Four cases of neonatal severe primary hyperparathyroidism occurred in three families; familial hypocalciuric hypercalcemia was present in each kindred. The diagnosis of familial hypocalciuric hypercalcemia was based on the following features; hypercalcemia in many relatives (eight to 16 per kindred), without other features of the multiple endocrine neoplasia syndromes; recognition of hypercalcemia before the age of 10 in one to three relatives; hypocalciuric hypercalcemia in all relatives tested (five to 14 per kindred); and abnormal serum calcium levels despite parathyroidectomy in all additional relatives (one to five per kindred) undergoing this operation. The association of two uncommon syndromes (neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia) in these kindreds suggests that the two syndromes share a common genetic cause within each kindred.

The effects of a mild zinc-deficient state in humans were studied. Four male volunteers received restricted zinc intake for several weeks under strict metabolic conditions. As a result of dietary zinc restriction, a decrease in zinc concentration of plasma, erythrocytes, leukocytes, and urine was observed. Changes in the activities of zinc-dependent enzymes in the plasma such as alkaline phosphatase and ribonuclease were also related to the dietary zinc status. An adverse effect of zinc restriction on total protein, total collagen, ribonucleic acid, and the activity of deoxythymidine kinase (a zinc-dependent enzyme) in the sponge connective tissue of the two volunteers in whom this test was done was noted. During the zinc restriction period, the ammonia level in the plasma was elevated. Weight loss occurred in all subjects as a result of dietary zinc restriction. Inasmuch as the zinc-deficient state was mild, this study provides a basis for developing diagnostic criteria for zinc deficiency in humans.

The clinical manifestations of cystinuria are localized to the urinary tract and result from the formation of cystine calculi. The findings of increased excretion of cystine, lysine, arginine, and ornithine in the urine at a time when the plasma levels of these amino acids were normal or low suggested to Dent and Rose (2) that a renal tu-1)ular reabsorptive site, shared by the involved amino acids, was defective. Investigations from our laboratory (3), using slices of human kidney, failed to confirm the hypothesis of Dent and Rose. Cystine did not compete with the dibasic amino acids in vitro, and although the transport of lysine and arginine was defective in cystinuria, cystine transport was unimpaired.Although evidence had been accumulating for over 60 years (4-6), it was not until 1960 that the concept of an intestinal transport defect in cystinuria emerged. Milne, Asatoor, and coworkers (7,8) noted that urinary and fecal excretion of the diamines, cadaverine and putrescine, was elevated in cystinuric subjects fed lysine and ornithine, respectively. These diamines are formed by bacterial decarboxylation of the dibasic amino acids. Hence, it was postulated that lysine and ornithine were poorly absorbed from the small intestine in cystinuria and were presented to colonic bacteria in increased amounts, resulting in excessive diamine formation and excretion. These authors provided further evidence for de-*Submitted for publication August 31, 1964; accepted November 27, 1964. A portion of this work was reported in a preliminary communication (1). fective gut absorption by showing that oral ingestion of arginine in cystinurics was followed by minimal elevations of plasma arginine compared to results obtained with control subjects. We have previously reported a defect in the uptake of lysine and cystine by jejunal mucosa from cystinuric subjects (1), an observation made simnultaneously by McCarthy and his associates (9).The present studies extend our previous observations and show that lysine and cystine are accumulated by saturable, energy-dependent processes in the human jejunum and that these two amino acids are mutually inhibitory in the gut. Furthermore, it is shown that some patients with cystinuria do not share the intestinal transport defect for cystine and lysine. MethodsAfter an overnight fast, peroral biopsy of the intestinal mucosa was performed with a Rubin tube placed at the ligament of Treitz under fluoroscopic control. A total of 75 biopsies was performed on 18 normal volunteers and 12 patients with cystinuria. The 14 male and four female volunteers were between the ages of 18 and 36 years; the seven female and five male patients were between the ages of 19 and 48. All patients with cystinuria had elevated concentrations of cystine, lysine, arginine, and ornithine in the urine, and all had formed several urinary calculi composed of cystine.The biopsy specimens weighing between 1 and 7 mg were placed in chilled, amino-acid free Krebs-Ringer bicarbonate buffer 5 to 10 minutes before incubation. The ...

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Cadmium accumulates slowly in the human body and a critically high level in the kidney can cause damage to the proximal renal tubule. Loss of Ca in the urine then contributes to extensive skeletal mineral loss. The bioavailability of Cd to animals and humans can be markedly affected by nutritional status and dietary intakes of essential and other nutrients. In general, deficiencies and excesses of interacting nutrients exacerbate and protect, respectively, against the adverse effect of Cd. These effects on bioavailability occur primarily via changes in intestinal absorption, although accelerated uptake by the kidney sometimes occurs. The chemical form of Cd that is consumed experimentally can also modify response. Many aspects of the relationships between Cd and nutrients are incompletely understood. From studies of population groups with high Cd intakes from certain foods, it appears that consumption of an adequate diet protects markedly againsthe adverse effects of Cd.