Interaction of cholera toxin and ganglioside G(M1).

The exotoxin produced by Vibrio cholerae is rapidly and firmly bound to the outer membrane of mammalian cells. With simple in vitro and in vivo methods and very pure gangliosides and allied glycolipids we have demonstrated that the monosialosylganglioside GM1 is the natural receptor for the cholera toxin. This ganglioside binds the toxin with a high affinity and inactivates it. The inactive derivative, choleragenoid toxoid has the same affinity to GM1 as the toxin. Ganglioside GM1 was isolated from the small intestinal mucosa of man, pig and ox in amounts of 0.1, 2.0 and 43 nmoles per g mucosa, respectively. These very large differences in the ability of the mucosal cells to bind cholera toxin. Exogenous GM1 was incorporated in vitro and in vivo in intestinal mucosal cells. The incorporation of GM1 increased the number of toxin-binding sites and increased the secretion of fluid in the gut. Vibrio cholerae sialidase did not hydrolyse the di- and trisialogangliosides of intact mucosal cells to the parent GM1-ganglioside, neither did it increase the number of cholera toxin-binding sites.


Brain neuraminidases and gangliosides.

A number of data of kinetics nature indicate that brain neuraminidases (the cytosol and the membrane bound enzyme) recognize the physical state of gangliosidic substrate, with immediate modification of the activity. The interactions between the enzyme(s) and the different physical forms of the substrate are still to be studied at the molecular level. The knowledge of these phenomena would greatly help understanding the role played by gangliosides in the neuronal plasma membrane.


Brain tumors studied by computerized tomography.

A brief description of the method and clinical application of CT is given. Various features and absorption values of different intracranial neoplasms are described and compared. The effects of CT on other special diagnostic procedures are discussed. It is emphasized that contrast medium enhancement significantly increases the sensitivity and specificity of the technique when applied to patients who have or are suspected of having cerebral neoplasms.


Chemotherapy of brain tumors.

Viewed in the light of recent advances and contemporary research, further refinements of surgery and radiotherapy hold little promise for the cure of glioblastomas, although both will continue to have important roles. Immunotherapy has quantitative limitations rendering it ineffective against tumors weighing much more than 1 mg (10(6) cells). Chemotherapy has neither anatomic nor quantitative restrictions, and in theory it has the potential for cure. Laboratory and clinical research have established the activity of several drugs whose important characteristics include penetration of the normal brain and activity against nonproliferating cells. Immediate objectives of current chemotherapeutic research are the identification of newer single agents, the formulation of more effective multiple drug protocols, and ultimately the application of chemotherapy in a multimodality approach to the cure of glioblastomas.


[Increase of mast cells in the peritoneal cavity of rats treated with atopic patient's serum].

In accordance with the experiments described by the author, the injection of atopic serum and the serum of patients infected with ascaris into the peritoneal cavity of the rats produces after 24 hours an increase in mast cells of the mesentery together with vascular congestion. The experiment was made in the following way: injecting 0.5 ml. of the serum in the peritoneal cavity and the observations were made after 24 hours in the ileum-cecal mesentery. The increase of mast cells is shown to have statistical significance in atopic serum (hay fever and atopic dermatitis) as well as in serum of patients infected with ascaris lumbricoides. The increase of the mast cells is seen particularly in the vascular areas. On the other hand, the injection of non-atopic serum and inactivated atopic serum by heat (56 degrees C, 2 hours) does not produce this increase in mast cells. This phenomenon of the increase of the mast cell population which the atopic serum produces is only observed after 24 hours and not in a shorter time (20 minutes). Also we would emphasize that the increase is due only to the application of the atopic serum without any need to apply the appropriate antigen. The results obtained are as follows:A) 6 control rats--38.6 mast cells/mm2 B) 7 rats + serum of patient with hay fever--88.5 mast cells/mm2 C) 4 rats + inactivated serum (56 degrees C 2 hours) from the same patient with hay fever. 47.0 mast cells/mm2 D) 4 rats + 4 serum from non-atopic persons--38.1 mast cells/mm2 B') 6 rats + 6 serum from patients with hay fever--89.0 mast cells/mm2 C') 4 rats + 4 serums from patients with atopic dermatitis. 108.0 mast cells/mm2 D') 4 rats + 4 serums from patients with ascaris lumbricoides--116.0 mast cells/mm2. Although it is known that the serum from atopic patients and those infected with ascaris lumbricoides has a high level of IgE we cannot be sure that this increase in mast cells in the rat is produced by the human IgE. The true cause of this phenomenon is unknown.


Diabetic retinopathy.

The course of diabetic retinopathy is related to the duration of the diabetes. If it is nonproliferative (small hemorrhages, microaneurysms and exudates), the risk of blindness after five years is 20 percent in patients over age 60, if it is proliferative (neovascularization and fibrosis), the risk of blindness after five years is 40 to 65 percent in all patients. While photocoagulation appears to be of benefit, vitrectomy seems a promising approach at this time.


Complications of cardiac pacemakers.

The roentgenogram is a valuable resource in the implantation and management of cardiac pacemakers. An understanding of the mechanisms of pacemakers and the principles of insertion is essential to the physician caring for patients with these devices. The roentgenogram can identify the type of pacemaker, the position of the electrode tip and the occurrence of lead fractures; it can also detect failing batteries.


Botanical trash present in cotton before and after saw-type lint cleaning.

The % by weight content of leaf-like, stem, boll, seed, and weed materials sifted (3360 mum greater than particle size greater than or equal to 595 mum) from visible wastes of the Shirley Analyzer was determined for a lint sample taken after ginning but before cleaning and for a second lint sample taken after one stage of saw-type cleaning. The % by weight content for bract and leaf increased with decreasing trash particle size. The content of cotton seed coat fragments decreased with reduction in trash particle size. Approximately 1/4 of the botanical wastes consisted of weed materials, including grass particles. Lint cleaning was ineffective in reducing the % by weight content of leaf-like trash. Some selective removal of stem trash occurred as a function of lint cleaning.


Serum protein changes during exposure to ozone.

Serial measurements of serum proteins in rabbits exposed to 0.4 ppm and 1.0 ppm of ozone revealed progressive changes in the concentrations of the various fractions: albumine concentration declined while alpha- and gamma-globulin concentrations increased.


Foundry air contaminants from green sand molds.

The major gases evolved from foundry molds have been determined in the laboratory. The principal gases evolved during pouring and shakeout of castings include hydrogen, carbon monoxide, carbon dioxide, methane and other low molecular weight hydrocarbons with smaller amounts of ammonia, hydrogen cyanide, and sulfur dioxide.


Effects in the liver of methylene chloride inhaled alone and with ethyl alcohol.

When high concentrations of methylene chloride in combination with high concentrations of ethanol were inhaled for one day by guinea pigs, the extent of the hepatic damage induced suggested an antagonism between the effects of the two agents. However, exposure for five days to approximately 500 ppm of methylene chloride plus high concentrations of ethanol suggested ethanol may potentiate the effects of methylene chloride.


Influence of legal standards on the practice of industrial hygiene.

Prescriptive standards for the work environment affect the professional practice of industrial hygiene. Among the advantages are: legal requirements reinforce professional recommendations; penalties encourage abatement of hazards; compliance should ensure a safe and healthful environment; recordkeeping requirements will provide a basis for future action. Among the disadvantages are: rigid evaluation procedures, reporting format, etc., discourage professional judgment and development of new methods; professional reports become legal documents; single standards do not focus on the total environment.


The effect of aerosol hair spray inhalation in the hamster.

Hamsters were exposed to a commercially available aerosol hair spray actuated for a total of 8 minutes over a 4-hour-period, 5 days/week. They were examined after 1, 2, 3, 4, and 6-week exposures, and 2,4 and 8 weeks after a 6-week exposure. There was a significant increase in the lung weight of exposed hamsters at every time point except 8 weeks after the 6-week exposure. Microscopic changes in the lung were characterized by the presence of a few to a moderate number of macrophages and neutrophils in the alveolar lumina. The number of macrophages and neutrophils appeared directly related to the duration of exposure. Lung changes were minimal during the first 2-weeks of exposure, and 8 weeks after the 6-week exposure (recovery period). Pathologic changes in the lungs of hamsters were reversible after cessation of the hair spray inhalation exposure.


Echoventriculography in acute myocardial infarction. III. Clinical correlations and implication of the noninfarcted myocardium.

Echoventriculography permits detection of regional abnormalities of left ventricular wall motion in acute myocardial infarction. Overall and regional performance of the left ventricle was related to the prognosis and clinical severity of acute transmural myocardial infarction in 30 patients. Although values for left ventricular size, ejection fraction and modified mean circumferential fiber shortening velocity were all abnormal (P less than 0.005), they did not differ among 8 patients with uncomplicated infarction, 12 with moderate left ventricular failure and 10 with pulmonary edema or shock. In contrast, magnitude of the summed wall motion amplitudes from seven standards regions around the left ventricle decreased in parallel with ejection fraction (P less than 0.001) and with clinical severity of infarction (r = -0.79, P less than 0.001). Function of the healthy myocardium with hypercontractile in 40 percent of patients, but this occurred only in patients with uncomplicated or moderately severe infarction. In patients with severe pump failure the "uninvolved" myocardium did not manifest a hypercontractile or even normal response despite infusion of catecholamines (-21 percent; r = -0.76, P less than 0.001). Four nonsurviving patients had the poorest ventricular function (as low as 10 percent of normal) as assessed by several segmental echocardiographic performance indexes. Performance of the noninfarcted myocardium therefore seems to have a role in deterioration of left ventricular pump function in acute myocardial infarction


Diabetic treatment and primary ventricular fibrillation in acute myocardial infarction.

The relation between mode of therapy and mortality rate and incidence of primary ventricular fibrillation was studied in 265 patients with diabetes mellitus and acute myocardial infarction. Sixty patients were being treated with diet only, 54 were receiving insulin and 151 were taking oral hypoglycemic agents. Fourteen patients (5.3 percent) had primary ventricular fibrillation, and all but one died. No statistically significant association was found between the incidence of primary ventricular fibrillation and the type of treatment for diabetes mellitus. Sixty-four (24.2 percent) of the 265 patients died during hospitalization. Mortality was greater among diabetic patients receiving oral therapy. However, after adjusting for age and sex, the difference among these three treatment regimens did not reach the P less than 0.05 level of significance.


Influence of dobutamine on hemodynamics and coronary blood flow in patients with and without coronary artery disease.

The influence of dobutamine on hemodynamics and coronary blood flow was studied in patients after routine cardiac catheterization. The data demonstrated that dobutamine is a powerful inotropic agent at a dose that has a relatively small influence on heart rate. In patients without coronary artery disease dobutamine greatly increased coronary arterial perfusion. In patients with severe coronary artery diseases dobutamine resulted in a much smaller increase in coronary perfusion, and the pattern of perfusion became more inhomogeneous. The results suggest that dobutamine has a potential inotropic value but raise concern about its influence on regional myocardial perfusion in patients with serious coronary artery disease.


Mitral valve malformation of Ebstein type in absence of corrected transposition.

The first documented case is reported of mitral valve malformation of the Ebstein type in the absence of corrected transposition. In this case, the ring of the inferior leaflet of the mitral valve was displaced downward into the left ventricle, dividing the latter into a proximal atrialized and a distal effective ventricular chamber. The anterior leaflet was not displaced. The chordae tendineae of both leaflets were thickened. The papillary muscles were hypertrophied and abnormal in architecture. The outflow tract of the effective left ventricle was shortened. The valve leaflets were thickened, and the mitral valve was probably insufficient.


Surgical correction of truncus arteriosus in infancy.

An 8 week old infant with severe heart failure from type 1 truncus arteriosus underwent successful corrective surgery employing the Rastelli procedure with use of deep hypothermia and total circulatory arrest. Postoperative hemodynamic studies showed complete closure of the septal defect, disappearance of truncal stenosis, but presence of mild porcine valve stenosis. This procedure is possible even in very small subjects and is preferable to palliative pulmonary arterial banding.


Effects of excess glucose and insulin on glycolytic metabolism during experimental myocardial ischemia.

The selective metabolic effects of glucose and insulin were tested in an intact working swine heart preparation. Supplements of glucose (26.6 millimolar [mM] and insulin (0.025 units/ml) were provided to 18 hearts, 9 control hearts (coronary flow 151 ml/min) and 9 hearts rendered globally ischemic (coronary flow reduced from 167 to 85 ml/min). These hearts were compared with 14 additional hearts (6 control and 8 ischemic) given no supplements (glucose 8.6 mM, no excess insulin). In hearts without supplements, ischemic significantly decreased mechanical performance, myocardial oxygen consumption, fatty acid oxidation and tissue high energy phosphate stores. Glucose consumption was reduced from 133 micromoles (mumol)/hr per g (before ischemia) to 58 mumol/hr per g (P less than 0.05), presumably from inhibition at glyceraldehyde-3-phosphate dehydrogenase. Data for control hearts with excess glucose and insulin were similar to data in control hearts without supplements except that glucose consumption and glycolytic flux were increased. Ischemia in treated hearts, as compared with untreated ischemic hearts, effected similar significant decreases in myocardial oxygen consumption, fatty acid oxidation and high energy phosphate stores and resulted in greater reductions in mechanical performance and in 10 minutes' less average survival time. Glucose consumption was reduced from 483 (before ischemia) to 242 mumol/hr per g (P less than 0.005) and inhibition at glyceraldehyde-3-phosphate dehydrogenase was again noted. Thus, excess carbohydrate and insulin hormone, when infused directly into the ischemic myocardium, did not provide an efficacious increase in either glycolytic flux or energy production. These findings suggest that an alternative explanation for the reported efficacy of glucose-insulin-potassium infusions must be sought.


Discrete subvalvular aortic stenosis in childhood. Study of 51 patients.

Fifty-one children with discrete subvalvular aortic stenosis were studied between 1951 and 1974. The three anatomic types of obstruction found were the thin membranous type (43 cases), the fibromuscular collar type (5 cases) and the tunnel type (3 cases). The obstruction was usually severe, and the median left ventricular to aortic systolic pressure gradient was 90 mm Hg. Progressive obstruction with an increasing gradient was documented in 10 patients by serial cardiac catherizations. Significant associated cardiac defects, present in 57 percent of patients, often masked the typical clinical and cardiac catheterization features of subaortic stenosis. The stenosis was often not discovered until after surgery for the associated defect. Forty patients underwent surgical resection of the discrete subaortic obstruction. After surgery significant left ventricular to aortic pressure gradients can be found at postoperative cardiac catheterization. These gradients may reflect inadequate resection of the more complex discrete obstructions or represent proliferation and regrowth of the previously resected subvalvular fibrous tissue. The criteria for operability of discrete subaortic stenosis should be the angiographic demonstration of a discrete subvalvular diaphragm and the presence of a resting left ventricular to aortic systolic pressure gradient of 40 mm Hg or more.


Pulmonary blood flow distribution in transposition of the great arteries.

Pulmonary blood flow distribution was studied by scintillation scanning of the lungs after the infusion of iodine- 131-labeled macroaggregates of human albumin before and after the Mustard operation in 53 patients with transposition of the great arteries. The patients were classified as follows: Group I (24 infants with uncomplicated transposition of the great arteries); Group II (18 patients with transposition and ventricular septal defect); and Group III (11 patients with transposition, ventricular septal defect and pulmonary obstruction). Before operation, 21 patients had a normal distribution of pulmonary blood flow, 10 had preferential flow to the right lung and 2 had preferential flow to the left lung. After operation, 19 had a normal pattern of pulmonary blood flow, 21 had preferential flow to the right lung and 3 had preferential flow to the left lung. The scanning studies have proved helpful in follow-up of patients to rule out recurrence of the shunt, pulmonary of systemic venous obstruction, development of pulmonary hypertension and occlusion of a palliative systemic-pulmonary shunt.


Echocardiographic localization of interatrial baffle after Mustard operation for dextrotransposition of the great arteries.

The position of the interatrial baffle was determined by echocardiography in 11 patients with complete transposition of the great arteries who had undergone the Mustard operation. The location of the interatrial baffle and the newly created systemic venous atrium and the pulmonary venous atrium behind the pulmonary arterial root was established by echocardiographic contrast studies during cardiac catherization. Angiographic analysis indicated that the segments of the systemic and pulmonary venous atria seen behind the pulmonary arterial root in the echocardiogram were, respectively, the superior limb of the systemic venous atrium and the posterior segment of the pulmonary venous atrium. The area of mitral-pulmonary valve continuity in the echocardiogram was used as a reference point for dimensional measurements of the systemic and pulmonary venous atria. It is suggested that longitudinal measurements of these structures by echocardiogram may help evaluate their growth in size. Fine to coarse fibrillatory movements of the atrioventricular valves and, more frequently, of the mitral valve were seen in the majority of patients.


Echocardiographic detection of large left to right shunts and cardiomyopathies in infants and children.

Diagnostic separation of infants with signs of cardiac failure (hypoglycemia, sepsis, myocarditis, hypoxemia) but no congenital cardiocirculatory malformation from those with a large left to right shunt is crucial in newborn management. Echocardiographic studies of 218 infants and children allowed group separation and distinction from normal by the assessment of mean velocity of circumferential fiber shortening (Vcf) and the ratio of left atrial to aortic root diameter at end-systole (LA/Ao). In normal premature and full-term infants, Vcf (1.51 +/- 0.04 [mean +/- standard error]) was significantly lower than in infants with a large shunt (2.12 +/- 0.08, P less than 0.01) and higher than in infants with nonstructural heart disease (1.18 +/- 0.06, P less than 0.001). LA/Ao ratios were comparable in the groups with a large shunt and nonstructural heart disease (1.14 +/- 0.1 and 1.26 +/- 0.2, respectively) and were significantly higher in both groups than in normal subjects (0.77 +/- 0.01, P less than 0.001). Similar echocardiographic distinctions could be made when 10 older children (aged 2 to 10 years) with cardiomyopathy were compared with 45 normal older children. Serial determination of these variables was of major assistance in patient management.


Echocardiographic manifestations of single ventricle.

Eight patients with single ventricle were studied echocardiographically. In six, the ventricular septum was not detectable; in two, a septal-like bulboventricular ridge was identified. Two atrioventricular (A-V) valves were found in all patients; in six, both valves were identified simultaneously with the transducer held stationary along the left sternal edge. Dextro-transposition of the great arteries was noted in three patients. The echocardiogram of one of four patients with levotransposition of the great arteries was consistent with later proved left A-V valve stenosis associated with Ebstein's malformation. Mitral-semilunar valve continuity was presented in five cases. Echocardiographically, the absence of the ventricular septum in a patient with two A-V valves make a diagnosis of single ventricle likely. The presence of ventricular septal-like echoes does not exclude the diagnosis of single ventricle since the right ventricular infundibulum may remain as a small outlet chamber separated from the left ventricle by an eccentric bulboventricular ridge.


Double outlet right ventricle: hemodynamic and anatomic correlations.

There are 16 possible variations of double outlet ventricle with regard to interrelations of the great arteries and to location of the ventricular septal defect. In a series of 62 cases, approximately two thirds of patients had the great arteries in a side by side relation, and most (28 of 41) had the ventricular septal defect in a subaortic position. In double outlet right ventricle with malposition of the great arteries, the ventricular septal defect was either subpulmonary or subaortic. Four of the 13 patients with subpulmonary ventricular septal defect had a supracristal defect with side by side relation of the great arteries (Taussig-Bing anomaly), and 9 patients had malposition of the great arteries with an infracristal ventricular septal defect. In all patients with subpulmonary ventricular septal defect, pulmonary arterial oxygen saturation was greater than systemic arterial saturation regardless of the relation of the great arteries. Forty patients had subaortic ventricular septal defect. In 24 of these patients, including 7 with malposition of the great arteries, systemic arterial oxygen saturation was greater than pulmonary arterial saturation. However, in 9 patients (25 percent) the reverse was true, as seen in complete transposition of the great arteries and in Taussig-Bing anomaly. Thus, pulmonary arterial oxygen saturation greater than systemic arterial saturation is not reliable evidence of a Taussig-Bing anomaly. Of the 25 patients with such saturation, only 4 had the Taussig-Bing anomaly.


Plasma heparin neutralizing activity in coronary artery disease.

Platelets contain heparin neutralizing activity that is released into plasma after platelet aggregation. Increased amounts of plasma heparin neutralizing activity were found in patients with acute myocardial infarction, unstable angina pectoris and stable arteriographically confirmed coronary artery disease. Plasma heparin neutralizing activity levels provide additional evidence for a role of platelet aggregation in coronary artery disease.


Metabolic consequences of glucose-insulin-potassium infusion in treatment of acute myocardial infarction.

Eighteen patients treated with glucose-insulin-potassium infusion for anaerobic support of acutely ischemic myocardial tissue were studied to ascertain the metabolic consequences of this therapy, for acute myocardial infarction. Twelve patients with acute myocardial infarction were treated in a conventional manner and served as control subjects. The glucose-insulin-potassium solution was composed of 300 g of glucose, 50 units of regular insulin and 80 mEq of potassium ion per liter, and was infused at a rate of 1.5 ml/kg per hour through the right atrial port of an indwelling Swan-Ganz thermodilution catheter. Serial measurements of serum electrolytes, cardiac and hepatic enzymes, glucose and osmolality were obtained every 4 to 6 hours for 4 days. Twenty-four urinary volume and potassium levels were measured daily. Pulmonary arterial end-diastolic pressure was measured hourly and the cardiac index daily for the duration of the study. Serum potassium increased to 5 mEq/liter during the infusion and to more than 6 mEq/liter after infusion in 28 percent of patients. No recognizable complications or arrhythmias accompanied this transient hyperkalemia. Potassium balance studies revealed a net total body potassium ion gain of 120 MEq during the study. The second most frequent finding was an elevation of serum glucose (mean 175 mg/100 ml); in all instances this was controlled with supplemental administration of insulin. The serum osmolality and fluid balance remained normal in all patients during the study. Serum glutamic oxaloacetic transaminase (SGOT) and fraction 5 of lactic dehydrogenase (LDH) were increased in 34 percent of the patients during the last 12 to 18 hours of the glucose-insulin-potassium infusion. Characterization of these enzymes suggested a hepatic origin for these changes. This study suggests that glucose-insulin-potassium infusion is a relatively safe procedure in which postinfusion hyperkalemia is the most serious potential complication.


The development of the elastic cartilage of the mouse pinna.

The development of the elastic cartilage in the mouse pinna was studied with the electron microscope. For descriptive purposes, the developmental process was divided into five stages. These begin with the onset of cartilage matrix production by chondroblasts. The second stage is the major mitotic stage although the cells now resemble chondrocytes and cartilage matrix production evidently continues. This is followed by a period during which cartilage matrix production appears to be the major activity of the chondrocytes. In Stage IV, the cells continue to produce cartilage matrix but at the same time they also produce lipid which comes to occupy most of the cell as a large lipid droplet. In the adult, Stage V, matrix production appears to be at an end and each cell contains a lipid droplet which is so large that the cells bear some resemblance to white fat cells and might be designated as lipochondrocytes. The adult cartilage matrix contains elastic plates in a three-dimensional honeycomb pattern. Between the elastic plates and the cells, the matrix contains elements similar to those seen in hyaline cartilage but it does not contain matrix vesicles such as those which have been associated with the calcification of cartilage. Two types of filaments differing in appearance, size, and location are seen within the chondrocytes. They have been designated cytofilaments and cortical filaments. Cytofilaments are dispersed throughout the cell and also contact the substance of the lipid droplet; cortical filaments (sub-plasmalemmal microfilaments) are located directly under the plasma membrane. They are thought to be involved in movement of the plasma membrane as a concomitant to extracellular fibrogenesis.


Morphogenesis of fetal rat duodenal villi.

To study the structural features of fetal rat duodenal mucosa associated with histogenesis of villi, duodena from 15- to 19-day fetuses were examined by light and electron microscopy. The duodenal epithelium of 15- to 18-day fetuses was stratified. Distinctive junctional complexes associated with membrane-bounded vesicles and cilia-like structures were seen in the deeper epithelial layers at 15 and 16 days. Small lumina, designated "secondary lumina," lined with a variable number of microvilli developed between epithelial cells at these junctional complexes during the sixteenth through eighteenth days. Degenerative changes and exfoliation of superficial epithelial cells were obvious in 17- and 18-day fetuses. In 18-day fetuses, aggregates of mesenchyme had invaginated the basal aspect of the stratified epithelium. Concomitantly, the number of epithelial layers overlying these mesenchymal projections was decreased. In 19-day fetuses, well formed, short duodenal villi lined by a simple columnar epithelium which included goblet and endocrine cells were evident. Injection of ferritin into the main duodenal lumen of 17-day fetuses failed to reveal continuity between the main lumen and the secondary lumina. However, continuity between many secondary lumina and the main lumen was demonstrated in 18-day fetuses. Thus, major morphological features associated with villus formation in fetal rat duodenum include: (1) formation of many secondary lumina in primitive stratified epithelium, (2) eventual fusion of these lumina with the main duodenal lumen, by their continued growth coupled with exfoliation of degenerating superficial layers and (3) upward growth of mesenchyme towards the lumen as cell exfoliation and expansion of secondary lumina take place.


The effects of preparative procedures for scanning electron microscopy on the size of isolated lymphocytes.

The diameter of lymphocytes, isolated from a sample of peripheral blood by Ficoll-Hypaque sedimentation, was determined after eight different steps in the preparative procedure for scanning electron microscopy (SEM). There was a 43% total reduction in mean cellular diameter of the lymphocytes studied, the diameter dropping from 8.4 mum prior to fixation, to a final diameter of 4.8 mum in the cells examined under the scanning electron microscope. The bulk of this shrinkage occurred during critical-point drying. In view of this finding, caution should be exercised in describing detailed cell surface morphology by SEM when similar preparative procedures are employed.


Comparative studies on the effect of cholesterol feeding on biliary composition.

The gallbaldder or hepatic bile from six species of animals had a uniformly low cholesterol content far below its maximum solubility. Cholesterol feeding for more than 1 month had little effect on the biliary composition in chickens, rabbits, and rats, but selectively doubled the absolute and relative concentration of cholesterol in the biles of hamsters, and increased the cholesterol concentration to a level of its maximum solubility in gallbladder bile of ground squirrels and hepatic bile of prairie dogs. The gallbladder bile of prairie dogs reached the boundary of metastable supersaturation of cholesterol and subsequently developed cholesterol crystals and gallstones. A circadian change of the relative concentration of bile acid, cholesterol, and phospholipid in the hepatic bile of the rats with chronic biliary drainage was also observed as a consequence of cholesterol feeding.


Effect of changes in dietary components on the serum bilirubin in Gilbert's syndrome.

Patients with Gilbert's syndrome were placed on low calorie diets and isocaloric diets sequentially severely reduced in carbohydrate, protein, or fat content. Significant increases in the serum bilirubin concentration occurred after the low calorie diet, but not after the isocaloric nutrient-depleted diets. Thus caloric deprivation per se and not changes in dietary components is responsible for diet-induced hyperbilirubinemia.


Potentially useful criteria for judging nutritional adequacy.

Four different diets designed to be of differing quality were fed to large groups of male weanling rats. These diets were: diet C consisting of commercial Rat Chow: diet CG, the same diet diluted with 70% glucose calories, diet A, a simulated "American" diet made up of 25 widely used foods, diet AS, the same diet supplemented with small amounts of 25 vitamins and minerals. The rats on these four diets were observed for 69 days under different circumstances and treatments to ascertain the existence of hitherto unused criteria which might advantageously be applied in nutritional studies. Among the less traditional criteria found to be significantly affected by the diet were: 1) voluntary consumption of food, 2) sleeping time after anesthesia, 3) weight gains after surgery, 4) healing time after surgery, 5) hair growth after clipping, 6) voluntary sugar consumption, and 7) recovery time after cyanide poisoning. These findings suggest that there are probably many other unexplored criteria which could be used advantageously in nutritional experimentation.


Studies of glycemia and glucosuria in diabetics after breakfast meals of different composition.

In series I, The effect of four isocaloric, ordinary diabetic breakfast meals on the blood glucose level and on the urinary glucose loss was tested in 9 adult diabetes and three healthy subjects (ages 60 to 75) as well as in five insulin-treated diabetics (ages 18 to 40). All breakfasts derived 20% of the energy from protein, 35% from fat, and 45% from carbohydrates (CHO). The oligosaccharides amounted to 5, 30, 45, and 65% of CHO, respectively. In series II, four isocaloric breakfast meals with CHO amounting to 35 or 70% of the energy, oligosaccharides furnishing one-third or two-thirds of the CHO at each level, were tested in the same way in eight of adult diabetics and in the three healthy subjects. The two breakfasts with the highest percentage of oligosaccharides in series I caused the smallest increase in the blood glucose level in the adult subjects. In the adults as well as in the juveniles, these breakfasts gave rise to clear symptoms of hypoglycemia and/or a feeling of a deficient satiety in several subjects. In juveniles, the initial blood glucose level turned out to be of greater importance for the outcome of the test than the kind of carbohydrates consumed. In series II, The CHO-rich meals caused significantly greater blood glucose increases than did the low-CHO meals. Despite the unexpected findings that ordinary diabetics breakfast meals, high in oligosaccharides, gave a smaller increase in blood glucose than did meals in which wheat starch predominated, the use of diets rich in oligosaccharides should be avoided because of the risk of overconsumption owing to hypoglycemic symptoms or to the deficient feeling of satiety.


Specially designed sweeteners and food for diabetics--a real need?

In the first part of this study, the effect of four isocaloric mixed breakfast meals on the blood glucose and urinary glucose losses was tested in nine adult diabetics and in three healthy subjects, ages 60 to 75. Three of the test meals consisted of a base diet supplemented with applesauce sweetened with sucrose, fructose, or sorbitol. In the fourth test meal, the starch was increased together with saccharine. In the second part of the study, analyses for free glucose and sucrose in several timed food preparations, ordinary as well as food preparations specially designed for diabetics, were performed. The amount of sucrose equivalents (S(eg)) in one ordinary serving of the various products was estimated. No significant differences among sucrose, fructose, and sorbitol-containing meals with respect to the effect on the blood glucose level or on glucosuria were found. The saccharine-containing meal gave a significantly greater blood glucose increase at 60 min only. The amount of sucrose in ordinary marinated foods, such as herring, cucumber, and common beet was negligible. Water-packed fruits supplied one half of the amount of S(eq) or less, compared with fruits packed in sorbitol-sweetened syrup. The amount of S(eq) in the latter products as well as in fruits packed in unsweetened juice equalled that of the fleshy substance of ordinary sucrose-sweetened products. It was concluded that fructose or sorbitol has no advantages over sucrose, as regards the effect on blood glucose in well-regulated adult diabetics, and that it seems unnecessary to have specially sweetened foods designed for diabetics.


Zinc nutrition of preschool children in the Denver Head Start program.

Low income diets provide relatively little zinc. This study was designed to evaluate the zinc nutritional states of 74 low income preschool children enrolled in the Denver Head Start Program. Zinc is necessary for normal growth, hence children were selected on the bases of low height percentiles. The mean (+/- SE) hair zinc concentration was 87.0 +/- 5.9 mug/g, and the mean plasma zinc concentration was 74.5 +/- 1.5 mug/100 ml. These levels were both lower (P is less than 0.005) than those of middle income children of similar age. Sixty-eight percent of the study group had a hair zinc concentration less than 70 mug/g and/or a plasma zinc concentration less than 68 mug/100 ml. These results indicate that inadequate zinc nutrition may be common among preschool children with low growth percentiles from low income families.


Relationship of mineral status and intake to periodontal disease.

A periodontal index (PI), based on visual and radiographic data, was used to evaluate the severity of periodontal disease in a group of 80 dental patients. The average PI was 3.1 +/- 1.8 SD (0=no detectable lesions; 8=most severe lesions). The PI was directly related to patient age (r=0.73; P is less than 0.01). The serum concentration of calcium copper, iron, magnesium, manganese, and zinc was measured. Regression of PI on the serum constituents demonstrated that serum copper was linearly related (r-0.64; P is less than 0.001) to the PI. The other serum parameters were not correlated to the PI. Dietary protein, calcium, and vitamin A were slightly related to the PI, based on a 24-hr dietary recall. Dietary trace elements were not related to the PI. These results indicate that the serum copper concentration, in some way is related to the severity of periodontal disease. Possibly the observation is linked to the role of copper in the inflammatory response since inflammation is a characteristic of periodontal disease.


Macrophage function in vitamin C-deficient guinea pigs.

Guinea pigs were fed a vitamin C-deficient diet and at various time periods thereafter their peritoneal cells were tested for biological activity. The serum levels of vitamin C in the deficient animals indicated a progressive state of ascorbic acid deficiency with time and this correlated well with clinical signs and symptoms of scurvy. Fewer macrophages were obtained from the peritoneal cavities of deficient animals and in structural appearance under the phase contrast and light microscope they were smaller in size. They showed no significant impairment in phagocytosis of bacterial cells. The macrophages, however, exhibited significantly reduced migration on glass as compared to the normal cells. In vitro addition of vitamin C partially reversed this reduced migration.


Vitamin E and C levels in infants during the first year of life.

The considerably lower vitamin E level found in cord blood and in newborns at birth than those found in the venous blood of mothers at delivery are not yet fully explained. In a group of 217 not selected newborns, we attempted to establish the relation between vitamin E and C levels at delivery and the changes during the first year of life. The mean serum vitamin E level rose from 0.37 mg/ml at 3 days to 0.80 mg/100 ml at 6 months and to 0.72 mg/100 ml at 12 months. On the other hand vitamin C mean levels lowered from 0.93 mg/100 ml in cord blood to 0.77 mg/100 ml at 6 months and to 0.73 mg/100 ml at 12 months. The rise of vitamin E values could be explained by the early use of infant solid foods with high vitamin and mineral content and by the increase of serum lipoproteins. Except at 3 days after delivery there were no individual values of serum vitamin E below the acceptable 0.35 mg/100 ml limit. However, serum vitamin C levels compatible with a moderate risk were very often observed, i.e., in 27.1% of infants at 6 months and in 30.5% at 1 year. Thus, vitamin E intake in infants was satisfactory with the usual diet but not vitamin C for which blood levels were not adequate. In view of these findings it appears necessary to evaluate periodically the vitamin E as well as vitamin C status in the infant population.


Intestinal bypass surgery for obesity decreases food intake and taste preferences.

Food intake was measured in 22 obese patients before and after jejunioleostomy for obesity. Most of the weight loss could be accounted for by the observed reduction of caloric intake. Malabsorption was also present as indicated by increased loss of fat in the stools, and decreased absorption of D-xylose and vitamin B12. A dislike for sweet tastes developed after surgery in most patients. Preferences for concentrated solutions of sucrose and glucose were reduced after patients showed a depression of food intake by a 440-calorie preload which had not been detected before surgery. These studies show a decrease in food intake after intestinal bypass surgery and suggest a role for taste or other gastrointestinal factors in regulating food intake.


A perspective view of dieting to lower the blood cholesterol.

As a guide to physicians, patients, and potential patients concerned with the prospect and practicalities of changing the diet to lower the blood cholesterol in the hope of preventing disease, estimates have been made of the importance of various items of food which figure prominently in relation to this topic. The measure of importance adopted is the predicted average servings of these foods, the prediction being based on the content of fatty acids and cholesterol. The major contributors, each adding more than 10 mg/100 ml to the plasma level, include brains, double servings of meat, one egg per day, and butter. At the other extreme, polyunsaturated oils and margarines actively lower plasma cholesterol while oysters, skim milk, and nuts have practically no effect. The relative importance of items, includeing the newer polyunsaturated ruminant meats and other products, has been charted for easy reference. The culinary costs involved in a cholesterol-lowering diet, considered not in monetary terms but as debits and credits in the food statement, must be balances against the potential benefits to be gained from disease prevention.


Folate levels among various populations in central Iran.

Serum folic acid levels (Lactobacillus casei assay) were determined in 467 subjects representing various socioeconomic classes from rural and urban central Iran. Of the subjects 170 were pregnant females in different trimesters. The mean serum folate levels of the various groups studied ranged from 7.5 to 11.1 ng/ml and are within the normal reported range of 5.9 to 21.0 ng/ml. Only two subjects had serum folate levels below 3.0 to 5.9 ng/ml. In anemic subjects (hematocrit is less than 37%), red blood cell folate levels were also determined and were significantly higher than nonanemic controls (558 +/- 56 versus 346 +/- 35 ng/ml of packed red blood cells, P is less than 0.01). This difference may be related to underutilization of folate in patients with iron deficiency (a common metal deficiency in this area). A probable explanation for the well maintained serum folate levels in late pregnancy as well as in other populations studied in this report may be the high dietary intake of Iranian bread made from wheat flour of high extraction rate.


Folate content of Iranian breads and the effect of their fiber content on the intestinal absorption of folic acid.

Folate deficiency is a relatively uncommon disorder in central Iran. In order to explain this finding; the acid content of various Iranian breads was determined, since bread is the staple food in Iran. Tanok, the village wholemeal bread, has an average "free" folate content (without conjugase incubation) of 0.34 mug/g. Sangask and Bazari, leavened breads made from flours of high extraction rates and widely consumed in towns and cities, have aberage "free" folate contents of 0.38 and 0.71 mug/g, respectively. The folate content of these breads are significantly higher than that of white bread from refined flour (0.13 mug/g) or oatmeal bread (0.09 mug/g). Iranian breads also have a high content of indigestible fiber (1.6 to 4.2% of dry weight). Since substances within the bread, such as fiber, may interfere with folate absorption by the small intestine, sequential folate absorption tests (tritiated pterolymonoglutamic acid) were performed in four subjects with meals of increasing fiber content and fasting. No interference with folate absorption was found. Furthermore, in vitro studies did not demonstrate the formation of insoluble complexes between bread fiber and folic acid, which might indicate decreased availability.


The haemostatic effects of the Chinese herbal drug Yunnan Bai Yao: a pilot study.

The effects of Yunnan Bai Yao on the bleeding time in rats and the blood clotting time in rabbits and man were studied. The medicinal preparation markedly shortened both the bleeding and clotting times; the decreases were significantly more intense than those inconsistently produced by starch or by starch with calcium. These preliminary findings suggest that the action of Yunnan Bai Yao appears not to be due to its pH (5.2) or to vasoconstriction, but other factors such as its calcium content or the physical effect of its particle size cannot yet be excluded.


Inhibition of the cardiovascular effects of acupuncture (moxibustion) by phentolamine in dogs during halothane anesthesia.

The cardiovascular effects of acupuncture, moxibustion by electrocautery, at Jen Chung (Go-26) and phentolamine (0.1 mg/kg-i.v.) alone were compared to phentolamine (0.1 mg/kg-i.v.) prior to moxibustion at Go-26 in groups of ten dogs under 0.75 percent halothane anesthesia. Cardiac output, stroke volume, heart rate, mean arterial pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2 and base deficit were measured over a two hour period. A significant increase (5% level) in cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure and a significant decrease in total peripheral resistance were observed following acupuncture, moxibustion with electrocautery, at Jen Chung (Go-26) in dogs under halothane anesthesia. These effects were inhibited by pretreatment with the alpha blocking agent, phentolamine (0.1 mg/kg-i.v.). The cardiovascular effects of phentolamine (0.1 mg/kg-i.v.) alone were similar to those of dogs in which phentolamine was administered prior to moxibustion.


Influence of ginseng on mating behavior of male rats.

Experiment on the mating behavior of male albino rats paired with receptive females established that in comparison with control animals, males under the influence of ginseng (a) began ejaculation earlier and repeated the action more often in a 45-minute observation period and (b) deposited more copulation plugs in 10 days. The data suggest that ginseng facilitates the mating behavior of male rats.


Acupuncture loci: a proposal for their classification according to their relationship to known neural structures.

Much confusion and frustration has been caused by the inability of workers in acupuncture to demonstrate the exact nature of acupuncture loci or to identify them in neuroanatomic terms. This study reviews 70 selected, commonly-used acupuncture loci. Loci were determined by their traditional descriptions and checked with a neurometer and calibration-stable stimulator. It was found that acupuncture loci may be classified into at least three types: Type I correspond to a known anatomical entity-the motor point of a muscle; Type II to the focal meeting of superficial nerves in the sagittal plane; and Type III lie over superficial nerves or plexuses. As a first step toward acceptance of acupuncture by the medical profession, it is suggested that a new system of acupuncture locus nomenclature be introduced, relating them to known neural structures. Perhaps an international committee of interested workers should be struck.


Organizing communities for change in health: implications of the experience of the People's Republic of China 1949-1974.

This article is an exploration of the way in which social developments in countries may have international impact, with specific reference to the implications of health care developments in the People's Republic of China. Even though the social systems of countries may be totally different, developments of value do get through the national boundaries, or are achieved independently as responses to similar problems.


Microdetermination of serum calcium by parallel fast analyzer.

An adaptation of a direct microdetermination of serum calcium based upon its colored reaction product with cresolphthalein complexone for use with a parallel fast analyzer is described. It is simple, reliable and clinically accurate. Twenty microliters of sample are employed in a final volume of 650 mul. Comparison studies with an atomic absorption method resulted in a correlation coefficinet (r) of 0.94. Replicate analyses at normal (8.5 mg. per dl.) and abnormal (12.1 mg. per dl) levels showed inter-day coefficients of variation of 3.2 and 2.3%, respectively. Assays of sera of male and female donors (age range: 17--60 years) showed normal ranges of 8.5--10.8 and 8.5--10.5 mg. per dl., respectively. Moderate hemolysis and jaundice and mild lipemia are associated with spuriously high results. Magnesium in serum showed no significant effect below 4.0 mEq. per l.


Changes in serum salivary isoamylases in Sjögren's Syndrome.

Quantitative polyacrylamide disk gel electrophoresis of sera from 27 patients with Sjögren's syndrome (SS) and 12 comparable normal subjects revealed that serum amylase activity in patients with SS varies due to changes in the salivary isoenzyme, while pancreatic isoamylase remains normal. The SS group can be divided into those patients with markedly increased salivary isoamylase and those with normal or low salivary isoamylase. At this time we cannot be certain whether this reflects different stages in a progressive disorder, or differences in the underlying pathologic processes. Analysis of amylase isoenzymes in serum previously has been shown to be of value in pancreatic disorders, and we have now demonstrated that changes in the salivary glands may also be relected in serum amylase isoenzymes. Study of patients with other salivary and pancreatic disorders will be needed to define the clinical utility of amylase isoenzyme analysis.


Learning objectives in resident training. Objectives in clinical chemistry.

The use of learning objectives has recently found extensive application in the evolution of medical school curricula; however, they have not been utilized systematically in the education of pathology residents. In attempting to define the end-point behavior or objectives of a resident during a rotation in clinical biochemistry, 567 midwestern pathologists, clinical chemists and medical technologists working in chemistry sections rated proposed objectives as essentail, desirable but not essential, or not needed. Twenty-four of 52 objectives were considered essential for the resident to achieve by 75% or more of the respondents. These included 10 of 33 related to technical knowledge, 5 to 10 related to business and supervisory skills, 5 of 5 related to investigative problem solving, and 4 of 4 related to communicating with persons outside of the laboratory. In general, respondents considered knowledge of principles more important than technical skills. Management, business and communicative skills were highly rated.


Pathology manpower needs in the United States.

By means of a set of questionnaires, the Joint ASCP/CAP Task Force on Manpower survey of fact and opinion regarding manpower problems and needs of pathology in the United States was completed. The response from pathologists approached 75%. From this survey, there appears to emerge an accurate picture of the number of pathologists in solo or group practice in the United States in terms of board certification and age group; so that over a five-year period, there will be a net addition of approximately 1,800 pathologists from 500--700 residents completing their training annually. This survey showed a demand of 22% of pathology practices seeking to fill funded positions with a projected need within the next five years of approximately 2,700 to meet primarily expanded patient loads. The number of pathologists in the graduate medical education "pipeline" revealed 2,153 residents with about 76% of the residency positions filled. A match of approximately 2,153 residents entering pathology practice against 2,160 vacancies anticipated in the next four years was identified. However, it is likely that there will continue to be a modest deficit of pathologists five years from now in view of the possibility that not all will enter practice. In conclusion, the demand for pathologists and supply from residency programs seem to match well in numbers so that supply and demand for pathology manpower are in approximate balance.


Reactive plasmacytic lesions of the bone marrow.

A consecutive series of 1,000 bone marrow aspirates was analyzed for percentage of plasma cells, incidence of plasmacytic satellitosis, associated clinical disease states, lymphoid follicles, lipid granulomas, hemosiderin content, and various combinations thereof. Plasmacytosis was a common finding, and tended to parallel the presence of lymphoid follicles, lipid granulomas and plasmacytic satellitosis. The latter is emphasized as a normal phenomenon, may reflect morphologically a physiologic response of the B cell system to antigenic stimulation, and is conspicuously absent in plasmacytic neoplasia. Various secretory forms of plasma cells are illustrated.


Ultrastructural features of the blood cells in a patient with Pelger-Huët anomaly.

A case of congenital Pelger-Hüet anomaly of the peripheral blood cells is described. Electronmicroscopic examination of the blood cells revealed nuclear bridges and appendices in the polymorphonuclear leukocytes. The number of cytoplasmic granules was diminished, but the size of the secondary granules was markedly increased. The eosinophils showed pronounced polymorphism of the granules, and the platelets showed a decrease in the alpha-granulomere number.


Fletcher factor deficiency and myocardial infarction.

The case of a patient who, while being treated for an acute myocardial infarction, was found to have Fletcher factor deficiency with a Fletcher factor concentration of less than 1% of normal is described. Fletcher factor deficiency is associated with defects in several interrelated systems, including clotting, fibrinolysis and kinin generation, all of which play a role in the pathogenesis and evolution of infarction. The development of myocardial infarction in a patient who had severe Fletcher factor deficiency emphasizes the importance of alternate pathways for activation of these systems.


Carrier detection in classic hemophilia by combined measurement of immunologic (VIII AGN) and procoagulant (VIII AHF) activities.

Accurate carrier detection in classic hemophilia has been difficult because of (1) technical problems related to the performance of both immunologic (VIII AGN) and procoagulant (VIII AHF) determinations, and (2) statistical problems related to the analysis of these data. VIII AHF was determined by a one-stage assay based on the partial thromboplastin time (PTT). VIII AGN was measured by the method of quantitative immunoelectrophoresis. The discriminant function U. = 0.67 1n (AHF) -- 3.17 AGN X 10(-3) was calculated for a validation group of 20 normal persons and for seven obligate carriers, and tested for accuracy of prediction on a cross-validation group of seven additional normal women and ten additional obligate carriers. A U. score of greater than or equal to 2.54 correctly identified 25 of 27 normal persons. Sixteen of 17 obligate carriers had U. scores below 2.54. In addition, of seven possilbe carriers, four were identified as normal and three as carriers. Five normal women taking oral contraceptives had disproportionately high U. scores. It is concluded that detection of carriers of classic hemophilia should be possible in the clinical laboratory by calculation of a discriminant function from combined measurements of VIII AGN and VIII AHF.


The usefulness of serum protein and erythrocyte enzyme polymorphisms in paternity testing.

Pehnotypings of serum proteins and erythrocyte enzyme polymorphisms were used in addition to classic erythrocyte antigens in a study of 281 paternity cases. This group was compared with 877 cases in which only the erythrocyte antigens were tested. In the study group 80 exclusions were found for 52 alleged fathers. The expanded test battery increased the exclusion rate by 62%. In addition to 30 direct exclusions, serum proteins and erythrocyte enzymes corroborated indirect exclusions obtained with erythrocyte antigen tests in eight instances.


Serologic evaluation of the Mono-Chek test.

An evaluation of the Mono-Chek test shows it to be easy to read, fast and simple. In accuracy it compares favorably with the Paul-Bunnell (P-B) test and the Davidsohn modification of the Paul-Bunnell (P-B-D) test and is equal to the Mono-Spot test.


Malignant lymphoma with a high content of epitheloid histiocytes (Lennert's lymphoma).

Fifteen patients with a rare malignant lymphoma characterized by a high content of epithelioid histiocytes are reported. This lymphoma, referred to as "Lennert's lymphoma," was originally thought to be a variant of Hodgkin's disease, but has both histologic and clinical differences. Although the infiltrate is polymorphous, diagnostic Reed-Sternberg cells are difficult to find and involvement of tonsils relatively common. Lennert's lymphoma bears some resemblance to immunoblastic lymphadenopathy in that some patients have a history of allergies, polyclonal hyperglobulinemia, and all lymph nodes demonstrate variable proliferation of immunoblasts. However, both vascular proliferation and the amorphous eosinophilic interstitial material characteristic of immunoblastic lymphadenopathy are lacking. The clinical course in this series was unpredictable with rapid death in six cases, chiefly from sepsis, 1--18 months following diagnosis despite therapy as for Hodgkin's disease. The remaining eight patients for whom follow-up data are available are in apparent clinical remission. Further cases and investigations are needed to determine the precise behavior of Lennert's lymphoma and to learn its exact status in relation to other malignant lymphomas or immunoblastic proliferations.


Evaluation of a Coulter Chemistry Unit.

Seventeen channels of a Coulter Chemistry Unit were evaluated. The evaluation included within-run and day-to-day precision, recovery, dilution, carryover and interference studies; as well as correlation studies between the Coulter Chemistry Unit and the procedures currently used in the author's laboratory. Criteria for acceptance of a procedure are outlined. Five channels of the particular instrument studied were found acceptable by the author's criteria, six channels had correctable defects, and six channels had either reagent or instrumentation deficiencies.


Some statistical implications of rounding in the College of American Pathologists Survey.

Quantitative measurements of constituent concentrations of Survey specimens are generally recorded to the nearest integer or to the nearest tenth. Questions have arisen as to whether this degree of rounding of measurements is appropriate when available laboratory equipment can determine results more precisely. Statisticians have studied the effects of rounding off on an variety of standard statistical procedures. In this report biases that may result for estimates of the mean and variance from several typical data sets obtained in the 1975 College of American Pathologists (CAP) Survey are examined. The study indicates that the amount of bias in the sample mean and variance is generally minimal.


An evaluation of statistical procedures designed to detect outliers resulting from a light degree of contamination in random samples of moderate size.

The literature on statistical outlier procedures applicable to the CAP Survey program is briefly reviewed. Limited Monte Carlo evaluations of selected procedures were performed. For a light degree of contamination in random samples of moderate size, it is shown that the application of these procedures has little effect on estimates of measures of central tendency and spread. Moreover, in this situation these procedures detect a very small percentage of the outliners.


A comparison of participant mean values of duplicate specimens in the CAP Chemistry survey program.

Six paired specimens of lyophilized human serum were circulated to participants in the CAP Comprehensive Chemistry Program. The intervals between circulations ranged from 13 to 33 weeks. Each specimen was analyzed for 21 constituents, and the six pairs of specimens provided 126 paired sets of data for statistical comparison. The mean values for all constituents reported by the participants for each pair showed close agreement. The median difference between the two mean values for 126 pairs was 0.6% of the concentrations of the constituents. Twenty-six individual pairs showed differences that were sufficiently large to be significant (p = less than .0005). The majority of these stemmed from differences reported by participants using the SMA 12/60. Although significant, these differences were so small that they exerted no demonstrable effect on the dispersion of the results reported by the SMA 12/60 users. One vial pair showed a loss of glucose. All six pairs showed a loss of triglyceride. There was a suggestion of loss of cholesterol and uric acid in one pair. These differences were small. This study demonstrates that a comparison of mean values in a large Survey program can provide a very sensitive method of monitoring the stability of the specimens. The study also suggests the repeatability of mean values in a large Interlaboratory Survey program far exceeds clinical needs, and the agreement may be closer than can be obtained by any other system of measurement.


The effect of analyte and analyte concentration upon precision estimates in clinical chemistry.

A significant statistical relationship between concentration and precision is shown for 11 of 14 clinical chemistry analytes, and quantitative expressions of these relationships are given. The relationships are not necessarily the same for automated and manual methods for a given analyte. Automated precision is not significantly better than manual precision for triglyceride, cholesterol and sodium. For 11 other analytes, automated precision is superior at some or all concentrations. State of the art precision is compared with criteria of medical significance. Only calcium shows significantly poorer precision than that required by medical goals.


Interlaboratory survey of enzyme analyses. I. Preliminary.

Enzyme survey specimens were prepared by spiking portions of a normal serum pool with creatinine, urea, and five enzymes (lactate dehydrogenase, creatine phosphokinase, alkaline phosphatase, and aspartate and alanine aminotransferases), and preparing admixtures of the spiked pools with the original serum. This admixture technic established linear interspecimen relationships that could be confirmed by analyses for creatinine and urea nitrogen. Both ethylene glycol-stabilized liquid serum specimens and lyophilized specimens were prepared as sets of six to eight samples having six concentrations of each enzyme. The sets were distributed on five occasions to about ten laboratories that were widely separated geographically, and the specimens were analyzed by a variety of methods, by various instrumental systems, and in different reaction conditions, and results were reported in diverse units. This report describes how the analytic data obtained through the use of these specimens that were specifically designed for survey purposes can be analyzed statistically to provide meaningful assessments of laboratory performance in enzyme analyses.


Clinical chemistry kits in the CAP survey program.

Pathologists began evaluating the pattern of use and the performance of clinical chemistry kits among participants in the Chemistry Survey Program. The results show that kits are widely used by all types of laboratories. The agreement among results obtained by kit users parallels the agreement among results obtained by users of manual methods. This agreement is adequate for some constituents and not for others.


Three-years' experience in interlaboratory testing of commercial digoxin kits.

Results of digoxin assays obtained from participants in Survey Programs of the College of American Pathologists over a span of three years are reviewed according to recovery rates and clinical interpretation of results obtained. Discrepancies in recovery rates by kits employing iodinated and tritiated antigens were observed in 1972 and 1973. More uniform recovery rates were observed in 1974. Clinical interpretation of the results obtained by participating laboratories was affected by the methods used during the first two years and by the apparent failure of individual laboratories to establish their own therapeutic ranges.


Serum albumin. A CAP survey.

The results of a 1974 survey of albumin measurements as performed by more than 1,300 laboratories are presented. The most widely used methods are the dye-binding technics: bromcresol green (BCG) and 2-(4'-hydroxyazobenzene) benzoic acid (HABA). These are followed by electrophoresis and salt fractionation. All methods yielded comparable albumin concentrations except electrophoresis, which manifested a consistent low bias. This close agreement is attributed, in part, to the normal-range concentration of albumin in the test specimen. Type of standardization, i.e., commercial serum, bovine serum albumin, human serum albumin, or pooled serum, did not appear to be a factor in the estimation of albumin in the normal serum submitted for analysis. Surprisingly, interlaboratory variation, from method means, was the lowest for salt fractionation and electrophoretic technics.


College of American Pathologists comprehensive chemistry survey bonus option. Iron-binding capacity.

The result of a special survey of TIBC determination involving approximately 1,100 participants of the CAP Comprehensive Chemistry Survey program is reported. TIBC results are method-dependent. There is also wide variation within method groups. The influence of reagent manufacturers is significant


The comprehensive blood bank survey program of the College of American Pathologists, 1974.

Results of the 1974 College of American Pathologists Comprehensive Blood Bank Survey Program show that ABO and Rh typing are still holding their percentage of excellent (99.48%) accuracy. At least some of the errors still occurring are due to clerical mistakes in filling out the forms and not to technical inaccuracy. Antibody detection shows good accuracy but varies, depending on the complexity of the problems--the easier the problem the higher the rate of concurrence, while the more complex the problem the more variance in results. Crossmatching accuracy is 99% correct or better on any but the most complex problems. Some of the problems involving interpretation of autoimmune hemolytic anemia are discussed.


The reticulocyte. An approach to definition.

Experiences of the CAP Survey Program in reticulocyte counts and morphologic identification of reticulocytes from 1971 to 1974 are reviewed. Problems of morphologic identification are reflected in an excessive variance of reticulocyte counts. Statistical sources of variations in counting are identified. The older, original descriptions and definitions of morphologic criteria are reviewed and discussed in relationship to Survey performance.


The role of regional quality control programs in the practice of laboratory medicine in the United States.

Since their initiation in 1967, Regional Quality Control Programs have expanded, and they are now accessible to all clinical laboratories in the United States. Based on input from large numbers of laboratories analyzing the same lots of control material for chemistry, hematology, and coagulation, the programs provide computer-generated intralaboratory statistics for day-to-day precision and interlaboratory comparative statistics for relative precision and accuracy. Nearly half the clinical laboratories in the United States currently participate in Regional Quality Control Programs in chemistry. These voluntary programs are coordinated by voluntary professional groups or by the manufacturers of control materials. Professionally directed programs are, for the most part, supervised by committees of state pathology societies.


Clinically unsuspected disseminated intravascular coagulation (DIC): an autopsy survey.

In a review of 768 consecutive autopsies, 21 (2.7%) clinically unsuspected cases of disseminated intravascular coagulation (DIC) syndrome were diagnosed by histologic examination. DIC was diagnosed by the presence of fibrin thrombi in arterioles, capillaries, venules, and medium-sized veins. Fibrin thrombi were found, in the descending order of frequency, in the brain, heart, lungs, kidneys, adrenals, spleen and liver. Most patients had multiple visceral involvement, with three showing fibrin thrombi in as many as ten organs. The density of fibrin thrombi was greatest in the spleen, followed by kidneys, liver, lungs, adrenals, brain, and heart. A review of clinical data showed that infections were the most common underlying conditions in 13 cases, including nine with positive bacterial cultures from blood or cerebrospinal fluid, or both. The results suggest that, despite increasing clinical recognition of DIC, a great number of patients remain unsuspected of having the DIC syndrome prior to postmortem examination.


A compound nevus in a benign cystic teratoma of the ovary.

The occurrence of a compound nevus in an ovarian benign cystic teratoma is presented. This appears to be the first report of this lesion in the ovary without coincident melanoma. The case illustrates a probable origin for ovarian melanoma and raises a question concerning the origin of the melanocyte.


Hepatitis B antigen card test III: sensitivity and specificity.

A simple, rapid hepatitis B antigen card test (card test III) with third-generation sensitivity has been developed. This test is a modification of the charcoal-particle agglutination-inhibition procedure. Sera from voluntary blood donors and hospital patients were tested by the new procedure, by the original inhibition technic, by reversed passive hemagglutination, and by radioimmunoassay. This comparison showed that CT III has a specificity equal to that of radioimmunoassay and is almost as sensitive.


Electrochemical method for the early detection of urinary-tract infections.

A method for detecting the presence of bacteria in urine based on measuring a change in potential between two electrodes was tested in a clinical microbiology laboratory. Initial tests were conducted with 13 bacteria commonly associated with urinary-tract infections; all of the test organisms were detected within 2--9 hours. A linear relationship was established between inoculum size and the time an increase in voltage was observed on a strip-chart recorder. No response was seen with sterile urine, but urine samples inoculated with Escherichia produced the expected positive response. One hundred twenty-eight urine specimens from hospitalized persons were simultaneously tested by the electrochemical detection method (ECDM) and by conventional bacteriologic procedures. Ninety-four per cent of 49 positive samples with counts of 10(5) organisms per ml. or more were detected within 4 hours and 100% at 10 hours with the ECDM. Twenty-nine specimens with counts less than 10(5) cells per ml. were detected in 3.5 to 9 hours; two samples (8%) in this group were positive within 4 hours. Fifty samples were negative for bacterial growth, and no increase in voltage was found with these samples.


Mucocutaneous lymph node syndrome in Denver.

Four children with acute febrile mucocutaneous lymph node syndrome (MLNS) were hospitalized in Denver over a two-year period. The children had most of the principle features of this recently described syndrome, including prolonged fever unresponsive to antibiotics, an erythematous rash, conjunctivitis, pharyngitis, and nonsuppurative cervical lymphadenitis. Three of the children exhibited characteristic desquamation from the fingertips or toes during convalescence. None developed clinical or electrocardiographic evidence of coronary thromboarteritis, the most serious complication of the disease. Additional cases undoubtedly will be reported in the United States as physicians become famililar with this new syndrome and learn to distinguish it from the other acute febrile exanthems.


Mucocutaneous lymph node syndrome in Arizona.

Mucocutaneous lymph node syndrome (MLNS) is a newly recognized entity, widely prevalent in Japan. It has also been reported in Korea, Hawaii, and Greece. We have recently seen four white children, 3 to 4 1/2 years of age, with MLNS, in Tucson, Ariz. They had all the principal signs and symptoms characteristic of MLNS.


Respiratory syncytial virus and influenza. Practical community surveillance.

Concurrent and sequential outbreaks of infection with respiratory syncytial virus (RSV) and influenza A virus were studied, utilizing a local surveillance system for infectious diseases that involved weekly reports from primary care physicians. The patterns of illness in the community and in hospital admissions were relatively specific for these two viruses, and differed according to whether RSV and influenza A virus occurred together or separately. This surveillance system appeared to be a practical and accurate indicator of the activity of RSV and influenza A virus in the community. Such a system may serve as a valuable means of relatively early detection of the local arrival of these viruses, and recognition of these illness patterns might aid the physician in diagnosis.


Chemotherapy of childhood medulloblastoma.

A number of chemotherapeutic agents have been shown to have anti-tumor activity against childhood medulloblastoma. Ten-year survival with optimal surgery and radiation therapy ranges from 5% to 25%. Carefully controlled clinical trials utilizing a combination of surgery, radiation therapy, and chemotherapy should be employed in the early stages of the disease in an attempt to define which drugs are most effective, and to improve the survival rate.


Hepatic hemangiomatosis. Successful management by hepatic artery ligation.

Successful management of severe congestive heart failure secondary to a hepatic hemangioma was accomplished by ligation of the hepatic artery in a 2-month-old infant. In the two years since the operation, follow-up observations including liver biopsy and hepatic angiography have indicated complete regression of the tumor. This report provides reassurance that this procedure is effective in the prompt control of severe heart failure, as well as in safely providing time for the spontaneous regression of the vascular tumor.


Trisomy for the distal half of the short arm of chromosome 9. A variant of the trisomy 9p syndrome.

Three patients with partial trisomy for the distal one half of the short arm of chromosome 9 were studied. These patients represent a mild clinical variant of the trisomy 9p syndrome.


Complications of obesity-hypoventilation syndrome in childhood.

The obesity-hypoventilation syndrome is rare in children, but it leads to serious complications and is associated with a high mortality. We report a child with this syndrome whose condition improved after intestinal bypass surgery. Review of the literature indicates that vigorous treatment of this disorder is necessary to prevent fatalities.


Serial liver biopsy observations in hepatitis B antigen carriers by light and electron microscopy.

Liver morphology and function were restudied after an interval of 1 1/2-2 years in 21 Chinese men with hepatitis B antigen (HBsAg). Antigenemia and mild liver histopathology disappeared in one individual who developed antibody to HBsAg(Anti-HBsAg). 20 subjects who were chronic carriers of HBsAg had mild histological abnormalities which were usually persistent and were more commonly lobular than portal. Particularly striking were focal necrosis, eosinophilic bodies, ground-glass cytoplasmic change, and, by electron microscopy, microtubular structures within cytoplasmic membranous cysternae. Interval development of chronic aggressive hepatitis was observed in only one subject. This study suggests that the great majority of HBsAg carriers have a good prognosis at least over a 1 1/2-2-year period, and that liver biopsy is most indicated in those with persistent liver function abnormalities.


The effect of phenobarbital on biliary lipid metabolism and hepatic microsomal drug metabolism in patients with cholesterol cholelithiasis.

Six patients with cholesterol cholelithiasis were studied before and after 3 weeks treatment with phenobarbital, 120 mg/day. The kinetics of cholic and chenodeoxycholic acid and biliary lipid composition were not significantly affected by phenobarbital treatment although hepatic mixed-function oxidase was stimulated by the treatment as shown by increased breath output of 14CO2 after administration of (14C)aminopyrine. It is concluded that treatment with phenobarbital is unlikely to be effective therapy for patients with cholesterol cholelithiasis.


Respiratory exchanges and acid-base balance during perfusion of ex vivo isolated pancreas.

We used the technique of ex vivo isolated pancreas, perfused with whole heparinized blood. The organ was stimulated by secretin (G.I.H. Stockolm, 0.1-5.0 clinic units/hr), and/or carbamylcholine (100-200 mug/hr). Oxygen consumption was increased under stimulation. This increase was a function of the dose of secretin and also of the bicarbonate output in the juice. Oxygen uptake increased further when carbamylcholine was super-imposed on secretin. This extra increase was independent of hemodynamic conditions of the organ perfusion. Arteriovenous difference in oxygen saturation did not increase when the gland was stimulated. It tended to decrease when the stimulation resulted in a marked vasodilatation. Thus, oxygen needs seemed to be neither the limiting factor of the response to a given stimulation nor the triggering mechanism of functional vasodilatation. Values of pCO2 were spread over a wide range from one experiment to another. However, it could be observed that CO2 efflux into the vein decreased under stimulation by secretin; in most experiments, CO2 efflux was even replaced by an apparent consumption of CO2 during the perfusion of the stimulated gland. Furthermore, arteriovenous pH difference increased following secretin stimulation. This increase was dose-related to secretin. These facts are discussed under the background of theories recently proposed for bicarbonate secretion.


Evaluation of gastric ulcerations.

All gastric ulcers diagnosed during the period November, 1969-May, 1974, were prospectively evaluated by roentgenography, fiberoptic gastroscopy, directed biopsy, and brush cytology. Gastroscopy was performed routinely in patients with radiologic diagnosis of gastric ulcer or questionable findings, and in symptomatic individuals with negative roentgenograms. A total of 123/142 ulcers, 109 benign, 14 malignant, were available for complete follow-up. Gastroscopy was correct in 106 of 109 benign ulcers visualized. Roentgenoscopy demonstrated 91 of 109, of which 7 were incorrectly called carcinoma. Gross diagnosis was correct by gastroscopy in 11 of 14 malignant ulcers. Radiology visualized 6 of 14; gross diagnosis was correct in 1 of 6 (5 called benign). Directed gastroscopic biopsy was negative for malignant changes in all 109 benign and 3 of 14 malignant ulcers. Total complete gastroscopic diagnostic failures were 4 of 123, for an overall accuracy of 96.7%. Overall roentgenographic accuracy was 70.8%.


Tropical sprue in American servicemen following return from Vietnam.

Moderately severe tropical sprue was diagnosed in two American servicemen 15 and 19 months after return from Vietnam. Intestinal parasites were not demonstrated, and clinical, laboratory, and jejunal histological abnormalities returned to normal following treatment with tetracycline and folic acid in one patient and folic acid alone in the other. Neither patient was anemic, although one had hypersegmented polymorphonuclear leukocytes and both had macrocytosis and megaloblastic bone marrows. In each of these patients, diagnosis was delayed because of the failure to consider tropical sprue in the differential diagnosis of diarrhea and weight loss. The findings in these patients indicate that individuals from nonendemic areas who reside in Vietnam are at risk of developing overt tropical sprue.


Pneumatosis coli associated with sigmoid volvulus and colonoscopy.

A case of interstitial emphysema involving the mesentery and serosa of the sigmoid colon after volvulus reduced by colonoscopy is presented. The case is reported as a form of pneumatosis intestinalis although it does not conform to the classical clinicopathologic picture of pneumatosis cystoides intestinalis. The infrequent occurrence of this condition in association with volvulus and/or colonoscopy is discussed.


Esophageal manometry in oculopharyngeal dystrophy.

Four cases of oculopharyngeal dystrophy (OPD) seen within five years are presented. The cardinal features of OPD are dysphagia and ptosis. The manometric abnormalities in OPD are similar to those seen in other myopathies; low pharyngeal pressures, abnormalities in relaxation and coordination of the pharyngoesophageal sphincter and weak aperistaltic swallows in the proximal esophagus. In addition, weak aperistaltic swallows frequently occur in the distal esophagus and may exacerbate dysphagia. Although there is no specific therapy for ODP, one patient showed marked improvement following cricopharyngeal myotomy.


Esophageal carcinoma with pseudohyperparathyroidism and hypercorticism.

An unusual case of bihormonal activity by squamous cell carcinoma of the esophagus is presented. It is a rare presentation of esophagus carcinoma because of the following reasons: 1. Synthesis of cortisteroids by esophageal carcinoma. 2. Pseudohyperparathyroidism caused by the same tumor. 3. Presentation of hypokalemic alkalosis as the initial manifestation and lack of specific gastrointestinal symptomatology of esophageal carcinoma.


Gastric pseudolymphoma. A spectrum of presenting features and diagnostic considerations.

Four cases of gastric pseudolymphoma are presented which illustrate the spectrum of presenting features. At times the differential diagnosis includes inflammatory and infectious diseases of the stomach as well as gastric neoplasia.


Exocrine pancreatic function in hepatic cirrhosis.

Exocrine pancreatic function was assessed by the standard test meal method of Lundh in a control group, and 13 patients with nonalcoholic, postnecrotic cirrhosis of the liver. In six of these patients, splenorenal shunts were performed and exocrine pancreatic function was assessed before and three months after operation. In three of the six, the secretin-pancreozymin stimulation test was also performed. An increased volume but normal trypsin output was observed in the unoperated cirrhotic patients. An increase both in volume and in trypsin was found in the cirrhotic patients after shunting using the test meal stimulation. There was no appreciable difference, however, when tested with secretin and pancreozymin. Hypersecretion in cirrhotics, with or without shunts, is probably due to a by-pass of the hepatic degradation of normal pancreatic secretogogues produced by the intestine.


Intestinal ganglioneuromatosis with the mucosal neuroma --medullary thyroid carcinoma-- pheochromocytoma syndrome. A case report and review of the literature.

A case of intestinal ganglioneuromatosis associated with medullary thyroid carcinoma, bilateral pheochromocytoma, mucosal neuromas and marfanoid habitus is reported. To our knowledge, only ten previous cases of intestinal ganglioneuromatosis associated with mucosal neuromas and medullary carcinoma of the thyroid have been reported. Our case represents the 11th such case, the seventh with the concomitant finding of pheochromocytoma and the second with documented parathyroid hyperactivity. The intestinal ganglioneuromatosis may represent a variation of the mucosal neuroma component of this rare syndrome and the multiorgan abnormalities may result from a genetically related disorder of a single cell system, the neural crest. The characteristic marfanoid habitus with the presence of mucosal neuromas raises the possibility of a serious underlying polyendocrine-neural disorder and should alert the clinician accordingly.


Crohn's disease presenting as a gastrocolic fistula.

A case of Crohn's disease which presented as a gastrocolic fistula is described. Clinical, laboratory and pathological descriptions are included. The incidence and various etiologies of gastrocolic fistulas are discussed.


Pneumopancreatogram associated with gas in the biliary tract.

A case is presented in which the entire pancreatic duct, including its secondary and tertiary branches, was visualized by the reflux of gas from the biliary ducts. This unusual finding suggests a possible mechanism of the association of pancreatitis with biliary tract disease.


Effect of Beta-sitosterol on cholesterol-cholic acid-induced gallstone formation in mice.

Beta-sitosterol has been shown to prevent gallstone formation in mice fed 1.2% cholesterol and 0.5% cholic acid (lithogenic diet). The incidence of gallstone formation in the mouse by the addition of 2.5% sitosterol in the lithogenic diet is about 35.5% in male and 25% in female. The condition of the liver, whether fatty or normal, did not correlate with the presence or absence of cholelithiasis. The serum and liver cholesterol levels of mice fed either sitosterol and cholesterol or sitosterol and cholic acid is lower than those of mice fed cholesterol or cholic acid alone. Elevation of liver phospholipid concentration was noticed in mice fed sitosterol or a combination of sitosterol with cholesterol or cholic acid or both cholesterol and cholic acid.


Antibody coated red cells with and without hemolysis in chronic ulcerative colitis.

A young female with ulcerative colitis associated with positive direct and indirect Coombs reaction and severe autoimmune hemolytic anemia is reported. Cortisone was beneficial and total colectomy was promptly followed by subsidence of the hematologic defects. Review of the literature suggests that this complication of ulcerative colitis is uncommon. It basis is unclear. It seems to be expressed through the presence of a "warm" auto-antibody. Colectomy should be strongly considered when severe hemolysis is present but not when the Coombs test is positive alone without significant hemolysis.


"Cycloperistaltic" intestinal segment: a new method to prevent excessive fluid loss in permanent ileostomies.

A 10-15 cm. long isolated intestinal segment, in which peristalsis has been altered to run in a circular fashion, was interposed in a series of permanent ileostomy-bearing dogs and in two clinical cases with severe diarrhea after total colectomy. Excellent results in both patients confirmed the experimental findings. Technically the method is easily accomplished by cutting the antimesenteric site of the intestinal segment lengthwise and resuturing it transversely. Two major advantages of this technic are postulated. First, the retarding action of the isolated loop does not depend on the great variations observed in peristaltic activity of the small intestine which in some patients results in obstruction. Second, the blood supply to the loop is unlikely to be impaired. Possibly both these advantages derive from the fact that the loop is twisted only 90% instead of 180 degrees required in the ordinary reversed loop interposition.


Colitis cystica profunda.

Colitis cystica profunda is a benign disease characterized by variably sized mucin-filled cysts beneath the muscularis mucosae. The clinocpathologic features of five patients are described. The accumulated evidence suggests that awareness of this entity both by clinicians and pathologists with help differentiate it from carcinoma and decrease the need for radical surgery.


The endoscopy corner: ileoscopy: I. evaluation of "ileostomy dysfunction".

Various causes of "ileostomy dysfunction" may be easily identified using the pediatric-size flexible fiberoptic endoscope. Direct visual inspection, photographs, and biopsies may be obtained from the area around the stoma up to a depth of 40-50 cm. within the small bowel.


Geographic patterns of lung cancer: industrial correlations.

A survey of lung cancer mortality by county in the United States, 1950-1969, revealed excessive rates among males in counties where paper, chemical, petroleum, and transportation industries are located. The industrial correlations were not attributed to urbanization, socioeconomic factors, or other manufacturing operations, and may account for part of the high risk of lung cancer previously reported in Southern US coastal counties.


Associations of coronary and stroke mortality with temperature and snowfall in selected areas of the United States, 1962-1966.

Daily temperatures and snowfall were related to coronary and stroke deaths in selected standard metropolitan statistical areas for the 5-year period 1962-1966. Typically an inverse approximately linear pattern of coronary heart disease (CHD) and of stroke mortality with temperature was seen over the greater part of the temperature range, with mortality reaching a low for days with average Fahrenheit temperatures in the 60's and 70's (15.6-26.6 C), and then rising sharply at higher temperatures. Snowfall was found to be associated with higher CHD and stroke mortality for a 5-, or 6-day period. Temperatures 1 and 2 days prior to death were also found to be associated with deaths from CHD and stroke. Very hot days appeared to exert a cumulative effect upon mortality in many of the areas.


Toxoplasma antibody prevalence in veterinary personnel and a selected population not exposed to cats.

To further elucidate the epidemiologic factors involved in the transmission of Toxoplasma gondii from cats to humans, veterinarians, animal hospital workers and a selected population of non-contact subjects were questioned about rural or urban residency, pets owned, contact with cats and whether their cats used a litter box in the house. Sera samples were tested at 1:128 dilution for toxoplasma antibodies using indirect fluorescent and hemagglutination techniques. None of the 60 non-contact individuals were seropositive. Of 60 contact subjects, 18.3% were identified as carrying antibodies. Other factors were not significant. Because only one veterinarian was seropositive, we propose that exposure to cats per se does not supply sufficient evidence upon which to expect a risk of toxoplasmosis infection. Direct or indirect association, personal hygiene, duration of exposure and the infectivity of the cats should be considered.


Short pregnancy interval, low birthweight, and the sudden infant death syndrome.

Pregnancy intervals were calculated for 54,369 later-born singletons delivered during 1969 in the State of North Carolina. Subsequent infant deaths among this cohort were categorized into probable sudden infant death syndrome (SIDSp), other postneonatal home deaths, all postneonatal hospital deaths, all neonatal deaths, and all deaths due to congenital malformations. Each death was matched with a control drawn from the population of infants surviving the first year of life. The matching variables were maternal age, race, mother's education and number of previous live births. All categories of death showed higher proportions of short intervals among cases than controls. Comparing the interval distributions by means of the X2 test for linearity produced significant results for only SIDSp and neonatal deaths. It was concluded, however, that short-pregnancy interval probably has a similar effect on the risk of death from all five cause of death groups. The introduction of birthweight as a fifth matching variable left no significant differences in the distributions of pregnancy intervals between cases and controls. This was interpreted as evidence that short pregnancy interval exerts its influence on risk of death in infancy through its effect on birthweight. The estimated reduction in prematurity and infant mortality that might result from the elimination of short pregnancy intervals was 5% and 6%, respectively.


Common-source epidemic of hepatitis due to glazed and iced pastries.

Sixty-one clinical cases of hepatitis occurred in Ogemaw County, Michigan, in late April and May 1968. The clustering of cases in time and the high attack rate for persons 10-19 years of age suggested a common source of exposure. Investigation implicated a local bakery, where one of the employees directly involved in the baking had had an icteric illness one month before the outbreak. Comparison of exposure histories of patients versus healthy family members established pastries covered with glaze or icing as the vehicle of infection. The glaze and icing were applied to the pastries after all baking had been completed. During the epidemic, immune serum globulin was given on a community-wide basis. No secondary cases of hepatitis were identified.


Bubonic plague from exposure to a rabbit: a documented case, and a review of rabbit-associated plague cases in the United States.

A 62-year-old woman developed bubonic plague with an epitrochlear bubo one to two days after skinning two cottontail rabbits. The implicated rabbits were later recovered from the patient's freezer, and Yersinia pestis was isolated from marrows of both rabbits. Although human plague cases in the United States have occasionally been traced to exposure to wild rabbits, this is the first documentation of plague infection in the actual rabbits to which the patient was exposed. All reported cases of rabbit-associated plague in the United States were then reviewed. Eight cases were characterized by direct exposure to rabbit tissues. Seven of the eight cases occurred in adult males who had hunted rabbits during winter months in plague-endemic areas. These patients had upper extremity buboes, and the case-fatality ration for the group was 50%. Three other cases in which rabbit exposure was indirect or its role less clear, were also analyzed.


Spontaneous hematologic remission in agnogenic myeloid metaplasia.

A 60 year old man had well documented agnogenic myeloid metaplasia with pancytopenia. Frequent red cell transfusions were required for two and a half years. Androgen therapy was not beneficial and was discontinued 26 months before a spontaneous hematologic remission occurred. The remission was documented by bone marrow biopsy and reticuloendothelial scanning of the marrow. Hepatosplenomegaly, poikilocytosis and expansion of the marrow space have persisted despite hematologic remission.


Nonmalignant monoclonal immunoglobulinemia, pernicious anemia and gastric carcinoma. A model of immunologic dysfunction. Report of two cases and review of the literature.

The association of an autoimmune disease with a monoclonal immunoglobulin is not exceptional and most probably results from a dysfunction of the immunologic apparatus. This study describes two patients with monoclonal immunoglobulin A (IgA) and M (IgM) gammopathy, respectively, in whom pernicious anemia and finally gastric carcinoma developed. One patient had autoantibodies to gastric parietal cell and to thyroid microsomal antigen which could not be identified with the M-component. This observation, together with the fact that pernicious anemia occurred in one case before and in the other case after the discovery of M-component, suggests that different clones of cells were responsible for both disorders. Sixteen cases in which the patients had the same association have been collected from the literature and the data are compared with ours.


Unilateral renal vein thrombosis and nephrotic syndrome. Report of a case with protein selectivity and antithrombin III clearance studies.

A case of the nephrotic syndrome with unilateral renal vein thrombosis is reported. The patient, an 18 year old man, presented with a six month history of edema and the recent development of a left-sided varicocele. An enlarged left kidney and a thrombus in the left renal vein were demonstrated roentgenographically. A biopsy specimen of the right kidney was interpreted as membranous glomerulonephritis. Selective renal function studies showed nearly identical creatinine excretion, and similar total protein excretion and protein selectivity from each kidney. Thus, the thrombus in the left renal vein did not influence glomerular filtration rate or quantitative or qualitative protein excretion. A high urinary output and a decreased serum level of antithrombin III were measured. These findings suggest a mechanism to explain the increased thrombotic tendency seen in this and other patients with the nephrotic syndrome.