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Biomedical subjects

S M Genuth

Publications and source records attributed to S M Genuth.

17 recordsLinked to original sources

Urinary 3-hydroxyadipic acid 3,6-lactone: structural identification and effect of fasting in adults and children.

Increased urinary excretion of medium-chain dicarboxylic acids is a general feature of disordered fatty acid metabolism. The physiological role of the metabolic pathways involved in dicarboxylic acid production has been a subject of controversy. In the present investigation, the existence of 3-hydroxyadipic acid 3,6-lactone, possibly representing a metabolic intermediate in the beta-oxidation of adipic acid to succinic acid, has been demonstrated. The identity of this compound was established by electron-impact mass spectrometry of its trimethylsilyl derivative and by comparison with synthetic authentic samples. 3-Hydroxyadipic acid 3,6-lactone is present in almost every urine sample we have examined. In the nonfasting state, urinary concentrations of 0.9 +/- 0.5 micrograms/mg creatinine were observed in the adults. During fasting, the urinary excretion of this compound increased with time. It reached 19.1 +/- 8.5 micrograms/mg creatinine by the end of the third day. The responses in children were even higher; urinary concentrations of 82 +/- 50 micrograms/mg creatinine were observed by the end of 36 hours. The urinary excretion of the lactone is closely correlated (r2 = 0.8) with that of adipic acid, an indicator of fatty acid omega-oxidation activity. Non-ketotic dicarboxylic aciduria appears to vary in different defects based on the ratio of urinary lactone to adipic acid.

Adipates

Effect of dietery weight loss on sex steroid binding sex steroids, and gonadotropins in obese postmenopausal women.

Measurements of SSBG, E2, T, and gonadotropins were performed in 12 obese postmenopausal women before, during, and after a supplemented fast. Weight loss (mean 18 kg) was associated with an increase in SSBG to levels above those seen in nonobese postmenopausal women, a decrease in serum E2 levels, unchanged T levels, and an increase in both gonadotropins. Thus we conclude that weight change or the circumstances associated with it lead to alterations in circulating levels of SSBG. These observations are consistent with the presence of elevated free T and possibly higher free E2 levels in obese postmenopausal women.

Body Weight

Experience with low-dose insulin infusion in diabetic ketoacidosis and diabetic hyperosmolarity.

Forty patients with diabetic ketoacidosis and eight patients with the diabetic hyperosmolar state were treated with low-dose insulin infusion in four teaching hospitals in the Cleveland area. The clinical and biochemical responses observed support previous favorable reports on this treatment modality. Two elderly patients with the hyperosmolar syndrome died. The advantages of this form of treatment over intermittent insulin schedules are emphasized. Early potassium administration, unless otherwise contraindicated, is recommended. Rarely, increasing doses of insulin may be required if insulin resistance is encountered.

Adolescent

Supplemented fasting as a large-scale outpatient program.

Although supplemented fasting is now established as an efficient means of achieving substantial weight reduction in massively obese persons, widespread application of this treatment is contingent on its successful adaptation to a large-scale outpatient regimen. Of 519 patients treated as outpatients, 78% lost a minimum of 18.2 kg during the course of treatment. The overall rate of weight loss was 1.5 kg/wk, with females averaging 1.3 kg/wk and males, 2.1 kg/wk. The majority of patients tolerated the regimen well and were able to continue normal daily activities without experiencing any serious side effects.

Body Weight

A case of idiopathic hypoparathyroidism and dietary vitamin D deficiency: the requirement for calcium and vitamin D for bone, but not renal responsiveness to PTH.

A patient with concurrent idiopathic hypoparathyroidism and dietary vitamin D deficiency was studied. Acute renal responsiveness to PTH was demonstrated by immediate increases in urinary cyclic AMP and phosphorus excretion. An impaired bone response to sustained PTH administration was demonstrated by absence of significant increases in serum calcium or urine hydroxyproline during 3 days of PTH administration. Skeletal responsiveness was restored either by raising the initial serum calcium with constant calcium infusion or by raising serum 25-OH-D levels to normal by administration of 1,000 units vitamin D daily. These results extend to the human, animal observations which suggest that vitamin D is required for the skeletal but not for the renal actions of parathyroid hormone.

Bone Resorption

Insulin secretion in obesity and diabetes: an illustrative case.

A patient with obesity and diabetes mellitus had insulin secretion studies done during a 3-year cycle of weight loss and regain in the course of which she progressed from frank diabetes to a normal state of carbohydrate tolerance and then back to her original diabetic state. The results suggest that therapeutic weight reduction not only reverses insulin resistance but also restores beta cell sensitivity and enhances beta cell capacity. The eventual re-establishment of a degree of obesity, hyperinsulinemia, and carbohydrate intolerance virtually identical to that originally seen is compatible with a primary disorder involving hypothalamic control of adipose stores and insulin secretion.

Adult

Effect of high fat vs. high carbohydrate feeding on the development of obesity in weanling ob/ob mice.

Mice with hereditary obesity (ob/ob) were fed isocaloric, isoprotein diets with varying proportions of carbohydrate-to-fat from the time of weaning to 18 weeks of age. Body weight, plasma glucose,and plasma insulin were determined at frequent intervals; body lipid and pancreatic insulin were determined at termination. Obesity developed when only carbohydrate was provided as caloric source (and in the presence of essential fatty acid deficiency), but obesity was greatly enhanced when 5% fat was added. Obesity also developed in the absence of dietary carbohydrate, even though hyperinsulinism was significantly reduced by this regimen. It is concluded that 1) both enhanced storage of dietary fat and lipogenesis contribute to obesity, the former more so than the latter; 2) the degree of hyperinsulinism does not determine the degree of obesity; 3) the development of hyperinsulinism does not require stimulation by exogenous oral carbohydrate.

Animals

Multiple endocrine adenomas in a patient with the Maffucci syndrome.

A patient with multiple cutaneous hemangiomas and skeletal dyschondroplasia (the Maffucci syndrome) was found to have a pituitary chromophobe adenoma, a parathyroid adenoma and two other neoplasms. The presence of two endocrine tumors suggested the syndrome of multiple endocrine adenomatosis, and raised the issue of an etiologic relationship between this disease and the Maffucci syndrome. Dyschondroplasia, however, has no known influence on the secretion of parathyroid hormone or any of the pituitary hormones. The Maffucci syndrome is associated with a high incidence of malignancy, but it involves primarily mesodermal derivatives whereas multiple endocrine adenomatosis affects tissues of ectodermal origin. The association of the two in our patient is probably fortuitous.

Adenoma, Chromophobe

Community screening for diabetes by blood glucose measurement. Results of a five-year experience.

The Diabetes Association of greater Cleveland screened 307,000 individuals in the metropolitan area for diabetes with a 75-gm. oral load of carbohydrate. Of these subjects 12,600 (4.1 per cent) had a two-capillary blood glucose level of greater than 139 mg. per cent and were defined as positive. Seventy per cent of the positives were retested, and 65 per cent of these again had two-hour levels greater than 139 mg. per cent. Seventy-one per cent of the original screening values were between 104 and 199 mg. per cent. The rate of positivity on retesting increased with the original screening bracket reaching 90 per cent at an original screening level of 240 mg. per cent or higher. The frequency of positive retests also increased with age irrespective of whether the original screening level was less than or greater than 200 mg. per cent. The implications of this large detection experience for conducting future mass surveys for diabetes are discussed.

Age Factors

Comparative response to parathyroid hormone in hyperthyroidism and hypothyroidism.

The effects of exogenous parathyroid hormone, administered for 3 days, were compared in six hyperthyroid and six hypothyroid subjects. Maximum increments were much greater in hyperthyroid than in hypothyroid subjects for serum calcium (3.5 mg/100 ml versus 1.6 mg/100 ml), urine calcium (476 mg versus 79 mg), urine hydroxyproline (56 mg versus 11 mg), and urine phosphorus (671 mg versus 192 mg). Maximum decrease in serum phosphorus (minus0.9 mg/100 ml versus minus 0.1 mg/100 ml) was also greater in hyperthyroid subjects. Serum parathyroid hormone immunoreactivity was significantly higher in hypothyroid subjects (0.48 ng/ml) that either normals (0.21 ng/ml) or hyperthyroid subjects (0.19 ng/ml). The data support the concept that excess thyroid hormone sensitizes and deficient thyroid hormone blunts the responsiveness of bone to parathyroid hormone. This may lead to a state of hypoparathyroidism in hyperthyroidism and hyperparathyroidism in hypothyroidism.

Adult

Laxative-induced hypokalemia, sodium depletion and hyperreninemia. Effects of potassium and sodium replacement on the renin-angiotensin-aldosterone system.

A patients with marked chronic hypokalemia (potassium, 1.7 to 2;3 meg/litre) and sodium depletion secondary to lazative abuse and dietary inadequacy was studied with respect to the renin-aldosterone system during sequential potassium and potassium-plus-sodium replacement. Extreme hyperreninemia of 20 Goldblatt units X 10-minus 4 was reduced to 0.9 with potassium replacement alone. Aldosteron excretion (15.8 mug/24 h) was initially low for a sodium-deprived state and high for a potassium-deprived state; it increased with potassium administration, but this rise was opposed by decreases in renin secretion induced by potassium and sodium administration. The results provide clinical confirmation of a dual effect of potassium on aldosterone secretion, with renin as a mediator.

Aldosterone