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Biomedical subjects

J Mockel

Publications and source records attributed to J Mockel.

At least 55 records · Page 3Linked to original sources

Effect of chronic oral testosterone undecanoate administration on the pituitary-testicular axes of hemodialyzed male patients.

Testosterone undecanoate (TU) or placebo was administered orally (for 12 weeks) in a double blind study, to 19 patients with chronic renal insufficiency on hemodialysis in a daily dose of 240 mg. Effect on plasma testosterone (T), dihydrotestosterone (DHT), androstenedione (A), 110H androstenedione (110A), FSH, LH and PRL concentration and the pituitary responsiveness to LH-RH/TRH stimulation was studied. These hormone levels were determined before the study and after 6 and 12 weeks of treatment. There was a rise in plasma androgen concentration in all treated patients. Mean plasma DHT, A and 110A increased at 12 weeks from 0.3, 0.85 and 1.13 ng/ml to 1.13 (p less than 0.05), 1.4 (p less than 0.05) and 1.44 (p less than 0.05) respectively. There was no change in plasma T or free testosterone. However, basal LH, FSH fell progressively from 5.51 and 5.51 ng/ml to 2.13 and 1.84 ng/ml (p less than 0.05). The level of significance of these changes was confirmed when the response to LH-RH was considered. Basal plasma PRL also decreased from 376 microU/nl to 306 (p less than 0.05), but PRL response to TRH remained unchanged. In contrast, none of these modifications were observed in placebo-treated patients. We conclude that oral TU restored to normal the pituitary-testicular axis. This form of treatment should be preferentially chosen instead of intramuscular injections in these frequently heparinized patients on hemodialysis.

Administration, Oral↗

Diabetes insipidus from metastatic oat cell carcinoma: recovery after brain irradiation.

A hypothalamic metastasis was demonstrated by computed tomography in a 71-year-old patient, with previously unknown small cell lung cancer, who presented with diabetes insipidus and biological signs of hypothyroidism and hypogonadism. Brain irradiation resulted in resolution of polyuria, elevation of thyroid hormones, improvement of pituitary responsiveness to hypothalamic releasing hormones, and complete disappearance of contrast-enhanced suprasellar metastasis.

Aged↗

Mechanism of cholinergic inhibition of dog thyroid secretion in vitro.

It has been previously shown that carbamylcholine (10(-5) M) decreases TSH-induced cAMP accumulation and hormone secretion in dog thyroid slices. The mechanism of the latter effect has been investigated in this work. The role of a decrease of cAMP level as the sole mediator of the inhibition of secretion was excluded: the inhibition persisted in the presence of 1-methyl-3-isobutylxanthine at 10(-4) M, which completely abolished the carbamylcholine-induced decrease in cAMP. Moreover, carbamylcholine also inhibited secretion when the slices were incubated with 0.4 mM (Bu)2cAMP. Scanning electron microscopic studies showed that carbamylcholine added at the same time as TSH blocked the formation of pseudopods in response to TSH within 2 min. The kinetic and morphological effects of carbamylcholine added at the same time as, or 90 min after, TSH were similar to those of cytochalasin B (3 micrograms/ml). After carbamylcholine addition at time 90 min, the stimulated secretion rate persisted unchanged for 46 +/- 10 min (mean +/- SD) (n = 6). During this period the colloid droplets disappeared from the cells. Carbamylcholine, like cytochalasin B, did not affect the basal secretion, which is independent of phagocytosis. It is concluded that carbamylcholine (10(-5) M) inhibits stimulated thyroid secretion at a step beyond cAMP accumulation by blocking pseudopod formation and not by inhibiting thyroglobulin hydrolysis or hormone diffusion.

1-Methyl-3-isobutylxanthine↗

Demonstration of prolactin at the ultrastructural level in a pituitary adenoma by the use of colloidal gold labelling.

A prolactin-secreting pituitary adenoma was removed in a 38-year-old man. The tumor was classified as a chromophobe adenoma on the basis of tinctorial staining, but immunocytochemistry revealed that cells reacted with anti-PRL serum. Electron microscopy showed secretory granules and evidence of high metabolic activity (well developed Golgi apparatus and rough endoplasmic reticulum). Immunoelectron microscopy by the immunogold staining method allowed a clear definition of prolactin containing granules.

Adenoma↗

Stimulation by forskolin of the thyroid adenylate cyclase, cyclic AMP accumulation and iodine metabolism.

Forskolin, a diterpene hypotensive drug, activates adenylate cyclase in brain and in some other tissues (Seamon et al., 1981). Forskolin activated adenylate cyclase in particulate preparations and enhanced cyclic AMP accumulation in slices of dog thyroid. These effects were maximal within minutes and remained constant afterwards. The action of forskolin on intact cells disappeared rapidly after washing. It reproduced two known cyclic AMP-mediated TSH effects: the activation of secretion and of protein iodination. Forskolin thus provides a very convenient tool for the study of the action of defined elevations of cyclic AMP level in thyroid cells. The activation by forskolin of adenylate cyclase was not reduced by Mn2+ which uncouples TSH and PGE1 action. This suggests that in the thyroid also, forskolin acts beyond the receptor level. The effect of forskolin on cyclic AMP accumulation was inhibited by the known negative regulators of this system in the thyroid, acetylcholine, iodide, norepinephrine, PGF1 alpha and adenosine. On the other hand, forskolin potentiated the effects of TSH, PGE1 and cholera toxin. These data show that, though it does not require the receptors for its action, forskolin does not uncouple them from the catalytic unit of adenylate cyclase.

Adenylyl Cyclases↗

[Ischemic pituitary apoplexy and cerebrovascular accident].

Operative findings of degenerative changes in pituitary adenomas are not uncommon; however, clinical apoplexy is rare. We report the case of a 43-year-old man who presents a sudden right hemiplegia with aphasia and right ophthalmoplegia, in relation with an ischemic pituitary apoplexy and cerebral vasospasm. A few cases of arterial obstruction or vasospasm associated with pituitary apoplexy have been reported in the literature. Cerebral arterial spasm has also been observed after pituitary surgery. Inclusion of blood or necrotic material in the subarachnoid space seems not to be the only mechanism of vasospasm. The role of hypothalamic dysfunction is considered.

Adult↗

High uric acid and urea clearance in cirrhosis secondary to increased "effective vascular volume".

Since urea and uric acid clearance are affected by the effective intravascular volume, we measured the fractional urea and uric acid excretion in cirrhosis. High urea and uric acid clearances were observed in 30 and 55 percent, respectively, of 20 consecutive cirrhotic patients with normal renal function. In seven patients with a high fractional uric acid excretion, 5 mg of isosorbide dinitrate every four hours for 24 hours induced a significant increase in the serum uric acid level (from 3.7 +/- 0.8 mg/dl to 4.4 +/- 0.8 mg/dl; less than 0.001) with a concomitant decrease in the fractional uric acid excretion (from 14.0 +/- 3.2 percent to 8.8 +/- 3.1 percent; less than 0.02). During the same test, the blood urea level increased from 3.3 +/- 1.1 mmol/liter to 4.1 +/- 1.2 mmol/liter (p less than 0.005) with a decrease in fractional excretion from 51 +/- 4.5 percent to 39 +/- 5 percent (p less than 0.001). The oral intake of sulfinpyrazone in six of these patients induced a normal uricosuric response. In two cirrhotic patients with ascites, 40 mg of furosemide associated with a 24-hour severe water restriction was also shown to normalize the high fractional excretion of both urea and uric acid. In nine patients with ascites, we observed a significant increase in blood urea and uric acid concentration despite the absence of change in creatinine clearance once ascites was removed by diuretics. On the basis of these findings, we believe that the high fractional excretion of both urea and uric acid frequently observed in cirrhosis is related to an increase in the effective vascular volume.

Blood Volume↗

Hypercalciuria in the syndrome of inappropriate secretion of antidiuretic hormone.

Mild hypocalcemia was observed in 6 out of 12 patients with SIADH associated hyponatremia, this was in fact related to low albumin levels resulting partly from body fluid dilution. In the 7 SIADH patients where it was measured, we observed an increased fractional calcium excretion (3.2 +/- 1.7%) as long as the patients were hyponatremic. This was corrected by water restriction (0.73 +/- 0.4%, p less than 0.01). We suggest that volume expansion was responsible for the increased calcium clearance, and not hyponatremia by itself, since in volume depletion hyponatremia, calcium clearance was within the normal range. Mild hypocalcemia and hypercalciuria is a common finding in SIADH-associated hyponatremia.

Calcium↗

[Fine-needle aspiration (F.N.A.) of thyroid cold nodules (author's transl)].

In a retrospective study of 100 patients operated on between 1974 and 1979 in our institution for thyroid cold nodules, an 8% incidence of thyroid cancer was found at surgery. Since 1979, F.N.A. was performed in 160 patients with thyroid cold nodules. Adequate cytological material was aspirated in 90% (144) of the cases; of those, a benign cytological lesion was diagnosed in 128 (89%) and suspicion of cancer in 16 (11%). To date fifty-one patients were operated: 41 with benign cytology and 10 with cancer suspicion; benignity was confirmed in 39/41 cases with benign cytology and malignity in 5/10 with suspect cytology. In conclusion, clinical diagnosis of thyroid cold nodules is greatly improved by the use of F.N.A. Despite the limitations of the technique, preoperative suspicion of cancer was increased 7-fold. Caution is recommended in the follow-up cases with benign cytology since, in these preliminary results, 2 false-negatives were found.

Biopsy, Needle↗

Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea.

Recent data have shown the role of urea in the urinary concentrating mechanism. We studied the effects of exogenous urea administration in hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In 20 patients with SIADH, we observed a positive correlation between serum sodium and blood urea levels (r = 0.65; p less than 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p less than 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p less than 0.001). The short-term administration of low doses of urea (4 to 10 g) resulted in correcting the "salt-losing" tendency of this patient. Longer term administration of high doses of urea (30 g/day) was attempted with the same patient as well as with a healthy volunteer subject with Pitressin-induced SIADH. in both patients, urea treatment lowered urinary sodium excretion as long as hyponatremia was significant (less than 130 meq/liter). Urea treatment also induced a persistent osmotic diuresis, allowing a normal daily intake of water despite SIADH. This was clearly shown during the long-term treatment of a third patient with SIADH who was taking 30 g urea/day during 11 weeks. It is concluded that urea is a good alternative in the treatment of patients with SIADH who presented with persistent hyponatremia despite the restriction of water intake.

Adult↗

The disposition of calcium within parathyroid tissue.

The disposition of 45Ca was studied in equine parathyroid gland slices. This preparation was shown to be viable by its ability to carry out protein synthesis, by the responsiveness of its respiration to effectors of oxidative phosphorylation, and by its calcium-inhibitable PTH secretion. 45Ca accumulates in the slices as the extracellular calcium is raised through the range in which physiological serum calcium concentration lies. The tissue slices behave as if they have no calcium pump: (a) depriving the cells of energy by treatment with antimycin A does not admit more calcium to the tissue, (b) a significant amount of calcium is not displaced by lanthanum, and (c) a divalent cation ionophore does not expose new calcium binding sites. An energy-dependent sequestration of calclum by the tissue seems unlikely: (a) calcium is very rapidly taken up, (b) more is taken up at 0 degrees C than at 37 degrees C, and (c) antimycin A does not affect the amount of calcium retained. We conclude that the parathyroid gland passively accumulates calcium, and that it is held intacellularly by a substance with a dissociation constant in the millimolar range.

Animals↗

The role of calcium and guanosine 3':5'-monophosphate in the action of acetylcholine on thyroid metabolism.

The role of calcium and guanosine 3':5'-monophosphate (cyclic GMP) in the regulation of thyroid metabolism has been investigated in dog thyroid slices. Carbamoylcholine enhanced glucose carbon-1 oxidation, protein iodination, cyclic GMP accumulation and decreased thyrotropin-induced adenosine 3':5'-monophosphate (cyclic AMP) accumulation and iodine secretion; it did not affect protein synthesis. The effects of carbamoylcholine were reproduced under various experimental conditions by supplementary calcium in the medium, ouabain, and in media in which Na+ had been replaced by choline chloride. They were inhibited by lanthanum. These results further support the hypothesis that free intracellular Ca2+ is the intracellular signal for carbamoylcholine effects and suggest that a Na+ -gradient-driven Ca2+ extrusion mechanism operates in the thyroid cell. Mn2+ reproduced the effect of Ca2+ on glucose oxidation, protein iodination and cyclic GMP accumulation in Ca2+ -depleted slices and medium, and thus mimicked some intracellular effects of Ca2+. On the other hand Mn2+ inhibited the carbamoylcholine effect on thyrotropin-induced thyroid secretion and cyclic AMP accumulation, and Ca2+ inhibited the Mn2+-induced cyclic GMP accumulation. This suggests that the two ions compete for the same channel. Similarly Mn2+ inhibited calcium effects in the presence of ionophore A23187. Procaine inhibited protein iodination under all conditions suggesting a primary effect; it also inhibited all carbamoylcholine and ouabain actions. However the drug did not inhibit the effects of choline chloride and its action was reversed by raising carbamoylcholine but not Ca2+ concentration; it is therefore doubtful that procaine acts by blocking Ca2+ channels. In media without added Ca2+, Mn2+ increased cyclic GMP accumulation but did not decrease thyrotropin-induced cyclic AMP accumulation or iodine secretion, which suggests that cyclic GMP cannot be the sole mediator of the latter two effects of carbamoylcholine.

Acetylcholine↗

Chronic alcoholism: a predisposing factor for hypocalcemia in acute pancreatitis.

The serum levels of calcium, corrected for serum albumin, were investigated in 65 consecutive patients with acute pancreatitis. Hypocalcemia was present in 55% of 38 patients in whom chronic alcoholism was the associated etiology, and in 26% of 27 other patients (p less than 0.02). In the alcoholic patients, the mean duration of hypocalcemia was significantly longer than in the non-alcoholic patients (5 vs. 1--2 days; p less than 0.001). The severity of pancreatitis seemed to be comparable in both groups of patients. This suggests that chronic alcoholism may be a predisposing factor for hypocalcemia in acute pancreatitis.

Acute Disease↗