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Biomedical subjects

D Le Roith

Publications and source records attributed to D Le Roith.

At least 55 records · Page 3Linked to original sources

Evolutionary origins of vertebrate hormones: substances similar to mammalian insulins are native to unicellular eukaryotes.

Tetrahymena pyriformis, Neurospora crassa, and Aspergillus fumigatus that had been grown in simple defined media were extracted with acid ethanol by a classic method for recovering insulin from pancreas. After filtration of the extracts on Sephadex G-50, distinct peaks of insulin immunoreactivity were recovered in the region typical of insulin. The gel-filtered material from the Tetrahymena had reactivity in the pork insulin radioimmunoassay about equal to its reactivity in the insulin bioassay (stimulation of lipogenesis in isolated rat adipocytes), and the gel-filtered material from neurospora had an immunoreactivity-to-bioactivity ratio of about 1:3. The material that stimulated lipogenesis could be neturalized by anti-insulin sera (i.e., 75-95% of the Tetrahymena material and 60% of the Neurospora material). Bioactive and immunoactive insulin was found in the conditioned medium equal in amount to that in the cells. The findings suggest that insulin did not arise evolutionarily in the intestinal or neural tissues of primitive vertebrates or complex invertebrates but rather has its molecular origins at least as far back as the simplest unicellular eukaryotes.

Aspergillus↗

Elevations in plasma ADH levels during PEEP ventilation in the dog: mechanisms involved.

In an attempt to define more precisely the various mechanisms involved in antidiuretic hormone (ADH) release during positive end-expiratory pressure ventilation (PEEP), experiments were performed on seven groups of dogs. PEEP-10 and PEEP-15 cmH2O caused significant elevations of plasma ADH from basal values of 24.9 +/- 5.2 pg/ml (mean +/- SE) to 64.6 +/- 14.2 and 106.0 +/- 20.6, respectively (P < 0.02, P < 0.005). The ADH levels returned to basal values after cessation of PEEP. This rise in ADH levels was prevented by an infusion of dextran prior to PEEP. The fall in blood pressure and cardiac output that occurred during PEEP was also prevented by the dextran infusion. Changes in ADH levels were unrelated to lung volume, left transmural pressure, and serum osmolality. Bilateral vagotomy and carotid sinus denervation was followed by an attenuated rise in ADH levels in terms of the percent rise above base line, but it did not significantly alter the absolute rise in ADH during PEEP. ADH levels were, however, reduced significantly by decreasing intracranial pressure by the removal of cerebrospinal fluid during PEEP. Propranolol administration prior to PEEP completely blocked plasma renin activity. Although the peak ADH levels were unaffected by propranolol, the rise was delayed. The results obtained indicate that a number of physiological factors may affect plasma ADH levels during PEEP. These include the carotid body and aortic arch baroreceptors as wells as sensors of intracranial pressure.

Animals↗

Nonoliguric vasopressin oversecretion in severely burned patients.

Eight burn patients with smoke inhalation were studied. High levels of plasma vasopressin and plasma cortisol in the presence of polyuria were observed. Stress and pain seem to be the main factors in the vasopressin oversecretion; the polyuria probably resulted from fluid administration and osmotic diuresis.

Burns↗

Amyloid goitre in familial Mediterranean fever.

Three patients known to suffer from familial Mediterranean fever (FMF), systemic amyloidosis and chronic renal failure developed large amyloid goitres. Amyloid goitre is an extremely rare complication of systemic amyloidosis not previously described in FMF. The clinical and pathological features of these three cases were similar to those previously described in amyloid goitre. In two of the patients abnormalities in thyroid function were consistent with those documented in chronic renal failure. There was evidence of hypothyroidism in a third patient. There was no evidence of amyloid induced dysfunction of other endocrine organs.

Adult↗

Bromocriptine in hyperprolactinemic amenorrhea: a possible early effect on ovarian steroidogenesis.

The effect of bromocriptine was studied in a 28-year-old cretin woman who presented with long-term untreated primary hypothyroidism, primary amenorrhea, hyperprolactinemia, and an enlarged pituitary fossa. Bromocriptine therapy lowered the plasma prolactin and caused an early rise in plasma 17 beta-estradiol levels and uterine bleeding, despite the failure of plasma gonadotrophins to respond to luteinizing hormone release hormone (LHRH) administration. Thus, it is suggested that bromocriptine may have an early direct effect on the ovary in hyperprolactinemic amenorrhea.

Adult↗

Medullary carcinoma of the thyroid.

Three patients with medullary carcinoma of the thyroid gland, one sporadic and two familial, are described. One of the patients presented at a late stage of the disease with evidence of wide dissemination and severe diarrhea, which was controlled by indomethacin. The value of venous catheterization and plasma thyrocalcitonin measurements in evaluating the extent of the disease was demonstrated in this case.

Adult↗

Renal function during treatment of inappropriate secretion of antidiuretic hormone with demeclocycline.

Two patients with the syndrome of inappropriate secretion of antidiuretic hormone were studied in a metabolic ward during treatment with 1.2 g demeclocycline daily. In both patients, demeclocycline treatment led to increased renal water excretion with consequent correction of hyponatremia and hypo-osmolality. Three episodes of reversible deterioration in glomerular filtration rate developed in these patients. Each episode was accompanied by clinical evidence of extracellular fluid volume contraction, and on each occasion there was an inappropriate natriuresis with daily urinary sodium excretion remaining above 50 mEq. Although demeclocycline effectively reverses the electrolyte abnormalities of this syndrome, the potentially dangerous side effects that may develop exclude the routine usage of the drug.

Demeclocycline↗

The effect of different preparations of human growth hormone on plasma renin activity in normal males.

The effect of acute administration of 2 preparations of growth hormone (hGH) on plasma renin activity (PRA) was studied in normal volunteers. 4 IU of standard, commercially available hGH II, Kabi, Sweden) were injected im into each of four normal subjects, and the PRA was determined in the basal state and at 30, 60, 120, 180, and 240 min after injection. Free fatty acid (FFA) was determined basally and at 15 and 210 min post-injection. The study was repeated on a different day in the same group using highly purified hGH (hGH I, 4 IU) virtually free of arginine-vasopressin. Four other normal subjects received 12 IU standard hGH (hGH II, Kabi, Sweden). There was no significant difference in PRA values with 4 IU of either preparation or with 12 IU of hGH II in any of the groups, although mean PRA was elevated in two of the patients receiving 12 IU hGH II. A rise in FFA occurred in all subjects, indicating the biological activity of hGH preparations. The possible significance of these findings to the renin-angiotensin system found in acromegaly is considered.

Acromegaly↗

Somatostatin and serum gastrin in normal subjects and in patients with pernicious anaemia, chronic liver and renal disease.

The effects of somatostatin (growth hormone release inhibiting hormone) on basal gastrin were studied in patients suffering from pernicious anaemia and chronic renal and liver disease, and during sequential arginine/insulin-stimulated gastrin release in normal subjects. When basal gastrin concentrations were normal (10-50 pg/ml) in controls and in patients who were in renal and liver failure, somatostatin had no effect on gastrin levels. Raised basal gastrin levels in pernicious anaemia and in 2 cases of chronic renal disease, were significantly inhibited by somatostatin with a half-life (T 1/2) of 3-4 minutes. Arginine infusion caused an insignificant rise in serum gastrin which was unaffected by somatostatin, whereas insulin hypoglycaemia significantly stimulated gastrin release, which was inhibited by somatostatin.

Adult↗

Disappearance rates of plasma growth hormone after intravenous somatostatin in renal and liver disease.

Plasma immunoreactive growth hormone (hGH) was measured before, during and after the administration of intravenous somatostatin to 3 patients with chronic renal failure and 4 with severe liver disease who had elevation of basal hGH. During somatostatin infusion, the hGH levels declined acutely in a linear fashion when log hGH was plotted against time. Rather surprisingly, the plasma hGH half disappearance time (t 1/2) was 27 min and 18 min in liver and renal disease respectively. These values do not differ from data obtained on normal subjects using exogenous hGH, labelled or unlabelled. Control data on normal subjects using this technique are not available as it was not possible to measure subnormal levels of plasma hGH with the required precision. It is possible that our findings of plasma hGH T 1/2 in liver and renal disease within the normal range reported using exogenous hGH might suggest that high levels of plasma hGH found in these two diseases are primarily caused by hypersecretion rather than impaired clearance.

Growth Hormone↗