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Biomedical subjects

D Barzilai

Publications and source records attributed to D Barzilai.

At least 37 records · Page 2Linked to original sources

Natural killer cell activity in post-necrotic cirrhotic patients as related to hepatitis-B virus infection and plasma zinc levels.

In view of the suggested physiological role of natural killer (NK) cells in immunosurveillance and defence against viral infections, we have investigated the relationship between hepatitis B virus (HBV) infection and NK activity against K-562 cells in patients with post-necrotic cirrhosis. Overall, the NK activity in cirrhotic patients did not differ from age- and sex-matched controls. However, cirrhotic males with evidence of HBV infection with or without HBs antigenemia tend to have lower NK activity than controls. Cirrhotic males without evidence of HBV infection do not differ from controls. Such a trend was not observed in the female cirrhotic patients examined. In addition significantly reduced NK activity was observed in cirrhotic patients with low plasma zinc levels. This relationship is of interest because of the known association between zinc deficiency and various immunodeficiencies.

Adolescent↗

Primary therapy for Cushing's disease with metyrapone.

A 13-year-old boy was diagnosed as suffering from pituitary-dependent Cushing's syndrome. He was treated with 2.0 g of metyrapone daily as the sole treatment for four years. All clinical and biochemical stigmata of Cushing's disease disappeared within a few months. The patient grew 23.0 cm in four years and regained normal health. No significant side effects of metyrapone were noticed. Administering the medication at 2 PM and 8 PM allowed higher cortisol levels in the morning and noon hours than in the evening and night, approximating the normal diurnal variation in cortisol production. We conclude that metyrapone may be considered the sole treatment in patients with Cushing's disease.

Adolescent↗

The dual effect of calcium on aromatization by cultured human trophoblast.

To study the effect of calcium ion on aromatization of an androgenic precursor to estradiol by the placenta, cultured term trophoblasts were used as a model system. Secretion of estradiol into the culture medium was regarded as indicating aromatization, since cells cultured with no androgenic precursors produced only insignificant amounts of estradiol. EGTA, verapamil and ionophore A23187 inhibited aromatization, while trifluoperazine, an inhibitor of the calcium-calmodulin complex, interfered with the stimulatory effect of cyclic AMP on aromatization. We conclude that calcium ion has an essential role in the aromatization of 4-androstene-3,17-dione to estradiol. The calcium-calmodulin complex is required for activation of aromatase by cyclic AMP. However, when flooded with calcium by ionophore A23187, the trophoblast is unable to effectively buffer calcium, and aromatization is inhibited.

Androstenedione↗

Correlation between insulin clearance and insulin responsiveness: studies in normal, obese, hyperthyroid, and Cushing's syndrome patients.

Insulin clearance and secretion determine the plasma insulin concentration. To elucidate the significance of these parameters in man, we employed the euglycemic insulin clamp technique to measure insulin sensitivity, insulin responsiveness, and insulin clearance, and we calculated the basal insulin delivery rate. In 27 patients (six normal, six obese, ten hyperthyroid, and five with Cushing's syndrome), insulin was infused at rates of 0.3, 1, 3, or 10 mU/Kg/min, and insulin concentration and glucose utilization were measured. C-peptide concentrations were measured before and during insulin infusion and decreased significantly, indicating a reduction of endogenous insulin secretion to 62% of basal in normals and a similar reduction in the other groups. Maximal responsiveness to insulin was a glucose utilization rate of 450 +/- 20 mg/min/m2 in normals, unchanged in obese, 42% increased in hyperthyroid, and 34% decreased in Cushing's syndrome patients. Sensitivity to insulin was decreased in all three abnormal groups. Insulin clearance rates were 1,050 +/- 80 mL/min/m2 for normals, not significantly changed in obese, 45% increased in hyperthyroid, and 33% decreased in Cushing's syndrome patients. All three abnormal groups showed hyperinsulinemia compared to normal. The basal insulin delivery rates were calculated as 7.0 +/- 0.3 mU/min/m2, with a threefold increase in obese and in hyperthyroid and no significant change in Cushing's syndrome patients. Insulin clearance correlated well with insulin responsiveness (r = .65, P less than 0.001), but poorly with insulin sensitivity (r = .36).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Low-set osmotic threshold for vasopressin release in a patient with prolactinoma.

This report describes a 38-year-old patient with prolactinoma, without adrenal or thyroid insufficiency, with syndrome of inappropriate secretion of vasopressin due to downward resetting of the hypothalamic osmoreceptors. Random measurements of plasma and urine osmolality revealed an inappropriately high urine osmolality for a given plasma osmolality. Simultaneous plasma vasopressin levels were within normal limits. Urine dilution after water load was normal. During infusion of hypertonic saline, the osmotic threshold was demonstrated at plasma osmolality of 267 mosmol/kg, which is markedly lower than the normal 287.3 +/- 3.3 mosmol/kg. Thirst sensation seemed to be intact. The defect in the osmoreceptor function might have been induced by the tumor mass or by chronic hyperprolactinemia.

Adrenocorticotropic Hormone↗

Osmotic threshold for vasopressin release in hyperprolactinemic patients.

Eleven patients with chronic hyperprolactinemia were tested to determine their osmotic threshold by isovolemic infusion of 5% NaCl. The results obtained demonstrate no statistical difference from known values in healthy volunteers. No linear correlation was found between levels of blood prolactin and the osmotic threshold, except for 1 patient who represents downward resetting of the hypothalamic osmoreceptors. The average time elapsed from the maximal dilution point to the osmotic threshold in hyperprolactinemia was found to be significantly shorter than in the normal population. We conclude that prolactin does not appear to participate in the osmotic regulation in man.

Adolescent↗

Cyclic nucleotide levels in human breast cancer and in rat mammary tissues during tumor development.

The levels of cyclic adenosine 3':5'-monophosphate (cAMP) and cyclic guanosine 3':5'-monophosphate (cGMP) were studied in dimethylbenz(a)anthracene (DMBA)-induced mammary tumors of Sprague-Dawley rats and in human breast cancer. In the rat carcinomas, these levels were significantly lower than in non-malignant tissues when calculated on the basis of DNA content, but higher (cAMP) or equal (cGMP) when calculated on the basis of weight. In human breast cancer the cyclic nucleotide levels were higher than in non-malignant tissues according to both methods of calculation. No correlation was found in human carcinomas between the cyclic nucleotide levels and mitotic index, nuclear grade, tumor size, or lymph node involvement. The rat tumors were subclassified according to state of differentiation, mitotic index, and state of development. Not all the sub-groups had cAMP levels different from normal values. Differences in cAMP levels between the sub-groups could not be correlated with tumor growth rates and/or mitotic index. Thus, cyclic nucleotides may not be useful in prognosis of breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗

The effect of inhibitors on insulin regulation of hormone secretion by cultured human trophoblast.

The effect of insulin in physiological concentrations on hormone secretion by human term trophoblast cell culture was studied in relation to insulin control of glucose transport and utilization. Specific inhibitors to these 2 functions were added to the culture, either alone to test for a dose response or with insulin. 2-Deoxy-D-glucose, which inhibits glycolysis, did not change the pattern of response of estradiol and placental lactogen (hPL) secretion to insulin. Phloridzin, an inhibitor of glucose transport, interfered with the stimulatory effect of insulin on hPL secretion, but stimulated insulin inhibition of estradiol secretion when added by itself. The results indicate that hPL response to insulin is dependent on glucose transport, but is independent of glycolysis. Estradiol response is dependent on glucose transport, but is independent of glycolysis.

Cells, Cultured↗

Insulin resistance in Cushing's syndrome.

Insulin resistance is well established in Cushing's syndrome, but its mechanisms are not completely understood. We performed the euglycemic insulin clamp technique on four patients with Cushing's syndrome, five obese patients and five normal volunteers, in order to determine the role of impairments in insulin responsiveness and insulin clearance in hypercorticism and obesity. Insulin was infused at 0.3, 1, 3 and 10 mU/kg/min, and steady-state glucose-infusion rates required to maintain euglycemia were determined. Glucose disposal at maximal insulin levels was 11.9 +/- 0.4 mg/kg/min in normals, with a 29% decrease in obese and a 42% decrease in Cushing's syndrome patients. Half maximally effective insulin concentrations were increased in both abnormal groups compared to normals. Maximal insulin clearance rates were 1460 +/- 200 ml/min/m2 in normals, not significantly changed in obese and 40% decreased in Cushing's syndrome patients. These results indicate that the insulin resistance in Cushing's syndrome is distinct from that occurring in obesity and is characterized by both decreased insulin responsiveness and decreased insulin clearance. These impairments could be caused by a common defect which may be at or distal to the glucose transport level.

Biological Transport↗

Increased insulin responsiveness and insulin clearance in thyrotoxicosis.

The euglycemic insulin clamp technique was used to evaluate in vivo insulin action in thyrotoxicosis (TTX). Insulin was infused at 0.5, 3 and 10 mu/kg per min, and the steady-state glucose infusion rate was determined in five TTX patients with fasting hyperinsulinemia and five healthy subjects. TTX is accompanied by a significant increase in insulin responsiveness, clearance and basal insulin delivery rate. Therefore, insulin resistance in TTX does not reside at the postreceptor peripheral tissue level, but may be the consequence of increased hepatic glucose production.

Blood Glucose↗

Reversible acute interstitial nephritis associated with indomethacin.

Nonsteroidal, anti-inflammatory drugs have been implicated in causing acute renal failure of several distinct patterns. We report a case of reversible acute renal failure associated with indomethacin therapy. Renal function recovered upon cessation of indomethacin treatment. Renal biopsy disclosed the presence of tubulointerstitial nephritis which was thought to have been responsible for the acute renal failure in this patient. Following presentation of this unusual side effect within the wide spectrum of renal and electrolyte disorders related to nonsteroidal, anti-inflammatory agents, we recommend that kidney function indices should be frequently tested in patients receiving indomethacin.

Acute Kidney Injury↗

The modulation of placental lactogen secretion by calcium: studies with cultured human term trophoblast.

Previous reports have documented the negative regulatory effect of calcium ion on the secretion of human placental lactogen by the placenta. Human term trophoblasts were dispersed from term placenta and maintained in monolayer cell culture. Incubation of the cultured trophoblast with EGTA produced a dose-dependent stimulation of placental lactogen secretion. The calcium ionophore A23187 inhibited hormone secretion. This inhibitory effect was eliminated by the addition of the calcium-calmodulin complex inhibitor trifluoperazine. It is concluded that calcium exerts a negative regulatory effect on the secretion of placental lactogen by a mechanism which requires the action of the calcium-calmodulin complex.

Calcimycin↗

Night blindness and liver cirrhosis as late complications of jejunoileal bypass surgery for morbid obesity.

A patient underwent end-to-side jejunoileostomy for morbid obesity, and 3 years later an end-to-end jejunoileostomy with ileotransversostomy was performed. Nine years later she presented with night blindness, severe diarrhea and mild jaundice and was found to have malabsorption with vitamin A and K deficiencies as well as asymptomatic liver cirrhosis. Her shunt was removed, and a gastric partition was performed. The night blindness and abnormal prothrombin time were corrected by the administration of vitamins A and K. This case demonstrates that complications may appear many years after jejunoileal bypass surgery, and therefore, the patients should remain under strict medical supervision indefinitely.

Female↗

Bridging hepatic necrosis in acute viral hepatitis.

Bridging hepatic necrosis has, in the past, been found to be of prognostic significance in patients with acute viral hepatitis. In two studies performed on a selected group of patients with acute viral hepatitis, one-third of the patients with bridging hepatic necrosis developed chronic liver disease. These patients differed from the average hepatitis patient in that they were more severely ill and a higher percentage of them had acute viral hepatitis Type B. As all army personnel in Israel who develop jaundice and are suspected of having acute viral hepatitis are hospitalized, regardless of their clinical state, they constitute a group of patients not preselected for severity of illness. Forty-eight soldiers diagnosed clinically and biochemically as having viral hepatitis were hospitalized during a 27-month period. After giving informed consent, 41 of them underwent a liver needle biopsy within a few days of hospitalization. Each histological specimen was coded, and was then examined for bridging hepatic necrosis by three independent observers. Fourteen patients (34%) were found to have bridging hepatic necrosis. Clinically, these patients could not be clearly separated from the group without bridging hepatic necrosis, although hepatomegaly was more frequent among them, and their mean leukocyte count and bilirubin and alkaline phosphatase levels were higher. During a follow-up of more than 1 year, patients in both groups recovered completely. Four patients, two in each group, consented to a second liver needle biopsy, which was found to be normal. We conclude that bridging hepatic necrosis seems to be more common than expected, and does not seem to have the severe prognostic significance attributed to it in the past.

Acute Disease↗

The role of calcium ion in luteal function in the rat.

The regulatory role of calcium ion was investigated in isolated 10-day-old corpora lutea incubated in vitro. The corpora lutea were induced in immature rats by a single injection of PMSG (15 i.u.) on day 30. We examined the effect of various incubation conditions on the increase (about 7-fold) in cyclic AMP (cAMP) concentration by LH (5 micrograms/ml) and its reversal by PGF2 alpha (10 microM). In calcium-free medium (+0.5 mM EGTA) the stimulation by LH was only slightly impaired, and PGF2 alpha was fully effective in suppressing it. Similarly, both LH and PGF2 alpha acted normally in the presence of 100 microM verapamil, a blocker of calcium uptake. Trifluoperazine (TFP, 3-300 microM) a potent inactivator of calmodulin, did not interfere with the action of PGF2 alpha. The effect of LH was increased by TFP (30 and 300 microM); this was probably due to inhibition of calmodulin-dependent phosphodiesterase, since the increase of the response to LH by IBMX (0.5 mM) plus TFP (30 microM) was similar to that by IBMX alone. Finally, the uptake of radioactive calcium was not increased by PGF2 alpha in the absence or presence of LH. These results do not support the suggestion that calcium ion mediates the hormonal regulation of cAMP in the rat corpus luteum.

Animals↗

Night vision in a case of vitamin A deficiency due to malabsorption.

Night vision was tested electroretinographically and psychophysically in a vitamin A deficient patient before and after therapy. Vitamin A deficiency resulted from malabsorption due to a jeujunoileal bypass operation. Before therapy the patient had severely reduced cone and rod function. After the reversal operation, accompanied by 5 injections of a total of 500,000 units of vitamin A, complete recovery of cone and rod functions was observed within 7 months. Shortly after therapy rod sensitivity reached the normal level, while the time course of rod adaptation remained slower than normal and the dark-adapted electroretinographic (ERG) responses were subnormal. At later stages the ERG responses reached normal amplitudes but rod adaptation stayed slow. Only after 7 months did night vision reach the normal level with regard to the time course of rod adaptation, rod sensitivity, and ERG responses.

Dark Adaptation↗

Hyperglucagonemia--a partial explanation for the increased amylase/creatinine clearance in pancreatitis.

Hyperglucagonemia accompanies several clinical conditions characterized by increased amylase/creatinine clearance. We tested the hypothesis that glucagon may be responsible for this augmented clearance. Therefore, a constant glucagon infusion was given to eight volunteers in order to attain physiological levels comparable to those obtained during acute pancreatitis. The amylase/creatinine clearance increased from 0.84 +/- 0.8% to a mean of 1.30 +/- 1.14% (p less than 0.001). This was, however, less than the clearance of 2.94 +/- 0.23% observed during acute pancreatitis. The rise in amylase clearance during acute pancreatitis is, therefore, only partially explained by the hyperglucagonemia.

Acute Disease↗