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The unique ability of Carbon-13 nuclear magnetic resonance analysis with cross polarization/magic angle spinning techniques to investigate chemical structures of solids is used to probe the chemical characteristics of several gallstone types. New pulse program techniques are used to distinguish various carbon atoms in studying the polymeric nature of the black bilirubinoid pigment of pigment gallstones. Evidence for the involvement of the carboxyl group and noninvolvement of vinyl groups of bilirubinoids in the polymeric bond formation is presented. Conjugated bilirubin structures are found to be present in some solid residues from pigment stones extracted with acidic methanol/chloroform.

Two hundred forty patients with benign gastric ulcer were treated in a controlled clinical trial to assess the effect on healing of cimetidine, antacids, and hospitalization. Inpatients and outpatients were randomly assigned to one of three treatments: cimetidine plus antacid, cimetidine plus dummy antacid, or placebo tablet plus antacid. In 206 patients who met criteria for analysis, ulcer healing as shown by endoscopy occurred by 12 days in 11 to 26% and by 42 days in 58 to 76%. There were no significant differences in healing between hospitalized and nonhospitalized patients or between treatment subgroups. Symptomatic response was equivalent in all groups. The median antacid consumption was 328 mEq of in vitro buffering capacity per day. Patients taking antacids experienced significant diarrhea compared with those taking no antacid. This investigation suggests that the effect of cimetidine is equivalent to that of large amounts of antacid, but because a true placebo group was not studied it is not possible to conclude from this study alone whether either agent influenced healing. In contrast to widespread belief, initiation of treatment in the hospital did not enhance healing, but because patients were not randomly assigned to inpatient and outpatient status no final conclusion about the effect of hospitalization on healing can be drawn.

A case of Mediterranean anemia in an adult aggravated by the development of chronic hepatitis and cirrhosis is reported. The effects of liver disease on the bone marrow and of anemia on liver disease are discussed. A short course of treatment with ACTH resulted in a rise in the blood count and apparent clinical improvement which were not accompanied by any improvement in the liver function tests, the hemolytic index, the blood smear or the hepatosplenomegaly. These benefits, moreover, were only temporary and probably represented a nonspecific response.

Summary 1.A method for the study of biliary motility in resting man was described. It employed a cholecystographic agent labeled with tracer amounts of a γ-emitting radioisotope and appropriate apparatus for measurement of radioactivity in the gall bladder region. 2.With physiological stimulation, radio-activity diminished irregularly for a variable time and became steady. The period of decrement was not exponential, but an exponential function could be fitted to it approximately to derive a measurement of over-all emptying rate at the half time of emptying. The amounts of radioactivity before and after emptying provided a measure of over-all emptying efficiency as the per cent of emptying. 3.With control of collimation and positioning, the over-all emptying rate and efficiency were reproducible in individual subjects. Evidence was obtained that radiation from isotope in bloodstream, liver, or intestine did not affect results significantly. 4.Analysis of the period of radioactive decrement uncovered numerous changes in its rate. Generally, these components of the process of biliary evacuation began inefficiently and became effective after a mean interval of 21 min, often with a single productive phase which accomplished a major portion of the entire evacuation. 5.It was postulated that the steps in biliary emptying were the resultant of the moment-to-moment interplay between gall bladder contraction and resistance in the biliary sphincteric mechanism. 6.Physiological stimulation with fatty meals and continuous intravenous infusions of cholecystokinin gave similar results, although differences in the components of the emptying process with the latter delayed the onset of efficient evacuation. In contrast to both methods of stimulation, rapid intravenous injection of cholecystokinin induced brief and incomplete biliary evacuation.

THE development of gynecomastia is an uncommon result of excessive steroid hormone production by adrenocortical tumors. The present report concerns the thirty-fourth occurrence of this phenomenon recorded in the world literature (1–16). The findings of relative adrenocortical insufficiency, increased excretion of estrogen-like materials in the urine and the successful isolation of steroids from the tumor (17) are of special interest in this patient. CASE REPORT A 28-year-old radio announcer noted the onset of intermittently tender nipples in March 1953 and of bilateral breast enlargement in September 1953. There was progressive increase in size during the next twelve months. The patient was sufficiently embarrassed by this cosmetic defect to request admission to the Salt Lake Veterans Administration Hospital in March 1955 for evaluation and treatment. He had noted a veiy gradual decline in libido and potency during the two years prior to admission. There were no other symptoms and no fluctuations in weigh...

Jejunal activity was studied by recording intraluminal pressures with fluid-filled catheters in dogs with luminal occlusion and luminal plus vascular occlusion of the ileum. Simple luminal occlusion of the ileum produced little change in jejunal activity. Occlusion of the arterial and venous supply to a segment of ileum produced an immediate and prolonged inhibition of jejunal activity. The jejunum, thus inhibited, responded promptly to methacholine. It was possible to block or relieve the inhibition of jejunal activity by the administration of the α and β adrenergic blocking agents, phenoxybenzamine and propranolol.

In this study the influence of old age on adrcnocortical function and cortisol metabolism was investigated, along with renal, hepatic and thyroid function in 15 young men (25–40 years old) and 50 old men (60–96 years old). By the criteria of 8-a.m. plasma levels of free and conjugated 17-hydroxycorticosteroids (17-OH-CS) and the plasma corticoid response to ACTH stimulation, no significant change in adrenocortical function could be demonstrated with advancing age. However, there was a progressive and significant decrease in the urinary excretion of 17-OH-CS with aging. Following intravenous administration of a standard dose, cortisol disappeared from the circulation at a significantly slower rate in the old men. The maximal levels of plasma conjugated 17-OH-CS observed after cortisol infusion were statistically the same for all ages, but the rate of decay from peak values was slower in the older subjects. These alterations in cortisol metabolism were associated with a significant increase in the level of ...

Two cases of acute diffuse pulmonary granulomatosis are reported. A causative organism was not recovered. Inhalation of dust, which was raised by bridge scraping in rural Maryland and which may have contained bat guano, is considered responsible for the illness. The syndrome of acute diffuse pulmonary granulomatosis and its etiology are reviewed briefly. Inhalation of finely divided organic matter containing Histoplasma capsulatum is suggested as the probable cause of this syndrome.

Levels of free and conjugated 17-hydroxycorticosteroids (17-OHCS) in plasma were measured after intravenous infusions of cortisol, tetrahydrocortisone (Tetra E) and adrenocorticotropic hormone (ACTH) in subjects wi h hyperthyroidism and hypothyroidism. After administration of cortisol to hyperthyroid patients, the levels of free 17-OHCS decayed more rapidly than normal, while those of conjugated 17-OHCS rose faster and to higher values than in normal subjects. The opposite occurred in hypothyroid patients. Conjugation of administered Tetra E was increased in hyperthyroid patients but was normal in those with hypothyroidism. Plasma concentrations of free 17-OHCS were influenced more by the rate of removal from plasma than by the adrenal response to ACTH in both types of subjects. Accordingly the level of free 17-OHCS after ACTH was a misleading index of adrenocortical function, as the rise was greatest in hypothyroid patients and least in those with hyperthyroidism. The level of conjugated 17-OHCS after in...

Jejunal and ileal absorption of D-galactose, 3-methyl-D-glucose, D-xylose, sodium and water were studied in vivo in normal and alloxan diabetic rats. Contrary to previous studies, there was no consistent increase in sugar absorption in diabetic over normal rats. Diabetic rats absorbed significantly more sodium and water than normals, probably on the basis of diabetes-induced dehydration, but the increased sodium absorption did not stimulate increased sugar absorption. Diabetic rats, as did normal rats, showed increased jejunal over ileal sugar absorption but salt and water absorption were not different between the intestinal segments.

The new magic-angle spinning and cross polarization techniques for obtaining a 13 C solid NMR spectrum are applied to the characterization of human cholesterol, mixed cholesterol-pigment, calcium bilirubinate and bilirubin pigment gallstones. The stones divide into two general classes: the cholesterol stones and the bilirubin pigment stones. The cholesterol stones are very similar to each other whereas the bilirubin pigment stones exhibit considerably more variation in spectral features. The importance of other material and polymerization in the bilirubin pigment stones is discussed.

Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.

In subjects with chronic renal disease, levels of free 17-hydroxycorticosteroids (17-OHCS) in plasma were measured at 8 a.m. and were normal. Conjugated levels were elevated, correlating inversely with endogenous creatinine clearance (Clcr.). After standard infusions of cortisol, free levels decayed exponentially but more slowly than normal, while conjugated levels rose further than in normal subjects. Conjugated, but not free, 17-OHCS again correlated inversely with Clcr. Cortisol was partially identified in the free fraction and tetrahydrocortisol and tetrahydrocortisone in the conjugated fraction of plasma following infusion. Urinary excretion of 17-OHCS and the increment after infusion were less than normal and correlated directly with Clcr. A patient with anasarca provided an exception to the noted patterns and correlations. In subjects with acute renal failure, elevated levels of conjugated 17-OHCS in plasma did not decline with the onset of diuresis but fell in parallel with levels of blood urea. D...

A standard anticholinergic drug was compared to a sustained-release preparation of the same agent. Two 6-hr. doses of glycopyrrolate were equivalent to one dose of a glycopyrrolate Extentab in suppressing basal gastric secretion in subjects with acid-peptic disease.

A prospective study in which the value of four stool screening tests of malabsorption was assessed demonstrated that the Sudan stain for fat, with or without heat and acid, microscopic search for meat fibers and radiotriolein excretion, but not the gelatin film tests, was accurate in 69–79% of studies. Accuracy was lowest in mild steatorrhea and because of this, screening tests were least helpful in patients in whom these tests might have realized their greatest potential value for clinical diagnosis. With high meat intake, stool meal fibers proved as good as, or better than, the other methods for testing for nonspecific malabsorption. The gelatin film test, stool meat fibers and the differential results of the Sudan test before and after heat and acid were of no specific value in distinguishing patients with pancreatic insufficiency from those with other causes of malabsorption; their use for this purpose should be abandoned.

INTRODUCTION CONSIDERABLE information concerning the metabolism of the 17-hydroxycorticosteroids (17-OHCS) has accumulated as a result of the introduction of methods for measuring the free material in various body fluids (1). However, a sizable fraction of the total 17-OHCS in the plasma and the major portion of the 17-OHCS in the urine are not measured by these methods because the corticoids are esterified with glucuronic acid. The recent development of methods for the estimation of 17-OHCS conjugated with glucuronic acid (2) has made possible an extension of our knowledge of 17-OHCS metabolism. Techniques for the measurement of free and conjugated 17-OHCS have been employed in our laboratory to study 17-OHCS metabolism in a variety of clinical situations. The results of such studies in normal human subjects arc presented in this communication. These observations will be compared in subsequent papers with observations made in patients with thyroid (3), liver (4) and kidney (5) disease.

ALBRIGHT and associates,1in 1942, described a group of patients with hypocalcemia, hyperphosphatemia, ectopic calcification and ossification, dyschondroplasia manifested by short metacarpal and metatarsal bones, and a characteristic short, round body and round face. Tetany, convulsive symptoms, lenticular opacities, and calcification of the basal ganglia were also present. Unlike persons with idiopathic hypoparathyroidism, these patients had normal parathyroid glands and there was little or no phosphate diuresis in response to the administration of parathyroid extract. Having named this syndrome pseudohypoparathyroidism, Albright and associates * postulated the presence of multiple, independent genetic defects to account for the stigmata noted and suggested that the hypocalcemia and hyperphosphatemia resulted from a failure of end-organ response to endogenous parathyroid hormone. Subsequently, there appeared case reports3of persons with some but not all of the stigmata described by Albright and associates. The term pseudopseudohypoparathyroidism has been applied to the condition in which hypocalcemia (and

A synthetic mixture of uroporphyrin isomers I, II, III and IV as free acids in the synthetic ratio of 1:1:4:2 was resolved by reverse-phase HPLC using a C0:PEL (ODS) 37-50 micron precolumn and a Micro Bondapak C18 analytical column eluted with acetonitrile (4%) in phosphate buffer (pH 6.95). Clinically important I and III isomers of uroporphyrin were readily resolved directly from acidified urine as porphyrin free acids.

Examination of ova and parasites from coprolites of probable human origin revealed eggs of the phylum Acanthocephala. Specimens were gathered from Danger Cave in Utah, an area heavily populatd with definitive rodent hosts for the Acanthocephala species Moniliformis clarki. It is postulated that prehistoric man developed Acanthocephala infection by ingesting the arthropod intermediate host, or that he was a victim of false parasitism by ingesting the whole rodent.

Recently the Food and Drug Administration approved cimetidine for the treatment of benign gastric ulcer. Approval was based in part on the results of our large multicenter trial involving 172 patients with benign gastric ulcer between 0.5 and 2.5 cm in diameter: 87 were randomly assigned to receive cimetidine (300 mg four times daily) and 85 to receive placebo. Cimetidine treatment resulted in significantly more rapid healing than placebo; after 2 and 6 weeks of therapy, 10.0% and 44.8% of patients receiving placebo were healed, as compared to 22.6% and 65.1% receiving cimetidine. The results of our study were compared with the time-response curve previously published (0, 4, and 8 weeks of therapy). The combined data yielded linear healing rates for the first 8 weeks of therapy (r greater than 0.99 for both cimetidine and placebo). These studies can be used to define expectations for healing of benign gastric ulcer, and we recommend follow-up intervals of 8 and, if unhealed, 16 weeks.

During the last decade the tremendous interest in the adrenocortical hormones has led to an appreciation of the central role of the liver in their metabolism. Early observations of corticoid metabolism in liver disease suggested that there was hyperactivity of the adrenal cortex. 1-5 This conclusion was based largely on measurements of the urine corticoids by techniques which did not detect the conjugated metabolites, the largest fraction of the adrenocortical endproducts. Studies utilizing more specific methods for the metabolites in plasma and urine have furnished data which are not in keeping with the earlier reports. 6-8 In man, the principal corticosteroids elaborated by the adrenal cortex are hydrocortisone (cortisol, 17-hydroxycorticosterone, pregn - 4 - ene -11β,17α,21 - triol - 3,20- dione, Compound F), corticosterone (pregn-4ene-11β,21-diol-3,20-dione, Compound B), and aldosterone (pregn-4-ene-11β,21-diol-3, 20-dione-18-al). The largest fraction is hydrocortisone (Fig. 1). The Porter-Silber reaction 9 measures the corticoids which react with phenylhydrazine because of their 17, 21-dihydroxy-20-ketone