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Biomedical subjects

S Wallach

Publications and source records attributed to S Wallach.

At least 55 records · Page 3Linked to original sources

Placental transport of chromium.

Since trivalent chromium (Cr+3) transport into certain tissues is rapid, the placental transport of injected high specific activity 51Cr+3 was studied in pregnant rats at days 17-20 of gestation. Three days after the intravenous injection of 51Cr+3, body retention of 51Cr was similar in pregnant and nonpregnant rats, but in the pregnant rats placentofetal uptake of 51Cr accounted for 25-30% of the 51Cr retention. The mean 51Cr content per placentofetal unit was 0.89 +/- 0.03% injected dose. Serum and tissue 51Cr contents per milliliter or gram in the pregnant rats were decreased by 50-80% except in uterus, which was unchanged. Tissue/serum 51Cr ratios were increased by 70-300% in the pregnant rats compared to the nonpregnant controls. These results indicate that the placentofetal unit is capable of extracting large amounts of Cr from the mother, and support the suggestion that maternal Cr is depleted during pregnancy. The data also suggest that body tissues may defend their Cr stores against Cr depletion by adaptive cellular Cr transport mechanisms.

Animals↗

Effects of furosemide on biliary secretion, pancreatic blood flow, and pancreatic exocrine secretion.

The effects of furosemide on biliary secretion and on pancreatic hemodynamics and exocrine function were studied by quantitative flowmetry and timed collections of biliary and pancreatic exocrine secretion in the anesthetized dog. Biliary flow and the output of its components (Na+, K+, Ca, Mg, 3-OH bile salts, and bilirubin) increased significantly following a furosemide injection of 0.6 mg/kg and rose progressively to 75-150 per cent above basal levels as the furosemide dose was increased to 9.6 mg/kg. Pretreatment with secretin had no influence on furosemide-induced biliary secretion. Furosemide doses of 4.8 and 9.6 mg/kg increased blood flow in the superior pancreaticoduodenal arterial bed by 30-60 per cent but did not alter flow in the inferior pancreaticoduodenal arterial bed or the pancreatic branch of the splenic artery. However, small increases were seen in flow in the latter two arterial beds after furosemide when secretin administration preceded furosemide. Basal pancreatic secretion was not affected by furosemide, but pretreatment with a submaximal sustaining infusion of secretin uncovered a furosemide action to increase pancreatic exocrine flow and the outputs of Na+, K+, Ca, Mg, and enzymes by 25-35 per cent. These data extend previous studies of the gastrointestinal vasodilator effects of furosemide to the pancreatic circulation and previous data demonstrating furosemide-induced ionic transport in nonrenal systems to biliary, pancreatic acinar, and ductular transport in both organs. Whether the augmentation of pancreatic blood flow is secondary to enhanced ion transport in the exocrine pancreas or to an effect on ionic cotransport in vascular smooth muscle is unknown.

Animals↗

Radiochromium conservation and distribution in diuretic states.

The effect of free water diuresis by three different modalities on body 51Cr conservation and distribution was studied in adult male rats. Despite massive diuresis, ADH deficiency had little effect on body 51Cr retention or relative tissue distribution of 51Cr but did induce 25-40% increases in serum 51C concentrations which were reversible by pitressin administration. Glucose feeding produced copious diuresis but no change in body 51Cr retention or relative tissue distribution of 51Cr. The serum 51Cr concentration decreased 23% in association with small increases in serum glucose and insulin concentrations. LiCl administration produced moderate diuresis with little change in body 51Cr retention and inconsistent changes in serum and tissue 51Cr distribution. These data indicate normal body retention of 51Cr despite body water pool turnovers of up to 100% per day. Hence, renal handling of Cr is flow-independent, presumably due to Cr reabsorption at a proximal site within the nephron. However, a marked restriction of Cr filtration by the glomerulus due to protein binding of Cr cannot be ruled out by these data. Differences in body weight, even if assumed to be due to altered extracellular fluid volume, are insufficient to account for the serum 51Cr data. Previous observations in adrenalectomized rats also do not support a role for aldosterone secretion secondary to extracellular fluid volume shifts. Therefore, the increase in serum 51Cr concentration in ADH deficiency may be due to an effect of ADH to promote cellular transport of Cr whereas the decrease in serum 51Cr concentration during glucose feeding is probably due to increased cellular penetration of Cr secondary to insulin action.

Animals↗

Three adult cases resembling hereditary bone dysplasia.

Hereditary bone dysplasia with hyperphosphatasemia is a generalized disorder of bone formation which begins in infancy, uniformly involves the skull and long bones and results in progressive deformities and short stature. This entity has been described 27 times under various names, including juvenile Paget's disease, but only two case reports have described the condition in adults. In the present report two siblings and an unrelated individual are described with features resembling hereditary bone dysplasia. In all three the condition developed in infancy but was first recognized in middle age. Clinical and radiographic features of short stature, extensive thickening of the calvarium with areas of "cotton wool sclerosis", and bowed deformities of the long bones were present. The serum alkaline phosphatase was elevated in one case and normal in two. One patient demonstrated a marked clinical and biochemical response to a six month course of disodium etidronate after failing to respond to a trial of salmon calcitonin. There were significant differences between these three cases and classic hereditary bone dysplasia as described in infants and children. The patients themselves also had variable features. These observations suggest that either hereditary bone dysplasia is indeed variable, especially as afflicted children pass into adulthood, or different skeletal diseases are presently being included under the general term hereditary bone dysplasia with hyperphosphatasemia.

Adult↗

Tissue chromium exchange in the rat.

This study of chromium (Cr) exchange in the rat combined measurements of 51Cr distribution and tissue Cr content to permit an assessment of tissue Cr exchange under control conditions and during varied Cr intakes. Liver Cr was found to be 50 to 100% exchangeable whereas pancreas Cr was only 34% exchangeable. In kidney, the specific activity of 51Cr exceeded that of serum by more than 100%, indicating a complex type of exchange involving both a rapidly exchanging Cr pool and an "inner" Cr pool with "sink-like" characteristics. Chromium deprivation of moderate degree reduced serum Cr and tissue exchangeable Cr pools but did not change total tissue Cr, 51Cr distribution, or glucose tolerance. Chromium supplementation and Cr overload increased serum Cr and total, exchangeable, and nonexchangeable tissue Cr pools but did not alter 51Cr distribution. These results indicate that the merging of tracer techniques with tissue Cr analyses yields a more complete view of Cr exchange than 51Cr distribution alone. The data support the hypothesis that specific transport characteristics exist in tissues that may regulate the biological role of Cr.

Animals↗

Radiochromium distribution in thyroid and parathyroid deficiency.

Body retention and tissue distribution of a 51chromium (Cr) tracer were studied in thyroparathyroidectomized (TPTX) rats and in TPTX rats after replacement with thyroxin, calcitonin, or parathyroid hormone. A tracer dose containing 1 ng Cr or less and 0.5 to 0.7 muCi of high specific activity 51Cr (Cr III) was injected intravenously in control, TPTX, and TPTX animals receiving hormone replacement. Three days later, the 51Cr content of the serum and various tissues was determined and the data were expressed as percent dose per milliliter or gram and as tissue: serum 51Cr ratios. TPTX resulted in a significant increase in total body 51Cr retention and 40 to 240% increases in serum and tissue 51Cr levels. Tissue:serum 51Cr ratios were uniformly depressed. Replacement with thyroxin completely or partially reversed these changes in all tissues studied except bone. Calcitonin and parathyroid hormone had no consistent effect on body, serum, or tissue 51Cr levels. These data, indicating that 51Cr distribution is influenced by thyroid hormone activity but not by calcitonin or parathyroid hormone, are compatible with the hypothesis that thyroid hormone controls cellular Cr transport.

Animals↗

Automated analysis of hydroxyproline with elimination of non-specific reacting substances.

A modified urinary hydroxyproline method is presented which utilizes an automated technique, Technicon instrumentation and Ehrlich's reagent. Acid hydrolysates are neutralized automatically. Non-specific reacting substances are determined simultaneously with each sample and subtracted as a blank. This method has been found to be superior to the use of charcoal-resin as an absorbent. After blank correction, the mean hydroxyproline excretion of normal and osteoporotic patients are similar. In all groups studied, including Paget's disease, the blanks reresent a significant fraction of total reacting substances and show wide variation between samples. Multiple samples from patients over a two year period show little variation in hydroxyproline excretion when corrected for non-specific reacting substances.

Autoanalysis↗

Radiochromium distribution in hypophysectomized and adrenalectomized rats.

The effects of hypophyseal and adrenal ablation (HYPOX, ADX) on trivalent radiochromium (51Cr) distribution and of GH and T4 replacement in HYPOX rats were determined. Hypophysectomy increased body retention of 51Cr by 20--35%, and hormonal replacement restored body retention to normal. Serum 51Cr was increased 300--800%, resulting in depressed tissue to serum 51Cr ratios. GH replacement partially restored the 51Cr distribution abnormalities in HYPOX rats to normal. The combination of T4 with GH enhanced the restoration of normal 51Cr distribution, and tissue to serum 51Cr ratios returned to baseline levels. ADX had no effect on body retention of 51Cr but had a small effect on increases in serum and tissue 51Cr levels. As a result, tissue to serum 51Cr ratios did not change. These data indicate that in the HYPOX state there is a marked disturbance in Cr metabolism which is due to deficiencies of both GH and T4. Whether or not adrenal hormones are envolved in 51Cr distribution will require further study.

Adrenalectomy↗

Neurologic disturbances in Paget disease of bone: response to calcitonin.

The neurologic manifestations of Paget disease and the therapeutic effect of calcitonin were studied in 49 patients. Twenty-four patients (49%) had neurologic disorders involving cranial nerves other than the auditory system, brainstem, spinal cord, or spinal roots and nerves. Eighteen of the 24 patients (75%) showed significant subjective or objective improvement after calcitonin treatment. The effect of calcitonin treatment on spinal cord compression was dramatic in three of six patients. The observations made of these patients support previous data suggesting that the neurologic signs and symptoms of Paget disease have their pathogenesis in both mechanical impingement and vascular distortion. The importance of early detection of neurologic signs and symptoms is emphasized, since prompt treatment with calcitonin may prevent severe complications.

Aged↗

Hormonal factors in osteoporosis.

Primary osteoporosis is a ubiquitous disease of unknown etiology. The condition undoubtedly has multiple causes and the metabolic pattern of bone loss may vary significantly from case to case. Five hormones, PTH, gonadal steroids, CT, T3 and T4, and glucocorticoids, and possibly a sixth, GH, have fundamental actions on bone metabolism and may therefore be causally involved in primary osteoporosis. A consideration of selected data on hormonal interactions culled from a much larger body of experimental and clinical data leads to the conclusion that in vitro studies, animal research, and data obtained in postmenopausal women with age-related bone atrophy, but not osteoporosis, have yielded considerable data relating to bone metabolism, but have failed to define the causes or treatment of primary osteoporosis. There has been excessive emphasis on hormonal reactions relating to bone metabolism and bone cell function, and too little concern for nonhormonal factors which might influence the kinetics of skeletal turnover through alterations in bone cell activity. A practical approach to the cause(s) and treatment in the only suitable model, the human with osteoporosis, is proposed with the expectation that a better insight into the pathogenesis of the condition will be achieved.

Adrenal Cortex Hormones↗

Management of osteoporosis.

Accelerated bone loss and diminished new bone formation in primary involutional osteoporosis far outstrip the rates seen in "normal aging." Their serious consequences can be mitigated with pharmacologic agents and adjunctive regimens.

Aged↗

Primary hyperparathyroidism and breast cancer.

Three cases demonstrating the coexistence of primary hyperparathyroidism and breast carcinoma with the disappearance of hypercalcemia following removal of parathyroid adenomas are presented. In these cases, the patients had the typical diagnostic findings of primary hyperparathyroidism. Reluctance to perform neck explorations in such patients does not appear warranted.

Adenoma↗

Paget's disease of the bone: observations after cessation of long-term synthetic salmon calcitonin treatment.

Thirteen patients with Paget's disease of the bone were treated with subcutaneous injections of synthetic salmon calcitonin (SCT) for a mean period of 22 months at doses of 50-100 MCR units daily or 3 times a week. They manifested symptomatic improvement and significant reductions in serum alkaline phosphatase and urinary hydroxyproline excretion during SCT administration. Following discontinuation of SCT, symptomatic improvement was maintained in 10 patients for up to one year, whereas a recurrence of symptoms was seen in only 3 patients. The serum alkaline phosphatase generally showed a return toward pretreatment values 6 months after discontinuation of SCT, whereas urinary hydroxyproline remained depressed for up to a year.

Aged↗

Effects of growth hormone in osteoporosis.

The effect of chronic administration of growth hormone (GH) to osteoporotic patients was studied using the techniques of total body neutron activation analysis, whole body counting, calcium tracer kinetics, photon absorptiometry, quantitative microradiography, and urinary hydroxyproline. Two dosage schedules were utilized for six months each: 2 units daily and 0.2 w3/4 units of GH daily (where W represents body weight expressed in kg). The lower dosage (2 units) did not produce any appreciable change in the indices studied. Following the higher dose, no evidence of any anabolic effect was apparent in most patients (i.e., no increase in total body levels of Ca, Na, K, P, or Cl). Increases were noted in the urinary calcium excretion rate and in the urinary hydroxyproline excretion. Bone mineral content decreased. The bone biopsies displayed an increase in bone formation and resorption surfaces in response to treatment, but these changes were not statistically significant. It may be concluded that under the conditions of this study, GH administration did not result in an increment in skeletal mass. Several side effects that are characteristic of acromegaly were observed, including hyperglycemia, hypertension, arthralgia, and the carpal tunnel syndrome. Because of the lack of demonstrated benefit and the associated complications of therapy, GH administration does not appear to be of value in the treatment of osteoporosis.

Bone and Bones↗

Paget's disease: New treatment for an old disease.

There are probably 2.5 million patients with Paget's disease in the U.S.; 125,000 of these have severe disease meriting specific treatment. While the diagnosis can often be made by inspection, or by measurement of the temperature of involved limbs, it is often missed. Nonspecific findings include pain, headaches, deafness, heart failure, neurologic deficits and renal stones. A specific diagnosis can usually be established by radiologic examination of the skeleton and measurement of the serum alkaline phosphatase level. Bone scans are often helpful. In moderate-to-severe symptomatic disease, calcitonin limits the unregulated chaotic bone resorption and exerts highly specific and effective suppressive activity.

Calcitonin↗