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Biomedical subjects

E Haug

Publications and source records attributed to E Haug.

At least 19 recordsLinked to original sources

[Familial hypocalciuric hypercalcemia].

Familial hypocalcuric hypercalcemia is a condition that is often incorrectly diagnosed and treated. We studied a family with seven members who had familial hypocalcuric hypercalcemia. In four of the family members it was difficult to make the diagnosis. A correct diagnosis was made in the other three on the basis of known family history. Subtotal parathyroidectomi was carried out on three of the family. After operation, two of these experienced a relapse, and one became permanently hypocalcemic.

Adult

Short-term effects of treatment with simvastatin on testicular function in patients with heterozygous familial hypercholesterolaemia.

The effects of simvastatin 40 mg per day for 14 weeks on the pituitary-testis axis of 19 men with familial hypercholesterolaemia have been examined in a single-blind study. Simvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol and triglycerides by 45% and 30%, respectively, and significantly increased high density lipoprotein (HDL) cholesterol by 15%. The alterations, which were stable 4 weeks after the start of treatment, were not associated with any significant change in sperm quality, the seminal plasma concentrations of various sex gland products (prostate-specific acid phosphatase, polyamines, citrate, fructose, alpha-glucosidase), or the serum concentrations of cortisol, testosterone, LH, FSH, or prolactin. It is concluded that a short-term reduction in circulating LDL-cholesterol has no marked effect on testicular function or sperm quality.

Adult

Primary hyperparathyroidism or hypercalcaemia of malignancy?

The introduction of two-site immunometric assays measuring intact parathyroid hormone (PTH) and radioimmunoassays measuring PTH-related peptide (PTH-RP) have simplified the evaluation of patients with hypercalcaemia. We present a 63-year-old man with recurrent hypercalcaemia after surgical treatment for primary hyperparathyroidism 3 years previously. PTH measured with a mid-region radioimmunoassay gave normal values, at the same level as during his primary hyperparathyroidism. Intact PTH was, however, clearly suppressed, and he had a highly elevated level of PTH-RP. This suggested that he had humoral hypercalcaemia of malignancy. The patient died after 2 months, and at autopsy an adenocarcinoma of the pancreas with no skeletal metastases was found.

Adenocarcinoma

Polycystic ovary syndrome: low-dose follicle stimulating hormone administration is a safe stimulation regimen even in previous hyper-responsive patients.

We studied 23 women with polycystic ovarian syndrome (PCOS), resistant to clomiphene citrate, who had a previous history of multifollicular ovarian development on gonadotrophin stimulation. Each woman had one cycle of gonadotrophin-stimulating hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) stimulation and then one cycle of low-dose follicle stimulating hormone (FSH) stimulation. All GnRHa/HMG cycles were multifollicular. On the low-dose FSH protocol, 10 cycles were unifollicular, while two to three follicles were observed in nine cycles, and four cycles were multifollicular. The ovarian hyperstimulation syndrome ensued in one of the FSH cycles versus 13 of the GnRHa/HMG cycles. Despite decreasing luteinizing hormone (LH) levels and increasing FSH levels, androgen levels increased during stimulation on both protocols. There was one pregnancy in the GnRHa/HMG cycles versus six pregnancies following the FSH cycles. In conclusion, low-dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate even in PCOS women with a previous record of multifollicular ovarian development.

Estradiol

Serum levels of intact parathyroid hormone in elderly patients with hip fracture living at home.

The serum levels of intact parathyroid hormone and cholecalciferol metabolites have been measured in patients with hip fracture above 70 years of age admitted to hospital from home-living conditions and compared with serum levels in age- and sex-matched home-living control subjects. It was found that patients with hip fracture had significantly lower levels of calcidiol (29.7 +/- 15.9 vs 46.0 +/- 27.8 nmol/l) and calcitriol (63.6 +/- 25.0 vs 91.1 +/- 39.5 pmol/l) with no difference in serum levels of intact parathyroid hormone (4.7 +/- 2.1 vs 5.3 +/- 3.3 pmol/l). The data suggest that secondary hyperparathyroidism is not an important risk factor in our population of patients with hip fracture.

Aged

The lipoxygenase inhibitor nafazatrom inhibits stimulated prolactin secretion in cultured rat lactotrophs (GH4C1 cells).

Arachidonic acid metabolites are involved in the regulation of prolactin (PRL) secretion from rat lactotrophs (GH4C1 cells). Phospholipase A2 (PLA2) stimulated PRL secretion, while the PLA2 inhibitor quinacrine reduced both thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulated PRL release. Hormonally stimulated PRL release was further increased in the presence of the cyclo-oxygenase inhibitor indomethacin. Nafazatrom, a lipoxygenase inhibitor, reduced stimulated PRL secretion regardless of the mechanism of stimulation [hormonally (VIP and TRH) or by increasing intracellular Ca2+ concentration by KCl or Bay-K and cAMP by forskolin]. None of the inhibitors used in this study had any effect either on the basal PRL secretion or on the production of cAMP. Lipoxygenase products seem to be involved in the regulation of PRL secretion, probably by affecting a late step in the signal transduction.

Animals

Transgenic mice that develop pituitary tumors. A model for Cushing's disease.

Transgenic mice that developed adrenocorticotropic hormone (ACTH)-producing pituitary tumors were generated with the polyoma early region promotor linked to a cDNA encoding polyoma large T antigen (PyLT). Light microscopic examination of the pituitaries showed normal morphology at 4 months of age, either unremarkable morphology or microadenoma formation at 9 months of age, and up to 5 mm large adenomas in clinically ill transgenic mice at 13-16 months of age. At age 9 months, transgenic mice weighed significantly more than corresponding control mice, but they began wasting at approximately 1 year of age. The adrenal glands of these older PyLT-1 mice showed a weight increase and exhibited a medullary hyperplasia. Subcutaneous transplants of transgenic pituitary tumors to nontransgenic, immunocompetent mice resulted in tumors with a morphology and ACTH immunoreactivity similar to the primary tumor. The effects of hypercorticotropism were more enhanced and occurred with a shorter latency in the mice carrying transgene pituitary transplants than in the PyLT-1 transgenic mice themselves. Moreover, these transplanted mice showed a weight increase with an axial deposition pattern and hypertrophy of the adrenal cortex that resembled the findings in human Cushing's disease. Plasma ACTH levels were significantly increased in clinically ill transgenic mice and even higher levels were found in the transplant mice. Thus, both murine models should be useful for studying Cushing's disease.

Adrenal Glands

Sera from preeclamptic women increase the content of triglycerides and reduce the release of prostacyclin in cultured endothelial cells.

UNLABELLED: The causes of the "endothelial dysfunction" accompanying preeclampsia are unknown. Women with preeclampsia have a marked hyperlipidemia which reflects altered lipid metabolism. We asked if the hyperlipidemic sera of preeclamptic women could cause altered endothelial cell properties. Cultured endothelial cells were incubated with sera from women with preeclampsia (PE) or normal pregnancies as controls. Fifty PE-sera were tested and in 45 cases the endothelial cells acquired a large number of sudanophilic granules which by electron microscopy had lipid appearance. In 31 incubations with 31 individual control sera cellular lipid granules were observed in 4 cases. The cellular triglyceride content was increased to 153 +/- 30 compared to 48 +/- 10 micrograms/mg cell protein in the control cells. Furthermore, the endothelial release of prostacyclin, measured as 6-keto PGF1 alpha, was 8.8 +/- 0.6 ng/mg cell protein in cells incubated with PE-sera as compared to 40.3 +/- 6.4 ng/mg in the control cells. CONCLUSION: The hyperlipidemic sera from preeclamptic women induced triglyceride accumulation in cultured endothelial cells. This was accompanied by altered endothelial function as demonstrated by reduced prostacyclin release.

6-Ketoprostaglandin F1 alpha

[Determination of intact parathyroid hormone in patients with calcium metabolism disorders].

We have used an immunoradiometric assay (IRMA) to measure intact PTH. The serum-levels of PTH followed a log-normal distribution in a population of 85 healthy post-menopausal women, with a geometric mean of 1.9 pmol/l and a range of 0.8-6.1 pmol/l. The correlation between measurements performed using the IRMA and a radioimmunoassay which measured the C-terminal portion of the PTH molecule was 0.85. It was only the IRMA, however, that could measure subnormal values. Two of 27 patients with primary hyperparathyroidism had PTH-values in the upper reference interval. The rest of the patients had elevated levels. Patients with hypercalcemia due to malignancy had subnormal or low normal (less than 2.5 pmol/l) PTH values. Half of the patients with hypoparathyroidism had PTH below the limit of detection. Four subjects with familial hypercalciuric hypercalcemia had normal (3) or slightly elevated PTH-levels.

Adult

Cholecalciferol metabolites attenuate cAMP production in rat thyroid cells (FRTL-5).

A rat thyroid cell line (FRTL-5) was used to study the effect of cholecalciferols on cAMP production. The active cholecalciferol metabolite, calcitriol, caused a reduction in basal and thyrotropin (TSH)-stimulated cAMP production. The inhibitory effects were demonstrated after 1 and 2 days, respectively. The maximum effect on both basal and TSH-stimulated cAMP production was observed after 3-4 days of treatment. The effect was detectable at 10(-10) and maximal at 10(-8) mol/l. Calcitriol was about 300 times more potent than calcidiol in attenuating cAMP production, whereas (24R)-hydroxycalcidiol in concentrations up to 3 x 10(-8) mol/l had no effect. After removal of added calcitriol the cAMP response to TSH returned to normal within 8 days. Calcitriol (10(-8) mol/l) also inhibited cell growth. Our results show that calcitriol at physiological concentrations inhibits both basal and TSH-stimulated cAMP production in rat thyroid cells. This indicates that calcitriol may modulate the effect of TSH on thyroid function and growth.

Adenylyl Cyclases

Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia.

We report a patient with recurrent hypoglycemia most likely caused by a solitary fibrous tumor of the pleura. After removal of the tumor, hypoglycemia resolved. The bland histologic picture of this tumor is emphasized. Electron microscopic and immunohistochemical observations support its non-mesothelial derivation. In vitro studies demonstrated that the tumor tissue produced insulin-like growth factor I (IGF-I), and its role as the cause of hypoglycemia is discussed.

Aged

Cardiac left ventricular function before and during early thyroxine treatment in severe hypothyroidism.

In some patients with severe hypothyroidism, thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even cured. Cardiac function in eight severely hypothyroid patients was studied by means of radionuclide ventriculography (RNV) at rest and during supine bicycle exercise before thyroxine treatment, and repeated during treatment before and after administration of 160 mg of oral verapamil. There was an exercise-induced fall in left ventricular ejection fraction (LVEF) in two patients before therapy, and in two additional subjects after 17 d on suboptimal doses of thyroxine. Verapamil attenuated the fall and induced a significant increase in LVEF during exercise (P less than 0.014). No abnormal regional cardiac wall movement (RWM) was observed. After 2 months of thyroxine treatment, LVEF increased significantly during exercise both before and after verapamil (P less than 0.012 and P less than 0.005). These findings are indicative of reversible coronary artery dysfunction. We recommend that, if feasible, thyroxine should be supplemented with verapamil during the early phase of treatment.

Adult

Prolactin response to secretin during the spontaneous menstrual cycle in women.

The effect of an intravenous infusion of secretin (2.0 CU/kg/h) on serum prolactin (PRL) and estradiol levels and plasma levels of vasoactive intestinal polypeptide and somatostatin (SRIH) was studied in 8 healthy and normally cycling women during the midfollicular phase (cycle day 7), at midcycle (day 14), and during the midluteal phase (day 21) of the menstrual cycle. When compared to basal preinfusion levels, a significant decrease in serum PRL levels was observed at steady state concentrations of plasma secretion (+30 to +60 min) both during the follicular (p less than 0.03) and the luteal (p less than 0.0001) phases. At midcycle a nonsignificant decrease was observed. A significant and negative correlation existed between serum PRL and plasma secretin levels in the follicular phase (r = -0.33; p less than 0.05) and in the luteal phase (r = 0.73; p less than 0.0001). The plasma concentrations of SRIH increased significantly at steady state conditions of secretin at midcycle (p less than 0.02) and in the luteal phase (p less than 0.04), while no effect was found during the follicular phase. A significant and positive correlation between plasma levels of SRIH and secretin was observed at midcycle (r = 0.63; p less than 0.002) and in the luteal phase (r = 0.46; p less than 0.02). No effect of secretin on plasma vasoactive intestinal polypeptide and serum estradiol concentrations was demonstrated. These results suggest that the suppression of PRL in the follicular phase of the spontaneous menstrual cycle can be ascribed to an effect of secretin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

In vivo and in vitro inhibition by ketoconazole of ACTH secretion from a human thymic carcinoid tumour.

We treated a patient with an ectopic ACTH-producing thymic carcinoid tumour with ketoconazole. The treatment decreased blood levels of ACTH and cortisol and relieved the patient's symptoms. Tumour explants secreted ACTH to the culture medium for at least 11 days. The tumour cells responded to high extracellular K+ concentration with increased ACTH secretion, whereas the hypothalamic ACTH-releasing hormone (CRH) and cortisol had no effect on ACTH secretion. Addition of ketoconazole to the culture medium decreased ACTH secretion showing that ketoconazole had a direct effect on the tumour cells.

Adrenocorticotropic Hormone

Calcitriol receptors in rat thyroid follicular cells (FRTL-5).

The FRTL-5 cell line is widely used as a model for normal thyroid follicular cells. These cells have retained their ability to alter cAMP production, cell proliferation, iodine uptake, and thyroglobulin synthesis in response to thyrotropin. We have previously shown that calcitriol attenuated both basal and TSH stimulated cAMP production dose-dependently in FRTL-5 cells. Cytosol fractions (105,000 g, 60 min, 4 degrees C) prepared from FRTL-5 cell homogenates possessed calcitriol-binding components with a sedimentation coefficient of approximately 3.7 S in high salt (0.3 mol/l KCl) sucrose gradients (5-20%). At 4 degrees C, specific binding increased rapidly during the first 4 h and reached a plateau after 8 h. The specific binding (18 h, 4 degrees C) was maximal at a [3H]calcitriol concentration of approximately 0.5 nmol/l. Scatchard analysis of the binding data indicated one single class of high affinity binding sites with Kd = 105 +/- 2 pmol/l and Bmax = 38.5 +/- 4.7 pmol/g cytosol protein (mean +/- SD, N = 6). In conclusion, our results suggest that the FRTL-5 cells possess functional receptors for calcitriol with the same physicochemical properties as the receptors found in normal rat tissues.

Animals

[Gonad function in men with alcoholic liver disease].

The connection between alcoholic liver disease and hypogonadism has long been recognized. In this study of 112 males admitted to a medical department, altogether 87 had alcoholic liver disease. Serum testosterone was depressed (less than 12 nmol/l) in 47 out of 51 (92%) patients with alcoholic liver cirrhosis and in 13 out of 36 (36%) with alcoholic fatty liver (p less than 0.001). Primary hypogonadism was found in 8% of the patients with alcoholic fatty liver and in 16% of the patients with alcoholic cirrhosis and secondary hypogonadism in 28% of the patients with fatty liver and in 76% of those with alcoholic cirrhosis. Serum sex hormone binding globulin (SHBG) was increased (greater than 40 nmol/l) in 65% of the patients with fatty liver and in 67% of the patients with alcoholic cirrhosis. Serum testosterone was significantly correlated to liver function tests Normotest (NT), bilirubin and albumin. In conclusion, hypogonadism is very common in men with alcoholic liver disease.

Adult

The mechanisms by which vasoactive intestinal peptide (VIP) and thyrotropin releasing hormone (TRH) stimulate prolactin release from pituitary cells.

The effect of vasoactive intestinal peptide (VIP) on prolactin (PRL) secretion from pituitary cells is reviewed and compared to the effect of thyrotropin releasing hormone (TRH). These two peptides induced different secretion profiles from parafused lactotrophs in culture. TRH was found to increase PRL secretion within 4 s and induced a biphasic secretion pattern, while VIP induced a monophasic secretion pattern after a lag time of 45-60 s. The secretion profiles are compared to changes in adenylate cyclase activity, production of inositol polyphosphates, changes in intracellular calcium concentrations and changes in electrophysiological properties of the cell membrane.

Adenylyl Cyclases