LH level was extremely low, and there was no response to LRH tests or ethinyl estradiol treatment. After gel chromatography, a small amount of LH, corresponding to 1/50th of the average for the patient's age, was detected at the position for normal LH. There was no GH response to insulin-induced hypoglycemia, while the cortisol increase was normal. Thyroid and adrenal functions were normal. The PRL level was within the normal range and increased slightly after estrogen treatment.

Adenoma↗

hCG and hCG subunits as tumour markers in patients with endocrine pancreatic tumours and carcinoids.

Serum levels of hCG, hCG-alpha- and hCG-beta-subunits were measured in 29 patients with APUD-tumours, 16 patients with endocrine pancreatic tumours (EPT) and 13 patients with carcinoids. Twenty out of 29 patients (69%) had elevated level of hCG and its subunits. Among patients with EPT, 11 out of 16 (69%) had raised levels of these peptides. Three patients with benign tumours had normal concentrations, thus giving a frequency of 85% in the group of malignant EPT. In patients with carcinoids 9 out of 13 (69%) had elevated serum levels of at least one of the components. A discordance in secretion pattern between the two types of APUD-tumours was noticed. Only one patient, a case with a carcinoid had raised levels of the complete hCG molecule. The levels of hCG-alpha were elevated in 23% of the patients with malignant EPT and 69% of the patients with carcinoids while the corresponding frequencies of raised hCG-beta levels were 69% and 8%, respectively. Three out of 4 patients with so-called non-functioning islet cell tumours had raised levels of the subunits. These results indicate that hCG subunits are valuable tumour markers in both of these APUD-tumours, and that malignant EPT predominantly secrete hCG-beta- and carcinoids hCG-alpha-subunits.

APUD Cells↗