Transient protein-losing enteropathy secondary to elevated caval pressures and caval obstruction after the Mustard procedure. Protein-losing enteropathy, documented by 51Cr-labeled albumin excretion studies, was demonstrated in a 24-month-old girl following the Mustard operation for complete transposition. Apparent postoperative inferior vena cava obstruction had been diagnosed by angiocardiograms and both caval pressure were found to be elevated. There was no evidence of primary renal or hepatic disease or cardiac failure. This problem may occur more frequently than has been recognized.


Anatomic variations in underdeveloped right ventricle related to tricuspid atresia and stenosis. In the anatomy of 416 hearts, the seat of tricuspid stenosis or atresia is examined, with special reference to Fontan-like surgical procedures. A classification is offered which includes cases with and without regular or inverted transposition, and with decreased or increased pulmonary flow. The size and thickness of the right atrium, the size and architecture of the right ventricle, the size of the pulmonary tree, the types of atrial and ventricular septal defects, the condition of the mitral valve, and the size and thickness of the left atrium and left ventricle are analyzed. In addition the various intracardiac and extracardiac abnormalities are enumerated. Reference is also made to the tendency of the aorta and pulmonary trunk to override the septum, in some cases producing double-outlet left ventricle. It is considered that many cases of tricuspid valve atresia and stenosis with or without transposition may be amenable to Fontan-like procedures in the proper age group. All the above anatomic considerations have a bearing on the suitability and type of operative tricuspid bypass procedures, and they may influence the prognosis of surgical therapy.


Leiomyosarcoma of the superior vena cava. A first case with resection. Leiomysarcomas, rare malignant tumors of the veins, are located predominantly in the inferior vena cava. We report our experience with a leiomyosarcoma in the superior vena cava of a 44-year-old white man. The lesion had been locally excised and then recurred 2 1/2 years later. The recurrent tumor was widely excised and the superior vena cava was repaired with a saphenous vein patch graft. The area of the recurrence was treated with cobalt 60 therapy. Four years later, 6 1/2 years after initial treatment, the patient is alive and well without evidence of recurrence.


The dynamic aortic root. Its role in aortic valve function. By attaching appropriate measuring devices to the wall of an intact aortic root at the level of leaflet coaptation, we have measured a 16 per cent diameter change during each cardiac cycle. The dimensional changes observed can by themselves explain aortic valve function and obviate the postulation that the leaflets shorten and lengthen during each cardiac cycle. The tissue composition of the aortic root and leaflets is more compatible with this theory than with other postulations. Such a dynamic aortic root may explain the longevity of the actual aortic leaflets, in that leaflet fatigue stress is minimized by changes in aortic root dimension.


Thrombus of inferior vena cava presenting as right atrial tumor. Roentgenographic, phonoechocardiographic, angiographic, and surgical findings. A large tumor of the right atrium was found to be only the precimal end of a bland thrombus of the inferior vena cava. Of special interest were certain echocardiographic findings, including persistent delay in closure of the tricuspid valve after successful removal of the thrombus.


Pulmonary valve cyst in an adult. Case report. A case is described of an asymptomatic woman who had typical findings of mild pulmonic stenosis. Right heart catheterization revealed a 44 mm. Hg gradient across the pulmonary outflow tract, and a filling defect was discovered by angiography. On surgical exploration, the defect was found to be a benign cyst attached to the anterior leaflet of the pulmonary valve.


Rapid overdrive pacing of refractory tachyarrhythmias in patients after open-heart surgery. The efficacy of rapid ventricular pacemaker overdrive in the treatment of supraventricular and ventricular tachyarrhythmias is presented as a new approach to the management of these rhythm disorders inpatients after cardiac surgery. This mode of therapy is exemplified in the control of heart rate and return of normal sinus rhythm in patients with both types of tachyarrhythmias refractory to conventional antiarrhythmic agents. In addition, the pathogenesis and mechanisms of pacemaker overdrive in termination these rhythm disturbances are delineated.


Quinidine syncope. A report of successful treatment with bretylium tosylate. Quinidine syncope is an unpredictable side effect of quinidine administrateion which has a mortality rate of 11.5 per cent when managed with conventional drugs and direct-current countershock. In 2 patients with quindine syncope, the arrhythmias were effectively controlled within 30 minutes following the slow infusion of 150 mg. of bretylium tosylate. This control is contrasted with 2 cases managed in the conventional manner. Bretylium tosylate is a quaternary amine with unique antifibrillatory properties and appears to have a significant role in the management of these arrhylmias.


The role of lymphatics in the formation of ascites complicating schistosomal hepatic fibrosis. The total protein content in plasma, ascitic fluid, thoracic duct lymph, hepatic and intestinal lymph was studied in a series of 15 patients suffering from schistosomal hepatic fibrosis and intractable ascites. Pure schistosomal cases with presinusoidal resistance to portal blood flow have excessive thoracic duct lymph low in protein. The main source of such excess lymph is the extra-hepatic portal bed. Ascitic fluid in such patients has a low protein content and has the character of a transudate. The bulk of such peritoneal fluid seems to originate largely from the excess extrahepatic portal lymph.


Percutaneous trans hepatic lymphography: evaluation in schistosomal hepatic fibrosis. The increased interest in lymph and lymphatics has cast its mantle over the portal circulation. Lymphography has contributed greately to our knowledge. In the present study percutaneous transhepatic lymphography showed some of the factors sharing in the production of portal hypertension in schistosomal hepatic fibrosis, and gave a further evidence that the liver is not a source of excess lymph production in hepatic lesions associated with presinusoidal block to portal blood flow. Hepatic lymphatics were opacified in cases with mixed cirrhosis and schistosomal hepatic fibrosis as the sinusoidal pressure is elevated with subsequent cases increase in hepatic lymph production.


Cervical lymphato-venous shunt in treatment of ascites in caval-constricted dogs and in patients with hepatic cirrhosis. Experimental observations and 7 years clinical experience. In experimental ascites produced by inferior vena caval constriction there is a pressure gradient at the thoracic duct-venous junction suggesting a functional obstacle to lymph flow. Abdominal fluid and protein are transported mainly by the right lymph trunk and not by the thoracic duct. External drainage of the thoracic duct or construction of a new, wider thoracic duct-venous anastomosis facilitates, however, transport of excess capillary filtrate formed in the liver and decreases fluid spillage into the peritoneal cavity. Construction of a cervical lymphato-venous anastomosis was attempted in 21 patients, 20 of whom had cirrhosis, and the operation was technically successful in 16 cases. Operation was helpful in cirrhotic patients with rapid ascites formation, who required less frequent abdominal paracenteses operation. The shunt was without benefit in prevention of oesophageal varix bleedings, and it should not be attempted in patients with icterus and severe deterioration of liver function.


Lymphographical findings in disseminated tuberculosis without radiological lung manifestations. Lymphographical findings are presented in three patients with verified tuberculosis. The diagnosis of tuberculosis was difficult in these patients because there were no actual changes in chest radiographs and the clinical findings were generally nonspecific. In each patient, lymphographic changes in lumbar lymph nodes were established. These changes corresponded to those described in the literature in connection with tuberculosis. Thus, the lymphographical findings can here be considered to be a further criterion for the diagnosis of tuberculosis. Lymphographical follow-up also proved beneficial in the follow-up of treatment results in one patient. Suspected tuberculosis, in which local findings cannot be made available by other means, can be regarded as one of the indications for a lymphography.


Lymphatics of the canine papillary muscles. A relatively dense concentration of lymphatics in the region of the papillary muscles of the canine left ventricle has been described. It is suggested that these channels may play a role in the development of pathologic changes affecting the mitral valve apparatus which could subsequently cause valve dysfunction.


The bicuspid nature of the valves of the peripheral collecting lymphatic vessels of the dog. A controversy presently exists about the structure of lymphatic valves, the bicuspid structure vs. the funnel-like architechture. This present study, along with a review of the literature was undertaken in an attempt to clarify this controversy. Twenty lymphatic valves from the collecting lymphatic channels draining the back paw region in four dogs were examined and several were photographed. The bicuspid nature and the three dimensional anatomy of these valves is clearly demonstrated.


The early postprandial dumping syndrome: clinical manifestations and pathogenesis. Our present concept of the pathogenesis of the early postprandial dumping syndrome is well summarized by Jesseph. Resection, division or bypass of the sphincter mechanism at the gastric outlet permits rapid passage of hyperosmolar material into the upper small intestine. This provides direct stimulation of the enterochromaffin (argentaffin) cells in the mucosa, which are highly concentrated here. The hyperosmolarity pulls fluid into the intestine resulting in a fall in plasma volume and distention of the intestine, further stimulating secretion by the argentaffin tissue. The plasma volume per se probably has little, if anything, to do with the symptoms produced although the outpouring of intravascular fluid into the intestinal lumen probably contributes to intestinal hyperperistalsis and the resultant symptoms of intestinal hurry. Although other sources are possible, studies to date would indicate that the argentaffin cells are the major source of humoral agents. In addition to serotonin, at least one vasoactive polypeptide, bradykinin, has been identified. It is likely that others are present and pharmacologic therapy will probably not be successful until these are more completely identified and characterized. The known biologic effects of serotonin and the kinins can certainly account for all the vasomotor and gastrointestinal symptoms characterizing the early postprandial dumping syndrome.


Gastric remnant carcinoma.

Gastric remnant carcinoma. Over 1200 cases of carcinoma of the gastric remnant have been reported in the literature. There is an increase of this type of carcinoma in postoperative stomachs with atrophic gastritis and intestinal metaplasia. The cause and effect relationships remain to be fully elucidated. In patients with late postgastrectomy symptoms, carcinoma of the gastric remnant should be considered in the differential diagnosis. In a study of 350 asymptomatic patients who were more than 20 years from Billroth II gastric resection, 14 carcinomas were discovered in the region of the stoma. Preoperatively, gross endoscopic appearance and multiple biopsies will usually provide the diagnosis. At the time of revisional surgery, frozen section of gastric biopsies or the resected specimen may be necessary to exclude the diagnosis. At present there is widespread interest in several procedures in the treatment of benign ulcer disease. In selected patients, proximal gastric vagotomy is receiving particular interest. It remains to be determined what, if any, gastric mucosal alterations occur. Since the pyloric mechanism is intact, no stoma is created and no portion of the stomach resected; long-term followup of these patients will be of interest. Information as to the cause of gastric remnant carcinoma can be forthcoming only by evaluation of all groups of patients requiring gastric surgery for benign disease. At the same time, further investigation of patients with gastric carcinoma without prior resection who have atrophic gastritis and intestinal metaplasia is also necessary. The histologic type of carcinoma that develops in the gastric remnant is usually more favorable for surgical cure than those seen in the intact stomach. This means that early diagnosis by radiologic and endoscopic study of postgastrectomy patients developing symptoms is highly desirable. Because of the long interval between gastrectomy and gastric remnant carcinoma these patients are often in the older age group. The location of the lesion in the remaining proximal stomach will nearly always require total gastrectomy. This plus the age factor means that the operative mortality will be rather high. We are unable to explain why in 22 years of observing postgastrectomy patients we have seen only one case of gastric remnant carcinoma. This patient was successfully treated by left transpleural transdiaphragmatic total gastrectomy with Roux-en-Y esophagojejunostomy. This method is particulary easy in the patient who has has an antecolic Billroth II gastrectomy. If the jejunum cannot be adequately mobilized through a radial incision extending laterally from the esophageal hiatus, we use a peripheral diaphragmatic incision in circumferential fashion. This gives excellent exposure of the upper abdominal contents and also preserves the phrenic nerve. As a result, ventilatory function of the left leaf of the diaphragm is preserved postoperatively.


Conformational transitions of polypeptides in ternary solvent systems. Phase diagrams for conformational transitions of polypeptides in ternary organic solvent systems containing two active and one inert component are calculated for a model which takes into account possible interaction of the two active components with each other as well as with the polypeptide backbone. The results of experimental determinations of conformational transitions and isothermal phase boundaries for poly(beta-benzyl L-asparate) (PBA) in three-model solvent systems are in generally good accord with the theory. The solvent systems are: (a) 1-chloropropionic acid-dichloroacetic acid (DCA)-1,1,2,2-tetrachloroethane (TCE), (b) monochloroacetic acid-DCA-TCE, and (c) dimethyl sulfoxide-DCA-TCE.


Hematologic abnormalities following gastric resection. The anemia observed in patients with partial gastric resection results from a complex interrelationship of deficiencies of these three important hematemics-iron, vitamin B12, and folic acid. Reliance upon morphological evidence of anemia in the peripheral blood smear may be difficult and confusing since deficiency of one hematemic may mask the coexisting deficiency of another. It is common for deficiencies of more than one hematemic to occur in these patients. A number of studies have demonstrated the masking effect of iron deficiency on concurrent vitamin B12 or folic acid deficiency. In addition, the morphologic hallmarks of iron deficiency may be modified by the presence of deficiencies of either vitamin B12 or folate or both. Full hematologic recovery may not occur until more than one hematemic is given to the patient. It is our policy at the University of Florida to rely on serum levels of these three hematemics, especially vitamin B12 and iron, to detect the cause of the anemia in a patient with partial gastric resection. Less reliance is placed upon the appearance of the peripheral smear because of the masking effect described above. If either the serum iron level or vitamin B12 level is decreased, we treat the patient with a preparation such as ferrous sulfate (300 mg. orally three times a day) and vitamin B12 (100 mug. intramuscularly once a month). We are less concerned with folic acid deficiency because of its relatively infrequent occurrence in this setting and because a good diet will usually suffice as adequate therapy for the folic acid deficiency when present. In patients who have had partial gastric resection but who are not anemic, we assess vitamin B12 absorption by the conventional vitamin B12 urinary excretion test (Schilling test) on a yearly basis since deficiency of this hematemic may lead to serious hematologic and neurologic sequelae. If the patient manifests decreased vitamin B12 absorption uncorrected by the administration of pancreatic extract or antibiotics, this patient is also treated with 100 mug. of vitamin B12 intramuscularly on a monthly basis. We have not evaluated the absorption of food B12 as suggested by Doscherholmen. Perhaps more attention should be paid to this aspect of vitamin B12 absorption in these patients. Indeed, because of the serious complications of vitamin B12 deficiency and the observations that deficiencies of this vitamin may occur even when the absorption of crystalline vitamin B12 is normal in the fasting state (the conventional Schilling test), some authors, such as Rygvold, have suggested that prophylactic vitamin B12 be administered to all patients with partial gastric resection.


Malabsorption following gastric resection. We have tried to stress the complexity of the bacterial ecology that may exist in the intestine of patients and experimental animals with small intestinal bacterial overgrowth. The multiplicity of organisms often makes the management of these patients quite frustrating. A number of metabolic derangements of varying severity may occur in any given patient. Although many of the observed abnormalities are secondary to disturbed events with the luminal environment of the small intestine, the significance of direct damage to the small intestinal epithelium has been emphasized. Since intestinal cultures are both cumbersome and difficult to perform on a routine basis, the use of labeled substrate breath tests will allow guided, outpatient therapy more easily than in the past. Since full correction of the malabsorption is seldom achieved with antibiotic therapy, nutritional supplementation deserves more attention than it has previously received.


The early postprandial dumping syndrome: prevention and treatment. The early postprandial dumping syndrome can be prevented or minimized by the appropriate selection of the operative procedure to fit the patient and the peptic ulcer problem he presents, and by proper attention to diet in the early postoperative period. When it does occur, the syndrome usually responds favorably to dietary management and tends to spontaneously regress in severity with time. For these reasons further surgery is seldom required for the early postprandial dumping syndrome. In the patient who fails to improve with diet therapy and time and has disabling symptoms often accompanied by progressive malnutrition, revisional surgery should be undertaken. It is the objective of the surgeon to alter the reconstruction in such a way that emptying from the stomach or gastric remnant is delayed. Therefore, the upper small intestine dose not receive a large, rapidly introduced hyperosmolar bolus to initiate the release of humoral substances causing the syndrome. All revisions utilized are potentially ulcerogenic and if vagotomy has not been a part of the original procedure, it should routinely be performed at the time of revision. Patients who have primarily has a Billroth II gastrectomy will frequently improve markedly with simple conversion to a Billroth I reconstruction. This is particularly true when the residual stomach is moderately large (i.e., after antrectomy) and when the gastrojejunal stoma is larger in diameter than the normal jejunum. Under such circumstances approximately 80 per cent of patients will improve sufficiently so that a more complex procedure need not be utilized at once. Under all other conditions we prefer a 10 cm. segment of reversed jejunum anastomosed proximally to the gastric stump and distally to a 40 cm. isoperistaltic Roux-en-Y jejunal limb. This procedure is so successful that one can justify its use as first recourse even in the anatomically favorable Billroth II patient. It should be pointed out emphatically that an isoperistaltic jejunal interposition (Henley loop) has little or no effect on the early postprandial dumping syndrome and should not be considered. Plicated loops of intestine to recreate a gastric reservoir frequently fail to empty satisfactorily and the incidence of satisfactory results is too low to consider their utilization in surgical treatment of the dumping syndrome.


Complications following gastric surgery in children. Although the diagnosis of peptic ulcer disease may be difficult in the pediatric age group, this problem is being faced increasingly by the physicians charged with the care of these children. Chronicity of symptoms has been documented in over 50 per cent of the patients demonstrating early peptic ulcers and therefore an aggressive approach to management has been advocated. Although the numbers are small, postgastrectomy syndromes of mechanical and nutritional nature appear less common in the young patient than in adults. Satisfactory growth and development are reported in nearly all series of patients followed after various gastric procedures. Both pyloroplasty and vagotomy and vagotomy and antrectomy appear to be extraordinarily well tolerated by the pediatric patient. Experimental evidence suggests that these patients should enjoy normal growth and development.


Monte Carlo calculations on polypeptide chains. IX. A study of the effect of long-range interactions on the helix-coil transition. A Monte Carlo statistical mechanical study of the helix-coil transition for a hard-sphere model of poly(L-alanine) has been conducted base on the theory of Lifson and Roig but including the effects of long-range interactions. A stochastic model of the kinetics of the helix-coil transition is presented, and a Monte Carlo stimulation of the kinetics based on this model was used to generate equilibrium chain samples, each chain of which consisted of Lifson-Roig weighted sequences of helix and coil residues. Each of the chains in this sample was then used many times by assigning at random specific sterically allowed coil states from a hard-sphere Ramachandran dipeptide map. Unperturbed properties were then calculated using this sample and perturbed properties by using only the non-self-conflicting subset. The properties calculated were the average degree of hydrogen bonding, the average length of a helical sequence, the mean-square end-to-end distance, the mean-square radius of gyration, and the distribution functions for the end-to-end distance and radius of gyration. This study was conducted at chain lengths 10, 34, and 85 residues. Helix-coil transition theory was fit to the perturbed transition curves in an attempt to ascertain if theory could then predict the perturbed values of the dimensions. For the hard-sphere model used in these calculations, it was found that current helix-coil transition theory does not predict the correct perturbed dimensions.


The afferent loop syndrome.

The afferent loop syndrome. The afferent loop syndromes result from obstruction to the afferent jejunal loop. Acute ALS results from complete obstruction, usually occurs early after surgery and runs a devastatingly lethal course unless promptly treated by reoperation. In chronic ALS the obstruction is intermittent and produces a clinical syndrome from which a diagnostic histroy can usually be obtained. Although the exact incidence is unknown, it is certainly not rare, especially in antecolic Billroth II gastrectomies. Treatment consists of doing away with the afferent loop. In gastroenterostomy alone takedown of the anastomosis with a Weinberg pyloroplasty is the treatment of choice. The safest and simplest treatment for patients whose original operation was Billroth II gastrectomy is conversion to a Roux-en-Y procedure. In all cases vagotomy should be added unless previously performed. No medical treatment is available and patients with no other contraindication should have revisional surgery if symptoms are clinically significant. Both acute and chronic afferent loop syndromes should be completely prevented by appropriate choice of the initial operative procedure. The vagotomized stomach should be drained by pyloroplasty, not gastrojejunostomy. Vagotomy and antrectomy should be reconstructed with a Billroth I gastroduodenostomy. The Braun enteroanastomosis should be utilized after subtotal gastrectomy for carcinoma. The wider application of parietal cell vagotomy for duodenal ulcer deserves close observation and further consideration.


Alkaline reflux gastritis.

Alkaline reflux gastritis. Any surgical procedure that ablates the pyloric sphincter mechanism permits increased reflux of duodenal fluid into the stomach or gastric remnant. Although it is reported as most common with Billroth II gastrectomy, our experience indicates that reflux is nearly as frequent after Billroth I gastroduodenostomy and is not at all infrequent after pyloroplasty. The precise constituents of duodenal fluid which damage the gastric mucosa remain controversial. The best present evidence is that the bile acids are probably essential, but that one or more other constituents of duodenal content are also necessary. The clinical history differs significantly from chronic afferent loop syndrome in that the quality of pain is different, pain tends to be more continuous and less closely related to food-taking, and bile vomiting does not provide dramatic relief, often containing food due to coexistent interference with gastric emptying. Diagnosis is confirmed by gross endoscopic findings and characteristic histopathologic changes in the endoscopic biopsies. Treatment with an interposed isoperistaltic jejunal segment has been disappointing. Only four of ten patients experienced lasting relief, indicating that the relatively short 10 to 12 cm. of jejunum does not adequately prevent duodenogastric reflux. We have, therefore, shifted to the Roux-en-Y duodenal diversion implanting the afferent limb 40 cm. caudad to the gastrojejunostomy. Results have been excellent in 24 of 25 cases with prompt improvement in gastric emptying, absence of bile vomiting, progressive regression in abdominal distress and progressive improvement in nutrition. Endoscopic evaluation at three to four months has indicated marked gross improvement and striking histologic improvement in 23 of 25 cases. The question is raised whether the Roux-en-Y reconstruction should not be used primarily, particularly if both vagotomy and antrectomy are to be performed for peptic ulcer. Both the afferent loop syndrome and alkaline reflux gastritis would be prevented, and it is doubted that the incidence of marginal ulcer would increase appreciably.


Gastrin and gastric surgery.

Gastrin and gastric surgery. The development of the radioimmunoassay for gastrin has resulted in significant increases in our knowledge of the physiology of the stomach and antrum, and in an objective recognition of the interaction of the gastrin and vagus mechanisms. Recent identification of multiple species of gastrin in the circulation, however, raises questions as to the significance of early experimental results. Until the various aspects of gastrin and their relative contributions in the normal state and in pathologic processes are identified, the significance of gastrin levels in the evaluation of patients with uncomplicated ulcer disease is unclear. Although many investigators have attempted to correlate changes in serum gastrin levels in response to various stimuli with the completeness of vagotomy or the likelihood of recurrence, it is too early to give any clinical significance to these reports. Several points in particular seem worthy of emphasis: 1. Preoperative serum gastrin levels are currently of no value in selecting an operation for the treatment of duodenal ulcer disease. 2. The difference in serum gastrin levels in response to feeding that may be shown to exist between groups of normal subjects and duodenal ulcer patients is not a value in diagnosing ulcer disease in a specific patient, nor in differentiating duodenal ulcer from other conditions. 3. The measurement of serum gastrin levels in association with Hollander tests, while perhaps of potential future benefit, does not improve the accuracy of the Hollander test nor do results necessarily relate to vagal innervation. 4. Postoperative serum gastrin levels are increased after vagotomy. The degree of hypergastrinemia after vagotomy does not correlate with risk of ulcer recurrence. 5. Hypergastrinemia (greater than 1000 pg. per ml.) in the presence of hyperacidity is essentially pathognomonic of the Zollinger-Ellison syndrome. Calcium and secretin infusions do not add to the diagnosis if clear-cut clinical and laboratory data are present. These differential tests are of value in identifying the Zollinger-Ellison patient who has borderline serum gastrin levels and in differentiation from the syndrome of the retained antrum. 6. In a patient with a recurrent ulcer following surgery in whom a drug-induced ulcer can be excluded and gastric outlet obstruction cannot be demonstrated, a serum gastrin level may be indicated. A serum gastrin value greater than 300 pg. per ml. (normal less than 200 pg. per ml.) in a fasting morning serum sample is significantly elevated, even after vagotomy, and warrants further investigation. Provocative testing of the gastrin response to calcium and secretin should elucidate the etiology of the recurrent ulceration in this type of patient.


Patient resistance and prognosis in amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis is usually considered a disease that will have a fatal termination in 1 to 3 years. A prospective study of 100 patients with this disorder revealed that 20 of them were living 5 years after the onset of their disorder. Review of other published series reveals that patients have been reported who lived for longer than 5 years and have then usually been reported as atypical cases, although the only way in which they are described as atypical is the duration of the disease. It is our assumption, based on these data as well as on additional clinical observations, that many patients with amyotrophic lateral sclerosis live for longer than 5 years and, rarely, they may have remissions of their illness. The possible significance of these observations is discussed.


Hemoccult stool tests: false-negative results due to storage of specimens. Stoll samples mixed with 0 to 38 mg of hemoglobin per gram of stool were tested for occult blood by the Hemoccult (HO) method when fresh and after storage for 1 to 14 days. The intensity of the HO reaction in fresh stool samples was directly related to the hemoglobin concentration, and approximately 8 mg/g was required for a positive reaction. After samples had been stored on HO cards for 4 days, the intensity of the HO reaction was decidedly less in all. Except at the highest concentrations studied, all became HO-negative or trace within 8 days. In contrast, samples of most concentrations that were stored in tightly capped containers prior to preparation of HO cards maintained a positive reaction intensity for 1 week. Nevertheless, the intensity of the HO reaction decreased significantly (P less than 0.01) with each method of storage. No false-positives were induced by storage during this portion of our study. Samples from 100 stool specimens sent to the clinical laboratory for determination of occult blood were also smeared on separate HO cards for testing immediately and after 4, 7, or 10 days of storage. Only one positive HO reaction was observed on an HO card prepared from a specimen initially classified as HO-negative. In contrast, up to 40% of the stored HO cards prepared from specimens initially classified as HO-positive were HO-negative when analyzed 4 days later.


Total respiratory resistance by forced oscillation in normal subjects. Total respiratory resistance (Rrs) was studied by the forced oscillation technique at a frequency of 3 cps in 76 normal subjects (36 men, 40 women), ages 21 to 64 years. Slopes (equivalent to specific conductance) assuming a linear relationship with zero intercept between 1/Rrs and thoracic gas volume (TGV) were computed. In women, expiratory slopes were significantly less than inspiratory slopes; moreover, slopes decreased significantly with height and were significantly less in current smokers. For men, there were no consistently significant relationships between slopes and phase, age, height, weight, or smoking habits. Predicted resistance and estimates of the 5th and 95th percentiles of inspiratory, expiratory, and average resistance are presented for all men combined and for currently nonsmoking women. The fact that, in contrast to men, asymptomatic, current women smokers showed an elevation in Rrs when compared to nonsmoking women merits further study.


Vaginal flora in asymptomatic women.

Vaginal flora in asymptomatic women. Four groups of 25 asymptomatic women--pregnant, premenopausal and taking oral contraceptives, premenopausal and not taking oral contraceptives, and postmenopausal--were studied for the presence in vaginal specimens of aerobic bacteria, anaerobic bacteria, fungi, Mycoplasma, Chlamydia, herpes simplex virus, mycobacteria, and Trichomonas. No significant differences in microbial flora were found among the groups.


Midline tilting between seeing and nonseeing areas in hemianopia. The line separating the seeing from the nonseeing parts of the visual field was found to be tilted away from the expected vertical position in 24 of 200 patients diagnosed as having various types of hemianopia, including homonymous hemianopia, homonymous quadrant hemianopia, homonymous scotomata, and bitemporal hemianopia. The causes of these defects include vascular accidents, trauma, tumor, and neurosurgery for convulsive disorders. Once discovered by standard monocular field testing methods, the existence of the tilting phenomenon was distinguished from testing artifact by employing binocular fixation and red-green glasses along with red and green test objects. A difference in the overlapping fields of the two eyes was found to exist only in areas where corresponding lines between seeing and nonseeing fields were separated by a tilting away from the vertical in one or both eyes. This can occur superiorly or inferiorly with homonymous scotomata, and in bitemporal hemianopia as well as in homonymous hemianopia or quadrant hemianopia. This incongruity of fields is possibly explained by a variation in anatomic determination of crossing from noncrossing fibers at the level of the retina.


Ricinoleic acid effects on rabbit intestine: an ultrastructural study. In fasting rabbits, segments of ileum and colon were perfused with ricinoleic acid. This fatty acid is the active principle of castor oil and stimulates intestinal fluid secretion. Biopsies taken from perfused segments were examined by electron microscopy after staining with lanthanum hydroxide and ruthenium red. These stains, which typically bind to extracellular surfaces, were used to assess the integrity of junctional zones between cells. In this study, ricinoleate did not alter ruthenium or lanthanum staining in junctional areas, a finding suggesting that ricinoleate does not cause fluid secretion by selectively disrupting these areas.


Decreased unscheduled DNA synthesis in nondividing aged WI38 cells. The ability of cells from young and old cultures of WI38 human fibroblasts to undergo unscheduled DNA synthesis was studied. Following inhibition of semi-conservative synthesis in media lacking arginine and containing a hydroxyurea block, cells were irradiated with u.v. light and repair replication was measured by determination of specific activity of DNA and by autoradiography. Unscheduled DNA synthetic capacity was significantly reduced in old cultures. Quantitation of silver grains revealed that this reduction was a result of decreased repair activity by individual cells, which correlated well with a similar decrease in the proportion of dividing cells in the population. This observation that unscheduled DNA synthesis is reduced in older cells is in apparent contradiction to some earlier reports, and the failure of other investigators to identify aging changes in repair capacity is discussed in relation to differences in experimental procedure.


Ovarian development in athymic nude mice V. The effects of PMSG upon the numbers and growth of follicles in the early juvenile ovary. The composition and growth patterns of the ovarian follicle population have been determined in early juvenile athymic nude mice and their phenotypically normal littermates. Nude ovaries contained significantly more primordial follicles and fewer trilaminar follicles at 10 days of age. The rate of growth of the oocyte nucleolus was significantly less than in control ovaries. Treatment with PMSG from days 7 to 9 restored the rate of oocyte nucleolar growth in nudes to control levels. PMSG also increased the number of follicles commencing growth in both nudes and controls and the differences in the numbers of primordial and trilaminar follicles were no longer detectable. The data demonstrate that abnormalities in the ovarian follicle population of the nude are detectable as early as the 10th day of life and can be reversed by treatment with exogenous gonadotrophin. These results are discussed in relation to the role of the thymus gland in ovarian development and the competence of the early juvenile ovary to respond to gonadotrophin.


Changes in the pattern of RNA synthesis in mouse limb cartilage during early development. Patterns of RNA synthesis using tritiated uridine were studied in organ cultures of mouse embryonic limb cartilage and epiphyseal cartilage from mice 5 days of age. The cold phenol-sodium dodecyl sulfate extracted RNA was characterized by methylated albumin kieselguhr chromatography and polyacrylamide gel electrophoresis. The general pattern of synthesis indicates the persistence of primarily low molecular weight tRNA and a diminishing synthesis of rRNA in the older cartilage. Data show that the increased radioactivity in the low molecular weight fraction is not due to the accumulation of rRNA breakdown products. These findings are discussed in relation to other age-related studies on RNA biosynthesis.


Urine sodium, potassium and osmolality in two rat strains selected for their different ethanol preferences. Urine sodium, potassium and osmolality were investigated during water and ethanol diuresis in two rat strains, AA and ANA, which drink voluntarily different amounts of ethanol. At the start of each experiment the rats were in a positive water balance. During ethanol intoxication the AA strain excreted more urine than the ANA strain. In ethanol experiments the osmolality of the urine was higher in the AA strain than in the ANA strain. With ethanol amounts of 2.4 g/kg body weight and 4.8 g/kg of body weight, urinary sodium and potassium output was greater in AA rats than ANA rats. When only water was introduced urine volumes and the excretion of sodium and potassium during 180 min were greater in ANA males than in AA males.


A lack of correlation between decline in growth capacity and nuclear RNA synthesising activity in ageing human embryo cells in culture. A reduced proliferative capacity has been demonstrated between young (passage 5/24) and middle (passage 17/24) aged human embryo diploid fibroblast cultures. This difference was noted in both logarithmically growing and plateau-phase cultures in terms of growth curves, DNA content per dish and ability to incorporate 3H-thymidine. This reduction in growth potential is not accompanied by any reduction in chromatin template activity, determined in nuclear "ghost" monolayer, using either the endogenous polymerase or an exogenous bacterial enzyme. Therefore the declining division potential as these cells pass from young to middle passage is unlikely to occur as an expression of alterations in nuclear RNA synthesis. It is, however, possible that the apparently continuous decline in growth potential with age might be caused by different events at various stages of the cells's lifespan.


Increased cholesterol content and esterification in rabbit aortic medial cells cultured in hyperlipidemic serum. Cells of early atherosclerotic lesions have an increased content of cholesteryl esters and enhanced rate of cholesterol esterification. The present study was carried out to elucidate whether these changes could be reproduced in a purely in vitro system. Cultures of rabbit aortic medial cells were incubated in a medium containing 10% of either normal rabbit serum (control cells) or serum from rabbits with cholesterol-induced hyperlipidemia (hyperlipidemic cells). The incorporation rate of [1-14C]oleate into cellular cholesteryl esters increased two- to threefold after four hours' incubation with hyperlipidemic serum and remained elevated during the rest of the eight days' study. After seven days' incubation the hyperlipidemic cells incorporated significantly more (+13%) oleate into triglycerides and significantly less (-15%) oleate into phospholipids than did the control cells. Cholesteryl ester content of the hyperlipidemic cells rose steeply for about two days, with a slower rise thereafter. In hyperlipidemic cells the esterified cholesterol content was significantly higher (315 ng/mug DNA) than in the control cells (79 ng/mug DNA). Hyperlipidemic cells showed a slow but significant rise of free cholesterol as well (from 1.15 mug/mug DNA in control to 1.50 mug/mug DNA). The results indicate that lipid changes resembling those in early atherosclerotic lesions can be brought about in vitro 0y treatment of aortic cells with hyperlipidemic serum.


Serum parathyroid hormone levels and serum calcium levels from birth to senescence. 1. Calcium and immunoreactive parathyroid hormone (iPTH) levels were measured in sera of 1334 normal subjects ranging from newborn to over 80 years of age. Albumin was measured in samples from the population of adults, which was 80% white, 15% black and 5% oriental. 2. Serum calcium and iPTH levels in children tended to be higher in the first three years of age; no sex differences were noted. Values for serum calcium and iPTH were higher in children than in adults. 3. Serum calcium, iPTH and albumin showed more variation in groups of white, black and oriental women than in similar groups of men. In white females the mean serum calcium remained fairly constant until age 60, whereas in black women it rose steadily from age 20-29 until age 50-59. Serum iPTH levels were lower in black women than in white women and usually were not measurable in oriental women. 4. In men (white, black and oriental) there was a steady decrease in mean serum calcium with age, and iPTH levels were not different from those observed in white women. 5. Although the number of samples from oriental women was small, the serum calcium was consistently lower and serum albumin was constantly higher than in white or black women, and iPTH levels usually were unmeasurable.


Molecular turnover numbers of different forms of mitochondrial monoamine oxidase in rat. Molecular turnover numbers of the different forms of monoamine oxidase in rat liver were estimated for serotonin, tyramine and beta-phenylethylamine by titration with irreversible inhibitors. The 'A' form was found to have a much higher turnover number for serotonin and a lower turnover number for beta-phenylethylamine than the 'B' form, while the turnover numbers for tyramine were in the same order of magnitude for both forms. The monoamine oxidase in the liver was found to have a significantly higher molecular turnover for tyramine and beta-phenylethylamine than that in the brain, heart and kidney. It was calculated that the 'A' form of monoamine oxidase amounted to about 20% and the 'B' form to about 80% of the total amount of monoamine oxidase in the rat liver mitochondrial preparation. The number of molecules per mitochondrion was also calculated.


On the visualization of central dopamine and noradrenaline nerve terminals in cryostat sections. Brain tissue from rats perfused with a mixture of glyoxylic acid and formaldehyde was frozen and sectioned in a cryostat. The cryostat sections were incubated in glyoxylic acid, dried and reacted with formaldehyde vapor. Using this technique cortical noradrenaline and dopamine containing nerve terminals could be visualized with high sensitivity in a reproducible way. The importance of several critical parameters was evaluated and it was found that the incubation of the cryostat sections in glyoxylic acid effectively inhibited the diffusion of catecholamines, particularly dopamine. Thus the fixation effect of glyoxylic acid was considered important besides the fluorophore formation. This modification of the Falck-Hillarp fluorescence technique is rapid, simple and reproducible and might be of value especially for quantitative measurements of the fluorescence.


The potential of the teaching hospital for the development of prepaid group practices. This paper deals with the development of a hospital based prepaid group practice at Long Island Jewish-Hillside Medical Center. The paper provides an historical perspective of the factors leading to the decision to develop such a Medical Group practice, the difficulties encountered in obtaining conceptual approval from the Medical Center's Board of Trustees and its medical staff, the negotiations between the Medical Center and Blue Cross-Blue Shield of Greater New York as the insurance company which agreed to market the program and to subsidize it in its developmental stage, factors relating to the contractual negotiations between the Medical Center and Blue Cross, the key elements of the negotiated contract from the standpoint of the prepaid group, and the nature of the subsidies provided to ensure a healthy fiscal beginning. The paper highlights the methods used in achieving the desired goals and the development of the Group, sets forth the resistance which other, similar hospitals might anticipate in undertaking such a venture of their own, and highlights the nature and the degree of commitment necessary to bring such a program into being.


Integrating mental health services into primary medical care. Primary care clinicians occupy a strategic position in relation to the emotional problems of their patients. Integrating mental health and primary medical services promotes available, coordinated, accessible, and less stigmatizing treatment by recognizing an indivisibility of the total person in illness and in health. Federal efforts to encourage Health Maintenance Organization (HMO) development as part of a national health program prompts serious attention to organizational arrangements for developing such an integrated program for medical-mental health care. We have found a team collaborative model in which mental health providers are members of a primary care team to be useful and promising. Supportive services are provided on a continuing basis through patterned relationships. Shared responsibility for patient care between physicians, nurse practitioners, physician assistants, and mental health workers provides built-in peer review and encourages intrateam consultation.


Patient knowledge and nurse role strain in three hospital settings. The relationship between patient medical and hospital knowledge and nurse role strain is examined within three contrasting types of general hospital. The nature of this relationship was found to differ greatly within each of the three hospitals. Interpretations of these findings focus upon differences in organizational structure and climate, staff orientation, and type of clientele group. These data suggest that cuation should accompany attempts to generalize across different types of hospitals when questions relevant to the patient role are posed.


The contractual model for prison health care. In New York City, the Department of Health is responsible for providing health services to 8 correctional facilities which receive 60,000 admissions annually. A large component of this prison health system is a contract with Montefiore Hospital, a voluntary institution, to provide medical services to the population on Rikers Island, a penal complex. This contractual agreement is unique in that an operating entity, Monefiore Hospital, has agreed to provide a "package" of health services to a defined prisoner population. The City agreed to reimbruse to the Hospital for the three year term of the contract, a total amount not to exceed +11.7 million. Because of delays in renovation of the prison facilities, for the majority of the period of the three year contract, only two prisons were served via the contractual route. Since 1973, the program has provided a range of services including screening of new prisoners, primary, emergency, infirmary and limited speciality care. Major improvements in laboratory and radiology services were implemented. The early experience with this program indicates that in this setting the contractual model possesses a number of distinct advantages over the direct delivery of prison health services. Disadvantages include a significantly higher cost.


Health care for elderly Americans: evaluation of an adult day health care model. This study was designed to analyze the cost and effectiveness of a day care program for the elderly. An experimental group of adult day care participants was compared with a control group of elderly people living in the community. The two groups were evaluated in terms of levels of physical and emotional functioning, behavioral independence in activities of daily living, institutionalization, interpersonal relationships, and re-establishment of life styles. Statistical tests of difference were used to determine if the two groups had improved or were maintained over the six-month study period (November 1973 to March 1974). The experimental group showed improvement and differed significantly from the control group in the areas of emotional functioning, self-maintenance, and interpersonal relationships. No significant differences were found in satisfaction with life styles for either group. The experimental group was somewhat, but not significantly, deficient in independence in daily living activities. Composite analysis of six combined scales indicated that the experimental group inproved in level of functioning over the study period while the control group regressed. Cost analysis of the Lexington Center indicates that adult day care services cost +12.99 per participant per day.


[The emptying process of the residual stomach after various methods of anastomoses (author's transl)]. Similar to the high pressure zone of the lower esophageal segment (LES) gastric emptying results from alternating intraluminal pressure in the antrum, pylorus and duodenum. Alterations of this antro-duodenal pressure zone depend on hormonal and nervous control mechanisms and are regulated by intraduodenal localized pH-, osmo- and fat-receptors. Experimental investigations in partially gastrectomized dogs emphasize the important role of the duodenum for gastric emptying. After resection of the lower half of the stomach and reconstruction of the orthograde passage between the gastric remnant and the duodenum by gastroduodenostomy (b i-anastomosis), a hormonally controlled gastric emptying comparable to that of the intact organ can be noticed.


[The importance of the Musculus canalis ani for continence and anorectal diseases (author's transl)]. The functional morphology of the M. canalis ani is described. Hitherto this muscle has not been studied in detail. The M. canalis ani is located inside of the M. sphincter ani internus and reaches through the spatium submucosum et subcutaneum of the analcanal. This muscle is part of a described "organ of continence". Its importance in the course of anorectal disease is shown.


[Endoscopical and radiological studies after papillotomy (author's transl)]. The paper deals with a controlled study concerning 36 patients who underwent surgical papillotomy. Cholangiographic examinations were performed by infusion and endoscopic retrograde instillation, in ten patients additional percutaneaus "blind" biopsy of the liver. Some new remarkable details could be evaluated at the papilla Vateri itself as definite anatomic alteration after papillotomy. Planimetric studies could be added on special details because of the good x-ray-contrasts by endoscopic filling of the biliary tract. With some special reserves the results after surgical papillotomy in 30 controlled persons can be classified as good.


[New method for security by colon anastomoses (author's transl)]. After examinaning the vascular supply of the parietal peritoneum helved peritoneal flaps were fixed in wound dehiscent colon anastomoses. If the vascular supply to the peritoneal flap was sufficient all animals survived without signs of stenosis. It was proved by microangiographic studies that there was an additional vascular supply to the anastomosed colon by the artery of the peritoneal flap.


[Postoperative enterocutaneous fistulae of the small gut (author's transl)]. Postoperative enterocutaneous fistulae are fortunately rate (1 : 1000), but they carry a mortality of about 50%. The authors analyse the development and treatment of fistulae in 30 patients. This depends on whether the cause of the fistula is connected with an anastomosis or not, on a variety of pathologic-anatomical criteria and in particular on the amount of fluid lost daily. If this loss is less than 500 ml/24 h the fistula can be regarded as relatively benign and in all probability conservative treatment alone will succeed. Fistulae with a fluid loss of more than 500 ml/24 h have a worse prognosis and require a combined conservative and surgical therapy. The key to this problem is the optimal time for surgical intervention, it lies around the 4th week. In case an early operation is necessary one must be prepared for an enterostomy or by-pass procedure.


Histopathologic correlates of otoneurologic manifestations following head trauma. The clinical course of patients dying of head trauma and the physiologic evaluation of audition in guinea pigs subjected to several forms of head trauma are correlated with the histopathologic findings in the brains and temporal bones. In the patients there was wide spread hemorrhage, edema, disorganization and disruption of neural tissue. Loss of Purkinje cells and other neural elements was prominent. The temporal bone findings in the patients included laceration of and hemorrhage into the VIIIth nerve as well as bleeding into the scala tympani. The membranous labyrinths demonstrated no specific changes secondary to the trauma. The guinea pigs developed a central form of hearing loss with elevated thresholds for evoked responses from the inferior colliculus and normal AC cochlear potentials. In the animals hemorrhage in the substance of the brain, necrosis of neural tissue, edema, disorganization and disruption were prominent. Although there was extravasation of blood in the tympanic and vestibular scalae, the membranous structures of the inner ears were well preserved.


Inner ear decompression sickness.

Inner ear decompression sickness. With recent increases in commercial, military, and sport diving to deeper depths, inner ear injuries during such exposures have been encountered more frequently and noted during several phases of diving: during compression, at stable deep depths, with excessive noise exposure in diving, and during decompression. The pathophysiology of these injuries differs, depending upon the phase of diving in which the injuries occur. In this report, 23 cases of hearing loss, tinnitus, and/or vertigo occurring during or shortly after decompression are presented. Thirteen of these cases occurred in helium-oxygen dives involving a change to air during the latter stages of decompression. A significant correlation is present between prompt recompression treatment, relief of symptoms, and lack of residual deficits. Current knowledge indicates that the management of otologic decompression sickness should include: 1. prompt recompression to at least 99 feet deeper than the symptom onset depth; 2. recompression using the previous helium-oxygen mixture when the injuries occur during or shortly after a switch from helium-oxygen to air during the latter stages of decompression; 3. the use of parenteral diazepam for symptom relief and cyclic inhalations of oxygen enriched treatment gases; and 4. the avoidance of further diving by divers who exhibit permanent inner ear injuries after the acute symptoms have subsided.


The knotted wire in stapes surgery: one possible factor in postoperative sensori-neural hearing loss. In four instances of revision stapedectomy in patients with sensori-neural hearing loss, with or without dizziness, a wire prosthesis was found with an extention beyond the knot which could impinge on the contents of the vestibule. Four commercially manufactured knotted wire prostheses were examined, and the end of three was found projecting beyond the knot. The wire piercing the membranous labyrinth appears to be one of the factors in causing further sensori-neural hearing loss after stapedectomy. A wire loop or piston prosthesis should be considered to eliminate the hazard of a trailing end of a knotted wire in stapes surgery.


Fractures of the edentulous maxilla and mandible. An evaluation and treatment of fracture of the edentulous maxilla and/or mandible is presented. The Le-Fort classification of maxillary fractures is the foundation for the program of care. Immobilization techniques are based upon the support of a fracture by suspension from the adjacent stable segments to the modified prosthesis. The mandibular fractures are repaired by interosseous wire fixation in the body and symphysis region, the other fracture sites are supported by circumferential wiring to the prosthesis for immobilization. General principles of time of repair, diet, types of healing factors are reviewed.


Cochlear implants: technical and clinical implications. Recent investigations using animal models and human subjects have helped to define the limits which are achievable in terms of information transfer with single-channel electrical stimulation of the auditory nerve. These studies are reviewed, and presented as a context for a description of the development of an implantable multiple-electrode multiplexing system which may provide control for several stimulus channels. While such a device may enable the stimulation of small segments of the auditory nerve independently, it does not contain any means of complex stimulus analysis and recording. This latter aspect of prosthesis development remains as the most formidable problem, from a technical viewpoint, that stands in the way of any significant progress.


Apnea and airway obstruction during feeding and sleep. Recent awareness of the magnitude of sudden unexplained deaths in apparently healthy infants has lead to an increased interest in those circumstances that are associated with or can elicit prolonged and serious apneic episodes. In the present studies, attention was directed toward the study of physiologic activity during sleep and feeding. Apneic episodes of varying durations occur during sleep which, in some instances, can be of sufficient length to warrant resuscitative intervention. A number of infants also reveal transient upper airway obstruction following brief periods of sleep apnea. This functional airway obstruction produces sudden and severe bradycardia. Similarly, infant feeding can induce dangerously prolonged periods of apnea and, in some infants, transient airway obstruction. Few detailed studies have been performed to identify the anatomical level or characteristics of the obstruction. Available evidence suggests that this can take the form either of muscle hypotonicity or hypertonicity. Two infants observed by means of direct laryngoscopy revealed transient failure of vocal cord abduction. These results have provided for the development of two theoretical models that can result in the sudden infant death syndrome; furthermore, continuous recordings of respiratory and cardiac activity during feeding and sleep can be extremely valuable in elucidating the mechanisms responsible for the sudden development of apneic and cyanotic episodes in infants.


Cardiac and pulmonary failure secondary to adenotonsillar hypertrophy. For over 15 years, upper respiratory tract obstruction due to adenotonsillar hypertrophy has been known to cause hypoxia, hypercapnia, increased pulmonary vascular resistance and thereby cor pulmonale and congestive heart failure. This is now an uncommon but not rare entity and three recent cases prompted this report. The typical patient is dyspneic with retractions, cyanosis, occasional periods of apnea and somnolence. Edema and hepatomegaly and at times splenomegaly are common. X-rays show cardiomegaly, which on electrocardiogram is found to involved mainly the right ventricle. The strict definition of cor pulmonale is right ventricular hypertrophy secondary to lung disease or abnormal pulmonary function, a definition that may logically be stretched to include abnormal respiratory function secondary to upper airway pathology. The mechanisms by which this occurs are generally agreed upon. Hypoxia has been demonstrated to cause pulmonary vasoconstriction. Acidosis and hypercapnia are thought by some to have the same effect. Pressure across the pulmonary vascular bed is also increased, as predicted by Poiseuille's law, by the high rate of blood flow required to maintain tissue oxygenation with poorly oxygenated blood. Conditions producing hypoxia of hypercapnia or both lead to hypertrophy and eventually to dilatation of the right ventricle. Three cases of children who underwent cardiac catheterization while suffering from cor pulmonale due to adenotonsillar hypertrophy are reported. Right ventricular pressure averaged 44/5, PAO2 72, pH 7.32, and PACO2 52. All were clinically improved following adenotonsillectomy. Cardiac catheterization was repeated in one case, with right ventricular pressure dropping from 44/5 to 21/2, pulmonary vascular resistance from eight units to three, and PACO2 from 62 to 44.


Medullary carcinoma of the thyroid gland. Endocrine as well as oncologic attributes mark this rare tumor as unique. It is derived from "C cells" resembling the parafollicular cells of lower animals; these cells elaborate Calcitonin which acts as a sensitive signal of the presence of the tumor. Other endocrinopathies are present in 70 percent of cases so that the tumor may present as part of a complex but increasing well known clinical picture. In 10 percent the tumor occurs as an autosomal dominant trait; in the remainder, the occurrence is sporadic. As expected the lesions are "cold" on I131 scan. The histologic appearance of amyloid is characteristic. Regional lymph node metastasis occurs early. The tumor deserves appropriate aggressive management. Essentially surgical therapy should begin early and vigorously; the minimum procedure should be total thyroidectomy. Frequent lymph node metastasis speaks for the need for radical neck dissection which should be extended into the superior mediastinum. Management should also include the frequently associated endocrinopathies, particularly pheochromocytomas which must be suspected and eradicted prior to treatment of the thyroid tumor. A genetic workup should be included. Six cases are described, ranging in age from the third to the eighth decade. Only two were free of disease at this writing, two were alive with their disease and two were dead of their disease. All were of the sporadic group, and only one had associated endocrinopathies. None of these cases were diagnosed preoperatively.


Acute acromegalic dyspnea.

Acute acromegalic dyspnea. A case of acute "acromegalic dyspnea" due to vocal cord fixation and subglottic mucosal hypertrophy is reported. The patient was treated by intubation, tracheostomy, stereotactic implantation of radioisotopes 192Ir and 198Au via the transsphenoidal route.


Pseudomonas meningitis complicating head and neck surgery. Three patients, each of whom had Pseudomonas meningitis as a sequela of an extensive head and neck operation, have been treated successfully. All three patients had cerebrospinal fluid leaks, and operative management of this complication is discussed. Antibiotic management included the parenteral administration of the recently developed drugs gentamicin, carbenicillin, and intrathecal gentamicin. Since extensive head and neck operations are being performed, with increasing frequency and since infectious complications are inevitable, it is mandatory that the otolaryngologist be familiar with current methods of managing these potentially lethal conditions.


Chondrodermatitis helicis: a clinical re-evaluation and pathological review. Chondrodermatitis helicis, or painful nodule of the ear, is an uncommon benign aural lesion which is seen and treated by dermatologists and otolaryngologists. Because of the sparcity of reports in the recent literature, our experience with 50 patients over a 10-year period is presented. The diagnosis is based on history and physical examination and biopsy need be performed only to confirm the diagnosis in atypical cases. Patients are generally middle-aged or elderly males. There are no associated systemic disorders with this condition. The lesions are discrete, grey to red in color, oval shaped with raised rolled edges, and a central ulcer or depression which often contains a crust or scale. The lesion is typically painful and tender and, for this reason, the patient seeks help shortly after the onset of symptoms. The characteristic histopathologic features are epithelial hyperplasia, collagen degeneration, focal fibrinoid necrosis, and inflammatory components. Clinically, the lesion is misdiagnosed in the majority of instances and is presumably, therefore, treated inappropriately. It should be stressed that this is a benign condition and initial management should be aimed at conservative therapy with local steroid injection or conservative non-deforming surgery. Wide excision, including removal of the underlying cartilage with appropriate reconstrictive closure should be reserved for the conservative treatment failures.


The role of cellular degeneration in the normal development of (rat) otocyst. From day 12 to 16 of gestation a highly circumscribed zone of cellular degeneration has been observed in the otocyst of more than 50 normal rats. This zone appears to be produced by selective or programmed cell death, and results in the elimination of unneeded cellular elements. That cells in this zone are also selectively destroying subcellular organelles as a first step in specialization is also discussed. Programmed cellular death has long been known in other systems and is often an obligatory companion to cellular specialization. The ear now joins the long list of organs which demonstrate this phenomenon.


An experimental model for the study of endolymphatic hydrops in sharks: implications for the clinician. In recent years, attention has focused on the role of the endolymphatic sac (ELS) and the endolymphatic duct (ELD) in the pathogenesis of endolymphatic hydrops (ELH). Changes have been noted surgically and radiographically by others in the ELS and ELD in patients with ELH. This report summarizes the development of a shark model with which to study the pathophysiology of ELH. The background material and overall results of anatomic, histopathologic, and ultrastructural studies using the model are presented. Possible implications for the clinical handling of ELH as a result of this work is emphasized.


Alkaloids of Carnegiea gigantea. Arizonine, a new tetrahydroisoquinoline alkaloid. The alkaloid composition of the giant cactus, Carnegiea gigantea Br. & R., was studied. Chromatographic separation led to the isolation of four tetrahydroisoquinoline alkaloids: carnegine, salsolidine, gigantine and arizonine. The structure of the new natural product, arizonine, was establihsed by spectroscopic data and total synthesis via two independent routes. Salsolidine is reported for the first time in the cacti. Also new to this species are 3-methoxytyramine and 3,4-dimethoxypenethylamine, which were identified in the alkaloid extract by gas chromatography-mass spectrometry. Dopamine was isolated from fresh plant material.


DIOXINS/*ISOLof West African medicinal plants. XV. Dinklacorine, a new biphenyl dibenzodioxin alkaloid from Tiliacora dinklagei. Dinklacorine was first isolated in 1974 from extracts of the roots of Tiliacora dinklagei Engl. (Menispermaceae) and designated TD-2. The ir, uv and mass spectra of dinklacorine were very similar to those of the dibenzodioxin biphenylalkaloid tiliacorine. However, the two alkaloids differed in their mp, specific rotation and nmr spectra. Methylation of dinklacorine with diazomethane afforded O-methyltiliacorine while treatment of dinklacorine with sodium methoxide and methyl iodide gave O-methyltiliacorine dimethiodide. However, prolonged treatment of tiliacorine and dinklacorine with diazoethane afforded different O-ethyl ethers. In addition, O-ethyldinklacorine dimethiodide and O-ethyltiliacorne dimethiodide were different. Furthermore, acetylation of the two alkaloids with acetic anhydride and puridine gave O-macetyl esters which were not identical. A considertation to these data and especially the mass spectral fragmentation patterns indicated dinklacorine to be a positional isomer of tiliacorine with the phenolic hydroxy group present in the biphenyl portion of the molecule on the opposite side to tiliacorine. Finally, a comparison of the cd spectra of dinklacorine and tiliacorine suggests that they have the same stereochemistry.


Alkaloids of Thalictrum. XV. Isolation and identification of the hypotensive alkaloids of the root of Thalictrum lucidum. Sixteen alkaloids, namely homoaromoline, obaberine, O-methyl-thalicberine, oxyberberine, thalidasine, thaliglucinone, thalrugosine, obamegine, oxyacanthine, berberine, columbamine, jatrorrhizine, magnoflorine, palmatine, thalifendine and base A chloride, plus the artifact, 8-trichloromethyldihydroberberine, were isolated from the alkaloid fraction of the roots of Thalictrum lucidum L. Of these, obamegine, thalrugosine, O-methylthalicberine, thaliglucinone, obaberine and homoaromoline were found to possess hypotensive activity in normotensive dogs. Thalidasine, homoaromoline, thalrugosine, thaliglucinone, obamegine, jatrorrhizine, and columbamine were found to possess antimicrobial activity against Mycobacterium smegmatis at a concentration of 100 mug/ml or less.


Tumor inhibitors. 114. Aloe emodin: antileukemic principle isolated from Rhamnus frangula L. A systematic fractionation of an ethanol-water (1:1) extract of the seeds of Rhamnus frangula L., guided by assays for tumore-inhibitory activity, led to the isolation of aloe emodin (1). This compound was found to show significant antileukemic activity against the P-388 lymphocytic leukemia in mice. A note-worthy vehicle-dependence of the testing results is reported. In the light of this vehicle-dependence, the re-examination of other anthraquinone derivatives is recommended.


Automated short range locator system.

Automated short range locator system. A computer operated system is described for determining the location of a subject fitted with a small sensing coil and telemetry transmitter. The system uses the geometric factors inherent in the value of the mutual inductance of a fixed and moveable coil. Results of a two-dimensional system are shown.


Screening of Chilean plants for anticancer activity. I. Extracts prepared from 519 samples of plant material were evaluated for anticancer activity against the usual systems. The results of the antitumor testing showed that 156 of these extracts gave initial indications of anticancer activity in one or more tumor systems. The activity was confirmed in 14 samples.


An electro-acoustical technique for the detection of knee joint noise. Distinguishing acoustical signatures of sound emitted by normal and pathological knee joints are picked up using a double microphone-differential amplifier setup. Extraneous background noise is minimized using the principle of "noise cancellation". Two identical sensitive condenser microphones and an F.M. recorder with flat responses in the audio range were used. Preliminary studies covering normal and diseased knee joints showed that their respective waveforms and spectral patterns are unique and proved to be a promising nondestructive diagnostic tool for early detection of knee joint cartilage damage.


The effect of external pressure on skin temperature distribution by thermography. 1) Serial thermograms were taken after the application of various intensities and durations of localized pressure on the medial surface of the human forearm. 2) Thermal response of the body surface to localized pressure was quantified. 3) It was found that usually a time period of between 1 to 3 minutes elapsed before the body surface attained a maximum elevation of temperature from the time the localized pressure is removed. 4) It was found that increased intensity of pressure (5 psi vs. 3 psi) and longer duration (20 minutes vs. 10 minutes) caused larger thermal responses. 5) It is suggested that high resolution medical thermography may eventually become a useful tool in the fitting of prosthetic and orthotic devices and for the prediction of pressure sores formation so prophylactic measures can be started immediately on immobilized patients.


A new biomedical mechanical impedance bridge. A system is described which measures directly the driving-point force, velocity and complex mechanical impedance of biological, non-biological and viscoelastic materials and structures. The system uses a single transducer and is capable of measuring the velocity responses to sinusoidal, linear, step and other forcing functions.


Iowa wrestling study: weight classification systems. Many wrestlers lose a large amount of weight in a relatively short period of time to become certified for interscholastic competition. In most states, there are twelve certified weight classes with intervals ranging from 6 to 18 pounds. Using anthropometric data obtained from 834 "average" wrestlers that were measured 5-8 weeks before competition, we predicted their "minimal" body weights and assigned them into arbitrarily designated weight classes of 6, 8 and 10 pound intervals. In addition, the 1973-74 and the 1974-75 certifying records for Iowa wrestlers were examined with regard to frequency distribution patterns. The results indicated that the majority of students were certifying for a weight classes. In fast, forty percent of the more than 8900 students were certified for the 119-138 classes and 57% of the population were located within the 112-145 weight classes. Inspection of the frequency distribution patterns of wrestlers assigned to the arbitrary classes also showed a marked concentration of wrestlers who weighed between 120 and 140 pounds and this relationship became more apparent when ten pound intervals were considered. From these findings we recommended that state high school associations consider: 1) allowing more than one wrestler per team to compete in a single weight class; 2) porviding more weight classes than the current twelve; and 3) promoting body composition assessments during the pre-season period in order to minimize the problems created by the "making of weight."


Iowa wrestling study: weight loss and urinary profiles of collegiate wrestlers. A longitudinal study was conducted with various members of the 1975 University of Iowa NCAA championship wrestling team to determine if excessive weight loss, accompanied by signs of dehydration, occurred at the college level of competition. Body weight changes from September to December indicated a mean loss of 6%, while skinfold totals (6 sites) changed from a mean of 58 mm to 37 mm. During a four-month period, mean weight losses of 10.2, 9.5, 8.0, 7.5 and 7.0 lbs occurred in intervals of 12, 4, 3, 2 and 1 day, respectively. Basal urines analyzed throughout the season usually contained 2-3 times the potassium excreted before the season started. Analyses of urines at various intervals during a 2-day time period prior to weigh-in showed a .003 increase in specific gravity, 160 mosm/1 increase in osmolarity, .10 decrease in pH, 45.3 mEq/1 decrease in Na+ concentration, and a 71.3 mEq/1 increase in K+ concentration which suggested that the wrestlers were dehydrated prior to competition. Total urinary electrolyte loss during the 2 days amounted to 3.7% of estimated total body Na+ stores and 3.0% of total body K+ stores. These data were similar to what had been reported for Iowa high school finalists and indicated that collegiate wrestlers were also competing while in a dehydrated state.


Weight and skinfold thickness changes during a physical training course. The effect of an intensive physical training program on body weight and skinfold thickness was compared in subjects who had initially small (group S), medium (group M) and large (group L) skinfold thickness representing mostly thin, normal and obese recruits, respectively. Weight and skinfold thickness at three sites (triceps, subscapula and abdomen) were measured at the beginning and end of a 6 week intensive military training program. Subjects were on an ad-lib diet. Seventy-one percent of the subjects in group S increased their body weight and 60% increased the sum of their skinfold thickness (SSFT) at the three sites during the training period. These increases were significant at P less than 0.001 and P less than 0.01 for weight and SSFT respectively. In groups M and L the trends for changes in SSFT were in the opposite direction, with 68% of the former and 98% of the latter showing decreases in SSFT. The mean decreases were significant at P less than 0.02 and P less than 0.001 for groups M and L respectively. While the subjects in group L lost weight significantly (P less than 0.001), those in group M reduced their weight only slightly. Our data indicate that changes in body fat, indicated by changes in SSFT, during several weeks of physical activity are not unidirectional and are related to the initial skinfold thickness.


Effect of physical fitness on the adrenocortical response to exercise stress. Serum corticosteroid (S.C.) responses were compared in two groups of middle-aged male subjects, one sedentary, one active (both N = 11, mean age 44 years), who performed graded bicycle ergometer exercise before (pre) and after (post) a 4 month physical fitness program. Pre-training exercise involved low and high work intensities which required similar percentage of predicted Vo2 max for the sedentary and active groups. Post-training exercise at identical work loads which resulted in lower work intensities due to training effects, was followed by increased work loads demanding higher work intensities in order to accommodate for the increased work capacity of the respective groups. The sedentary group (pre) and the active group (post) showed significant elevations in S.C. during high intensity exercise and recovery. The active group had significantly lower S.C. during low and high intensity exercise and recovery (pre), and during rest and low intensity exercise (post). The sedentary group had significantly lower S.C. at identical work loads which resulted in a reduction of relative work intensity from pre to post-traing tests. Results suggest both fitness status and training effects in the adrenocortical response to exercise stress, although psychological factors may be involved.


The effect of saddle height on oxygen consumption during bicycle ergometer work. The effect of saddle height upon oxygen consumption during bicycle ergometer work was measured. Five subjects were tested on a continuous work protocol from 50 watts to 200 watts in 25 watt increments at experimental saddle heights of 100%, 103%, 106%, 109%, and 112% of inside leg length measured from the ischium to the floor. Data were recorded on Vo2, Vco2, VE, and heart rate. It was found that Vo2 progressively increased as saddle height increased; the highest Vo2 occurred at the highest experimental setting of 112%; the most effective saddle positions in the experiment as measured by lowest Vo2 per unit of work were 100% and 103%; and there was no significant difference between the VO2 AT 100% AND 103%. It was concluded that in light of our data and earlier data showing power output to be maximized at 104% (by our measurement method), the saddle height of choice should be approximately 103% to 104% of leg length. A convenient and objective method for setting seat height is presented.


Trend analysis of the % VO2 max-HR regression. The purpose of the study was to mathematically model the regression of percent of maximal oxygen consumption (% VO2 max) on relative (% of max) heart rate (HR). The 26 subjects (Ss) were classified based on activity levels into high, medium, and low-fitness. Each S performed a series of treadmill walks and runs ranging from 30 to 100% of max VO2. Percent of VO2 max and relative HR were determined during each exercise bout. The data were subjected to a trend analysis utilizing multiple regression techniques. The associated Rs were: linear 0.966, quadratic 0.971, cubic 0.971, and quartic 0.977. The second and fourth order terms statistically accounted for more of the variability than their predecessors, but these differences were not of practical significance. There were no statistically significant differences among the fitness subgroup regression slopes or intercepts for any of the sets of regression equations. The bivariate equation was Y = 1.369-X-40.99 (Y = % VO2 max and X=relative HR) with a standard error of the estimate of 5.67 % VO2 max.


The validity of self-perceptions regarding physical and athletic ability. High school males (N = 109) and junior high school males (N = 112) administered the Physical Estimation and Attraction Scales (PEAS), the Tennessee Self-Concept Scale (TSCS), and a physical fitness battery. Previous research results were replicated in the h.s. group in that fitness and self-esteem were not significantly related but Estimation (of physical ability) correlated significantly with both fitness and self-esteem (p less than .01). Similar results were obtained in the jr. h.s. sample. Additionally, the validity of the Estimation (EST) scale was extended to include significant relationships with indices of emotional adjustment other than self-esteem. EST scores were shown to be influenced to significant but not inordinate degree by certain response bias tendencies. Negatively phrased EST items were denied significantly more often than positive EST items were affirmed and were more highly related to both response bias and emotional adjustment scores. Controlling for response bias influence by partial correlation failed to extinguish the significance of EST validating relationships. It was concluded that these relationships exist independently of response style or response set.


Degenerative hip disease in adolescent athletes. The effect of conducted training begun at an early age on the femoral head tilt was studied in male adolescent competitive sportsmen and physical education students. The control group consisted of army recruits. The femoral head tilt proved to be smaller in both sportsmen and physical education students when compared with the control subjects. The results suggest that sports activities started at an early age would not contribute to epiphysiolysis and through that to later development of osteoarthritis in the hip joint.


Turf-toe: a shoe-surface related football injury. Plantar capsule-ligament sprain of the great toe metatarsophalangeal joint, herein referred to as "turf-toe," is discussed with emphasis on two apparantly predisposing factors, playing surface hardness and shoe stiffness. Surface hardness studies have previously been performed by the authors on natural grass and AstroTurf. A study of football shoe flexibility is presented and the results correlated with the occurrence of turftoe. We have not encountered this entity in players wearing relatively stiff conventional seven posted football shoes or the more flexible soccer style shoe on natural grass fields. We have found it to be a not uncommon injury among players wearning the soccer style shoe on AstroTurf.


A cinematographic analysis of overground and treadmill running by males and females. Cinematography was used to biomechanically compare individually selected overground jogging and running velocities with equated treadmill jogging and running by adult males and females. All subjects were regular joggers but not competitive track or cross-country runners. No significant differences were recorded in stride length, stride rate, support time or non-support time for males or females when jogging at velocities of between 3.33 and 4.78 m/s (x = 3.70) or 3.45 and 4.80 m/s (x=3.97) respectively. However, it was demonstrated that at velocities of 4.82 - 6.2 m/s for males (x - 5.41) and 4.85 - 5.76 m/s for females (x = 5.29) significant differences did occur between overground and treadmill running. For both males and females stride length decreased, stride rate increased, and the period of non-support was also significantly less when running on a treadmill as compared to running overground.


Forces and duration of impact, and grip tightness during the tennis stroke. The present study is concerned with the problem of the most desirable grip tightness during and after the impact phaseeof the tennis stroke. Moreover, impact forces and durations for different ball velocities are also investigated. Three series of experiments were conducted in order to obtain information on impact forces and durations, responses of the racket to impacts for loose and tight grips, and the magnitudes of the vibrations of the racket transferred to the hand in actual strokes. The experimental results were found to be in accordance with the predictions of a mathematical model of the system racket-hand. A simpler model, which neglects bending and possible translations of the racket, turns out to be inadequate for the present purpose. It is found that a tight grip increases both the impulse imparted on the ball and hence the power of the stroke, and the vibrational shocks which must be absorbed by the hand. The contrary holds true for a loose grip. An investigation on a top-class player revealed that he uses a tight grip in all his strokes. The possibility of a connection between grip tightness during and after the impact phase and the occurrence of the well-known "tennis elbow" is also discussed. Avoidance of the impact recoil was found to be impossible.


Muscle fiber composition and enzyme activities of elite distance runners. Muscle biopsies were obtained from the gastrocnemius of 14 elite distance runners, 18 middle distance runners, and 19 untrained men. The middle distance runners were all highly trained, but had significantly slower performance times than the elite runners at distances greater than 3 miles. Fiber composition and mean cross-sectional areas were determined from muscle sections incubated for histochemical activity. A portion of the specimen was used to determine succinate dehydrogenase (SDH), lactate dehydrogenase (LD/Y and phosphorylase activities. All subjects were tested for maximal oxygen uptake on a treadmill. As previously demonstrated by others, the elite runners' muscles were characterized by a high percentage (79%) of slow twitch (ST) fibers. On the average, the crosssectional area of their ST fibers was found to be 22% larger than the FT fibers (P less than 0.05). SDH activity of whole muscle homogenates from elicte and middle distance runners was 3.4- and 2.8- fold greater, respectively, than that measured in the untrained men. Since the LDH and phosphorylase activities were similar for the runners and untrained men, it appears that training for distance running has little influence on the enzymes of glycogenolysis.


Covert anticoagulant ingestion: study of 25 patients and review of world literature. Twenty-five patients with covert ingestion of oral anticoagulant drugs were studied. Most of the patients were women who were either connected with the medical profession or were previously treated with antigoagulants. The most common findings were ecchymoses, hematuria, and a markedly prolonged prothrombin time. The anticoagulant drug was identified in the plasma of all 25 patients. Most patients responded promptly to administration of vitamin K1. The most common motives were malingering and suicide. The world literature was reviewed for covert ingestion of oral anticoagulant drugs and 48 other cases were found. The correct diagnosis is important to focus the physician's attention on the psychiatric rather than the somatic aspects of the disorder.


The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients. The records of a series of 700 patients with inflammatory bowel disease, 498 with Crohn's disease and 202 with ulcerative colitis, have been analyzed to determine the relative incidence and characteristic features of their extra-intestinal manifestations. The group with Crohn's disease included 62 with colitis, 223 with ileocolitis, and 213 with regional enteritis. A consideration of the clinical patterns and an understanding of their pathophysiology suggested a subdivision into two main groups: one "colitis related" and one related to the pathophysiology of the small nonspecific third group. Group A, colitis related, comprises joint, skin, mouth, and eye disease. The complications might be immunologically determined, were closely associated with active inflammation, and often responded to medical or surgical treatment of the underlying bowel disease. They occurred in 36% of the entire series of patients: joints were involved in 23%, skin in 15%, and mouth and eye each in 4%. Pyoderma gangrenosum was observed most often in ulcerative colitis and erythema nodosum most often in granulomatous colitis. The incidence of Group A complications was higher in disease involving the colon (42%) than in disease restricted exclusively to the small bowel (23%). There were interrelationships among the various members of Group A, with multiple manifestations occurring in a third of affected patients. Group B, related to small bowel pathophysiology, includes malabsorption, gallstones, kidney stones, and non-calculous hydronephrosis and hydroureter. Disorders in this group were generally related to the severity of the disease in the small bowel and tended to persist even in the absence of active inflammation. In contrast to Group A, this group occurred most frequently in small bowel disease, and least in colonic disease. Malabsorption was virtually confined to the patients with small bowel disease (10% incidence), while gallstones and renal stones were also both more frequent in Crohn's disease (11% and 9% respectively), the latter usually in association with small bowel resection or ileostomy. Group C, found in a small percentage of patients, consists of nonspecific complications, including osteoporosis (3%), liver disease (5%), peptic ulcer (10%), and amyloidosis (1%).


Improvement of growth hormone response to stimulation in primary aldosteronism with correction of potassium deficiency. Potassium depletion frequently occurs in primary aldosteronism and has been implicated as the cause of the impaired carbohydrate tolerance frequently associated with this syndrome. Glucose, insulin, and growth hormone regulation were studied in a 42-yr-old, male patient with an aldosterone-secreting adenoma when the patient was potassium-depleted and again after potassium repletion. Potassium repletion was documented by serial body potassium measurements, with an increase in body potassium from 2400 mEq to 2850 mEq after 400 mg spironolactone and 80 mEq supplemental potassium chloride were administered daily for 7 days. Potassium repletion resulted in improvement of the patient's glucose tolerance test, with a decrease in the peak glucose level from 184 mg/100ml to 130 mg/100ml and an increase in the peak insulin level from 46 muU/ml to 85 muU/ml. Intravenous administration of arginine resulted in a subnormal insulin response of 28 muU/ml in the base-line test and an increase to 59 muU/ml after potassium stores were repleted. Growth hormone response to arginine infusion was also initially minimal at 12.5 ng/ml, increasing markedly to 26 ng/ml after potassium replenishment. Insulin-induced hypoglycemia resulted in a depressed growth hormone response of 8 ng/ml when the patient was potassium-deficient, but a normal response of 30 ng/ml after potassium repletion. These observations demonstrate that impairment of both insulin and growth hormone responses to stimulation occur in primary aldosteronism with potassium depletion. These abnormalities may be reversed by potassium repletion.


Mechanism of action of phenethylbiguanide (phenformin) in man. III. interrelationship between ethanol and phenethylibiguanide (PBG) in normal and diabetic subjects. A standard 4-hr ethanol infusion (236 mg/min) after a 3-day fast with and without phenformin (25 mg q.i.d.), with blood drawn every hour for 8 hr, was performed on five normal subjects, eight obese nondiabetics, seven obese chemical diabetics, and four nonobese diabetics. Control infusion induced in all subjects a decline in blood sugar levels during and/or after the alcohol challenge, with a parallel decrease in basal plasma insulin. Hypoglycemia and the decrease in insulin secretion were associated with increased plasma free fatty acid concentration. Addition of phenethylbiguanide (PBG) to the preparatory 3-day fast resulted in a greater drop in the blood glucose levels of the normal control subjects, obese and nonobese diabetics; in the obese nondiabetics, however, significantly lower degree of blood glucose decrease than control was elicited. Furthermore, obese nondiabetics altered their blood glucose-insulin interaction with apparent increased responsivess of the B cells of PBG. The results suggest that effects of phenformin on blood glucose levels are more dependent on the metabolic state of the patient than on a property of the drug itself.


Plasma catecholamine concentrations in hyperthyroidism and hypothyroidism. Using a modification of the fluorometric method of Anton and Sayre, we have measured the plasma epinephrine (E) and norepinephrine (NE) concentrations in patients with thyroid dysfunction. There was no significant difference in plasma E in hyperthyroid or hypothyroid subjects, the values being similar to those observed in normal subjects. There was a striking relationship between age and plasma NE in the euthyroid individuals (r = 0.685, p less than 0.001, n = 41). Observed plasma NE concentrations were similar in control subjects (21.05 +/- 1.6 ng/100 ml; mean +/- SEM) and hyperthyroid patients (22.33+/- 2.0 ng/100 ml). However, plasma NE was significantly increased in hypothyroidism (35.46 +/- 3.9 ng/100 ml; p less than 0.01) and remained statistically different when the age factor was excluded (31.31 +/- 2.67 ng/100 ml; p less than 0.025). There was no correlation between plasma NE and serum thyroxine (T4), free thyroxine (FT4), or triiodothyronine (T3), in any of the three groups studied. These data indicate that hyperthyroidism is accompanied by normal plasma NE concentrations and that hypothyroidism is associated with significantly increased plasma NE concentrations, possible in an attempt to compensate for the lack of thyroid hormones.


Studies on obesity. III. effect of triiodothyronine (T3) on thyroglobulin autoantibodies in euthyroid obese subjects. Effect of T3 therapy on tanned red cell agglutinating thyroglobulin (TRC-TG) antibodies in 10 obese subjects without apparent thyroid disease was investigated. Six other obese subjects without thyroid dysfunction and of approximately the same mean age who also had circulating TRC-TG antibodies served as control subjects and were untreated. In vitro thyroid tests (TSH, total and free T4) performed before T3 therapy, as well as clinical examination, showed thyroid function to be normal in all subjects, and there was no evidence of thyroiditis. TRC-TG antibodies were present in low to moderate titers of 40-1280 in control subjects as well as in subjects selected for T3 treatment. Therapy with T3 was started at 50 mug/day and gradually increased to a maximum of 250 mug/day, depending on clinical needs. T3-treated as well as untreated obese control subjects were all maintained on a high protein, low fat, low carbohydrate diet. Duration of T3 therapy varied from 2-8 mo, and in all but one T3-treated subject, TRC-TG antibodies completely disappeared. In the one exceptional case, TRC-TG antibody titer decreased from 1280 to 80 after 7 mo of therapy. In non-T3-treated obese control subjects, antibody titers remained at the same levels throughout the observation period, thereby indicating a lack of spontaneous regression of circulating immune response. Therapy with T3, by inhibiting TSH, may have caused regression of inapparent immunologic thyroid lesion, thus leading to the disappearance of circulating TRC antibodies; alternatively, T3 specifically may have accelerated catabolism of thyroid antibodies. The latter possibility is favored in the absence of clinical and laboratory evidence of thyroiditis in T3-treated subjects.