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Biomedical subjects

M Sheinfeld

Publications and source records attributed to M Sheinfeld.

35 records · Page 2Linked to original sources

Do cyclic AMP concentrations in saliva reflect PTH biologic activity?

The aim of this study was to investigate whether the concentration of cAMP in saliva might reflect the biologic activity of parathyroid hormone (PTH), as nephrogenous levels of cAMP reflect parathyroid function. Patients with primary hyperparathyroidism (HPT) with elevated levels of PTH, nephrogenous cAMP, and serum calcium were found to have cAMP levels not significantly different from control subjects. When the levels of these parameters were reduced following parathyroidectomy, salivary cAMP concentrations were not affected. Similarly, an oral calcium loading test (which decreased both PTH and nephrogenous cAMP in normal subjects) failed to influence salivary cAMP levels. Basal salivary cAMP concentrations were low in secondary hyperparathyroid patients due to chronic renal failure and rose almost fivefold following dialysis despite the stable plasma cAMP levels and salivary flow rate. We conclude that salivary cAMP concentrations do not appear to be influenced by changes in circulating biologically active PTH. However, salivary cAMP concentrations do change in response to certain perturbations; this suggests that they are regulated by some other modulator(s).

Adolescent

Cellular immune functions in patients with primary hyperparathyroidism: effects of histamine and cimetidine.

The possibility of a link between parathyroid hyperfunction and cellular immune functions was studied in primary hyperparathyroid (1 degree HP) patients. The effect of cimetidine on lymphocyte functions in 1 degree HP patients and control subjects was also investigated. Histamine-induced suppressor activity of lymphocytes from 1 degree HP patients was significantly greater than that of controls. Cimetidine addition to both normal and 1 degree HP lymphocyte cultures abolished histamine-induced suppression. In vivo administration of cimetidine, while ineffective towards normal lymphocytes, depressed phytohemagglutinin stimulation of 1 degree HP lymphocytes, indicating possible immunological damage caused by this drug, which is frequently used in the treatment of patients with 1 degree HP.

Cimetidine

Plasma levels of adenosine 3',5'-monophosphate in the fetoplacental unit and maternal circulation at delivery.

Adenosine 3',5'-monophosphate (cAMP) was measured in matched samples of maternal plasma (MV) and umbilical artery (UA) and vein (UV) of 14 normal infants born following an uncomplicated vaginal delivery. There was good correlation between UA and UV cAMP levels, which seems to indicate that the fetoplacental unit maintains a constant equilibrium of the nucleotide concentration in the umbilical circulation. There was a markedly increased UA cAMP concentration at term relative to that of MV, as well as an arteriovenous gradient of plasma cAMP level (UA greater than UV) in the fetoplacental circulation, which strongly suggest that the high cAMP levels in the cord blood originate mainly from the fetus.

Adult

L-Thyroxine-induced leukopenia in a patient with Hashimoto's disease: involvement of suppressor-cytotoxic T cells.

A study of in vitro reactivity to L-T4, as assessed by peripheral blood lymphocyte transformation, was carried out in a patient with Hashimoto's disease who developed leukopenia during treatment with L-T4. L-T4 stimulated lymphocyte transformation in this patient. The proliferating cells were of T lineage and further typing demonstrated that they bore the OKT8 antigen. Cell-mediated immune reactions mediated by OKT8+T cells might have caused the leukopenia, although other mechanisms involving cytotoxic antibodies or antibody-dependent cell-mediated cytotoxicity cannot be excluded.

Female

Effect of metoclopramide--a dopaminergic blocker and endogenous cortisol on TSH secretion in critically ill men.

In 17 critically ill men, low levels of FT4, TT4, TT3 and elevated levels of rT3 and cortisol were found. In spite of the low levels of circulating thyroid hormones, TSH levels of the critically ill men were significantly lower than those of the control group, with no correlations to the high cortisol levels. After iv injection of metoclopramide (MCP), a dopamine (DA) receptor blocker, the TSH and prolactin (Prl) increments in the critically ill patients were significantly lower than in the controls. No correlation was observed between basal cortisol levels and integrated TSH response to MCP. It is suggested that increased DA tone or high cortisol levels are not responsible for the lower basal TSH levels and for the blunted TSH or Prl responses to MCP in the critically ill. High levels of cortisol may be responsible for the altered TT4 peripheral metabolism to TT3 and rT3 in these patients.

Adult

Hyperthyroidism due to inappropriate TSH secretion with associated hyperprolactinaemia--a case report and review of the literature.

A patient with inappropriate thyrotrophin (TSH) secretion is described. She initially presented with classical hyperthyroidism during pregnancy, responded to propylthiouracil and, subsequently, had a normal delivery. Hyperthyroidism persisted and 7.5 months later a subtotal thyroidectomy was performed. After a further 16 months, mild symptoms of hyperthyroidism recurred. She again responded to propylthiouracil, but developed galactorrhoea. At that stage, it was noted that she had persistently elevated circulating TSH in the presence of elevated T4 and T3 levels. Her symptomatology was mild, although objective indices of thyroid activity, including pulse rate, BMR, sex hormone binding globulin and cholesterol, were indicative of hyperthyroidism. CT scan and tomography of the sella were normal. She had a markedly exaggerated TSH response to thyrotrophin releasing hormone (TRH). Basal TSH and responsiveness to TRH was suppressed by high dose dexamethasone. The TSH response to TRH was partially suppressed by exogenous T3, but there was no effect on basal TSH levels. TSH also decreased slightly with L-dopa and bromocriptine. Circulating TSH rose markedly during methimazole administration. TSH alpha and beta subunits were elevated and appropriate for the high TSH. In addition, both subunits increased following TRH. The patient had basal hyperprolactinaemia with an impaired prolactin (PRL) response to TRH and metoclopramide. PRL suppressed with L-dopa and bromocriptine. The remaining anterior pituitary function was intact. Most of the laboratory findings argue against the presence of a TSH producing pituitary tumour and the most likely cause for inappropriate TSH secretion in this patient is selective resistance of the thyrotroph to thyroid hormones. A mild element of peripheral resistance might also be present. The hyperprolactinaemia could be related to lactotroph resistance to thyroid hormone. The complexities of treatment in this patient are stressed. Therapy was initially attempted with low dose dexamethasone, but this had no effect. T3 treatment produced an exacerbation of her symptomatology and did not influence basal TSH, thyroid hormones, or 131I uptake. Bromocriptine administration for 11 months partially suppressed basal TSH without influencing T3 and there was an increase in T4. Methimazole did decrease her T4 and T3, but TSH and PRL rose to even greater levels. Her hyperthyroidism was eventually controlled with an ablative dose of 131I. Thyroid hormone will be given in an attempt to suppress her TSH.

Adult

Effect of acute cimetidine administration on indices of parathyroid hormone action in healthy subjects and patients with primary and secondary hyperparathyroidism.

To evaluate the acute effect of histamine H2-receptor blockade with cimetidine on PTH concentrations and its endogenous biological activity, we studied the effect of iv administration of cimetidine (50-mg bolus followed by 500 mg/60 min infusion) in normal subjects and patients with primary and secondary hyperparathyroidism. No significant changes in serum concentrations of calcium, phosphate, or immunoreactive C-terminal PTH were found in any group. However, the control group had decreased calciuria, increased phosphaturia, and decreased tubular reabsorption of phosphate, while the primary hyperparathyroid group had increased phosphaturia, increased nephrogenous cAMP excretion, and decreased tubular reabsorption of phosphate. In both of these groups, the finding suggest an increase in PTH-like biological activity. These findings suggest that cimetidine is not useful in the diagnosis or medical management of hyperparathyroidism. In fact, the changes in renal calcium and phosphorous excretion indicative of PTH-like biological activity along with a decrease in creatinine clearance in the primary hyperparathyroid group suggest a relative contraindication to the use of this drug in these patients.

Adult

Endogenous cortisol and thyroid hormone levels in patients with acute myocardial infarction.

Thyroid hormones and cortisol levels were serially measured over seven mornings and evenings in 23 consecutive patients with acute myocardial infarction (AMI) or acute coronary insufficiency (ACI). The patients were divided into two groups, high level cortisol (HLC) and low level cortisol (LLC) groups, according to mean morning and evening cortisol levels. The transient increase in plasma rT3, decrease in T3 and TSH was significantly greater in the HLC group. A diurnal variation in cortisol levels was observed in the LLC group 48 h and in the HLC group 72 h after admission. Taking the 23 patients together, no significant correlation was observed between infarct size (peak CPK levels) and the altered rT3, T4 or TSH levels. However, a significant correlation was obtained between the maximal change in T3, rT3 or TSH and the mean cortisol levels preceding these alterations, as well as between cortisol levels and infarct size. It is suggested that cortisol rather than infarct size may be the dominant factor involved in the alteration of thyroidal levels in AMI patients.

Adult

A spot sample test for the estimation of urinary or nephrogenous cAMP in the evaluation of parathyroid function.

The measurement of urinary or nephrogenous cAMP is considered to be a reliable index of parathyroid function. This test usually involves timed urine collections which renders it logistically burdensome. We have therefore assessed the validity of using spot urine samples for this purpose, 2-hour urine collections were compared to spot samples for the estimation of urinary and nephrogenous cAMP in 10 patients with hypercalcemic primary hyperparathyroidism and 22 control subjects. The results demonstrated: (1) a considerable overlap between the primary hyperparathyroid and control groups when the urinary and nephrogenous cAMP values were expressed as a function of creatinine excretion. (2) A satisfactory separation between the two groups when the 2-hour urine and spot sample levels of urinary cAMP--and even more so nephrogenous cAMP--were expressed as a function of glomerular filtrate (i.e. nmol cAMP/100 ml glomerular filtrate). (3) An excellent correlation (r = 0.91, p less than 0.001, n = 32) between 2-hour urine collections and spot samples for both urinary and nephrogenous cAMP levels. The feasibility of using a spot sample for measuring urinary or nephrogenous cAMP without impairing its diagnostic efficacy considerably simplifies the logistics of the test. This is of particular importance for ambulatory patients.

Adult

Assessment of the calcium loading test in differentiating between various forms of idiopathic hypercalciuria.

The oral calcium loading test for the differential diagnosis of the various forms of idiopathic hypercalciuria has raised much interest, since it might provide the basis for a selective, optimal treatment of the different hypercalciuric states. We have assessed the ability of this test to differentiate between the two major forms of idiopathic hypercalciuria: renal and absorptive hypercalciuria. The test was performed in 32 idiopathic hypercalciuria patients. Based on generally accepted criteria that have been established according to the results of calcium and cAMP measurements in plasma and urine, 31% of the patients could be classified as having renal hypercalciuria and 13% as having absorptive hypercalciuria, whereas the remaining 56% did not fit either of these categories. In view of the expense and logistics involved in performing the test, the finding of an approximately 50% efficacy rate in distinguishing between the forms of idiopathic hypercalciuria raises serious doubts regarding the value of its routine implementation.

Adult

Carcinoembryonic-like substance in breast fluid discharge in benign and malignant breast disease and in milk of lactating women.

In a search for a simple noninvasive test for early detection of breast cancer, radioimmunoassay was used to determine carcinoembryonic (CEA) levels in the serum and breast fluid of 26 women presenting with spontaneous breast discharge, and in the serum and milk of 34 postpartum lactating women. In 54 milk samples from 34 healthy nursing mothers, the mean CEA level was 62.6 +/- 49.2 ng/ml (mean +/- SD) (range 5 to 252 ng/ml). The highest levels were found during the first days after delivery. Serum CEA levels measured in 18 of the 34 mothers were negative in 12 cases and normal (10 +/- 5.3 ng/ml) in six. No correlation was found between CEA levels in milk and those in serum. In the women with spontaneous breast fluid discharge, CEA levels in the breast fluid measured less than 300 ng/ml in 10 cases, 300 to 1,000 ng/ml in 9 cases and greater than 1,000 ng/ml in 7 cases. None of the 19 women with CEA values below 1,000 ng/ml had a malignancy. Four of the seven women with the highest CEA levels were found to have breast cancer. Serum CEA levels were within the normal range in both the malignant and nonmalignant cases. We conclude that CEA levels are markedly elevated in breast fluid discharges in nonlactating women, and that the highest levels may be associated with malignancy.

Adult

Congenital adrenal hyperplasia diagnosed in a middle-aged woman.

Short stature, severe hirsutism, an enlarged clitoris and lack of vaginal introitus were manifest in a 55-year-old female karyotype, male phenotype patient brough up as a female. The hormone profile suggested congenital adrenal hyperplasia due to 21-hydroxylase adrenal enzyme deficiency. Follicle-stimulating hormone and luteinizing hormone levels were 122.5 and 100.3 mIU/ml, respectively, within the normal range for a postmenopausal woman. Computerized axial tomography revealed a large cystic tumor connected to the right adrenal gland. Both the right adrenal gland and the cyst were removed. The adrenal cortex showed diffuse hyperplasia and contained a well-defined nodule. The case was interesting because we had the opportunity of examining a patient of advanced age with untreated congenital adrenal hyperplasia and because of the very rare combination of adrenogenital syndrome with nodular hyperplasia and a cystic tumor, which was most probably a degenerated adenoma.

Adrenal Glands

Plasma thyroxine changes of the Apollo Crewman.

Blood drawn from Apollo crew member; to the mission, at recovery, and postmission was used to examine the effect Apollo mission activities have on tyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that apollo activities and environment caused the postmission increase in serum cholesterol may be one result of the increased thyroxine activity.

Aerospace Medicine