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Studies are presented in two male patients with primary hyperparathyroidism who had developed salt-wasting nephropathy in the course of their disease. Both of them had nephrocalcinosis and markedly impaired renal function and exhibited an abnormal decrease in the fraction of filtered sodium reabsorbed by the renal tubules. Both patients showed impaired intestinal absorption and negative balances of calcium and phosphorous and had osteitis fibrosa cystica. Thus salt-wasting nephropathy is an additional and previously undescribed complication of primary hyperparathyroidism.

Irreversible second-phase aggregation of platelets in diabetic patients is prevented in vitro by 5, 8, 11, 14-eicosatetraynoic acid (TYA), a competitive inhibitor of the labile aggregationstimulating substance (LASS) which is formed from arachidonic acid. Thus, inhibition of prostaglandin synthesis inhibits platelet aggregation in diabetic subjects. These findings indicate that platelets from diabetics are subject to control by intracellular mechanisms operative in the regulation of platelet function in normal individuals.

THE recent finding of elevated levels of gonadotropins in tumor tissue and urine by bioassay in 4 cases of bronchogenic carcinoma strongly suggests the production of gonadotropins by these neoplasms.1 We have obtained proof of secretion of gonadotropin by a primary pulmonary neoplasm with the demonstration of an arteriovenous gradient of a serum gonadotropin concentration across the tumor bed by the use of a sensitive and specific radioimmunoassay technic for follicle-stimulating hormone (FSH). Luteinizing hormone (LH) concentrations were also determined by a radioimmunoassay technic. These findings are reported below. Methods Tissue Extracts Fresh tissue was obtained at operation and at . . .

Possible cause-effect relationships in producing vegetation canopy reflectance are discussed. Hemispherical reflectance and even bidirectional reflectance measurements are shown to be inadequate to predict or understand vegetation canopy reflectance in many situations. Among the additional important parameters necessary for prediction and understanding of vegetation canopy reflectance are leaf hemispherical transmittance, leaf area and orientation, characteristics of other components of the vegetation canopy (stalks, trunks, limbs), soil reflectance, solar zenith angle, look angle, and azimuth angle. The effects of these parameters on vegetation canopy bidirectional spectral reflectance are described.

The effects of calcium infusion (15 rag Ca/kg body wt) on urinary hydroxyproline and phosphorus have been studied in 4 patients with hyperparathyroidism, 3 patients with hypoparathyroidism, 7 normal subjects, 13 stone formers, 4 patients with chronic renal insufficiency, 2 patients with acromegaly, 1 patient with sarcoidosis, 1 with hyperthyroidism, 1 with Paget's disease, 1 with milk-alkali syndrome and 1 with pseudohypoparathyroidism. Calcium infusion lowered urinary hydroxyproline and phosphorus 14% or more below control levels in all subjects except those with hyperparathyroidism, hypoparathyroidism or pseudohypoparathyroidism. The decreases in urinary hydroxyproline and phosphorus occurred on the day of infusion in all subjects except 2 with chronic renal insufficiency, in whom they occurred on the day after infusion. The results indicate that the test may be of value in evaluating parathyroid function.

Three principal findings have resulted from this study: (1.) The plasma insulin response to glucose loading is lower in prediabetics than in normal individuals. This phenomenon, while apparent when the glucose and insulin curves are expressed as a function of time, can be better demonstrated and quantitated by expressing plasma insulin concentration as a function of glucose concentration during the early portion of the glucose tolerance curve. The findings in this report suggest the sensitivity of the pancreatic β cells of prediabetics to glucose stimulation is lower than that of normal persons. (2.) A low plasma insulin response to glucose loading is also seen in nonobese diabetic subjects. However, since these patients had elevated plasma glucose concentrations with insulin levels like those of the prediabetics, one must suspect that insulin in this group was less effective than in prediabetics in exerting its influence on blood glucose. Whether this is due to antagonists to insulin action or to physiologic defects in the immunoreactive insulin molecule has not been determined in this study. (3.) The same method of relating plasma insulin to glucose concentration was used in assessing the insulin secretion in an obese diabetic population. Diabetics with fasting glucose values in excess of 150 mg. per 100 ml. reveal a decreased insulin response to glucose stimulation. These findings suggest a decreased sensitivity of the β cells to glucose stimulation in this group.

A circadian rhythm in the urinary excretion of cyclic 3′,5′-adenosine monophosphate (cAMP) was demonstrated in 8 normal volunteers throughout a 48-hr period and studied under standardized conditions. The peak excretion occurs around noon particularly 9 am–12 midday with the nadir from 6 pm–9 pm. A post midnight rise was observed in 6 of the subjects. The demonstrated fluctuations were found to be statistically significant (p < 0.05). The daytime relationship of renal phosphate handling to urinary cAMP was determined revealing a direct correlation between cAMP excretion and phosphate clearance, and an inverse relationship between cAMP/g creatinine and tubular reabsorption of phosphorus.

A new case—the ninth—of documented xanthinuria is reported. The patient has no symptoms attributable to xanthine oxidase deficiency. Xanthinuria was detected after discovery of hypouricemia on chemical profile screening of serum. Twenty-four hour urine, with the patient on a low purine diet, showed mean values of 2.9 mg uric acid, 287 mg xanthine and 76 mg hypoxanthine. Urinary excretion of orotic acid and orotidine was normal.

Resection of 1,720 gm. of adipose tissue did not alter a chemical diabetic glucose tolerance and a late excessive plasma insulin rise in a patient with benign symmetric lipomatosis. This suggests that other factors than a feedback from adipose to the beta cell are responsible for the hyper-insulinemia of obesity.

In view of the tendency toward vascular disease in diabetes mellitus, we studied platelet aggregation in 15 normal, 7 prediabetic, 12 latent, and 20 frankly diabetic subjects. Platelets from latent and frank diabetics showed increased platelet aggregation 4 minutes after adding adenosine 5'-diphosphate (60% verus 29% at 1.0 mu-M), epinephrine (46% versus 14% at 0.25 mu-M), and collagen (72% versus 17% at 0.25 mu-g/ml). Three prediabetics had increased platelet aggregation. Platelet sensitivity to aggregating agents was most marked in frank diabetics, intermediate in latent diabetics, and least in prediabetics. Second-phase platelet aggregation was reversed with acetylsalicylic acid, intravenous tolbutamide, and oral glucose administration. We conclude that platelet aggregation may be increased early in diabetes mellitus and may be involved in the genesis of diabetic microangiopathy. Prospective studies on the effect of therapeutic agents such as acetylsalicylic acid on the natural course of diabetic vascular disease are indicated.

Glucagon-free insulin in doses of 0.003 to 0.2 units per kilogram of body weight was infused into the pancreatic artery and portal vein during anesthesia or in fully recovered dogs. The changes in blood glucose concentrations were not significantly different between the two sites of infusion with any of the doses employed. These data indicate that insulin does not affect endogenous insulin secretion by a direct pancreatic mechanism. It may operate by reducing the blood glucose or via some other metabolic change. Similar experiments were conducted with glucagon (0.2 μg.) in anesthetized dogs. Glucagon infusion into the pancreas or liver failed to affect insulin or glucagon secretion as evidenced by peripheral venous glucose response.

Renal handling of insulin was studied over plasma insulin levels of 6 to 40 μU per milliliter in 13 patients by renal-vein catheterization. The kidney in normal subjects and 7 patients with moderate renal insufficiency — glomerular filtration rate (GFR) over 22.5 ml per minute per kidney per 1.73 M2 — removed 39 ± 4 per cent (SD) of the insulin from arterial plasma. Severe renal insufficiency (GFR less than 6) reduced insulin uptake to 9 per cent in four subjects, two with diabetic glomerulosclerosis. Mean GFR in normal subjects was 61 ± 11 (SD) and renal insulin extraction —renal plasma flow (RPF) × % uptake — was 106 ± 28 (SD). These findings suggest that a decreased uptake of insulin by damaged kidneys accounts in part for the diminished insulin requirements seen in patients with diabetic glomerulosclerosis and that all the renal uptake of insulin cannot be explained by glomerular filtration alone.

A case of multiple endocrine adenomata and polycystic kidneys is reported. Functioning adenomata of the parathyroids and pancreas were removed surgically and a pituitary adenoma was associated with galactorrhea and amenorrhea. Serial plasma glucose and insulin determinations during sixteen months of observations confirmed the temporary efficacy of tumor resection and partial pancreatectomy for islet cell adenomata. The suspected presence of multiple pancreatic islet cell adenomata, not removed at surgery, was confirmed when hyperinsulinism and hypoglycemia returned several months postoperatively. With benzothiadiazine therapy, plasma glucose levels rose and insulin concentrations fell, suggesting that these drugs exert a diabetogenic effect primarily through inhibition of insulin secretion. This effect does not appear to be mediated through an adrenal mechanism since it was seen in spite of bilateral adrenalectomy in this patient. Evidence is presented which conflicts with the usual explanation for diabetic glucose tolerance curve in patients with functioning islet cell adenomata. In vitro studies with apparently uninvolved pancreas slices revealed that insulin secretion was stimulated by increasing concentrations of glucose. Insulin release occurred in vivo following oral glucose. Portal venous plasma insulin levels fell markedly only after resection of the normal tail of the pancreas. These findings indicated that there was no suppression of insulin output from the apparently uninvolved pancreas by the hyperinsulinemia associated with the tumor. During glucose tolerance testing, hyperglycemia was associated with hyperinsulinemia, a finding which supports a peripheral insensitivity to insulin's hypoglycemic action as a probable mechanism for the diabetic glucose tolerance in this patient. Finally, evidence is presented that apparently uninvolved pancreatic tissue responds in vitro to mannose, glucose, leucine and tolbutamide. The response to glucose can be blocked by 2-deoxyglucose, an agent which blocks the metabolism of glucose 6-phosphate. These findings suggest that insulin release in man is related to glucose phosphorylation or some product of glucose 6-phosphate metabolism.

SUMMARY Studies of immunoreactive insulin (IRI) and human growth hormone (HGH) secretion were undertaken in a subject with chronic hypoglycemia associated with hepatoma. Fasting IRI concentrations were below 3 μU./ml. at glucose concentrations of 30 mg./100 ml. IRI secretion was not stimulated by acutely administered glucose, tolbutamide, glucagon or arginine. IRI concentrations rose after tolbutamide when plasma glucose was raised to 100 mg./100 ml. by sustained glucose infusion. Fasting ILA (muscle, adipose) levels were not elevated. Fasting HGH concentrations were below 5 mμg./ml.; secretion was stimulated by arginine despite hypoglycemia. During glucose administration, HGH concentrations rose to 45 mμg./ml. as FFA levels fell from 2,250 to 233 μEq./L. Estimated total glucose utilization rate was high (7.5 mg./kg./hr. at a plasma glucose concentration of 100 mg./100 ml.). Conclusions (1) Glucose, or some metabolic product is required for human insulin secretion; (2) HGH secretion after arginine is not inhibited at low glucose concentrations; (3) FFA may exert an inhibitory role in HGH regulation; (4) Hypoglycemia in our subject with hepatoma was associated with increased glucose utilization, not with hyper-insulinism.

A state of hypercoagulability associated with changes in the clotting factors and platelet function has been postulated to be important in the increased thrombotic complications in diabetes mellitus. A fifty-nine-year-old man was admitted with severe diabetic ketoacidosis and shock. Shortly after restoration of his gross fluid and electrolyte imbalance, he developed extensive bleeding into his lungs and gastrointestinal tract. His serum was grossly lactescent. His blood was incoagulable. The existence of disseminated intravascular coagulation was indicated by a decrease in the platelet count and in the levels of fibrinogen, plasminogen, and Factors V and VIII. Plasminogen activator, plasmin, and fibrinogen degradation products all were increased in the plasma, as were cholesterol, triglycerides, phospholipids, total lipids, and free fatty acid concentrations. Postmortem examination revealed widespread hemorrhages. Microthrombi characteristic of platelet aggregates were present in his lungs and kidneys. Serial dilutions of his lipidemic plasma up to 1:150 resulted in increased ADP-induced aggregation of normal platelets. We postulate that the strong influence of the patient's plasma on platelet aggregation was the initial event leading to his disseminated intravascular coagulation. The finding of a platelet aggregation-enhancing factor in other diabetic subjects may shed light on the mechanism of thrombogenesis in diabetes.

Abnormal glucose tolerance tests and blunted plasma insulin responses returned to normal in three patients and improved in a fourth after removal of a pheochromocytoma. In two subjects phe...

This paper presents an analysis of the literature regarding the effect of control of diabetes on retinopathy. In diabetics with age of onset before forty years of age and with a duration greater than fifteen years, there is a significantly higher incidence of retinopathy in those judged to have been under poor control than in those with better control. Those patients with poor control had a significantly higher incidence of the more severe forms of diabetic retinopathy. While this association does not necessarily imply a cause and effect relationship, it is not compatible with a point of view which accepts poor control as of little consequence in diabetes.

Excerpt To the Editor:We have recently had the opportunity to study plasma glucose and insulin levels in a fifth patient with pheochromocytoma and would like to add our findings to those which we r...

Although pancreas transplantation in man is experimental and is carried out infrequently, lessons learned in this surgical event are applicable to more common abdominal procedures. Avoidance of pancreatitis in the graft, prevention of blowout of duodenal closure, and preservation of graft arterialization and venous outflow are of paramount importance. Physiologic principles learned in gastric, intestinal, and vascular surgery are utilized to achieve these objectives. A case report identifies the type of patient who is a candidate for pancreaticoduodenal and kidney grafting, and arteriographic and gastrointestinal contrast studies demonstrate the physiologic principles involved in the operation.

Excerpt Therapy has not previously altered the relentless progression of disseminated coccidioidomycosis. More than 50% mortality1continues despite treatment with a variety of agents.2, 4In the las...

A shock-like state occurred early during the performance of a standard glucose tolerance test in a patient with hypopituitarism. The reaction is interpreted as a dumping syndrome resulting from fluid transudation into the jejunum in a patient who was already hypotensive and hypovolemic.