Cardiac pathology after valve replacement by disc prosthesis. A study of 61 necropsy patients. Clinical and necropsy observations are described in 61 patients who had one or more cardiac valves replaced with a discoid prosthesis of the Hufnagel type. The most common (31 percent) cause of death among the 45 patients who died early (less than 65 days after operation) appeared to be prosthetic disproportion; that is, the prothesis was too big for the aorta or ventricular cavity into which it was inserted so that inadequate space was present between the margins of the disc and the endocardium of ventricle or intima of aorta. Prosthetic thrombosis occurred in only 3 of the 45 patients who died early, but poppet movement appeared considerably altered in each. In contrast, thrombi were observed on a prosthesis in 14 of the 16 patients who died late (4 to 47 months [average 21] postoperatively), but in none did the thrombi appear of sufficient size to alter poppet function. Escessive bleeding occurred in 11 (24 percent) of the 45 early deaths and was primarily related to the insertion of a patch in the root of the aorta. Uncorrected valvular disease either by itself or by its ability to alter function of the prosthesis appeared responsible for death in 6 (13 percent) of the 45 patients who died early and in 2 (6 percent) of the 16 who died late. Insertion of a mitral poppet disc in a patient with uncorrected aortic regurgitation, even of mild degree, may be hazardous because the aortic regurgitant jet stream may interfere with proper function of the mitral disc. Likewise, insertion of a poppet disc only in the aortic valve position in a patient with combined aortic and mitral regurgitation may considerably increase the degree of mitral incompetence because the aortic prosthesis is intrinsically obstructive. Disc wear or variance was observed in all but one prosthesis in place for more than 1 year. Although hemolytic anemia of significant degree was not observed in any of the 16 patients who died late, the occurrence of renal hemosiderosis in 13 of the 16 patients indicates that the poppet disc prosthesis is considerably traumatic to erythrocytes. Thus, this type of prosthesis is not an ideal substitute cardiac valve. It clots, despite anticoagulant therapy, it is intrinsically stenotic, portions of it, that is, the disc, degenerate, and it causes hemolysis to erythrocytes.


Ischemia in aortic stenosis: hemodynamic prediction. The records of 12 patients with aortic stenosis previously studied by Fallen et al. in 1967 before and after infusion of isoproterenol were reviewed to assess the value of hemodynamic indexes in predicting myocardial ischemia--defined as less than 5 percent transmyocardial lactate extraction or lactate production. Potential subendocardial blood supply was estimated from a diastolic pressure-time index (DPTI), calculated from the tension-time index (TTI). The ratio DPTI/TTI was used to estimate the supply/demand relation. Of eight patients with aortic stenosis but without associated coronary artery disease, four (Group A) metabolized lactate normally after administration of isoproterenol, and four (Group B) had biochemical evidence of ischemia. Three of four patients (Group C) with aortic stenosis and associated coronary artery disease had abnormal glycolysis after administration of isoproterenol. Calculated aortic valve areas were comparable in all groups. In patients with aortic stenosis alone, abnormal lactate metabolism occurred whenever DPTI/TTI was less than 0.30 (P smaller than 0.01) (Group B). Two of three patients with aortic stenosis and associated coronary artery disease (Group C) showed abnormal lactate metabolism when DPTI/TTI was greater than 0.6; this ratio was below 0.3 in the third patient. These results suggest that the supply/demand relation calculated from these readily obtained indexes may be useful (1) in predicting in which patients with aortic stenosis ischemia will develop, (2) in distinguishing the role played by associated coronary artery disease, and (3) as an adjunct to calculation of valve area since the quantitation of associated aortic regurgitation is not necessary.


Abnormal segmental contraction velocity in coronary artery disease produced by isometric exercise and atrial pacing. Since isometric exercise by sustained handgrip leads to a sizable increase in aortic pressure this maneuver was used in addition to atrial pacing to increase the imbalance between oxygen demand and supply in two groups of patients. Both groups were studied by left heart catheterization and cineangiography in the right anterior oblique projection, at rest, during atrial pacing and during combined pacing and handgrip exercise. Group 1, the control group, consisted of 10 patients without coronary artery disease having an ejection fraction of 0.61 to 0.82. Group 2 was composed of 10 patients with definite obstructive disease of one or more of the three main coronary arteries. At rest, ejection fraction was normal or nearly normal (range 0.54 to 0.78). Regional myocardial contraction performance was assessed by determining mean segmental shortening velocities at the basal (VSB), middle (VSM) and apical (VSA) short ventricular axes. Whereas at rest there was no significant difference between the two groups or any of the three velocities, during pacing, VSM and VSA were significantly smaller in Group 2 than in Group 1 (P smaller than 0.02). During pacing combined with handgrip exercise the difference between the two groups was clearly accentuated, all three velocities being highly significantly decreased in Group 2 (VSB, P smaller than 0.01; VSM and VSA, P smaller than 0.001). When evaluated individually the patients of Group 2 had in 9 segments during pacing values for VSB, VSM and VSA that were below the range of the normal subjects. During pacing combined with handgrip a newly abnormal shortening velocity was observed in 12 segments (VSB abnormal in 3 of 7, VSM in 4 of 7 and VSA in 5 of 7 instances). In conclusion, the combination of atrial pacing and handgrip exercise appears to be a useful stress maneuver to identify temporarily dysfunctioning segments in patients with coronary artery disease in whom atrial pacing alone is not sufficient to induce ischemic contraction disorders.


Effects of hypoxemia on the extent of myocardial necrosis after experimental coronary occlusion. Arterial oxygen tension is variable in patients with acute myocardial infarction, and the effect of hypoxemia on the extent of myocardial necrosis after coronary occlusion has not been defined. In 11 anesthetized open chest dogs the left anterior descending coronary artery or one of its major branches was occluded for 20 minutes, and 10 to 15 epicardial electrocardiographic leads were recorded in the distribution and vicinity of the site of occlusion. Average S-T segment elevation and the number of sites showing S-T segment elevation greater than 2 mv, 15 minutes after occlusion were used as indexes of the severity and extent of ischemic injury. After occlusion with an inspired oxygen concentration of 20 percent these indexes were, respectively, 2.0 plus or minus 0.5 mv (mean plus or minus standard error) and 3.6 plus or minus 0.8 sites; the respective values increased to 3.3 plus or minus 0.5 mv (P smaller than 0.01) and 6.7 plus or minus 0.7 sites (P smaller than 0.01) after occlusion with an inspired oxygen concentration of 10 percent, and arterial partial pressure of oxygen decreased from 92 plus or minus 5 to 45 plus or minus 3 mm Hg. In 23 dogs the occlusion was maintained for 24 hours and the S-T segment elevation 15 minutes after occlusion was compared with myocardial creatine phosphokinase (CPK) activity and histologic appearance 24 hours later. In control dogs (inspired oxygen concentration of 20 percent) sites with no S-T segment elevation 15 minutes after occlusion showed normal myocardial CPK activity 24 hours later, whereas in sites with S-T segment elevation exceeding 2 mv there was an inverse relation between S-T segment elevation in each site and its myocardial CPK activity 24 hours later. Histologic examination revealed early myocardial necrosis in 98 percent (82 of 84) of sites with S-T segment elevation greater than 2 mv. In experimental dogs (inhaling a 10 percent oxygen concentration for the first 8 of the 24 hours of occlusion) many sites that showed no S-T segment elevation before hypoxemia was induced exhibited S-T segment elevation before hypoxemia was induced exhibited S-T segment elevations 30 minutes later and showed abnormally low CPK activity and histologic evidence of early necrosis. We conclude that after experimental coronary occlusion, hypoxemia is deleterious because it substantially increases myocardial damage.


Digitalis in experimental acute myocardial infarction. Differential effects on contractile performance of ischemic, border and nonischemic ventricular zones in the dog. The effects of digoxin priming dose of 0.04 mg/kg body weight followed by infusion of 0.02 mg/kg per min) on local tension and length characteristics of the nonischemic, border and ischemic left ventricular zones were studied in 30 dogs using Walton-Brodie strain gauge arches and mercury-in-Silastic segment length gauges. Total tension in the nonischemic zone increased to 130.9 plus or minus 5.3 percent (P smaller than 0.001) of the control level in association with parallel changes in preejection and ejection tension and rate of rise of tension when infusion of digoxin was instituted 15 to 30 minutes after ligation. Consistent increases in tension variables were noticed when infusion of digitalis was initiated 45 to 60 minutes or 2 to 3 hours after ligation. Segment length remained unchanged. In the border zone, total tension decreased to 68.9 plus or minus 5.9 percent (P smaller than 0.01) after infusion of digitalis. When infusion of digitalis was instituted 45 to 60 minutes or 2 to 3 hours after occlusion, similar increases in total tension and other tension variables were seen. Segment length again showed no significant changes. There was an increase in total tension in 5 of the 12 ischemic zones studied when digitalis was infused 15 to 30 minutes after coronary arterial ligation, whereas a consistent (3 to 5 percent) decrease in tension was observed when infusion of digitalis was instituted 45 to 60 minutes and 2 to 3 hours after coronary occlusion. There was no increase in segment length. In summary, digitalis uniformly increased contraction of the nonischemic and border zones after coronary arterial ligation, but the effects on contraction and aneurysmal bulging in the ischemic zone were minimal.


Left axis deviation and left anterior hemiblock among 8,000 Japanese-American men. Electrocardiographic patterns of left axis deviation and left anterior hemiblock, defined by a frontal plane QRS axis of minus 30 degrees to minus 44 degrees and minus 45 degrees to minus 90 degrees, respectively, with normal QRS duration, were found to be fairly common (2.6 and 1.5 percent, respectively) in a community population of 8,000 Japanese-American men aged 45 to 69 years. More than 60 percent of men with these electrocardiographic patterns had no other cardiovascular abnormalities, and the incidence of fatal or nonfatal coronary heart disease and stroke in this group during observation periods of 3 to 6 years was not significantly different from that of control normal men. A significant association was found between these electrocardiographic patterns and the prevalence of hypertension, myocardial infarction and stroke. However, the association of myocardial infarction with left anterior hemiblock appeared to be coincidental and was attributed largely to the similarity of the electrocardiographic manifestations of left anterior hemiblock and inferior wall myocardial infarction. Men with left axis deviation were fatter and had higher blood pressure than the control population. No such difference could be demonstrated for men with left anterior hemiblock although this group was significantly older than control subjects and men with left axis deviation. The results of our study suggest that there are qualitative differences between the causative mechanisms and clinical features of left axis deviation and those of left anterior hemiblock.


Optimal resources for ultrasonic examination of the heart. The echocardiographic examination is described and the current status of ultrasound in cardiac diagnosis is summarized. Planning guidelines are provided for hospital-based echocardiographic laboratories including resource criteria for professional personnel and training, equipment, space and support systems. Minimal case loads for maintaining quality performance of the examiner are recommended and various administrative patterns for organizing an echocardiographic service are discussed. Approaches for establishing professional fees and emerging applications of diagnostic ultrasound in cardiovascular medicine are briefly reviewed. There is a description of the procedure for conducting an adequate cardiographic examination in children and adults.


Bacterial endocarditis with ruptured sinus of Valsalva and aorticocardiac fistula. A case is presented of bacterial endocarditis with a ruptured sinus of Valsalva and formation of an aorticocardiac fistula from the right coronary sinus into the right atrium and right ventricle. The pathologic, clinical and surgical aspects of bacterial endocarditis complicated by a ruptured sinus of Valsalva and an aorticocardiac fistula are analyzed. This complication of bacterial endocarditis is still uncommon, but alertness to its diagnosis makes possible early and successful surgical treatment.


Unruptured sinus of Valsalva aneurysm.

Unruptured sinus of Valsalva aneurysm. An unruptured congenital sinus of Valsalva aneurysm (behind the right aortic valve cusp) is described as an incidental necropsy finding in an 82 year old man. Review of previous reports on aneurysms involving only one of the three aortic sinuses discloses that few cases have been described, and that these lesions are rarely diagnosed during life. It is probable, however, that unruptured aortic sinus aneurysm (involving only one sinus) is more common than previous reports indicate, but that, among patients with congenital sinus aneurysm, rupture is likely to occur.


Recurrent myocardial infarction and angina in a woman with normal coronary angiograms. A case is reported of recurrent myocardial infarction and angina pectoris in a woman with normal coronary arteries documented by coronary angiogram. The recurrence of infarction in contiguous areas of the heart supplied by the left anterior descending coronary artery and the association of the anginal syndrome implicate coronary arterial spasm as the probable cause.


A complex junctional system in endothelial and connective tissue cells of the choroid plexus. Endothelial and connective tissue cells of the choroid plexus have been studied by the freeze-etching technique. The endothelial cells of pre- and postcapillary segments are coupled by a complex junctional system consisting of a combination of tight and gap junctions. Connective tissue cells revealed the same intercellular contacts. Furthermore two different types of gap junctions occurring in membranes of the connective tissue cells are described.


The mode of lymphocyte migration through postcapillary venule endothelium in lymph node. The pathway of migration of lymphocytes across the walls of the postcapillary venules was studied in lymph nodes of rats. By means of serial sections, it was determined that lymphocytes enter the venule wall through the endothelial cells and not through the intercellular spaces. After the endothelial cell has been penetrated, the lymphocytes enter the intercellular spaces, from where they gain access to the lymphatic parenchyma. It cannot be excluded, however, that in some instances the path of migration of a lymphocyte is entirely through an endothelial cell from lumen to subendothelial space. While perforating an endothelial cell, a migrating lymphocyte may be in simultaneous contact with the vascular lumen, the intercellular space, and the subendothelial tissue.


Renal morphology of freshwater trout.

Renal morphology of freshwater trout. The nephron of the euryhaline freshwater salmonids is composed of the renal corpuscle and the renal tubules. Throughout much of the renal corpuscle, only the lamina densa separates the fenestrated processes of the endothelial cells from the foot processes of the visceral epithelium. The renal tubule consists of five distinct segments. The neck segment is short and intermittently ciliated; it lacks the mucous cells which appear in the neck segment of some teleosts. The proximal segment bears a dense bruch border and is both structurally and functionally divisible into a first and a second segment. The first portion is typified by the presence of short apical tubules, variously sized apical vacuoles, and numerous lysosomes. The second proximal segment is distinguished by the abundance and distribution of mitochondria throughout the cytoplasm. Infoldings of the basilar plasmalemma are especially prominent in this region. A cilated intermidate segment intervenes briefly between the proximal and distal portions of the tubule. The distal segment consists of cuboidal cells which bear scattered, short microvilli, small vesicles and multivesicular bodies. Renal tissue from several species of trout was examined in order to establish the basis for a common pattern of histological and ultrastructural characteristics within the family Salmonidae. In all species examined, renal structure was very similar and could readily be compared with that previously described in other freshwater and marine species.


Effect of an energy-reduced dietary regimen in relation to adipose tissue cellularity in obese women. Twenty-eight obese women were divided after arbitrary statistical guidelines obtained from control studies into hyperplastic (increase in fat cell number) (n equal to 10), hypertrophic obesity (increase in average fat cell size) (n equal to 11), and a remaining group (n equal to 7). All these subjects were treated on an outpatient basis with an energy-reduced diet (1,100 kcal/day) until weight decrease failure occurred. The fat cells of the femoral and gluteal regions were larger than in the abdominal region in hypertrophic obese subjects. This regional fat cell size profile was found also in middle-aged and young controls. The hyperplastic obese subjects on the other hand had larger fat cells in the abdominal site. At failure of therapy enlarged fat cells in either of the two obesity groups had decreased to the size of fat cells of controls. Fat cell number remained unchanged. Thus the hypertrophic obese patients ended up with a normal body fat while hyperplastic obese subjects had a pronounced remaining obesity. The results suggest that when the fat cell size in different regions of an individual are known, as well as the total fat cell number, the success of an energy-reduced dietary regimen might be approximately predicted both in terms of remaining total body fat and in regional fat depot decrease.


Regional variation in glycolytic enzyme adaptation to dietary sugars in rat small intestine. This investigation evaluated the adaptive response of the glycolytic enzymes, fructose-1-phosphate aldolase, fructose-1, 6-diphosphate aldolase, and pyruvate kinase, to dietary sugars throughout the small intestine. In addition, the effect of prior diet on this adaptive response and on the enzyme distribution pattern along the small intestine was studied. Rats were fed 40% glucose, 68% sucrose or carbohydrate-free diets for 6 days (baseline diet), followed by one of three isocaloric test diets (40% glucose, 68% sucrose or carbohydrate-free for 3 days. In other groups of tats isocaloric diets of 68% glucose, 68% fructose or 34% glucose + 34% fructose, fed for 4 days, were compared. Enzymes were assayed in the mucosa of the duodenum (D),and in 5 equal (by length) segments from the Ligament of Treitz to the ileocecal valve (J1, J2, J3, I1 and I2). Enzyme specific activities  were significantly higher in the proximal (D-J1-J2) than distal segments (J3-I1-I2) on all diets (P smaller than 0.001). Enzyme activities after test diet periods were determined only by the test diet, and were independent of the baseline diet for all segments. The 68% carbohydrate diets increased enzyme activities significantly more (P smaller than 0.001) than the 40% glucose or carbohydrate free diets, in all segments. On the 40% glucose diet, activities were significantly higher (P smaller than 0.05) than on the carbohydrate free diet in D and J1, but not distally. The data suggest that there is an intrinsic gradient of enzyme activity from the proximal to the distal small intestine which persists despite dietary manipulation, and that all segments of the small bowel show adaptive increases to dietary sugars.


Prevention of folate deficiency by food fortification. III. Effect in pregnant subjects of varying amounts of added folic acid. Maise meal fortified with folic acid was administered to subjects in late pregnancy in a daily dose of either 500 or 300 mug of folic acid. Changes in hematological and folate nutritonal status were compared to those in subjects receiving 300 mug folic acid/day in tablet form, and also in subjects in a previous study who received unfortified maize meal (control group) or meal containing 1,000 mug folic acid/day. In all groups receiving folic acid, red cell and serum folate levels rose progressively, and the rate of rise increased with increasing doses of folic acid. Maize meal containing a daily dose of 500 mug folic acid produced an effect similar to that of 300 mug daily in tablet form. Maize containing 300 mug added folic acid daily was effective in preventing the progression of folate depletion in late pregnancy.


Prevention of folate deficiency by food fortification. IV. Identification of target groups in addition to pregnant women in an adult rural population. In a rural Negro population subsisting on a predominantly maize meal diet, the incidence of folate deficiency was 43.8% in nonanaemic women in late pregnancy, 32.1% in nonpregnant women, and 18.6% in adult males. More than one-third of all subjects older than 60 were deficient. No instance of unequivocal vitamin B12 deficiency was revealed in 431 subjects sampled, and it is considered that the hazards of giving a small daily dose of folic acid in this population are negligible. These findings warrant food fortification with folic acid in this and similar population groups.


Effect of maternal malnutrition on the bone density of the neonates. Bone density measurements were made in 15 paried mothers and neonates of well-to-do group and in 21 age and parity matched mothers and their neonates of the poor socioeconomic community using radiodensitometry. Radiodensities of all bones studied in the mothers and neonates of high income group were significantly higher than those of corresponding bones of the mothers and neonates of poor community. This may be a reflection of maternal malnutrition on the intrauterine development of the bone. A close correlation was observed between the bone density of mothers and neonates in the poor income group. Bone density had no relation with birth weight.


Effect of milk and casein on the absorption of supplemental iron in the mouse and chick. Milk is an attractive vehicle for introducing iron supplements into iron-deficient infants and children. This study compares the effects of milk and caseins on the whole-body absorption of radioactive iron complexes in an attempt to resolve the controversy over whether milk and its constituent phosphoproteins seriously impair iron absorption. Evidence is presented to clarify the role of the calcium-casein micelles of cow's milk in binding iron donated by the ferric-nitrilotriacetate (NTA) complex. The absorption of iron from isolated Fe(III)-casein complexes was studied in mice as a function of the casein--to--Fe ratio and was compared with the absorption of Fe(III)-NTA at equivalent levels. Even at casein--to--Fe ratios higher than those found in conventional iron-supplemented cow's milk (10-15 mg Fe/qt; casein P:Fe congruent to 34), absorption of iron(III) from the casein or NTA complex was not significantly different. There was no significant difference in the absorption of iron administered to mice and chicks as ferrous ion, ferric-NTA, or ferric fructose; nonfat cow's milk did not inhibit the absorption of these iron compounds. For the chick, in fact, milk significantly enhanced the absorption of iron from the ferric-NTA chelate. In order to affect iron absorption significantly casein would have to be present considerably in excess of that found in conventionally supplemented cow's milk.


Protein requirements of men in a hot climate: decreased urinary nitrogen losses concomitant with increased sweat nitrogen losses during exposure to high environmental temperature. In two separate experiments 8 healthy young men were given an egg-milk formula at a level of 0.7 g protein/kg per day, and were exposed to high environmental temperature (34--37 C, 7 hours daily) or cool temperature (21--26 C, all day), alternately. In the first experiment a 16-day hot period was followed by a 20-day cool period and finally by a 20-day hot period. Daily urinary nitrogen (N) loss of the last 8 days of cool period, 82.2 mg/kg, was significantly higher than that of the last 8 days of the 20-day hot period 69.7 mg/kg. Daily skin N loss was significantly lower during the last 8 days of the cool period (3.5 mg/kg) than during the last 8 days of the 20-day hot period (11.9 mg/kg). Urinary N and skin N lossess were negatively correlated (r equal to -0.905) in these periods. In the second experiment a 28 day hot period was followed by a 20-day cool period. Skin N loss diminished from 12.3 mg/kg daily during the last 12 days of the 28-day hot period to 4.1 mg/kg during the last 12-days of the cool period. At the same time, urinary N loss increased significantly from 81.4 mg/kg during the 28-day hot period to 95.2 mg/kg during a cool period. Urinary N and skin N losses were again negatively correlated (r equal to -0.620) during these periods. Results of these studies indicate that when skin N loss increases during high temperature, urinary N loss decreases gradually, but total N loss does not increase.


Effect on fecal output of various dietary nitrogen sources in pig-tailed monkeys (Macaca nemestrina) fed fiber-free, semisynthetic diets. Fiber-free liquid diets containing isonitrogenous amounts of various dietary nitrogen sources were fed to five adult male pig-tailed monkeys (Macaca nemestrina) with a mean weight of approximately 10 kg. All liquid diets supplied 3.0 g N/DAY PER MONKEY AND MAINTAINED THE ANIMALS IN A POSTIVE NITROGEN BALANCE. Initial baseline fecal output data were obtained by feeding the animals a commercial solid monkey chow. The dietary nitrogen sources fed were a) egg white protein, b) an enzymatic hydrolysate of fish protein supplemented with L-amino acids to simulate the egg albumin pattern, c) a mixture of pure L-amino acids simulating the egg pattern, d) a casein hydrolysate supplemented with amino acids, and e) an amino acid mixture with Rose's pattern. Total fecal matter, dry fecal matter, percent of moisture, fecal  nitrogen, lipids and ash were determined for a 10-day period for each experimental diet. A very significant difference (P smaller than 0.001) was noted between each liquid diet and the solid chow, but no significant differences were found between the various fiber-free liquid diets, pointing to the effect of fiber as a major factor affecting fecal output. Monkeys fed liquid diets excreted fecal matter with a mean of 12.9 g/day, of which 4.7 g/day was dry feces (fecal dry matter 28.5%). Fecal nitrogen was found to be 0.25 g, fecal lipids were 0.19 g, and fecal ash was 0.59 g/day per monkey, respectively.


Metabolic effects of glucose in brief and prolonged fasted man. The protein-sparing capability of glucose was investigated in overweight subjects prior to and during the performance of prolonged therapeutic fasts. Blood (for hormones and substrates) and urine (for nitrogen and ketoacids) specimens were collected prior to, during, and subsequent to the performance of the following studies. Three subjects ingested, as their only source of calories, 37.5 g of glucose every 6 hours for 7 days (glucose I). The same group of subjects was then fasted for 3 weeks following which the above glucose protocol was repeated (glucose II). In both groups, glucose administration diminished nitrogen excretion, urea being decreased in the first group and ammonia in the second.


Vitamin B6 requirements of women using oral contraceptives. Fifteen women who used combined estrogen-progestogen oral contraceptives and nine control women were given a vitamin B6-deficient diet for 4 weeks and the same diet supplemented with 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride for an additional 4 weeks. At weekly intervals a variety of indices of vitamin B6 nutrition were measured to determine rates of depletion and repletion. The tryptophan load test (2.0 g) was significantly different in the contraceptive users. However, other indices, including urinary cystathionine (3.0 g L-methionine load), urinary 4-pyridoxic acid, plasma phosphate, and erythrocyte alanine and aspartate aminotransferases, were not significantly different. Since altered tryptophan metabolism persisted in contraceptive users even when other indices of vitamin B6 nutrition were normal, we suggest that the use of oral contraceptives specifically affects tryptophan metabolism by some means other than through a vitamin B6 deficiency.


Dietary levels of vitamin E and polyunsaturated fatty acids and plasma vitamin E. Seventeen daily diets (breakfast, lunch, and dinner) were analyzed from a 35-day menu cycle fed to students, under contract in the University dining halls. This 35-day menu cycle was repeated 6.6 times over the course of two 15-week semesters and registration and final examination periods. The average 2, 500 kcal diet collected during the sixth and seventh menu cycles contained 96 plus or minus 26 g fat of which 19.5 plus or minus 1.8% was linoleate and 28.7 plus or minus 14.2 mg total tocopherol of which 7.5 plus or minus 3.5 mg was RRR-alpha-tocopherol. Blood samples obtained from 26 female undergraduate student volunteers contained adequate levels of plasma total vitamin E, 1.09 plus or minus 0.25 mg/100 ml, despite the observation that 71% and 65% of the diets analyzed did not meet the value tabluated in the eighth edition of "Recommended Dietary Allowances" for adult females in terms of RRR-alpha-tocopherol or total vitamin E activity, respectively. These data emphasize the importance of the average long-term consumption of this fat-soluble vitamin rather than daily intake.


Recommended dietary allowance for vitamin E: relation to dietary, erythrocyte and adipose tissue linoleate. The general trend toward increased consumption of polyunsaturated fatty acids is apparent in the linoleate level of adipose tissue (13.0 plus or minus 1.3%) and erythrocyte lipids (14.0 plus or minus 1.9%) in the present group of female undergraduate student volunteers compared to values reported in the early 1960's. On the basis of the level of linoleate in their diets (19.5 plus or minus 0.8%), it is also apparent that further increases in tissue lipid linoleate levels are to be anticipated, which in turn will result in an increased requirement for vitamin E. It is suggested that adipose tissue linoleate levels in the general population be used as a baseline for the periodic evaluation and revision of the recommended dietary allowance for vitamin E. The recommended dietary allowance could then be phrased in terms of the quantity of vitamin E activity to be consumed per gram linoleate in 100 g adipose tissue fatty acids. A recommendation of 0.6 IU vitamin E activity/g linoleate in 100 g adipose tissue fatty acids is tentatively suggested.


Carbohydrate and lipid metabolism in the Alaskan Arctic Eskimo. The effect of a low total carbohydrate low sucrose diet on various parameters of lipid and carbohydrate metabolism was studied among residents of a North Slope Alaskan Eskimo village. For comparative purposes a group of Eskimo youths consuming a higher carbohydrate institutional diet was also stidied. Those Eskimos consuming their native diet had unusually low serum triglycerides and very low density lipoproteins and normal glucose and tolbutamide tolerance tests. Eskimos on a higher carbohydrate diet exhibited significant elevations of triglycerides and minor alterations in glucose tolerance testing. Differences in cholesterol intake between these groups were accompanied by changes in serum cholesterol and low density lipoprotein levels. Unusually high levels of free fatty acids without ketonemia in the North Slope sample were noted as well.


Titrating dietary linoleate to in vivo platelet function in man. Platelet aggregation time significantly increased within 48 hours in response to an increase in dietary linoleate of 4% of calories while disaggregation time decreased significantly in 96 hours. A change as small as 0.5% of calories was associated with significant alterations within 4 days. In this group, dietary linoleate appears to be related to platelet function by the equations Aggregation time equals 41.14 plus 2.79 linoleate Disaggregation time equals 11.04 minus 25.52 linoleate.


Effect of oral contraceptive agents on vitamin nutrition status. Effects of low estrogen combination type oral contraceptives on some of the biochemical parameters used for assessing vitamin nutritional status were investigated in a group of women who had used the pill for 6 to 12 months. Another group of women was examined initially and then at one or more points of time within the first 6 months of treatment. Following changes were observed in women treated with oral contraceptives: 1) increased excretion of kynurenic acid and xanthurenic acid following tryptophan load; 2) increased EGOT activity and also an increase in vitro stimulation of EGOT with added PALP; 3) increased plasma vitamin A levels; 4) fall in erythrocyte folate levels; 5) fall in erythrocyte transketolase activity with no change in vitro stimulation with TPP; and 6) fall in erythrocyte riboflavin concentration associated with a decrease in erythrocyte glutathione reductase activity and increase in vitro stimulation with FAD. Most of these changes were observed during the first few cycles of oral contraceptive treatment.


Insulin, glucose and triglyceride relationships in obese African subjects. Aspects of carbohydrate and lipid metabolism were studied in 50 nondiabetic African subjects living in Johannesburg. Twenty-six of them were overweight, invariably associated with a high-carbohydrate intake. In general, the obese group demonstrated significantly raised serum insulin levels, normal glucose tolerance, normal fasting serum triglycerides, and significantly elevated serum cholesterol concentrations. However, the degree of obesity was not significantly correlated with any of these metabolic variables--notably basal or stimulated insulin levels. This suggests that the obese state, per se, was not the major cause of the hyperinsulinemia, and that other factors influenced individual insulin responses or sensitivity. Inconsistently excessive dietary carbohydrate ingestion and an unusual degree of physical activity may have been important. A striking correlation emerged between fasting serum triglycerides and insulin concentrations (both basal and stimulated); the possibility that this reflects acceleration of hepatic triglyceride synthesis by insulin is discussed. The concept of obesity invariably producing insulin resistance and progressive compensatory hyperinsulinism may not apply in all environmental conditions.


The structure of cell membranes involved in intercellular communication. The molecular structure of mouse hepatocyte gap junctions is investigated with corrlated electron microscopy, biochemistry, and x-ray diffraction technics. These studies reveal that the gap junction is composed of a hexagonal lattice of protein subunits, connexons, which pierce the hydrophobic membrane and establish a structural basis for intercellular hydrophilic channels or pores. By digesting liver-cell membranes with trypsin, a preparation of open- and closed-gap junction vesicles can be generated; this preparation will permit direct permeability measurements across the gap junction membranes in an in-vitro system.


Modifying the immunogenicity of cell membrane antigens. Tumors and transplants. The immunogenicity of an antigenic cell is a distinctly different property from its antigenic composition. Two clinical problems might well be beneficially affected by modifying the immunogenicity of cell membrane antigens: Can the immunogenicity of tumor-specific antigens on malignant cells be increased so that effective immunity to the tumor will lead to its destruction? Conversely, can the immunogenicity of histocompatibility antigens on grafted organs be minimized so that they will survive a foreign host? Evidence is accumulating to indicate that under certain conditions a tumor vaccine can be developed utilizing autochthonous tumor cells, removed from the host, chemically modified in vitro, and reinjected into the original host which will effectively, augment specific immunologic defenses against residual tumor cells. Similarly, the moderately immunosuppressed host will tolerate grafts after suitable immunogenic modification in vitro. Both approaches may have ready clinical application, even before the mechanisms have been worked.


Effectiveness of an early secondary prevention program in an inner-city elementary school. The adaptation of an early secondary prevention program to an inner-city elementary school is described. The program utilizes nonprofessional workers as the primary helping agents with maladapting children in kindergarten through third grade classes. The program also involves consultation with classroom teachers and parents and an after-school activity group. A community advisory board helps provide accountability to the community and increased program impact in the community. Evaluation of the program provides support for program effectiveness in improving the adaptation of program children.


Brief hotline training. An effort to examine impact on volunteers. In response to community needs and pressures, increasing numbers of small crisis centers and hotline services have emerged. This emergence of services has been possible in part because of the mounting number of eager and interested volunteers. These services want and need training for the volunteers. This article examines the problem of evaluating the kind of information and the kind of training that hotline volunteers were given in a brief training program.


Planning primary prevention strategy. A survey of the effects of business location on Indian reservation life. It was hypothesized that the introductions of a new business or industry into a high-poverty-level Indian reservation community would produce conditions that could have both positive and negative effects on mental health. A questionnaire surveying the impact of business location on reservation life was sent to all field offices of the Bureau of Indian Affairs. Survey results supported the expectation that business development may affect community life in a variety of ways. Respondents cited approximately twice as many positive effects as negative ones. Furthermore, it was found that relatively few Indians were actually employed and consequently exposed to either type of effect. Implications of the survey for planning primary prevention strategies which would minimize the pathogenic influences of business development are discussed.


Childhood sarcoidosis. Progressive systemic illness with micronodular pulmonary involvement. A 9-year-old black girl had progressive generalized sarcoidosis. Chest roentgenograms disclosed severe, disseminated micronodular infiltrates, and pulmonary function was severely decreased. Results of a liver biopsy disclosed granulomas consistent with sarcoidosis. She responded dramatically to corticosteroid therapy, both clinically and radiologically.


Cardiophrenic adenopathy in Hodgkin disease. Hodgkin disease can involve diaphragmatic lymph nodes adjacent to the heart. When nodes at the cardiac apex are involved, the roentgenographic appearance simulates  that of the normal pericardial fat pad. Though, to our knowledge, no cases have been reported in which this was the only intrathoracic manifestation of Hodgkin disease at the time the patient was first seen and the condition was diagnosed, it may be the only manifestation of relapse, as was true in the case presented.


A new arthrogryposis syndrome with facial and limb anomalies. A new familial syndrome of facial and limb anomalies was shown in a 4-month-old girl. Small mouth and jaw with limited jaw movement were seen in infancy, with growth to relatively normal size and movement in adulthood, but with a persistent, deep, horizontal depression just above the chin. Mild short stature and microcephaly as well as large ears with lack of the anthelix were present in family members. Severe flexion contractures of the hands and feet were present and led to subluxation of fingers and club feet in the most severely affect child. Marked variability among family members was seen, but a dominant inheritance seems likely.


Systemic lupus erythematosus in a 1-year-old child. An 11-month-old girl had systemic lupus erythematosus with a widespread skin rash. She manifested five of the criteria necessary for the diagnosis: oral ulcerations, alopecia, positive lupus erythematosus preparations, convulsions, and thrombocytopenia with leukopenia. Direct immunofluorescence showed deposits of IgG and C3 at the dermoepidermal junction of both abnormal and clinically uninvolved skin, and in subepithelial deposits along the glomerular basement membrane.


Inappropriate antidiuretic hormone secretion in an infant with severe pneumonia. A 6-week-old boy with severe pneumonia developed hyponatremia as a result of the syndrome of inapropriate antidiuretic hormone secretion (SIADH). Cerebral edema and seizures occurred after administration of fluids and diuretics. Fluid restriction and resolution of the pneumonia corrected the severe electrolyte imbalance. The possibility of SIADH should be considered in cases of severe and resistant pneumonia in infancy.


Critical weight at menarche. Critique of a hypothesis. The critical weight hypothesis in relation to menarche, which is known as the Frisch-Revelle model, has been examined. Since, in eight samples, girls reached menarche at weights spanning a 71.4-kg (157-lb) range, Frisch and Revelle's concept of a critical weight of 47 to 48 kg (104 to 106 lb) cannot be applied meaningfully to individuals. Neither can the suggestion of an invariant mean weight be accepted, because significant differences occur among the mean menarcheal weights for several samples of normal white girls. Finally, when stature is held constant, there is some evidence that girls who reach menarche at younger ages are heavier than those who begin menstruating at older ages. Apparent reductions in variability when the estimated amount of total body water is used instead of body weight may result from statistical artifacts associated with regression analysis.


Ambulatory pediatric fellowship programs. Pediatric ambulatory fellowships are post-residency training program designed to prepare pediatricians to deliver, organize, and evaluate primary pediatric care. A survey of the members of the ambulatory Pediatric Association details the funding, structure, content, and outcome of these training programs. The Ambulatory Pediatric Association has recently approved guidelines for the standards and content of these fellowship programs.


Fetal electroencephalography. Relationship to neonatal and one-year developmental neurological examinations in high-risk infants. Sharp wave activity in fetal electroencephalograms was found to have a significant relation to neurological findings at 1 year of age but not to neurological findings obtained during the neonatal period. Neonatal neurological findings were significantly related to those at 1 year of age.


Pneumatoceles following hydrocarbon ingestion. Report of three cases and review of the literature. Three cases of pneumatocele formation secondary to hydrocarbon ingestion are reported and analyzed along with 12 from the literature. The cases display a spectrum of clinical severity. After a period of 3 to 15 days, during which most patients became asymptomatic, pneumatoceles were noted radiologically, usually as an unexpected finding on follow-up roentgenograms. No instances of pneumothorax or empyema were noted. Resolution has been observed radiologically after periods varying from 15 days to 21 months. The incidence of this complication is probably greater than previously realized.


Infants with congenital heart disease. Food intake, body weight, and energy metabolism. Growth failure in infants with congenital heart disease was investigated by studies of food intake, change in body weight, oxygen consumption, carbon dioxide production, and lean body mass. Infants with congenital heart disease weighed less initially and gained less weight during observation than normal infants. The daily intake of calories per kilogram body weight was inadequate for some infants and considered generally adequate for others. Lean body mass was normal, and the quantity of oxygen used for metabolism was similar in both groups. Infants with congenital heart disease were not found to be hypermetabolic when oxygen consumption was related to lean body mass. The growth failure seen in these infants appears to be most appropriately related to inadequate calorie intake rather than to any other factor studied.


Neonatal familial hypercholesterolemia.

Neonatal familial hypercholesterolemia. Hypercholesterolemic and normal neonates from hypercholesterolemic kindreds were studied for 6 to 30 months. Sixteen of 22 hypercholesterolemic neonates and eight of 11 normal neonates came from families with "monogenic" hyperlipoproteinemia. At 6 or 12 months of age, plasma cholesterol level was greater than 200 mg/100 ml in eight of the 16 neonates with hypercholesterolemia. Four of these eight had cholesterol levels greater than or equal to 290 mg/100 ml at ages 6 to 18 months. On low cholesterol intake, at ages 6 to 12 months, five of seven infants with hypercholesterolemia had cholesterol levels less than 200 mg/100 ml. One of eight normal neonates from families with hypercholesterolemia had cholesterol levels greater than 200 mg/100 ml at ages 6 to 12 months. Neonatal diagnosis of familial hypercholesterolemia provides an opportunity for long-term primary prevention in a group at high genetic risk for premature is chemic heart disease.


Androgen Therapy in an "excessively" tall boy. An "excessively" tall, early pubertal boy was treated with androgen for a period of 33 months. Sexual development and fusion of epiphyses was accelerated with achievement of shorter stature than that predicted prior to therapy. Testicular size did not appear to be impaired by the therapy. Androgen administration in this young boy appeared to be effective in shortening the eventual adult stature.


Pacemaker therapy in children with complete heart block. Permanent pacemaker therapy in children with complete heart block is necessary occasionally. Ten patients ranging in age from 8 months to 15 years were treated with an implanted P-wave, synchronous epicardial pacemaker. Indications for implantation were persisting postsurgical heart block, congestive failure, syncopal attacks, and arrhythmias. There were two deaths not attributed to pacemaker malfunction. The remaining eight children have been followed up for 38 to 108 months. There have been 27 pulse generator replacements. Twenty-three were for battery exhaustion, three for electromechanical failure, and one was due to arrhythmia. Rhythm disturbances have occurred on eight occasions. There have been no infections. It is concluded that the implanted P-wave synchronous pacemaker is an effective method of therapy when indicated for children with complete heart block.


Occlusive vertebrobasilar artery disease associated with cervical spine anomaly. A 6-year-old boy developed a flaccid hemiplegia and dysarthria following several transient episodes of nausea, vomiting, and ataxia. An anomly of the dens was discovered, permitting subluxation of C-1 on C-2. A segmental occlusion of the right vertebral artery and an aneurysm of the left vertebral artery were found at the C-2 level, as well as a thromboembolic occlusion of the rostral end of the basilar artery. It appeared that the repeated cervical subluxation produced occlusive, aneurysmal, and embolic vascular disease, and that clinical symptoms were the result of ischemia in the territory perfused by the vertebrobasilar arteries.


Ampicillin-associated diarrhea--A prospective study. A prospective study of 200 consecutive patients receiving ampicillin for various reasons revealed that bowel habits changed in 16% and diarrhea occurred in 4.5%. No case of pseudomembranous colitis was found. The incidence with which bowel habits changed increased with larger total doses of antibiotic. Oral and intravenous routes causedthe same incidence of altered bowel habits. This study provides a proper comparison group to place clindamycin-associated colitis in proper perspective.


Effect of increased intraabdominal pressure on lower esophageal sphincter pressure. This study evaluates the effect of intraabdominal pressure increases on lower esophageal sphincter (LES) pressure in normal subjects and in patients with reflux esophagitis. Intraabdominal and intragastric pressure were increased by abdominal compression, the Valsalva maneuver, and leg raising. In normal subjects changes in pressure recorded from the LES equaled the changes in gastric pressure induced by abdominal compression and Valsalva. Consquently the LES-gastric pressure gradient remained unchanged. During leg raising, pressure recorded from the LES increased more than gastric pressure, thereby increasing the LES-gastric pressure gradient. Although statistically significant, the LES pressure increases associated with leg raising were modest, unrelated to initial sphincter pressure, and unaffected by atropine. When individuals demonstrating a "common cavity" phenomenon were exculed, LES pressure changes during abdominal compression were similar in patients with esophagitis and in normal volunteers. Consequently, response of the LES to abdominal compression generally does not separate patients with esophagitis from normal subjects. We believe that the LES responses to increased intra-abdominal pressure observed in this study are better accounted for by mechanical factors than by a physiologic adaptive response of intrinsic LES tone.


Exocrine pancreatic function in juvenile diabetics. In 11 juvenile diabetics and 13 control subjects, the secretin-pancreozymin test was performed. Duodenal-volume losses were corrected by use of radioactive vitamin B12 as marker substance. As compared to normal subjects, juvenile diabetics had significantly decreased pancreatic outputs of amylase, trypsin, chymotrypsin, and to a lesser degree, of bicarbonate. Clinical evidence of disease of the exocrine pancreas was missing. There was no discernible relationship between the abnormality of external pancreatic function and the duration of diabetes mellitus or the dose of insulin required. Possible factors that may be responsible for the exocrine deficiency of the pancreas in juvenile diabetics are discussed.


Oropharyngeal dysphagia Manometric and cine esophagraphic findings. The manometric and cineradiographic features of 14 patients with oropharyngeal dysphagia are described. Failure of the upper-esophageal sphincter (UES) to relax completely and incoordination of UES relaxation with pharyngeal contraction were noted as was poor initiation of swallows and disorganization of pharyngeal contraction. The relative merits of cine esophagography and esophageal manometry in evaluating oropharyngeal dysphagia are assessed, and a functional classification for this disorder is proposed. Clinical improvement in 4 of 5 patients who underwent UES myotomy for severe intractable dysphagia did not always correlate with improvement in manometric and cine studies.


Inflammatory pseudotumors (inflammatory fibrous polyps) of the small intestine: A clinicopathologic study. The clinical and pathologic features of 25 inflammatory pseudotumors of the small intestine are reported. These rare lesions, which clinically may simulate neoplasms, consist of localized, frequently polypoid masses composed of inflamed fibrous and granulation tissue. Inflammatory pseudotumors may produce intussusception and small-bowel obstruction. Some are found at laparotomy performed for other reasons. The diagnosis of inflammatory pseudotumor usually can not be made until the lesion is examined histogically. Their etiology remains unknown, but their relationship to intestinal ulceration is discussed. Problems in differential histologic diagnosis are considered.


Transplantation antigens in Crohn's disease: Linkage of associated ankylosing spondylitis with HL-Aw27. The complete HL-A antigen profile was examined in 77 patients with Crohn's disease,11 of whom had unequivocal ankylosing spondylitis. There was no significant difference in the frequencies of the HL-A antigens between these 77 patients and 600 normal controls. 10 male patients with Crohn's disease possessed HL-Aw27; all of these had unequivocal ankylosing spondylitis. This antigen may, therefore, be a useful marker of spondylitis in Crohn's disease.


The role of bile reflux in the development of cold-restraint gastric lesions. The study was designed to test whether or not bile reflux is necessary for the development of gastric mucosal lesions during cold-restraint stress in the rat. 40 male Sprague-Dawley rats were studied. They were randomized into 4 groups. Group 1 underwent sham operations with no cold-restraint stress. Group 2 underwent sham operations. Group 3 underwent pyloric ligation. Group 4 underwent bile duct ligation. Groups 2, 3, and 4 were subjected to cold-restraint stress for 3 hours at 4-6 degrees C in a Bollman cage. After the experimental procedure, the stomachs were removed under ether anesthesia, the severity of lesions was recorded, and blood from the hearts was obtained for hematocrit readings. The mean lesion scores of all groups exposed to cold-restraint stress were similar and much higher than that of the unrestrained sham-operated group (P smaller than 0.001). Also, mean hematocrit readings in all groups exposed to cold-restraint stress were lower than in the control group (P smaller than 0.05). There was a correlation between severity of mucosal lesions and hematocrit reading (rs=0.57, P smaller than 0.001). The results obtained allow the following conclusions: (1) Bile reflux is not necessary for formation of cold-restraint stress lesions in the rat. (2) Hematocrit readings appear to be a useful measure of blood loss secondary to experimental mucosal lesions.


Use and abuse of gastric function tests by British and American gastric surgeons. The use of gastric function tests by American and British gastroenterologic surgeons in different clinical situations has been studied by questionnaire. Clinical practice on both sides of the Atlantic is generally similar. The major difference in the type of test employed is that pentagastrin cannot be used in clinical practice in the United States. Surgeons in the USA were much more liberal in their indications for gastric secretory tests than were their British counterparts. Significantly more tests were used by American surgeons, if x-ray evidence of duodenal or gastric ulcer existed, and to evaluate a post-gastrectomy patient, whether symptomatic or not. The British surgeonswere much less likely to allow the results of secretory tests to influence their surgical approach. The authors discuss indications for and the clinical value of gastric secretion tests and conclude that in most instances far too many tests are being employed.


Lower-esophageal webs.

Lower-esophageal webs. A case of a true lower-esophageal web is reported. The web was not visualized on radiological examination, but was visualized and removed by endoscopy. The purpose of this report is to point out that true lower-esophageal webs are different from lower-esophageal rings. Lower-esophageal webs occur much less frequently than lower-esophageal rings but must be included in the differential diagnosis of dysphagia.


Leukocyte migration test in Crohn's disease, ulcerative colitis, and ankylosing spondylitis using Crohn's colon homogenate, mitochondrial, and microsomal fractions. Leukocytes from 33 patients with Crohn's disease, 20 patients with ulcerative colitis, and 20 patients with ankylosing spondylitis were tested for evidence of abnormal migration in the presence of preparations of colon from a patient with Crohn's disease. None of the patients was on treatment with immunosuppressive drugs. The test was also performed with leucocytes from 12 health subjects. Significant alteration was seen in the Crohn's disease group, particularly when the antigen used was mitochondrial or microsomal fraction of colon mucosa, whereas the patients in the ulcerative colitis group showed reactivity only with the whole colon homogenate and not with the subcellular fractions. The ankylosing spondylitis group showed no statistical difference from the normal controls with any of the antigens.


The immune response to phi chi 174 in man. II. Primary and secondary antibody production in patients with Crohn's disease. 10 patients with Crohn's disease in various states of activity have been injected with 3.3 times 10-9 plaque-forming units of the bacteriophage phi chi 174, as a test for their capacity to produce antibodies. 9 patients had a completely normal primary and secondary antibody response. One patient had higher levels of preimmunization antibodies than have been encountered in normal subjects and developed a secondary (IgG) response to the first dose of antigen. We conclude that there is no evidence of a general disturbance of antibody-producing capacity in subjects with Crohn's disease.


Significance of gastric secretory changes in the pathogenesis of stress ulcers. Analyses of gastric juice withdrawn 3 hours after the pylorus was ligated and of plasma corticosterone and blood glucose after animals were exposed to rotational stress revealed that gastric secretion was highest in controls, intermediate in stressed rats that developed ulcers, and lowest in stressed rats that did not develop ulcers. Neither high nor low gastric secretion correlated with stress-ulcer formation. When initial mucosal ischemia and secretory inhibition, which occurred in all stressed rats, were considered, those that developed ulcers manifested gastric hypersecretion when compared with those that did not develop ulcers. The pathogenetic significance of gastric hypersecretion in stress-ulcer formation is discussed and correlated with mucosal microvascular changes during stress. Mean plasma corticosterone was highest in stressed rats that developed ulcers, next highest in stressed rats that did not develop ulcers, and lowest in control rats. Compared with normal rats, mean blood glucose was lowest in stressed rats and highest in controls. Hypoglycemic changes were more marked in stressed rats that developed ulcers than in stressed rats that did not develop ulcers.


Effect of intragastric infusion of tobacco powder on DNA content of gastric aspirate. The DNA content in gastric aspirate was measured before and during intragastric infusion of 0.1 or 0.2 g/hr tobacco powder. The infusion of 0.1 g/hr caused an insignificant rise in the DNA content but infusion of 0.2 g/hr of tobacco caused a marked and rapid rise in the DNA content of gastric aspirate during the hour of infusion. The effect of tobacco was transient (ie, only during the period of infusion). These observations indicate that the increased exfoliation of surface epithelial cells of human gastric mucosa with tobacco infusion is dose related.


Radioselenium pancreozymin-secretin test as a clinical test for pancreatic exocrine function. The appearance of radioselenium in the protein fraction of duodenal aspirates has been studied after an intravenous injection of 75-Se-selenomethionine. The continuous flow of pancreatic juice was stimulated by pancreozymin at 120 minutes and by secretin at 140 minutes. A good distinction between normal subjects and patients with pancreatic disease was obtained by measuring 75-Se-radioactivity in the protein fraction of duodenal aspirates; either cumulative radioactivity during the combined 80-minute post-pancreozymin-secretin period, or maximum 75-Se-specific activity during the postsecretin period was used as an index. The test presented here might be a useful and sufficiently reliable method for detecting abnormal pancreatic exocrine function. This test can be performed along with the conventional pancreozymin-secretin test, serum enzyme response to pancreozymin and secretin, and pancreatic scintiscanning.


Lowered serum cholesterol following the ingestion of a hydrophilic colloid. An attempt was made to test the possible clinical application of the cholesterol-lowering effect of hydrophilic colloids. 10 patients with high mean serum cholesterol levels during a 3-week control period and 9 with normal mean levels were each fed 11.5 g daily of undiluted hydrophilic colloid for 5 weeks. Serum cholesterol decreased significantly in 8 of the 10 (80%) patients with control-period hypercholesteremia and 6 of the 9 (66 2/3%) with control-period normal levels. These findings tend to confirm the observation that a simple and commonly used type of medication for chronic constipation, particularly in the elderly, may be a useful adjunct in the management of hypercholesterolemia.


Inflammatory pseudotumors (inflammatory fibrous polyps) of the esophagus. A clinicopathologic study. When they involve the gastrointestinal tract, inflammatory pseudotumors, composed of inflamed fibrous and granulation tissue, produce localized, frequently polypoid, masses. These rare lesions have been described in the stomach, small intestine, and colon. Only two have been previously reported in the esophagus. In this paper, 4 cases of inflammatory pseudotumor involving the esophagus are presented. These lesions usually occur in the esophagus as raised, occasionally pedunculated, masses and may be mistaken on radiologic examination and in the operating room for a neoplasm, usually a leiomyoma. Theories concerning pathogenesis of these lesions are considered and the differential diagnostic criteria are discussed.


Variability of serum gastrin levels in Zollinger-Ellison syndrome. Studies with two antisera to gastrin. A patient with recurrent peptic ulceration and presumed Zollinger-Ellison syndrome whose serum gastrin concentration varied widely is reported. Two antisera, one directed predominantly against nonsulfated gastrin and the other measuring both sulfated and nonsulfated gastrin, showed that in addition to wide variation in gastrin levels, this patient secreted his gastrin predominantly in the sulfated G34 form. The possibility of variable serum gastrin levels, which may reflect either spontaneous vaiation in gastrin output from Z-E tumors or differing specificity of the antiserum utilized in the immunoassay, may be of importance in the diagnosis and management of patients with the Zollinger-Ellison syndrome. Because of gastrin heterogeneity in the Z-E syndrome, this study reinforces the concept that a broad spectrum antibody, detecting all gastrin components should be routinely used in detection of patients suspected of having the Z-E syndrome.


Primary adenocarcinoma of the esophagus arising in a columnar-lined esophagus. A patient presenting with dysphagia and weight loss was found to have a large midesophageal mass. Five biopsies indicated only adenoma but a brush cytology specimen under direct vision was diagnostic of adenocarcinoma. Esophagotomy and resection of tumor, with follow-up radiotherapy were performed; histologic examination confirmed the diagnosis. To date, there has been no recurrence of the tumor. This patient was subsequently found to have a columnar-lined esophagus. Since columnar-lined esophagus may predispose to malignancy, this case illustrates the diagnostic importance of direct-vision cytology in patients with columnar-lined esophagus.


Silent pancreatic pseudocyst. An unusual cause of extrahepatic biliary obstruction. Extrahepatic biliary obstruction due to mechanical obstruction of the common bile duct is a relatively rare complication of pancreatic pseudocyst. When jaundice does occur, clinical or laboratory evidence of associated primary hepatobiliary disease or acute pancreatitis has invariably been present. The patient described had a 3-month history of painless juandice, 40-lb weight loss, pruritus, and hepatomegaly, but no clinical or biochemical evidence of acute or chronic pancreatitis. After initial evaluation, including an abdominal echogram and a transhepatic cholangiogram, carcinoma of the head of the pancreas was diagnosed preoperatively. At laparotomy, a small pancreatic pseudocyst obstructed the terminal portion of the common bile duct. This case illustrates that a pancreatic pseudocyst should be considered in the differential diagnosis of obstructive jaundice, even in the absence of clinical evidence of pancreatitis or pseudocyst formation.


Hormonal control of gastrointestinal motility. The motor responses of the gastrointestinal tract to a meal are tuned to provide the optimal conditions for digestion and absorption of food. Hormones released from the mucosa of the intestinal tract play an important role in regulating and integrating the various motor events which occur. Complex feedbacks, both nervous and humoral, control the release of intestinal hormones and also modify their actions. Preliminary studies suggest that abnormalities in the secretion or action of various gastrointestinal hormones may play an important role in the production of motor disorders of the gastrointestinal tract.


Diffuse small bowel involvement in malignant histiocytosis. The extremely unusual patient reported here had malignant histiocytosis with extensive gastrointestinal involvement. The presenting symptoms were those of a gastrointestinal disorder and barium studies of the upper gastrointestinal tract revealed an infiltrative process of the entire small bowel. A biopsy of the small bowel demonstrated abnormal malignant cells and the diagnosis of malignant histiocytosis was considered and confirmed at postmortem. Strongyloidiasis, which was also found in this patient, may represent a hyperinfestation phenomenon due to altered host-parasite balance.


The Nonreflux Determinant of Esophagitis. Fifty randomly selected patients were examined clinically, esophagoscopically and biopsy specimens were taken transesophagoscopically from the lower third of the esophagus. In addition, upper gastrointestinal series and gastro-secretory studies were done in all subjects. In 15 cases, in vitro DNA synthesis using tritiated thymidine was measured. No clear correlation was found between clinical manifestations, esophagoscopic appearances and histopathologic findings (Table III). Eleven (27.5%) of the 40 patients with normal esophagoscopy showed abnormal histology, whereas two of the remaining 10 patients with esophagitis by esophagoscopic criteria showed normal histology. Thus, without biopsy about one-third of the cases of histologic esophagitis can be overlooked. In the over all series, there were 19 (38%) cases with histologic esophagitis. In eight (42%) of the 19 patients with histologic esophagitis, the lesion was confined to the lamina propria. In addition to inflammatory infiltrate and fibrosis, a thickened epithelial basal layer and relatively lengthened papillae were found to be important histological signs of esophagitis. Cases with thickened basal layer showed marked labeling with radioactive DNA precursor (H3 Thymidine) after two hours of incubation, compared with the other group of patients (normal esophageal mucosa histologically or histologic esophagitis without a thickened basal layer). This is thought to be a sign of increased regeneration and repair capacity. The lamina propria did not show any labeling in either group of patients at the end of two hours. Therefore, it is concluded that the esophageal epithelium has greater regenerative capacity and can repair itself and return to a normal appearance while the inflammatory process is ongoing in the lamina propria. Besides predisposing factors such as esophagogastric sphincter dysfunction and reflux of digestive enzymes, a local tissue reaction or cell proliferation and repair capacity of theesophageal epithelium must play an important role in the development of nonspecific "peptic" esophagitis.


Electrocardiographic monitoring during coloscopy. Electrocardiographic abnormalities were observed in 15 of 23 patients (65%), five with known heart disease, who were monitored for one hour prior to, during and for one hour after coloscopy. In one patient, ischemic S-T depression, 2 mm. below the resting level, persisted during the one hour following coloscopy. In all other patients, the electrocariographic abnormalities disappeared before the end of the monitoring period.


Idiopathic intestinal pseudo-obstruction. This is a case report of a patient with a variant of idiopathic intestinal pseudo-obstruction (IIPO). The patient, a 53-year old female with polycystic kidney disease, had intermittent episodes of intestinal distention with megaduodenum and megasigmoid noted at roentgen study and postmortem examination. The etiology of this abnormality is unclear and no significant changes in the innervation of the bowel were noted on gross or histologic study.


Arteriographic diagnosis of a juvenile colon polyp. A juvenile colon polyp was demonstrated by inferior mesenteric arteriography in a 21-year old man with recurrent, massive, unexplained gastrointestinal bleeding. The arteriogram demonstrated a mucosal blush at the tip of the polyp along with a solitary prominent draining vein in the stalk and a nest of draining veins at the base of the stalk.


Diverticulosis in an unused colon.

Diverticulosis in an unused colon. It has been suggested that diverticulosis is the result of uncoordinated muscle activity of the colon in response to normal physiologic stimuli such as eating, emotions and the urge to defecate. This results in spasm of the longitudinal muscle with the heaping up of circular muscle bundles, creating interhaustral folds along the colonic wall adjacent to the mesentery. Narrowing of the lumen and shortening of the colon results which is enhanced by a low residue diet and prevented by a bulky diet. Segmentation results when muscular contraction approximates these interhaustral folds. Higher intraluminal pressure is produced in the areas of segmentation which enhances the development of diverticulosis in the bowel between interhaustral folds where there is a thinning of the circular muscles and where vessels pierce the colonic wall. The case presented herein supports these hypothesis in that the patient has experienced the extreme in a low residue diet for 50 years.


Analysis of the mechanism of action of calcium-induced exocrine pancreatic secretory changes in the dog. In conscious dogs, provided with gastric and duodenal fistulas (Thomas cannula), the effect of an acute i.v. calcium infusion (10 mg./kg./hr.) on the plateau levels of secretin-induced (GIH, 1 CU./kg./hr.) pancreatic juice parameters were analyzed without or with previous cholingergic blockade by a continuous atropine perfusion (1.5 mg./hr.). In the former condition, i.v. calcium raised all pancreatic juice parameters, mainly protein concentration (148%) and output (173%). During atropine blockade, i.v. calcium changed neither flow rate nor bicarbonate output of secretin-induced pancreatic secretion. On the other hand, i.v. calcium exerted a reduced but still evident effect on protein concentration (85%) and output (40%). Intravenous calcium enhances secretin-induced pancreatic secretion plateau values through two mechanisms, mainly by raising the cholinergic tone of the whole "pancreon" and, partially, through a direct stimulus-secretion coupling effect on the acinar cells. Acute hypercalcemia induces the formation of protein plugs in the pancreatic secretion. They are excreted in the course of many days in both basal and secretin-stimulated pancreatic juice.


The retrogastric transventricular approach for drainage of the "supragastric" pancreatic pseudocyst. The majority of pancreatic pseudocysts develop in a retrogastric situation and are amenable to transgastric cystogastrostomy through the anterior gastric wall. We have encountered two pseudocysts in an unusual situation, in which adherence of the anterior gastric wall to the anterior parietal peritoneum precluded this approach. A retrogastric exposure through the lesser sac allowed for the creation of a cystogastrostomy through the superior aspects of the anterior and posterior gastric walls, adjacent to the lesser curvature of the stomach. This type of drainage is successful despite the theoretical failure to satisfy the dictum of dependent drainage.


Comparison of the effect of different forms of a protein test meal on gastric acid and gastrin secretion. In three mongrel dogs with fundic pouches, the effect of a chopped versus a blenderized test meal on gastric acid output and gastrin secretion was investigated. The blenderized test meal caused a greater increase in acid output and gastrin secretion than the chopped test meal.


Concomitant acute lupus erythematosus and primary pneumococcal peritonitis. The acute surgical abdomen, a synonym for peritonitis requiring surgical intervention, can be mimicked by lupus peritonitis and, in children, by pneumococcal peritonitis. The former is best treated by systemic steroids and, the latter by penicillin; neither is well served by surgical intervention. We have reported here a young woman with the concomitant occurrence of both conditions. If peritoneal tap and immediate bacteriologic gram staining of recovered aspirate were carried out in patients with a history of acute lupus, such similar cases could be detected preoperatively. An attempt at antibiotic treatment could then be instituted as a first measure.


The radiology corner. Gastric myeloma.

The radiology corner. Gastric myeloma. Gastric myeloma is a rare malignant tumor composed of atypical plasma cells and represents, as a rule, only the initial manifestation of widespread myelomatous proliferation. Roentgenographically, it may be indistinguishable from carcinoma of the stomach or it may present as a large intramural mass, often situated along the greater curvature of the stomach. The association of a malignant looking gastric lesion with clinical or radiographic evidence of multiple myeloma should strongly suggest the diagnosis.


Medical observations and bias.

Medical observations and bias. Many clinical and epidemiologic studies are based on different physicians' readings. A method to calibrate the various examinations is described. The standard reader's and others' results are plotted in a correlation diagram. Their readings are characterized by three parameters: frequency of agreement, average difference in size, and variance. In each study, the acceptable range of deviation from the standard reader should be decided. The standard reader is characterized by two requirements: a) that he is consistent, i.e., that a second reading shows a high rate of agreement, a small difference and a small variance between the two readings, and b) that he is reproducible, i.e., that other experienced doctors accept his classification and arrive at the same result. When statistical tests are used, it is understood that systematic errors are not present in the basic data. If this is not the case, the validity of the statistical tests is lost and results distorted or even meaningless. The second part of the study discusses types of bias encountered in epidemiologic studies and gives examples showing that the quantitative significance of bias can be considerable.


Epidemiologic survey of rubella in a military recruit population. A seroepidemiologic surveillance of rubella infections in arriving male and female Navy recruits indicated that from 82-90% of young adults have hemagglutination (HA) titers of 1:10 or greater. Subsequent to the establishment of a new male recruit camp, there was a 10- to 11-month hiatus of low level rubella infection in the population. Once endemic rubella was established, more than 73.3 per cent of those with no detectable initial titer seroconverted. There was no reported rubella infection at an isolated female recruit camp of about 500 women even though the proportion of susceptibles was similar. However, once the female recruit camp was relocated within the male camp, their experience with rubella became comparable. A small (6.8% men, 5.6% women) number of recruits with pre-existing HA antibody titers had a four-fold or greater rise in titer during training. The great transmissibility of rubella virus in a closed population was illustrated and the ineffectiveness of herd immunity in this setting was evident.


Role of the pharmacist in an allergy clinic. The duties performed by pharmacy residents assigned to an allergy clinic, on a rotating basis, are described.  The pharmacists are responsible for preparation and control of allergenic extracts, obtaining patient histories, performing allergy testing procedures, refering patients to community health clinics, and patient consultation.


A pocket aide-memoire on drug interactions. A pocket size "slide-rule" type device designed to be used by physicians, pharmacists and nurses as a memory aid on potential drug-drug interactions is described.  Color-coded symbols on the device indicate both the type and clinical significance of the potential interactions involving 56 drugs or groups of drugs.


Hyperosmolar cold storage kidney preservative solution. A hyperosmolar kidney preservative solution which can maintain kidneys from experimental animals viable for up to 72 hours is described.  Using the criterion of a one-month failure rate, the cold storage preservation method was found to be superior to machine preservation methods.  Sachs' solution was found to be superior to all other cold storage solutions.  The most important aspect of the hyperosmolar kidney preservative solution appears to be its ability to maintain normal intracellular electrolyte composition and to prevent cellular damage due to swelling.  The present formula requires that the basic solution and a magnesium chloride additive solution be prepared separately and combined before use.  A stable combined solution is proposed which can be sterilized by membrane filtration.


Acute psychotic reaction to procaine penicillin. A case of a 23-year old black female admitted for treatment of an acute psychotic episode 48 hours after being treated with i.m. procaine penicillin G is reported.  Literature reports of nonallergic psychotic responses to i.m. injections of aqueous procaine penicillin G are reviewed.  Possible mechanisms for the reaction are discussed.  Recommended drugs for treatment of the reaction include phenobarbital and chlorpromazine.


Online drug interaction surveillance.

Online drug interaction surveillance. An online computer-based system to monitor prospectively for potential drug interactions in a hospital setting is described.  The system, developed at Stanford University Medical Center, is fully operational and is used to inform pharmacists, nurses and physicians as to the severity and speed of onset of potential drug interactions.  In addition, the system can produce prescription labels and patient-drug profiles for the pharmacy and serves as a retrieval source of drug interaction information.  Each report provides information regarnding the pharmacological effect and mechanism of the interactions, as well as statements involving relevant clinical findings associated with these interactions.


Semiquantitative test for iodine vapor above "complexed" iodine solutions. A test to determine the extent to which free iodine exists in the vapor phase above the surface of "complexed iodine" solutions is described. The procedure is based on the qualitative starch-iodine test. The results can be related to the degree of complexation occurring between the polymer used in the preparation and iodine. Four products were tested: nonylphenoxypoly ethanol-iodine complex; polyvinyl pyrrolidine-iodine complex; popoxamer-iodine complex; and nonylphenoxypoly ethanol and polyvinyl pyrrolidone iodine complex. Free iodine in the vapor phase of the first product was detected in 90 minutes; the time for the other three was five days. For the tincture of iodine control, the time was 30 minutes.


The clinical spectrum of light chain myeloma. A study of 35 patients with special reference to the occurrence of amyloidosis. During a 40 month interval, 35 patients were seen with a plasma cell dyscrasia in which the only detectable monoclonal immunoglobulin abnormality consisted of excess production of either type kappa or type lambda light chains (Bence Jones protein). This group constituted 17.3 per cent of the total number of patients with plasma cell dyscrasias and 25.7 per cent of the patients with myeloma identified during the same period. Variable initial clinical presentation, the absence of a typical monoclonal serum spike and the unreliability of commonly used urine protein tests made recognition of the disorder difficult in many patients. Sulfosalicylic acid and p-toluene sulfonic acid proved valuable in screening for ueine protein. Definition of "proteinuria" by quantitative, electrophoretic and immunochemical studies was essential for diagnosis. Bence Jones proteinemia was present in 80 per cent of the patients; panhypogammaglobulinemia and lytic bone lesions were demonstrable in more than 60 per cent. Although no specific morphologic abnormality of marrow plasma cells was evident by light microscopy, the absence of rouleau on peripheral blood smear was a helpful diagnostic clue. Although patients with lambda light chains presented with more Bence Jones proteinuria, this did not correlate with the severity of initial renal functional impairment or with survival when compared to patients with kappa light chains. No other clinical or laboratory observation differentiated the groups with kappa light chains from those with lambda light chains. Amyloid was identified in seven patients. Their course was dominated by the features of primary systemic amyloidosis instead of the usual findings of classic myeloma. Patients with amyloidosis had lower initial serum albumin levels, fewer lytic bone lesions and reduced survival compared to patients without amyloidosis.


Central nervous system disease in systemic lupus erythematosus. Therapy and prognosis. The effect of corticosteroid therapy in 28 patients with 52 episodes of neuropyciatric disease in systemic lupus erythematosus (SLE) was elevated. Categories of organic central nervous system disease were seizures (eight patients), organic brain syndromes (nine patients), aseptic meningitis (four patients) and a variety of focal neurologic findings (seven patinets). Fourteen pateints had 15 episodes of functional psychosis without other evidence of neurologic disease. Although there was a general correlation between clinical and serologic evidnce of active SLE and the development of organic neurolgic disease, there was no evidence that therapy with very large doses of corticosteroids was beneficial. Of the deaths in this series, two were due to probable active SLE involving the central nervous system wheras five were attributable to complications of therapy. The long-term morbidity, likewise, was high in the patients who recieved large doses of corticosteroids. In all, 12 patients had major complications of corticosteroid therapy. Functional psychosis was usually preciptated by corticsoteroid therapy and respond to a reduction in steroid dosage and administration of psychotropic drugs.


Treatment of Wegener's granulomatosis of lung. Thirteen patients with Wegener's granulomatosis have been treated with cytotoxic agents. Only one died from the disease whereas two died of infectious complications of therapy and one of heart disease. Seven of the nine survivors are well without medication; one is alive with renal insufficiency and one is in the 5th year of treatment. Cholorambucil was least toxic and should be tried first. Cyclophosphamide was more effective than cholorambucil or azathioprine but, because of side effects, should rarely be used initially. Differentiation of Wegener's granulomatosis from lymphomatiod granumatosis, which it resembles clinically, roentgenologically and pathologically, is important since the latter disease responds differently to cytoxic drug therapy.


Surface alterations due to endotracheal intubation. The varied complication of prolonged endotracheal intubation, including tracheal stenosis, stricture and tracheomalacia, are thought to be directly related to lateral tracheal wall pressure. To investigate the initiation, relevance and duration of these changes, studies were undertaken to assess the effects of intubation on the surface anatomy of the trachea by scanning electron microscopy. Tracheal mucosal morphology was studies in (1) anesthetized "normal" dogs; (2) d-ogs sacrificed 2 hours after intubation with cuff deflated or inflated to the "just seal" point using a cuff system producing the lowest tracheal wall pressure; and (3) dogs intubated for 2 hours and then examined at 2 and 7 days after extubation. Intubation without cuff inflation resulted in distinct linear areas of nearly complete ciliary denudation along the tract of tubal insertion within 2 hours. Inflated cuffs produced similar but more widespread changes especially over tracheal rings, indicating that pressure in areas of least resiliency significantly contributes to these alterations. Regeneration of cilia could be seen 2 days after extubation, but many anatomic features remained distorted; at 7 days, regeneration was nearly complete, but isolated areas of denudation could still be identified. Scanning electron micrographs of human tracheas taken at autopsy from patients who had had prolonged intubation with the same cuff system correlated well with those obtained from dogs.


An appraisal of the nitroblue tetrazolium reduction test. The available literature on the nitroblue tetrazolium reduction test is reviewed. The mechanism of this test is poorly understood. There are two basic methods of performing the test, namely, the stimulated and the spontaneous methods. However, the test procedure has not been standardized, and numerous modifications have ensued resulting in a number of technics. The stimulated test has proved to be valuable for screening patients or carriers with chronic granulomatous disease of childhood. It is one of the useful tests in studying neutrophil dysfunction. On the other hand, extensive accumulated data indicate that this test, be it stimulted or spontaneous, cannot be relied upon as an absolute test to differentiate bacterial from nonbacterial infectious disease as there have been numerous false-positive and false-negative results. When this test is used, the result should be interpreted in the context of other laboratory test results and the clinical picture of the patient. Preliminary data indicate that in certain diseases, if the initial test is positive in a particular patient, it may be useful as one of the follow-up tests to ascertain the activity of the disease process.


Anterior myocardial infarction patterns in the mitral valve prolapse-systolic click sydrome. Two young women with the mitral valve prolapse-systolic click (MVP-SC) syndrome had electrocardiographic and vectorcardiographic evidence of transmural anterior myocardial infarction in the absence of clinical and arteriographic evidence of coronary disease.


Erythropoietin assay by hemagglutination-inhibition. The immunochemical assay (HAI) for erythropoietin is accurate enough to detect small quantities and sensitive enough to demonstrate consistently and quantitatively the presence of erythropoietin in serum and urine. It will be the purpose of this report to describe in detail the procedure for the assay, the usefulness and value of erythropoietin testing in the clinical laboratory. The relationship of erythropoietin levels in serum and urine in the classification of diseases of the red blood cells are discussed. There is presently no  other method available for the measurement of erythropoietin that permits the detection of extremely small differences, sensitive enough to demonstrate consistently and quantitatively the presence of small amounts of erythropoietin.


Determination of normal values from a hospital population. With multi-channel biochemical screening becoming more widely used, it is necessary that normal values be established that will pertain to the population being screened. Statistically, results derived from a sample can be applied only to the population from which the sample was drawn. Thus, normal values derived from the typical sample of "young American volunteers employed in the hospital and apparently healthy" cannot validly be applied to members of a hospital population. Logically, it would be more valid to examine the values of a large sample of patients and determine the normal values by use of statistical methods. Presented in this paper are sections of an extensive statistical study performed on a hospital population using the SMA-12/60. It is hoped that this study may serve as useful guidelines for those technologists who believe that normal values should be established for a given laboratory, method and population.


An investigation of continuing education hypotheses about laboratory personnel. The Kendall-Tau test with ties was utilized in testing for both level of significance and direction of relationship in hypotheses on continuing education for working laboratory personnel in the State of Iowa. Findings reported from a response group of 422 active laboratory personnel indicated that: (i) all educational levels of personnel are interested in continuing education; (ii) all laboratory personnel based on year of certification are interested in continuing education; (iii) supervisory personnel have a more marked interest in continuing education than line technologists/technicians; (iv) females are less willing to sacrifice for participation in continuing education than males; and (v) personnel in smaller hospitals have an interest in continuing education that is perhaps less than those in larger hospitals.


The safe use of dimethyl sulfoxide in the laboratory. Dimethyl sulfoxide is being increasingly utilized in medical laboratories and in experimental clinical situations. The drug must be considered dangerous since there has been one reported case of fatal allergic reaction and numerous reports of liver damage following exposure to dimethyl sulfoxide.  Caution must be exercised in the handling of the drug as it can aid the entry of other drugs into the human body. Although dimethyl sulfoxide is not highly flammable, normal safety precautions used with any flammable solvent are the minimal requirements for safe use of this drug.


Primary renal candidiasis with renal granulomata and salt-losing nephropathy. A patient is reported whose illness was characterized by chronic renal failure associated with persistent salt-wasting, chronic nephrolithiasis, and candiduria which was documented to be arising from the upper urinary tract. Intravenous amphotericin B was effective in eradicating candiduria. However, bilateral nephrectomy was ultimately performed which revealed extensive involvement of the renal parenchyma with classic caseating granulomas apparently related to renal candidiasis. Severe medullary erosion and tissue loss existed which appeared to result in disproportionate medullary destruction which was probably the most significant factor in explaining the patient's salt-losing state. The patient has since been satisfactorily managed with maintenance hemodialysis.


Still's disease in an adult: A link between juvenile and adult rheumatoid arthritis. A 52-year-old man developed rheumatoid factor negative, chronic, symmetrical polyarthritis associated with high intermittent fever and morbilliform evanescent rash at the onset. A detailed investigation and follow-up for two years failed to reveal any secondary cause. The onset and course resemble Still's disease in children. The synovial membrane histology and electron microscopy were consistent with early rheumatoid arthritis. Adult onset Still's disease reported in the literature is reviewed and compared with Still's disease in children.


Cardiac performance during pregnancy: serial evaluation using external systolic time intervals. Indirect systolic time indices were used to evaluate serial changes in left ventricular function during pregnancy in 13 normal patients and five patients with compensated cardiac conditions. Changes in both groups tended to parallel each other. In both groups, serial LVET index decreased, PEP index increased, and PEP/LVET ratio increased. Q-S2 index decreased in the normal group in midpregnancy and was inconsistent in the cardiac group. In the immediate postpartum period, LVET index returned to baseline values but PEP and PEP/LVET remained increased in both groups. Results of multiple comparison tests demonstrated that the largest (or smallest) value of each systolic time interval during pregnancy was observed in either the periods of the weeks 28 to 34 or 34 to 38. No significant differences were noted in intergroup comparison between the normal and cardiac groups. These data suggest that consistent changes in cardiac function may be determined during pregnancy by the noninvasive technique of indirect systolic time interval evaluation. These changes may reflect a change in left ventricular contractility, preload or afterload. The differences may persist even in the immediate postpartum period when cardiac output and heart rate have decreased to normal, suggesting residual changes in intrinsic left ventricular function. In patients with compensated heart disease, indirect tests of left ventricular function generally reflect the changes in normal pregnant women.


Relapse of staphylococcal endocarditis after clindamycin therapy. A 25-year-old black female heroin addict presented with Staphylococcus aureus endocarditis. Because of a history of penicillin allergy, therapy was gegun with cephalothin (Keflin); lack of clinical response led to the use of clindamycin. Response was excellent. After six weeks of treatment she was discharged well, only to return six days later with recurrent endocarditis. The organism, confirmed by sensitivity and phage typing, was identifcal to that causing the inital episode. This patient illustrates the apparent failure of clindamycin to eradicate a deep-seated intravascular infection with a sensitive organism.


Antibodies to spermatozoa. V. Antibody activity in human cervical mucus. Efforts were made to seek sperm antibody activity in human cervical mucus (C.M.). A procedure of extraction was developed, as well as methods for measurement of total protein and of immunoglubulin level. The antibody testing was done by the Kibrick (K-B-M) and F-D methods. In clear contrast with negative control serum and negative C.M. samples, positive activity could be found in the C.M. extracts from several infertile women. Some of these manifestations were seen as positive K-B-M agglutination, whereas some were seen either as agglutination or immobilization in the F-D test; hence, three kinds of observation can be indicative of sperm antibody in extracts of cervical mucus.


The physiologic significance of portal vs. peripheral injection of insulin in man. The site and rate of entry of insulin into the body may affect its metabolic actions. This study tested for the first time in man the hypothesis that the mode of action of endogenous insulin differs from peripherally injected insulin. In 11 nondiabetic and six diabetic patients we compared the effects on peripheral glucose utilization (PGU) and degree of hypoglycemia of the following: (1) glucagon-free insulin rapidly injected and slowly infused into the portal circulation via percutaneous splenic puncture; (2) peripheral intravenous inslin; (3) peripheral intravenous sodium tolbutamide. The arteriovenous glucose difference (A-V) and (A-V)/A ratios were calculated as parameters for measuring PGU. In nondiabetics our experiments showed: (1) similar magnitudes of hypoglycemia for insulin given by both routes, and (2) a significantly smaller (A-V)/A and therefore PGU, after the intraportal route, particularly after a slow infusion. Intravenous tolbutamide produced marked hypoglycemia and a small PGU comparable to that of slow intraportal infusion of insulin. In diabetics, results were similar. These findings suggest that, compared to the action of peripherally administered insulin, intraportally injected exogenous insulin or tolbutamide-induced endogenous insulin has a greater hepatic and a lesser peripheral effect on glucose metabolism.


Assessment of diagnostic aspiration curettage as an outpatient procedure. Aspiration curettage proved acceptable to patients and medical staff when incorporated into a busy outpatient practice. The diagnostic reliability of curettings obtained was shown to be 93.5 per cent accurate. In all patients where mucus only is obtained, where symptoms persist or recur, or when aspiration curettage is too distressing, conventional curettage is mandatory.