Cardiac shape and function in aortic valve disease: physiologic and clinical implications. Left ventricular shape and function were studied in 12 normal subjects, 18 patients with pressure overloading secondary to isolated aortic stenosis and 20 patients with volume overloading due to aortic regurgitation. End-diastolic volumes were mildly increased in aortic stenosis but greatly increased in aortic regurgitation. Average ejection fractions were normal in aortic stenosis but depressed in aortic regurgitation. Ventricular shape (eccentricity), normal (elongated) in nearly all patients with aortic stenosis, showed in diastole various degrees of abnormal roundness in patients with aortic regurgitation. As ventricular function declined in aortic regurgitation, the ventricles also became more round in systole. After valve surgery, clinical results were generally better in patients with aortic stenosis than in patients with aortic regurgitation. Among the latter, changes in eccentricity and ejection fraction were the best predictors of surgical outcome. It is postulated that chronic volume loading, as exemplified by aortic regurgitation, may induce basic alterations in architecture and fiber alignment of the left ventricular wall. Such changes may exert significant influence on the clinical course of these patients.


Peripheral venous contrast echocardiography. Contrast echocardiography is the technique of injecting various echo-producing agents into the bloodstream and, with standard echocardiographic techniques, observing the blood flow patterns as revealed by the resulting cloud of echoes. These techniques have only recently been utilized to evaluate various cardiac defects. Two physical properties of these agents characterize their usefulness: (1) clouds of echoes can be observed downstream as well as at the injection site, and (2) the echo-producing quality of these agents is completely lost with a single transit through either the pulmonary or the systemic capillary bed. Thus, detection of resultant echoes in both the venous and the arterial blood pool is indicative of abnormal shunting. In 60 patients with a spectrum of cardiac defects and a wide range in age of presentation, studies were made of (1) the feasibility of performing contrast echocardiography with superficial peripheral venous injections, and (2) the clinical usefulness of this relatively noninvasive technique in detecting and localizing intracardiac right ot left shunting. Most superficial peripheral veins could be utilized, and the resultant contrast echograms were reproducible and similar in quality to those obtained more central (caval) injections. Right to left shunts could be localized in the atrial, ventricular or intrapulmonary level. Characteristic flow patterns were also recognized for tricuspid atresia and common ventricle.


Effect of cholestyramine on digoxin absorption and excretion in man. Six subjects receiving digoxin therapy for heart disease were studied on two occasions with a single oral dose of 0.5 mg of tritiated digoxin. In every study, all stools and urine were saved for 1 week. Before the second study, treatment with cholestyramine, 4 g every 6 hours, was begun and continued throughout. In three patients, a third study was performed after cholestyramine treatment had been continued for 1 month. Results showed that after cholestyramine administration serum levels, stool output and urinary output of tritiated digoxin varied over a wider range, but cholestyramine had no net short-term effect of any of these variables. After 1 month of cholestyramine administration, there was a small statistically significant increase in stool output of tritiated digoxin and metabolites. In vitro studies suggested that cholestyramine is likely to be a weak digoxin binder in the gut and that changes induced by this resin in digoxin metabolism are not likely to be due to drug binding.


Echocardiogram in common (single) ventricle: angiographic-anatomic correlation. Common ventricle is a rare congenital anomaly in which the ventricular chamber receives blood from two separate atrioventricular (A-V) valves or a common A-V valve. Diagnosis of common ventricle was established in 55 patients aged 3 months to 33 years (mean 10 years) at cardiac catheterization in all 55 and at operation or autopsy in 24. In common ventricle with two angiographically demonstrable A-V valves (47 patients), the echocardiographic features included: (1) simultaneous recording (in the same sonic beam with the transducer held stationary) of the echoes of an anterior and a posterior A-V valve without an intervening septal echo (45 of 47 patients); (2) absence, on a base to apex scan, of the ventricular septal echo in the usual position separating the A-V valves (47 of 47 patients); (3) recording, in patients with common ventricle and outflow chamber, of this small outflow chamber anterior to the A-V valves (20 of 23 patients); and (4) recording of echographic continuity of the posterior A-V valve and great artery (27 of 31 patients). In common ventricle with a common A-V valve (8 patients), the echocardiographic features included: (1) a single demonstrable A-V valve, located posteriorly in the ventricle, which showed a large amplitude of excursion during diastole; and (2) absence of a second A-V valve echo or ventricular septal echo. Eight patients were studied postoperatively after surgical correction by ventricular septation. Echographic features included visualization of a prosthetic septum that produced a dense echo and divided the common ventricle into "right" and "left" ventricular chambers. This septum had a large excursion anteriorly during systole. Because common ventricle is now amenable to surgical correction, echocardiography should play an important role in assessment of ventricular anatomy in this complex congenital cardiac defect.


Ventricular inversion without transposition of the great arteries. A rarity found in association with atresia of the left-sided (tricuspid) atrioventricular valve. Clinical and morphologic features are described in a 13 week old male infant with ventricular inversion without associated transposition of the great arteries but with concomitant atresia of the left-sided (tricuspid) atrioventricular valve. Isolated ventricular inversion without situs inversus or visceral heterotaxy has previously been reported in English in only three patients, none with tricuspid atresia.


Transposition of the great arteries with intact ventricular septum and patent ductus arteriosus. At the time of initial balloon atrial septostomy a patent ductus arteriosus was found with angiography in 39 of 81 infants with transposition of the great arteries with intact ventricular septum. By angiographic criteria the ductus shunt was considered small in 21 infants and large and significant in 18. In contrast to the usual clinical presentation of neonates with transposition and intact ventricular septum, 12 of these 18 infants with a significant patent ductus arteriosus had only slight cyanosis and 8 presented with tachypnea out of proportion to the degree of cyanosis. Ten of the 18 infants had no continuous murmur, bounding pulses, mid-diastolic rumble or differential cyanosis. Clinically occult narrowing or closure occurred, presumably gradually and relatively late, in six infants. Acute early narrowing or closure, spontaneous (six infants) or surgically produced (three infants), occurred usually within the 1st month of life and was associated with a marked decrease in arterial oxygen saturation in eight infants, often with a rapid clinical deterioration. Persistence of a large patent ductus arteriosus for several months appears to be associated with an increased incidence of early pulmonary vascular disease. Therapeutic considerations for the infant with a large patent ductus arteriosus after initial balloon atrial septostomy include: (1) careful initial follow-up of the infant in clinically stable condition in case the ductus arteriosus should acutely narrow or close and the patient require urgent palliative or corrective surgery; (2) urgent early closure of the ductus in the infant with overt left heart failure with concurrent atrial septectomy or preferably primary corrective surgery; and (3) elective closure of a persistent significant patent ductus arteriosus before age 4 months with concurrent corrective surgery in the infant in clinically stable condition.


Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Incidence of myocardial infarction and death from coronary heart disease. The incidence of myocardial infarction and death from coronary heart disease was studied in defined samples of 45 to 68 year old Japanese men in Japan, Hawaii and California. The incidence rate was lowest in Japan where it was half that observed in Hawaii (P less than 0.01). The youngest men in the sample in Japan were at particularly low risk. The incidence among Japanese men in California was nearly 50 percent greater than that of Japanese in Hawaii (P less than 0.05). A striking increase in the incidence of myocardial infarction appears to have occurred in the Japanese who migrated to the United States; this increase is more pronounced in California than in Hawaii.


Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Coronary heart disease risk factors in Japan and Hawaii. Various risk factors were evaluated to explain a significantly greater incidence of coronary heart disease in men of Japanese ancestry resident in Hawaii compared with men resident in Japan. The independent predictors of incidence of coronary heart disease in both Japan and Hawaii were systolic blood pressure, serum cholesterol, relative weight and age. These factors appeared to influence incidence similarly in both areas because in each case the correlation coefficients for Japan and Hawaii did not differ significantly. The hypothesis that the greater incidence in Hawaii could be attributed to differences in levels of these risk factors was tested with the Walker-Duncan method. The four variable multiple logistic function describing the probability of coronary heart disease in Japan was applied to the cohort characteristics observed in Hawaii. The estimated incidence thus obtained was not significantly different from that actually observed in the men resident in Hawaii. Therefore the increased coronary risk profile in Hawaii compared with Japan can account for the greater incidence of coronary heart disease in the former. Current cigarette smoking was significantly related to the risk of coronary heart disease in Hawaii but not in Japan. This difference requires further investigation.


Weight gain, thermic effect of glucose and resting metabolic rate during recovery from anorexia nervosa. Rate of weight gain, together with metabolic rate before and after a glucose meal, were studied in a group of 15 female anorexia nervosa patients as their weight was being restored to normal levels. The previously obese anoretic patients gained weight more rapidly, on the same food intake, than those who were of normal weight before their illness began. The increase in metabolic rate (as treatment progressed) was less in the previously obese patients, who also showed a tendency for the metabolic rate to increase less after a glucose meal than the patients with no history of obesity. The thermic effect of glucose was greater in patients with anorexia nervosa than in a comparable control group of six female students.


Cholesterol metabolism in patients with resection of ileum and proximal colon. Compartmental analysis of the disappearance curve of serum cholesterol specific activity after an intravenous administration of a tracer does of cholesterol-4-14C was carried out in five patients with resection of the distal small intestine, cecum, and proximal colon. The data fit best a two compartment model in all five cases with the rapidly exchangeable pool of 16.6+/-3.2 g (mean +/- SD, 60% of the mean of 15 normal subjects) and the slowly exchangeable pool of 31.5 +/- 10.9 g (65%). The reduction of the pool sizes was associated with a shorter mean transit time of cholesterol, 22.15 +/- 8.07 days (40%) and increased turnover rate, 2.42 +/- 0.72g/ day (172%). Direct fecal analysis for the neutral sterols and bile acids derived from the exchangeable pool confirmed the turnover rate obtained from the compartmental analysis. The increased fecal excretion was mainly in the bile acid fraction. The study suggests that the ileal and proximal colon resection results in bile acid malabsorption which, in turn, increases hepatic cholesterol and bile acid synthesis. The synthetic rates, however, could not compensate totally for the excretory rate. Therefore, the pool size decreased to a new low steady state of equilibrium.


Effect of diet composition on metabolic adaptations to hypocaloric nutrition: comparison of high carbohydrate and high fat isocaloric diets. The metabolic consequences of two hypocaloric diets were assessed in 10 obese men. The study, performed on a metabolic ward, compared the response of these men to two cholesterol-free liquid formula diets of differing composition (10 kcal/kg per day, 70% carbohydrate, 20% protein, 10% fat versus 70% fat, 20% protein, 10% carbohydrate) but identical in calories. These were administered for 14 days in a random order and each diet was preceded by a 7-day control weight maintenance diet (30 kcal/kg per day, 40% carbohydrate, 20% protein, 40% fat). The low calorie diets were well tolerated by the men and effected similar losses of nonaqueous body weight. Fasting glucose and insulin decreased significantly in these men after they ingested either weight loss diet for 14 days, but the change in each parameter was greater for high fat as compared to high carbohydrate (15% versus 7% and 67% versus 35%, respectively, P less than 0.01). In contrast, fasting glucagon concentration decreased in these subjects to a greater extent in response to the high carbohydrate diet (35% versus 16%, P less than 0.01). This adaptive response thus resulted in a 50% fall in insulin:glucagon molar ratio for high fat and no change for high carbohydrate weight loss. Despite these hormonal alterations no change in glucose tolerance was observed. Fasting serum triglyceride and cholesterol levels declined in these subjects to a greater extent following the high fat compared to the high carbohydrate regimen (45% versus 28%, P less than 0.01 and 8% versus 3%, not significant, respectively). These changes reflected decrements in very low density lipoproteins alone. Despite similar increments in free fatty acid levels, (350% versus 270%, not significant) serum ketone body (beta-hydroxybutyrate and acetoacetate) concentrations increased 7-fold on the high fat diet compared to the high carbohydrate diet, P less than 0.001. The hyperketonemia of these men in response to the high fat, low calorie diet suggested the occurrence of a shift in hepatic free fatty acid metabolism toward ketogenesis rather than triglyceride synthesis. The associated decrease in the insulin: glucagon molar ratio raised the question of a possible role for these hormones in the adaptation.


Dimethylhydrazine-induced colon tumors in rats fed diets containing beef fat or corn oil with and without wheat bran. Male rats of the Sprague-Dawley strain were fed semisynthetic diets containing either 20% beef fat or corn oil with and without 20% wheat bran. Half of the animals received four weekly doses and the other half received eight weekly doses of dimethylhydrazine, 30 mg/kg, by intragastric intubation. The percentage of rats with tumors of the colon of all types was significantly higher in animals fed no bran than in those fed bran. Likewise, the percentage of rats with polypoid neoplasms of the colon was higher in rats fed no bran, but there was no significant difference in the percentage of rats with malignant tumors of the colon with respect to the feeding of bran. No significant differences were found between rats fed corn oil and those fed beef fat with respect to either the incidence or the kinds of colon tumors. Malignant tumors of the colon, causing death, occurred earlier in rats fed corn oil as compared to those fed beef fat. The percentage of rats with tumors of the colon and the numbers of tumors per tumor-bearing rat were significantly increased in rats given eight doses of dimethylhydrazine or compared to those given four.


Placental phosphatase of maternal serum: relationship to pregravid weight, prenatal weight gain, and infant birthweight in normal human pregnancies. Serum placental phosphatase (heat-stable alkaline phosphatase, HSAP) was measured in the following gravidae with normal weight gain: 71 normal weight normal subjects (NWN), 26 overweight normal subjects (OWN), and 28 underweight normal subjects (UWN); and in the following gravidae with excess gain (XsG), small gain (SmG), or weight loss (WtL): 11 NWN-XsG, seven NWN-SmG, seven OWN-SmG, two OWN-XsG, three OWN-WtL, and five UWN-XsG. The NWN regression equation between 31 and 40 weeks was: Y = 0.66X - 18.44. Overweight subjects' HSAP values were typically below and underweight subjects' values were above the regression line, providing that the weight gain was not less than normal in the overweight group or greater than normal in the underweight group. The average difference from the NWN regression line for each subject was designated "deltaHSAP." The differences between the mean delta HSAP values was statistically significant for: NWN versus OWN, NWN versus UWN, OWN versus UWN, NWN-XsG versus NWN-SmG, NWN-SmG, NWN versus NWN-XsG, and OWN versus OWN-WtL. The higher delta HSAP values were associated with relative caloric insufficiency, the lower values with relative caloric excess. A low degree of inverse correlation was found between infant birthweight and delta HSAP (r = -0.37; P less than 0.002).


Effect of maternal dietary amino acid pattern on rat offspring. The effect of lifetime feeding to gravid rats of diets containing different indispensable amino acid patterns on body and brain composition of the offspring was studied. Two groups of rats were fed, from weaning to delivery, either experimental diet B or diet I. Both diets contained the same amount of total nitrogen (3.14%), available lysine (0.4%) and "complete protein to total protein ratio" (22.5%), but whereas diet I provided an excess of indispensable amino acids over the amount of limiting amino acid, diet B supplied all of the indispensable amino acids in marginal amounts and in a rather well balanced pattern. The nitrogen content of diet B was matched to the nitrogen content of diet I by addition of a mixture of dispensable amino acids. A control group fed stock diet (C) was run simultaneously. Birth body weight, carcass nitrogen to water ratio, and brain weight of pups were significantly lower in B than in I. The figures for I were not significantly different from the controls. Brain DNA content in B was significantly lower than in C, but in I it was lower than for both B and C. Nitrogen to water ratio and brain DNA content of group B were low when compared to the standard curves for our colony; however, DNA content was normal for the degree of body development. On the other hand, in group I brain DNA was preferentially affected, as if body and brain maturity were dissociated.


Nutrient intake of treated infants with phenylketonuria. Growth, energy, and nutrient intake of 88 treated infants in the Collaborative Study of Children Treated for Phenylketonuria were evaluated longitudinally and compared to normative data and by treatment group. Growth parameters (height and weight) did not differ according to treatment group assignment, nor did they differ from normative data. Subjects in treatment group 2 had a significantly higher intake of phenylalanine than did subjects in treatment group 1. Differences in intake of other nutrients disappeared when intake was compared on an energy or body weight basis. Differences in intake by males and females also disappeared when compared on an energy and a body weight basis. From none to 10% of the subjects had energy intakes below two-thirds of the 1968 Recommended Dietary Allowances (RDA). Low individual energy intakes were more commonly found in the first and fourth quarters, and only during the first quarter of infancy did mean energy intake meet the RDA. From 48 to 80% of subjects had intakes of preformed niacin below two-thirds of the 1968 RDA. Few subjects had low intakes of protein, iron, or vitamin A, and intakes of all subjects were greater than 67% of the RDA for calcium, phosphorus, thiamin, riboflavin, and ascorbic acid. It is suggested from the data presented that a supplemental casein hydrolysate supplies adequate essential amino acids and nitrogen to support normal growth in infants when protein and energy intakes are fed at the levels described.


Phenylalanine-tyrosine deficiency syndrome as a complication of the management of hereditary tyrosinemia. A male infant with type I hereditary tyrosinemia developed a phenylalanine-tyrosine deficiency syndrome after receiving a synthetic diet which was low in these amino acids. The syndrome was characterized by growth failure, anorexia, lethargy, and hypotonia. Hypophenylalaninemia and hypotyrosinemia were discovered. The blood concentration of most other amino acids were increased. Supplementation of the patient's diet with phenylalanine and tyrosine resulted in a prompt and dramatic reversal of both clinical and biochemical abnormalities. Dietary therapy had no effect on the child's hepatic cirrhosis.


The impact of quality of diet and other factors on birth weight of infants. Quality of the mother's diet, expressed as a NAR index, was significantly correlated (r = 0.301, P less than 0.05) with birth weight of the infant. Eight women who reported that they had smoked during pregnancy had infants with significantly lower birth weights (P less than 0.01), gained less weight during prenatal care (P less than 0.01), and had a lower NAR index (P less than 0.10) than 32 women who said they did not smoke during pregnancy. The relationship of birth weight to 44 maternal and environmental factors was examined by multiple regression analysis to isolate variables significantly and independently related to birth weight. This analysis showed that birth weight of the infant was positively related to number of weeks of gestation, overall dietary quality, delivery weight of the mother squared, age of the mother squared, and number of previous pregnancies squared, and negatively related to weeks of gestation squared, iron and protein intake, age of mother, number of people in the household, and number of cigarettes smoked by the mother per day. Nine factors accounted for up to 86% of the variability in birth weight. Inclusion of quality of the diet improved the prediction equations by 6 to 8%.


Vitamin C, the common cold, and iron absorption. A sizable segment of the population was found to be taking large quantities of vitamin C to reduce the number or severity of upper respiratory infections. To determine the affect of this supplementation on iron balance, multiple radioiron absorption tests were performed in 63 male subjects. The increase in iron absorption from a semisynthetic meal was directly proportional to the amount of ascorbic acid added over a range of 25 to 1,000 mg. The ratio of iron absorption with/without ascorbic acid at these two extremes was 1.65 and 9.57, respectively. The relative increase was substantially less when the test meal contained meat. A large dose of vitamin C taken with breakfast did not effect iron absorption from the noon or evening meal. A telephone survey of 100 individuals revealed that 67 were taking supplemental ascorbic acid in doses ranging as high as 2 g daily. The average intake of supplemental ascrobic acid in this population was 280 mg daily. If taken only with breakfast, this level of supplementation would produce a nearly 2-fold increase in the amount of iron absorbed daily. If taken in divided doses with each mean, the increase in iron absorption would be more than 3-fold.


Studies of the elderly in Boston. I. The effects of iron fortification on moderately anemic peole. It has been reported that large numbers of elderly Americans are moderately anemic because of iron deficiency anemia. In the present study, information has been obtained concerning blood composition, health, and nutritional habits of 779 people over 60 years of age, institutionalized or free-living in the Boston area. This paper presents the results of their blood examinations. Two hundred twenty-one of the free-living people examined who showed hemoglobin levels between 9 and 12.9 g/dl agreed to participate in an iron fortification study. Two-thirds of them received iron-fortified grain products daily for 6 to 8 months. The rest received the same foods without added iron. At the end of the experimental period a marked increase in hemoglobin levels averaging 1.4 g/dl was observed in both groups. This appeared to be attributable to an undefined intervention effect; no measurable effects attributable to the iron fortification were observed. Three months of daily ferrous sulfate administration to those whose hemoglobin levels remained below 13 g/dl was without effect. Examination of the data obtained suggests that the cause of the moderately low hemoglobin levels initially observed was not occult bleeding or folic acid or iron deficiency.


Intestinal regulation of hepatic cholesterol synthesis: an hypothesis. The serum cholesterol level in man is predominantly dependent on the rate of endogenous synthesis. The liver is the main site of cholesterol synthesis and this activity is in turn intimately related to the ingestion of food. When no food is present in the intestine, as during periods of total parenteral nutrition, both normal individuals and patients with familiar hypercholesterolemia show a pronounced lowering of their serum cholesterol. The establishment of a portacaval shunt makes this a permanent change. This and other evidence lead us to postulate the existence of an intestinal factor capable of stimulating hepatic cholesterogenesis. The function of this factor would be to increase the synthesis of chol


Relationships between diseases and their etiological significance. All the results of a common cause will be related to one another. Consequently observed inter-relationships between diseases suggest some common causative factors. Certain characteristically western diseases have been shown to be related to one another in a number of different ways, including their order of emergence. This order with increasing age in western countries is the same as that of their emergence with the passage of time following the impact of western culture in developing countries. These observations are consistent with the hypothesis that they share some causative factor, and the removal of fiber from plant foods has been postulated to be such a factor.


A semilongitudinal study of food intake, anemia rate and body measurements of 6 to 24-month-old children in a Jerusalem community. Food intake of 120 infants at 6 and 12 months old and 110 toddlers at 18 and 24 months old in three neighborhoods in a Western part of Jerusalem was determined by the 24-hr recall technique. Mean caloric intake was below the recommended dietary allowance, protein intake was twice the recommended dietary allowance, iron intake was low, and a high rate of mild anemia was found. Anemia rate and severity were more pronounced in a poor neighborhood. The different rate of anemia in the three neighborhoods in partly explained by the differences in sources of iron. Food intake did not vary by social class or mother's education. Using the weight/height ratio 9 to 12% of the children were overweight and 3 to 7% were obese. The impact of Mother and Child Health clinics on feeding practice is emphasized.


Lack of correlation between thyroid size and body growth in an area of endemic goiter. There is conflicting information in the literature about the relationship between thyroid size and body growth in endemic goiter. This study reports  data from highland Bolivia where 408 children were examined for thyroid size, height, weight, head circumference, and academic performance, the latter as measured by teacher evaluation. The presence or size of goiter showed no consistent correlation with height, weight, or head circumference. School performance was significantly correlated with all other variables in boys and not in girls, but there are severe limitations involved in the use of school grades alone for assessment of intelligence. Height and weight were less than for normals in the United States at each age level, but did not differ from those of other Quechuan children in neighboring Peru who were reportedly nongoitrous. Our data support the conclusion that there is no clear relationship between thyroid size and body growth in areas of endemic goiter.


The complement-fixation test in the diagnosis of congenital toxoplasmosis. We present serologic results on 26 patients with congenital toxoplasmosis and on 22 of their mothers. The infection was severe (central nervous system involvement) in 12 patients, 12 had only ocular manifestations, and two were asymptomatic. The dye test results were positive on all specimens, and were positive at a titer of 1:1,024 or higher if collected from patients younger than 2 years of age. The complement-fixation test (CFT) results were positive on all specimens from patients younger than 2 years of age and on 69% of specimens collected from older patients. These serologic results are contrasted with those obtained on two control groups: (1) 46 uninfected infants followed up after birth because of substantial antibody titers in their mothers during pregnancy; and (2) 190 infants and children tested because toxoplasmosis was tentatively included in the differential diagnosis of the current illness. In both control groups the positive results on the CFT were limited almost exclusively to cord blood specimens or specimens collected during the first 2 weeks of life. Lower CFT titers in follow-up specimens suggested that the antibodies were maternal in origin. These two tests are valuable in providing laboratory support for the diagnosis of congenital toxoplasmosis, particularly the test for the comparatively short-lived complement-fixing antibody.


Arterial hypertension in infants with hydronephrosis. Report of six cases. Six infants with hydronephrosis developed hypertension during the first year of life. Five of them, all with proved or suspected acute urinary tract infection, had transient hypertensive episodes lasting for 7 to 17 days. One of the five infants, who had ureteropelvic junction obstruction and unilateral hydronephrosis, remained normotensive after nephrectomy. The sixth patient, with bilateral hydronephrosis and elevated peripheral vein renin activity, has had persistent hypertension. We discuss possible mechanisms underlying hypertension in these infants and suggest that young patients with hydronephrosis may be unusually predisposed to acute hypertensive episodes.


Bacterial meningitis. Limitations of repeated lumbar puncture. A retrospective chart review of 47 pateints with bacterial meningitis was conducted with respect to current guidelines used to define an adequate duration of antimicrobial therapy. Fifty percent (19/38) of patients had an inadequate response to therapy as defined by repeated lumbar puncture (LP) findings (ie, a cerebrospinal fluid (CSF) blood cell count greater than 50/cu mm and/or a CSF glucose value less than 45 mg/100 ml) at the end of therapy. No cases of relapse were seen. Persistent CSF abnormalities were not associated with the presence of complicating disease but were associated with prolongation of antimicrobial therapy beyond 13 days. Patients having persistent CSF abnormalities at the time antibiotics were stopped had a higher CSF blood cell count and a lower glucose value on initial lumbar puncture than those not having persistent abnormalities (P less than .001). These results emphasize the limitations of the role of repeated LP in defining an adequate duration of antimicrobial therapy.


A measles outbreak in a New England community. Perspectives. Between May 30 and June 29, 1974, 28 cases of measles occurred in schoolchildren in a residential New England community. The index patient probably contracted the disease on a school field trip 11 days before the onset of her illness. Of the other 27 cases, 15 had received live measles vaccine before age 1, and ten had no history of vaccination or disease. Four documented vaccine failures did occur in children vaccinated after age 1, but this was not an unusual number compared with the total number of vaccinees evaluated during the investigation. Control measures for susceptible persons including vaccination or modifying doses of immune serum globulin for exposure occurring more than 24 hours earlier. No additional cases of measles were reported for one month after the epidemic.


Encephalopathy with erythema infectiosum. A 9-month-old boy developed encephalopathy associated with the noset of erythema infectiosum, which resulted in permanent neurologic sequelae. This is the second reported case of encephalitis following erythema infectiosum and the first, to our knowledge with permanent sequelae.


Test strip meconium screening for cystic fibrosis. The Boehringer-Mannheim Corporation (BMC) strip test is extremely reliable in indicating an albumin content above 20 mg/gm of dried meconium. All infants born during one year in 14 Milwaukee area hospitals were tested. Of 16,224 newborns, two were diagnosed correctly as suffering from cystic fibrosis and two were missed. False-positive tests were obtained in 0.9% of infants (prematurity, melena, gastroschisis, and intrauterine infection). The strip test is, at present, the best available but not the perfect screening method for cystic fibrosis.


Hepatic hemangioendothelioma. Angiographic appearance and apparent prednisone responsiveness. A 6-month-old girl was seen because of multiple cutaneous hemangiomas, hepatomegaly, and failure to thrive. A liver scan with technetium Tc 99m sulfur colloid showed two filling defects in the left lobe. Diffuse nodular hepatic lesions characteristic of hemangioendotheliomas were disclosed by celiac angiography and confirmed by biopsy. Congestive heart failure, present in many infants with this syndrome, was not manifest. Prednisone was administered, 2 mg/kg, on alternate days. Liver size and cutaneous hamangiomas promptly regressed in size and "catch up" linear growth occurred during six months of treatment. Congestive heart failure did not develop. Sixteen months after treatment, liver size and a second hepatic scan were normal.


Osteomyelitis as a complication of umbilical artery catheterization. A retrospective study of 400 infants requiring umbilical artery catheterization performed from 1969 to 1971 at Indiana University Medical Center and Marion County General Hospital disclosed six cases of associated osteomyelitis. A similar review of approximately 550 cases of umbilical artery catheterization at Harbor General Hospital from 1972 to 1974 revealed an additional case. The causative organism was Staphylococcus aureus in each instance. Mean onset of symptoms following catheter removal was ten days. In all instances osteomyelitis occurred on the side ipsilateral to insertion and distal to the catheter tip. Postulated mechanisms include bacterial contamination of the catheter, thrombus formation, and local hypoxia from partial occlusion of the vessels by a large catheter.


Respiratory syncytial virus in early infancy. Circulating antibody and the severity of infection. Forty-one children less than 6 months of age from whom respiratory syncytial virus (RSV) was isolated were divided into groups of varying severity of illness. No relationship was demonstrated between severity of illness and the complement fixation titer to RSV in cord sera, acute sera, or convalescent sera. An increase in IgM level of greater or equal to 15 mg/100 ml in association with the RSV infection was seen more frequently in infants who had higher IgM levels in their acute sera than in infants who had lower levels.


Acute copper intoxication. Pathophysiology and therapy with a case report. We report a case of cupric sulfate intoxication in a child who had a serum copper level of 1,650 mug/100 ml. His course was accompanied by hemolytic anemia and renal tubular damage. We review the pathophysiology of copper metabolism and intoxication. We also review modes of therapy, with specific reference to the initial approach, using dimercaprol (BAL) and edetic acid rather than penicillamine.


Effect of three ophthalmic solutions on chemical conjunctivitis in the neonate. In an attempt to reduce chemical conjunctivitis after silver nitrate prophylaxis, three different ophthalmic solutions (sodium chloride, sterile water, and a boric acid-sodium borate solution) were used to irrigate the eyes immediately after prophylaxis in 450 neonates. Sterile water significantly reduced (P less than .02) the prevalence of chemical conjunctivitis when compared to the conventional sodium chloride rinse. A significantly greater prevalence of chemical irritation in low-birth-weight infants was also noted (P less than .02).


Diet in children heterozygous for familial hypercholesterolemia. Effects of a cholesterol- and saturate-poor, polyunsaturate-rich diet on plasma total and low-density lipoprotein (LDL) cholesterol levels were assessed in 23 children between the ages of 2 and 7 who were heterozygous for well-documented familial hypercholesterolemia. Sixteen of the 23 children, whose mean age at inception of diet was 4.8 years, sustained 10.5% and 11.3% reductions in total and LDL cholesterol levels after six months on diet (P less than .001). Total and LDL cholesterol levels were normal in only one of these children after six months. After one year on diet, three of 11 children had normal values for total and LDL cholesterol. Six of the 23 children, all 2 years old, had been previously maintained on low-cholesterol diets since age 1 or earlier, and three had normal cholesterol levels at the initial sampling for this study. After one year of follow-up in the study, the plasma cholesterol level was normal in five of these six children. Dietary therapy in the 2- to 7-year-old children heterozygous for familial hypercholesterolemia provided mean overall reduction of total and Ldl cholesterol levels between 6% and 15%, and appeared to be the most effective when instituted in children at ages 1 or 2.


A syndrome of microcephaly and cataracts in four siblings. A new genetic syndrome? We describe a syndrome of microcephaly, with extreme failure to thrive, (severe spasticity), kyphoscollosis, cataracts, and hip dysplasia in four siblings. The syndrome could be a new one, although it has several features resembling those described by Lowry et al. It is suggested that this syndrome is inherited as an autosomal-recessive condition.


Acute disseminated staphylococcal disease in childhood. From 1964 to 1974 we treated 15 children who had acute disseminated staphyloccal disease. The majority were previously-well males over 5 years of age. Thirteen of 15 patients had one or more cutaneous lesions characteristic of staphyloccal septicemia. Fifty percent of extracutaneous foci of staphylococcal infection were not detected on hospital admission and one third of these lesions were noted for the first time at autopsy. An absolute polymorphonuclear cell count of greater than 10,000/cu mm or an absolute band-form count of greater than 500/cu mm, or both, correlated with the presence of one or more inadequately treated sites of infection. These foci were responsible for bacteremia continuing after the initiation of antimicrobial therapy and for prolonged fever. The overall mortality was 27%; three of the four deaths occurred in patients with predisposing medical conditions. In addition to prolonged antimicrobial therapy, all patients should be evaluated carefully for the presence of occult metastatic sites of staphyloccal infection.


Sickle cell anemia in an American white boy of Greek ancestry. A 7-year-old American white boy of Greek ancestry had sickle cell anemia. The disease in this patient was not accompanied by painful episodes or recognizable hematologic complications, although he did demonstrate considerable delay in skeletal maturation. The patient sought medical attention for a dermatologic problem that was ultimately diagnosed as pityriasis rubra pilaris. To our knowledge, this is the first demonstrated example of sickle cell anemia in a white male described in the United States.


Sequential use of insulin and levodopa to provoke pituitary secretion of growth hormone. More than one method of stimulating human growth hormone (hGH) release is necessary to adequately evaluate the secretory capacity of pituitary somatotropes. In this study, sequential insulin-induced hypoglycemia (ITT) and oral administration of levodopa were used to study hGH release in 30 short normal children and adolescents and in five children with hypopituitarism. In the normal subjects, hGH levels greater than 5 ng/ml were achieved in 26 of 30 with the ITT and in 28 of 30 following administration of levodopa. Each of the normal children responded to at least one test. None of the children with hypopituitarism demonstrated hGH secretion during the study. We conclude that sequential administration of insulin and levodopa is a reliable, convenient, and safe method of assessing the release of hGH by the pituitary somatotropes during childhood.


Acute neonatal subdural hematoma following breech delivery. We describe two term infants born by complicated breech deliveries, each of whom suffered an acute subdural hematoma. Both infants required repeated subdural taps; in one case a parietal burr hole was needed. Despite stormy neonatal courses, follow-up examination of the first infant at 26 months showed him to be normal, and in the other only a mild left esotropia was found at 22 months. Acute neonatal subdural hematoma is rare, but symptoms and signs are distinctive and the condition is remediable; immediate recognition and treatment is important.


Total anomalous systemic venous drainage. Total drainage of systemic blood into the left atrium is an exceptional finding in absence of severe intracardiac malformation. In our patient, a boy 3 years and 4 months old, the left superior vena cava, the inferior vena cava, and the coronary sinus drained into the left atrium; there was no right superior vena cava, and the only associated anomaly was a large atrial septal defect. This rare form of cyanotic congenital heart disease was correctly diagnosed and successfully corrected.


Myocarditis in juvenile rheumatoid arthritis. Three children are described who have had myocarditis as part of juvenile rheumatoid arthritis (JRA). The diagnosis was established by the appearance of cardiomegaly or congestive heart failure or both in the absence of substantial pericardial effusion or extra cardiac cause. Myocarditis, in these cases, occurred on a background of severe, active systemic disease. No pathologic specimens from hearts of acute cases are available, but an autopsy specimen of one child who died after two months of treatment with high doses of steroids showed diffuse changes typical of the "dilated ventricle" type of cardiomyopathy. Treatment with high doses of adrenocorticosteroids has been rapidly successful in controlling the acute phase, while digoxin must be used with extreme care because of high incidence of toxicity to glycosides.


Effect of varying doses of chenodeoxycholic acid on bile lipid and biliary bile acid composition in gallstone patients: a dose-response study. In a dose-response study, a formulation of chenodeoxycholic acid (chenic acid) with complete bioavailability was fed at doses of 0, 250, 500, 750 mg for randomized 6-week periods to 13 patients with radiolucent gallstones. The proportion of chenic acid in biliary bile acids increased in direct relation to dose. Lithocholic acid also increased, but ursodeoxycholic acid showed no significant change. Bile saturation decreased with increasing dose, but response was variable and achieved significance only at 750 mg/day. Cholesterol saturation was negatively correlated with the proportion of chenic acid in biliary bile acids: When biliary bile acids contained greater than 70% chenic acid (and ursodeoxycholic acid), bile became unsaturated, on the average. The data suggest that a dose of at least 10-15 mg/kg may be necessary to obtain desaturation in many gallstone patients.


Visit to the gastroenterology INSERM units of France. On personal invitation, which is here gratefully acknowledged, of Professor C. Burg, the general director of the Institut National de la Santé et de la Récherche Médicale (INSERM), I had the privilege and pleasure to spend the month of October 1976 in France touring Gastroenterology INSERM Units. The INSERM is the French analog of the National Institute of Health (NIH) in the United States. The purpose of my visit was to see the organization and performance of these research units, compare them with what I know about the gastroenterology research laboratories in the United States, and exchange scientific information with the French researchers on the topics of mutual interest. Professor Serge Bonfils was chosen with his kind approval as the host of my visit. His INSERM Unit (number 10) at the Hospital Bichat in Paris, was elected as the "Host Unit" where my visit started and ended, and where the visits to the other units were organized. I owe him sincere gratitude for his guidance and help. After completing my tour, I was left with the feeling that what I had seen would be of interest to American gastroenterologists. Dr. John Farrar, the editor of this journal, encouraged me to review my tour and my impressions.


Hepatic abscess: ultrasound as an aid to diagnosis. Diagnostic ultrasound has two major advantages over conventional imaging methods. It is able to distinguish solid from cystic masses and it is safe, using no ionizing radiation. The new technique of grey scale ultrasonography allows visualization and improved delineation of internal organ structure. Ultrasonography and radionuclide liver scans are complimentary examinations because of technical limitations and diagnostic advantages inherent in each technique. Early, combined use of these two imaging techniques should lead to an earlier diagnosis of hepatic abscess.


Normal sugar uptake in vitro by small-bowel biopsies from a patient with cholera. We have investigated the 3-O-methyl-D-glucose (3MG) absorption by jejunal biopsies obtained from a patient with cholera. The absorption of 3MG (as measured from the determination of intracellular accumulation of this sugar) was found to occur against a concentration gradient and to be a saturable process that follows Michaelis-Menten kinetics. There was no appreciable difference in 3MG absorption between the biopsies from the normal volunteers and those from the patient with cholera.


Eosinophilic ascites. A case report and review of the literature. Hypereosinophilic syndrome is a multisystem disease with progressive valvular dysfunction as a prominent feature. Ascites has not been recognized as a part of this syndrome. This paper presents a patient with hypereosinophilic syndrome who initially developed ascites and was recognized to have cardiac disease. The differential diagnosis of eosinophilic ascites is discussed.


Functional evaluation of colon transplants used in esophageal reconstruction. Studies were performed on the mechanical activity of iso- and antiperistaltic colon segments used to replace the esophagus. Transplants were challenged with a semiliquid bolus and/or a 0.1 N HCl solution, considered as common stimuli for an in situ esophagus, and the mechanical activity was investigated by means of synchronized manometric and cinefluorographic recordings. Basal activity of the interposed colon was limited to occasional monophasic waves of the segmenting type; the acid solution and the semiliquid bolus constantly elicited a peristaltic motor response transporting the contents to the gastric fundus or, in antiperistaltic colon, from the distal to the proximal part.


The effect of coherin on the basic electrical rhythm of the dog ileum in vivo. Coherin, a substance isolated from the bovine posterior pituitary gland exists as a complex which is dissociated to yield at least two distinct enteroactive polypeptides, coherin A and B, and a third having little or no activity, coherin C. The effects of intravenous injection of nondissociated coherin (coherin G-25), coherin A, coherin B, vasopressin, and normal saline solution on the BER of the ileal Biebl loop in fasting dogs were investigated. The BER patterns in preinjection and postinjection periods were compared for each substance. The effects on the BER of each substance were compared with that of saline. Monopolar recordings were made from six electrodes 5 mm apart inserted into the ileal musculature of the Biebl loops. Coherin A significantly altered the electroenterograms in two ways. It increased phase locking in the ileal BER of the fasting dog and increased the amount of caudad BER propagation.


Effects of age on lactose malabsorption in Oklahoma Native Americans as determined by breath H2 analysis. Breath H2 excretion was used to determine lactose malabsorption in 30 health females and 30 healthy males between the ages of 3 and 64 yr who were at least 7/8 Native American. The test meal consisted of 5 ml reconstituted nonfat dry milk (0.25 g lactose) per kg of body weight. On the basis of breath H2 tests in 15 control subjects with normal oral lactose tolerance tests, a response factor of 20 ppm was selected as the upper limit for lactose absorbers. Of the 60 subjects in the study group, 36 (60%) were classified as lactose malabsorbers since they had a response factor of 20 ppm or greater of breath H2. Only 3 of 20 children (15%) who were under the age of 12 yr were nondigesters of the small lactose dose used in this study. Approximately 82 percent (82.5%) of subjects who were 13 yr and older were lactose malabsorbers. Adolescence appears to be the period in which malabsorption of lactose becomes evident in Native North Americans.


Acid and gastrin levels after bombesin and calcium infusion in patients with incomplete antrectomy. In 17 patients with postoperative recurrent peptic ulcer, incomplete antrectomy (I.A.) was found by endoscopic biopsies in 5. No evidcence of I.A. was found in the remaining 12 patients. Gastric acid output and gastrin levels were measured in basal conditions and following a calcium I.V. infusion (4 mg/kg hr of Ca++ over 4 hr) and a bombesin (BBS) I.V. infusion (15 ng/kg min over 90 min). Basal gastrin levels were significantly differnt in the two groups of patients: BBS infusion augmented significantly serum gastrin levels in all patients with I.S., while BBS infusion had no significant effect on serum gastrin levels in the group of patients without I.A. Acid output following BBS infusion showed a pattern similar to the pattern seen for gastrin. Calcium infusion augmented gastric acid secretion and gastrin levels in the patients with I.A.; however, the response to calcium could not clearly separate in all instances patients with I.A. from patients without I.A. It is concluded that the "BBS infusion test" may be heplful in the diagnosis of I.A. in patients with postoperative peptic ulcer.


Diagnostic value of biopsy, guided lavage, and brush cytology in esophagogastroscopy. In a prospective study 96 patients with esophageal and gastric lesions were investigated by multiple endoscopic biopsy, brush cytology, and guided lavage cytology. The aim was to evaluate the diagnostic accuracy of each of these methods in a prospective study. 50 malignant and 46 benign lesions were found. The final diagnosis was proven by operation or autopsy in 53 cases, by multiple endoscopic follow-up in 31, and by clinical control in 8. No follow-up was possible in 4 patients. The malignant lesions were diagnosed by multilple biopsy in 86.0%, by brush cytology in 84.0%, and by lavage cytology in 50.0%. The diagnostic yield of lavage cytology was thus significantly lower (P less than 0.01). It is concluded that a combination of multiple biopsy and brush cytology is the most valuable aid in endoscopic diagnisis of esophageal and gastric malignancy with a diagnostic accuracy of 96%.


Relationship between disposal rate of exogenous gastrin and sensitivity to stimulation of acid secretion by this hormone in dogs. The effect of graded doses of synthetic human gastrin and pentagastrin on gastric secretion from the innervated and denervated stomach was measured in dogs. The circulating levels of gastrin during the infusion of this hormone were also estimated. The increase in gastrinemia for a fixed dose of exogenous gastrin differed from dog to dog. The dose for half-maximal response to gastrin was negatively correlated with the observed increase in serum gastrin. This suggests that the disposal rate of gastrin influences the calculated sensitivity of the parietal cells to this hormone. In the gastric fistula and in the pouch, maximal acid responses for gastrin and pentagastrin were linearly correlated, but doses for half maximal responses were not. This indicates that step-dose infusion of pentagastrin may be used to estimate the maximal acid response to gastrin, but it is not proven that such a test is useful to estimate the sensitivity of the parietal cells to gastrin in individual dogs.


Inflamed duodenal diverticulum. Preoperative radiographic diagnosis. The sixth reported case of duodenal diverticulitis diagnosed preoperatively is presented. A review of the literature indicates that most duodenal diverticula are asymptomatic and require little special management. Rarely, acute inflammation can develop, and duodenal diverticulitis must be included in the differential diagnosis of all acute upper abdominal conditions, especially in the radiographic differential of emphysematous cholecystitis and retroperitoneal emphysema.


The usefulness of stool screening for diagnosing cholelithiasis in acute pancreatitis. A description of the technique. Screening stools for gallstones in patients with acute pancreatitis has been found to be a valuable diagnostic procedure in clinical practice. It is particularly helpful to know that a patient with pancreatitis has gallstones and, therefore, the disease is probably caused by the passage of these stones. A detailed description of the technique employed for stool screening is presented. The procedure was applied in 51 patients recovering from an attack of gallstone pancreatitis,in 51 control patients with known gallstones disease but without acute pancreatitis, and also in 10 patients with acute alcoholic pancreatitis Gallstones were found in the feces in 47 of the 51 patients with gallstone pancreatitis (92.1%), in only 6 of the 51 control cases (11.8%) (chi square = 62.84; P less than 0.0001), and in none of the 10 patients with alcoholic pancreatitis. In the group with gallstone pancreatitis, the finding occurred within 10 days after the attack. Oral cholecystography was also accomplished an average of 12.7 days after the attack in 38 of the 61 pancreatitis patients (28 with biliary and 10 with alcoholic pancreatitis). In 27 of the 28 patients with gallstone pancreatitis (96.4%) and in 4 of the 10 patients with alcoholic pancreatitis, radiologic evidence of cholelithiasis was found. There were 19 patients with gallstone pancreatitis who did not have a cholecystogram accomplished because of jaundice, recurrent pancreatitis, previous cholecystectomy, and pregnancy. These results suggest that screening stools is as accurate and reliable as cholecystography for the diagnosis of gallstones in individuals with pancreatitis. In addition, this method has three definite advantages over cholecystography: There are no contraindications; it requires no special equipment or personnel; and it can be used much earlier than cholecystography in patients recovering from an attack of acute pancreatitis. Screening stools for gallstones should be considered an elective diagnostic procedure for current clinical application.


Distribution and persistence of hepatitis B surface antigen and antibody in a Melanesian population. The population of Graciosa Bay, Santa Cruz, British Solomon Islands Protectorate, was tested for HBsAg and anti-HBs in 1973 and 1974. Both the antigen and antibody occurred more often in males, presumably due to a higher exposure rate. None of 28 infants under one year of age had antigen and only one of 50 individuals under two years (2%) did. The prevalence of antigenemia was higher in older children and did not decline with increasing age. This pattern is contrasted to that found in other populations which is characterized by onset during the first year and a decrease in prevalence in older age groups. The ratio of antigenemia prevalence to that of antibody is significantly higher in the population under six years of age (p less than 0.01), indicating that younger infected people tend to be asymptomatic carriers while older individuals tend to have produced antibody. Three of 28 individuals with antigen detectable by immunodiffusion in 1973 had lower levels, detectable only by reversed passive hemagglutination after one year. The age specific prevalence of anti-HBs increases to a peak of 34% in the 15-19 year age group and declines thereafter.


Biliary function studies in patients with celiac sprue. Eleven patients with celiac sprue were studied. Biliary function in the basal state and gallbladder response to perfusion of the small intestinal mucosa with magnesium sulfate was assessed. It was shown that bilirubin output in basal conditions is decreased in these patients and that magnesium sulfate does not stimulate gallbladder contraction. In addition it was shown that in 4 of the 11 cases studied there was a complete lack of bile reaching the duodenum in the basal state as well as in 7 of 11 cases in the digestive period. That gallbladder function was intact was shown by the normal response to intravenous CCK-PZ administration, and the patency of the common bile duct was demonstrated by intravenous cholangiography. Thus the already impaired fat absorption in celiac sprue is magnified by the lack of bile delivery, and this is probably due to an alteration in the synthesis or release of endogenous CCK-PZ.


Limited family clustering of hepatitis B surface antigen in a Melanesian population. The entire population of Graciosa Bay, Santa Cruz, Solomon Islands, was tested for hepatitis B surface antigen (HBsAg) by reverse passive hemagglutination and antibody to HBsAg (anti-HBs) by passive hemagglutination. Analysis of the distribution of HBsAg in relatives of HBsAg carriers and non-carriers showed clustering only in children of carrier mothers. Similarly, there was no clustering of total exposure as measured by serologic tests except in children of carrier parents primarily due to the antibody and antigen of children of carrier mothers. This distribution pattern is probably due to cultural and environmental factors which increase exposure between HBsAg carriers and people who are not related to them and also reduce the amount of contact between siblings.


Epidemiology of hepatitis B in two Alaska communities. In 1973, epidemiologic and serologic data related to hepatitis B infection were collected from the residents of two remote Alaskan Eskimo villages located in an area of high hepatitis incidence. A total of 418 sera were tested by solid-phase radioimmunoassay for heaptitis B surface antigen (HBsAg) and antibody to that antigen (anti-HBs). The overall infection prevalence of 54.8% in the two villages included a 13.9% prevalence of HBsAg and a 40.9% prevalence of anti-HBs. Families containing an individual with HBsAg had significantly higher infection prevalence than those without an antigen carrier. Larger households had higher proportions of infected members than smaller households. The data suggest that efficient transmission of hepatitis B virus occurs within the household setting in these villages by other than classically established parenteral routes.


Intensive hepatitis surveillance in Minnesota: methods and results. After a large foodborne outbreak of hepatitis A in April 1974, the Minnesota Department of Health attempted to improve ongoing hepatitis surveillance with a system based on 1) a large centralized blood bank, which reports results of tests for hepatitis B surface antigen (HBsAg) on suspected hepatitis patients; 2) private physicians, who are encouraged to report cases; and 3) an epidemiology aide, who contacts all detected patients and their physicians. During the first year of this system, we detected 932 cases (24.5 per 100,000), a threefold increase over previous years, and obtained detailed epidemiologic data on each case. Although physicians diagnosed 61% of these cases as hepatitis A (or non-B) and 39% as hepatitis B, they tested only 53% of all patients for HBsAg. Sixty-seven per cent of the tested patients were HBsAg-positive, but only 17% of the untested patients had illnesses diagnosed by physicians as hepatitis B. This suggests that many patients with clinically-diagnosed viral hepatitis who are not tested for HBsAg may be erroneously diagnosed by physicians as having non-B hepatitis. Thirty-three per cent of HBsAg-positive patients with known occupations, not including housewives and students, worked in meidcally-related occupations. For 51% of the HBsAg-positive patients, we could not identify recent parenteral exposure to hepatitis B.


Foodborne hepatitis A infection: a report of two urban restaurant-associated outbreaks. The cities of Portland, Oregon, and Buffalo, New York, each experienced a restaurant-associated foodborne outbreak of viral hepatitis type A during 1975. Although there were several food handlers ill with viral hepatitis A in each of the restaurants involved, each outbreak was the apparent result of food contamination by a single food handler. In the Buffalo outbreak, food contamination was documented to have occurred for a brief period of time six days prior to onset of any symptoms in the index case. These outbreaks point out the uncommon occurrence of food contamination by individuals ill with type A viral hepatitis, the usefulness of two types of food questionnaires in identifying the vehicle(s) of transmission, and the apparent lack of benefit of widespread immune serum globulin administration as a control measure in this setting.


The e antigen and vertical transmission of hepatitis B surface antigen. The relationship of e antigen (eAg) and its antibody (anti-e) to vertical transmission of hepatitis B surface antigen (HBsAg) from chronic asymptomatic HBsAg carrier women to their children was investigated in Taiwan. Sera from 20 of the 62 women studied were positive for eAg (32%); serum from only one woman was positive for anti-e (2%). A total of 85% of the babies born to eAg positive mothers became HBsAg carriers, while only 31% of the babies became carriers when the mother was eAg negative. Maternal e antigenemia correlated with a high HBsAg titer, and both parameters were equally good predictors of vertical transmission.


Hepatitis and hepatitis B-antigen in Greenland. II: Occurrence and interrelation of hepatitis B associated surface, core, and "e" antigen-antibody systems in a highly endemic area. The distribution of hepatitis B surface antigen and antibody (HBsAg and anti HBs), hepatitis B core antibody (anti-HBc), and the heaptitis B associated "e" antigen-antibody system (HBeAg and anti-HBe) were studied in three areas in Greenland previously shown to be endemic for hepatitis B. Overall prevalence of HBsAg and anti-HBs ranged from 47 - 81%, thus confirming the existence of a hyperendemicity of the hepatitis B agent in some polar areas. Anti-HBc occurred closely correlated to HBsAg and anti-HBs but appeared to be a less sensitive indicator of previous infection. HBeAg and anti-HBe were found in HBsAg-positive sera only. The presence of HBeAg correlated to a high titer of HBsAg and to young age and it occurred more frequently in east coast than in northwest coast Greenlanders. The "e"-antibody in contrast prevailed in old age groups and in sera with a low titer of HBsAg.


The Lutheran and secretor loci: genetic linkage analysis. Linkage analysis of Lu and Se and 31 other loci indicate that Lu:Se are not closely linked to ABO, ACP1, Co, Do, Est.D,Fy, GC, Gm, GLO:HLA, GPT, Inv, Jk,K,MN,P,PGD,PGM1, Rh,Sc, UMPK OR Yt. Lod scores for 18 families informative for Lu:Se gave no evidence for sex differentiation in recombination fraction: theta for males was 0.07, and for females, .08.


Characterization of beta-D-N-acetylhexosaminidase isoenzymes in man-Chinese hamster somatic cell hybrids. A series of man-Chinese hamster hybrids were investigated with the use of an anti-Chinese hamster hexosaminidase serum, a specific anti-human hex A serum and an anti-human hex B serum. The expression of human hex A was found to be dependent on the presence of hex B. A heteropolymeric molecule is formed independently of hex B, which consists of Chinese hamster and specific hex A moieties. It has an electrophoretic mobility nearly identical to hex A. A relationship between the absence and presence of the heteropolymeric molecule, mannosephosphate isomerase (MPI), and pyruvate kinase (PK-3), assigned to chromosome 15, was established. With respect to the two locus subunit model, the gene coding for the alpha subunit, specific for hex A, has been localized on chromosome 15.


G6PD Ube, a glucose-6-phosphate dehydrogenase variant found in four unrelated Japanese families. A total of 6,120 Japanese males were screened for glucose-6-phosphate dehydrogenase deficiency (G6PD). Five cases with the deficiency were discovered. Two of them and an additional two cases have the same variant, G6PD Ube, characterized by moderate enzyme deficiency, fast moving enzyme activity on electrophoresis, high Ki Nadph, utilization of substrate analogues, kinetics, pH optima, and stability. This variant was distinguished for G6PD A- and from other Oriental variants by biochemical parameters. Differences in the frequency and type of the variants between southern Asia and Japan, suggest that the Japanese who have been isolated on islands where malaria is not endemic, may have developed their own variant traits.


Comparison of GdA and GdB activities in Nigerians. A study of the variation of the G6PD activity. We report a comparison between G6PD enzyme activities in lysates from GdA and GdB Nigerian healthy males. We confirm the previously reported higher mean activity of G6PD B. An analysis of the enzyme activity variation has been performed: the relative amount of variation found to be associated with this polymorphism is about 8%. A comparison has been made with other genetic polymorphisms.


A computer-based videodensitometric system for studying banded human chromosomes illustrated by the analysis of the normal morphology of chromosome 18. A computer-based, high-resolution, high-speed system is described for the digitization of television images of human G-banded chromosomes, on-line directly from a microscope. The digitized data are processed by a computer to determine the total length and centromere index of individual chromosomes and to obtain an integrated density profile representing the band pattern. The density profile is reduced by the computer to a series of dark and light bands, each with a defined position, width, and density. The results are displayed by the computer on a television monitor in a form that simulates routine laboratory preparations and that allows cytogenetic inspection. The system is easy to operate, and it includes a wide range of options for operator interaction to ensure reliability. The results of the computer analysis of the no. 18 chromosomes from five cells from each of 10 different persons demonstrated the usefulness of the system for detecting, measuring, and analyzing individual bands in human populations and its application to establishing band patterns of chromosomes in different states of contraction.


Commingling in distributions of lipids and related variables. In a sample of nearly 8,000 Japanese males, the distributions of casual cholesterol and triglyceride, hematocrit, glucose, uric acid, diastolic blood pressure, and weight (covariance adjusted) could not be normalized by a power transform and were significantly better fitted by a mixture of distributions. The evidence for admixture was nonsignificant for systolic blood pressure, significant but unimpressive for height and weight, and strong for the remaining variables. The minor component corresponded to high values, in low frequency except for triglyceride and glucose. These results favor an interpretation of elevated levels in terms of distinct entities, genetic or environmental or both, rather than cumulative small effects only. These entities appear to be megaphenic (i.e., with effects exceeding one phenotypic standard deviation). Consequences of this hypothesis are discussed.


Correspondence analysis of HLA gene frequency data from 124 population samples. Correspondence analysis, a variant of principal components analysis, is used to interpret and compare gene frequencies of the HLA system for 124 samples from different populations studied in the Fifth and Sixth International Histocompatibility Workshops. The major advantage of this analysis is that populations and HLA genes are represented simultaneously with respect to the same axes in multidimensional space. This permits the visual interpretation of genetic differences between populations, the relative participation of each gene in the dispersion, and the correspondence between populations and genes. By this method a clear separation of ethnic groups in the world is obtained. Furthermore, within Europe the separation of samples from different countries is concordant with their geographical distances. The HLA system appears sufficiently polymorphic to define a population by its gene frequencies.


A genetic and epidemiologic study of periodontal disease in Hawaii. II. Genetic and environmental influence. In order to determine the relative influence of genetic and environmental factors in periodontal disease, path analysis has been applied to 241 nuclear families. Common family environment was represented by an index. The data failed to detect significant heritability, and common family environment proved to be a major determinant in the variation of periodontal health.


Exclusion of chromosomal mosaicism: tables of 90%, 95% and 99% confidence limits and comments on use. Tables specifically tailored to the exclusion of cytogenetic mosaicism at three confidence levels are presented. The consequences of the assumption of independence in application of the binomial theorem to this question are discussed. The tables are most applicable to the number of cells evaluated from cultures in which all mitoses are arrested in the first in vitro division. For long-term cultures the tables are conservatively applicable to the number of separate colonies evaluated. If n cells have been evaluated from phytohemagglutinin stimulated peripheral blood after 72 hr in cultures, the tables are applicable to between n/2 and n cells.


Frequency of an electrophoretic variant of hair alpha keratin in human populations. A previously reported electrophoretic variant in hair keratin was looked for in a number of different racial groups. Only Caucasian samples showed the variant with the exception of one American black and one American Indian where Caucasian admixture is likely.


Lupus nephritis. Clinical course as related to morphologic forms and their transitions. An intensive study of the course of lupus nephritis has been undertaken in 88 patients in whom strict morphologic criteria were utilized in classification. All were treated with steroid, and 17 received cytotoxic drugs in addition. Focal proliferative lupus nephritis generally follows a benign course except in the occasional instances when transition to the diffuse proliferative or membranous forms occurs. Membranous lupus nephritis, when characterized by persistent nephrotic syndrome, leads slowly to renal failure, but this progression is aborted in the one-third in whom remission of the nephrotic syndrome can be achieved. A fatal outcome occurs within five years in the majority of those with diffuse proliferative lupus nephritis and the nephrotic syndrome, often in association with necrotizing renal vasculitis, severe hypertension and accelerated renal failure. A small number with the diffuse proliferative form have a remission and then show only mesangial abnormalities, usually, however, with the appearance of glomerular sclerosis. Progressive glomerular sclerosis is observed in some patients and may be a sequel of the remission of the diffuse or focal proliferative lesions, or it may represent still another form of lupus nephritis. Mesangial immune deposits with or without proliferation, at times in the absence of clinical renal disease, are observed early in the course of systemic lupus erythematosus (SLE) and may proceed to the diffuse proliferative or membranous forms. The present observations serve to emphasize the importance of strict morphologic classification in the comparison of different treatment regimens for lupus nephritis. In view of the grave prognosis of established diffuse proliferative lupus nephritis, which probably evolves from a mesangial involvement common to all patients with SLE from its onset, early therapy may be the key to the management of lupus nephritis.


Survival of a patient with intestinal anthrax. A patient with intestinal anthrax, the first documented surviving patient to be described in detail, presented with an acute condition within the abdomen. Intestinal anthrax should be considered in the differential diagnosis of abdominal conditions in areas in which anthrax is prevalent, especially when a history is available of ingesting putrid or improperly cooked meat. Clinical and therapeutic details are given as a guide in future cases.


Echocardiographic appearance of ruptured aortic cusp. Serial echocardiograms of a patient with enterococcal endocarditis and aortic insufficiency suggested the presence of vegetations on the aortic valve with progression of the lesion to frank prolapse of an aortic valve cusp. At surgery, the patient was found to have a flail noncoronary cusp to which an 8 mm vegetation was adherent. Anatomic correlations are presented, and a possible mechanism for the unusual echographic findings is discussed.


Subclinical chronic pancreatitis in type I hyperlipoproteinemia. Severe pancreatic exocrine insufficiency was demonstrated in a 41 year old man with familial type I hyperlipoproteinemia (fat-induced hyperlipemia). Plasma triglyceride concentration failed to increase significantly with increased dietary fat intake, and fecal fat excretion was markedly increased. Indices of intestinal function were normal. Pancreatic enzyme therapy resulted in reduced fat excretion and increased plasma triglyceride concentration. Secretin stimulation tests revealed impaired duodenal fluid volume, bicarbonate and pancreatic enzyme responses. Insulin-dependent diabetes mellitus had been diagnosed three years earlier. No attacks of acute pancreatitis had occurred in the preceding 20 years, and it is suggested that pancreatic damage may have resulted from repeated subclinical pancreatic insults due to elevated plasma lipid levels. This report is the first to indicate that pancreatic exocrine insufficiency may occur as a late complication of hyperlipemic disorders in the absence of recurrent acute pancreatitis. Steatorrhea may not be apparent because of therapeutic restriction of dietary fat, and the first manifestation of pancreatic exocrine disease may be an amelioration of fat-induced hyperlipemia.


Clinical and roentgenographic spectrum of pulmonary tuberculosis in the adult. In order to define the roentgenographic manifestations of pulmonary tuberculosis in the adult, we reviewed a 12 month experience with newly diagnosed patients with active pulmonary tuberculosis in two Boston hospitals. Of 88 patients, 30 (34 per cent) presented with roentgenographic manifestations other than those associated with "usual" postprimary disease. At least 12 patients (13.5 per cent) had primary tuberculosis, including two subjects over 60 years of age. Six patients (6.8 per cent) had disease confined to the lower lung fields, eight patients (9 per cent) had tuberculomas and four (4.5 per cent) had miliary tuberculosis. Twenty per cent of the patients were totally asymptomatic. With the shift of tuberculosis care to community hospitals, knowledge of the varied roentgenographic manifestations is of increasing importance for the practicing internist.


Airway function in sarcoidosis.

Airway function in sarcoidosis. Airway function was studied in 18 patients with sarcoidosis, aged 18 to 49 years. Eleven of the patients were smokers. All patients had the characteristic functional changes of restrictive lung disease: decreased lung volumes and single breath diffusing capacity, and increased static transpulmonary pressures. Abnormal airway function was demonstrated in every patient by at least one test, and nearly always by multiple tests. Specific airway conductance was abnormally low in two patients. The ratio of the 1 second forced expiratory volume to the forced vital capacity was decreased in six patients. Frequency dependence of dynamic compliance was demonstrated in eight patients. The ratio of closing volume to vital capacity was increased above age-corrected predictions in all but two patients. Upstream airway resistance was abnormally increased in 16 of the patients. These results suggest that airway dysfunction is not uncommon in sarcoidosis.


Therapy of the idiopathic nephrotic syndrome with alternate day steroids. Eighty-one adult patients with the idiopathic nephrotic syndrome were treated with prednisone, 60 to 120 mg, on alternate days. Treatment was continued with diminishing drug doses for up to 10 years. Biopsy specimens were categorized as showing lipoid nephrosis 36 per cent, focal sclerosis 12 per cent, diffuse proliferative 22 per cent and membranous nephropathy 30 per cent. Patients with systemic causes of the nephrotic syndrome were excluded. Proteinuria decreased to normal or to less than or equal to 3 g with a greater than or equal to 50 per cent decrease from base line in 83 per cent of the patients with lipoid nephrosis, 30 per cent of the patients with focal sclerosis, 50 per cent of the patients with diffuse proliferative nephritis and 71 per cent of the patients with membranous nephropathy. Improvement occurred in those with focal sclerosis, diffuse proliferative nephritis and membranous nephropathy only after prolonged treatment (14 to 15 months). Stable or improved renal function occurred in 97 per cent of those with lipoid nephrosis, 50 per cent of those with focal sclerosis, 73 per cent of those with diffuse proliferative nephritis and in 83 per cent of those with membranous nephropathy. Death or dialysis occurred in 12 per cent of the patients, and complications coincident with treatment occurred once every 12 patient years. Compared to other series of patients with the idiopathic nephrotic syndrome, therapy of our patients with prolonged alternate day steroids resulted in (1) decreased protein excretion, (2) maintenance of good renal function and (3) decreased number of complications of therapy.


The effect of ascorbic acid on uric acid excretion with a commentary on the renal handling of ascorbic acid. Under spontaneous conditions in man and dog, very little ascorbic acid is excreted in urine. Ascorbic acid clearance (C ascorbic acid) is promptly augmented when plasma ascorbic acid is increased by intravenous injection. No net tubular secretion of ascorbic acid is demonstrable in either man or dog when plasma ascorbic acid is elevated to levels as high as 12 mg/100 ml in man, and 28 mg/100 ml in the dog. Nevertheless, both in men and the Dalmatian dog, when the glomerular filtration rate (GFR) is decreased, excreted ascorbic acid in relation to the amount filtered is exaggerated so that C ascorbic acid:GFR approaches unity. It is possible that secreted ascorbic acid is masked under ordinary circumstances, with a more significant contribution of secreted ascorbic acid to total urinary ascorbic acid becoming apparent under conditions of low GFR. In man, when the plasma ascorbic acid level is raised to above 6 mg/100 ml, C urate:GFR rises from control value of 0.081 +/- 0.020, to 0.116 +/- 0.026. In both mongrel and Dalmatian dogs an effect of ascorbic acid on urate excretion is not conclusively shown. The uricosuric effect of ascorbic acid in man may be due to competition with uric acid for renal tubular reabsorptive transport. The difference in the metabolism of ascorbic acid in the dog as compared to man may help account for the inconsistent effect of ascorbic acid on uric acid excretion in the dog.


Serum myoglobin in myocardial infarction: the "staccato phenomenon." Is acute myocardial infarction in man an intermittent event? When serum was sampled frequently and soon after acute myocardial infarction, myoglobinemia was extremely common, occurring in 12 of 13 selected patients. Myoglobin first appeared in the serum within a few hours after infarction, but not consistently earlier than creatine phosphokinase. The peak level of serum myoglobin was reached appreciably earlier than the peak values of serum creatine phosphokinase activity. Time of earliest myoglobin appearance in the serum, peak level of myoglobin measured, and duration of detectable myoglobin release all correlated poorly with clinical and biochemical estimates of severity of myocardial infarction. There was no correlation between myoglobin levels and infarct size as estimated from creatine phosphokinase kinetics. Myoglobin appeared in the serum in multiple short "staccato" bursts, or episodes, often lasting only one to two hours. The hypothesis is suggested that the pattern of myoglobin appearance is a reflection of the episodic nature of acute myocardial infarction. Although isolated myoglobin determination may not be useful at present, for quantification of total myocardial damage, its pattern of release may be a sensitive marker for studying the time course of infarction, and may be useful to evaluate therapeutic interventions designed to interrupt an ongoing syndrome of myocardial necrosis.


Systemic lupus erythematosus within the first two decades of life. Forty-nine patients with systemic lupus erythematosus (SLE) during childhood and adolescence presenting over a period of 17 years were followed during treatment with prednisone and azathioprine. The average period of follow-up was 5.7 years. Detailed analyses of clinical parameters of renal function and sequential changes in glomerular abnormalities by percutaneous renal biopsy are reported. Therapy was directed towards normalizing the results of urinalysis and renal function, eliminating proteinuria and maintaining normal serology (normal serum complement and negative antiDNA titers). The 10 year survival of the entire group was 86 per cent. A survival of 73 per cent and 87 per cent over this interval in patients with diffuse and focal proliferative lupus nephritis, respectively, was achieved. The major cause of mortality in this series was infection. It appears that intensive observation and monitoring of serologic parameters in SLE, along with aggressive steroid and immunosuppressive therapy, lead to a prognosis in SLE more favorable than previously reported.


Male pseudohermaphroditism due to steroid 5-alpha-reductase deficiency. A new inherited form of male pseudohermaphroditism has been investigated in a pedigree of 24 families with 38 affected males. At birth, the affected males (46 XY) have a clitoral-like phallus, bifid scrotum and urogenital sinus. The testes are in the inguinal canals or labial-scrotal folds. The Wolffian structures are normally differentiated; there are no Mullerian structures. At puberty a muscular male habitus develops with growth of the phallus and scrotum, voice change and no gynecomastia. The subjects have erections, ejaculations and a libido directed towards females. They have decreased body hair, a scant to absent beard, no temporal hair line recession and a small prostate. Testicular biopsy reveals a normal testis. The mean plasma T levels in affected adults are significantly higher, and the mean plasma DHT levels are significantly lower when compared to those in normal subjects. The plasma T:DHT ratios range from 35 to 84 compared to 8 to 16 in normal subjects. After the administration of hCG, the T:DHT ratios in affected male children range from 74 to 162 compared to 3 to 26 in the control subjects. In affected adults, mean plasma LH and FSH levels are significantly higher than in normal subjects. In the affected subjects, the metabolic clearance rates of T and DHT are normal, but the conversion ratio of T to DHT is less than 1 per cent. The endogenous mean urinary E:A and E-OH:A-OH ratios, and the urinary E:A and E-OH:A-OH ratios after the infusion of radioactive T are significantly higher than in normal males. Inheritance is autosomal recessive with some sibling sisters showing the same biochemical defect, and obligate carrier parents showing an intermediate defect. These data support our thesis that the defect in these male pseudohermaphrodites is secondary to decreased steroid delta 4-5 alpha-reductase activity. The affected subjects provide a clinical model for delineating the roles of T and DHT in sexual differentiation and development. This entity also demonstrates an inherited disorder of steroid metabolism in which the basic enzyme deficiency resides in the target tissues.


Sudden death in the year following myocardial infarction. Relation to ventricular premature contractions in the late hospitals phase and left ventricular ejection fraction. Both depressed left ventricular ejection fraction and ventricular arrhythmias have been associated with a poor prognosis following acute myocardial infarction. To assess the relative role of each of these parameters in predicting mortality in the early period after hospitalization for myocardial infarction, 24 hour ambulatory electrocardiographic tape recordings and gated cardiac blood pool scans were obtained in 81 patients approximately two weeks after their admission to the hospital for myocardial infarction. Lown class 0 to II ventricular premature contractions during this period were classified as uncomplicated ventricular arrhythmias and Lown class III to V ventricular premature contractions were classified as complicated ventricular arrhythmias. Ejection fraction was calculated from biplane images of gated cardiac blood pool scans. In 35 patients the ejection fraction was greater than or equal to 0.40; only three of these had complicated ventricular arrhythmias. In 45 patients the ejection fraction was less than 0.40; 26 of these had complicated ventricular arrhythmias. Eight patients had documented ventricular fibrillation or instantaneous death during a mean 7.0 moonth (range 2 to 16 months) follow-up period outside the hospital. Although the number of patients studied was small, and there were only eight sudden deaths, life table analysis projected a one year mortality of 66 per cent in patients with complicated ventricular arrhythmias and 31 per cent in patients with an ejection fraction less than 0.40. All eight patients who died suddenly were in the subgroup of 26 patients with an ejection fraction less than 0.40 and complicated ventricular arrhymias; none was in the subgroup of 19 patients with an ejection fraction less than 0.40 and uncomplicated ventricular arrhythmias (P less than 0.02). Although a low ejection fraction may suggest a poor prognosis following myocardial infarction, the presence of complicated ventricular arrhythmias significantly increases the risk of sudden cardiac death in the early period after hospitalization in patients with low ejection fraction.


Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Daunomycin, like its anthracycline analog adriamycin, is a cardiotoxic antitumor antibiotic. Reports on 5,613 patients receiving daunomycin were reviewed for cardiotoxicity. Two distinct patterns of cardiotoxicity were defined, congestive heart failure (cardiomyopathy) and electrocardiographic changes. Dose-response curves were constructed using the percent incidence of cardiomyopathy versus the total dose of daunomycin in mg/m2. There was a dose-response relationship between the total dose of daunomycin and the development of cardiomyopathy, both in children and adults. The children seem more susceptible to the drug-induced cardiomyopathy. The electrocardiographic changes in the children and adults did not show a dose-dependent relationship, were present consistently even at the lowest dosage levels, and did not predict for subsequent development of cardiomyopathy. The dose-response curves constructed enable the clinician to judge the relative risk of developing cardiomyopathy at a given total dosage level and allows comparison of the human experience with the experimental animal model data.


Interrelations among blood pressure, blood volume, plasma renin activity and urinary catecholamines in benign essential hypertension. Interrelations among blood pressure, circulatory volume, plasma renin activity (PRA) and urinary catecholamine excretion rates were studied in normal subjects and in patients with benign essential hypertension. Mean plasma or blood volumes related to lean body mass, products of blood volume and the logarithm of PRA, and catecholamine excretion rates did not differ significantly between normal and hypertensive subjects. In both normal subjects and hypertensive patients, blood pressure levels correlated positively with the noradrenaline excretion rate (r = 0.40 and 0.36, respectively; p less than 0.025) but not with adrenaline excretion, circulatory volume or the volume-renin product. The logarithm of PRA correlated inversely with mean blood pressure in normal subjects (r = 0.40; p less than 0.001) but not in hypertensive patients; however, there was no convincing evidence for an inappropriate blood pressure-PRA relationship as a prominent feature in the hypertensive patients. PRA did not correlate with blood volume. Patients with low PRA relative to sodium excretion (21 per cent of hypertensive population) were consistently normovolemic, but they tended to be older and excreted less (p less than 0.025) adrenaline than patients with normal or high PRA. The patient subgroup with high PRA relative to sodium excretion (11 per cent of population) was hypovolemic (p less than 0.02); despite this, urinary sodium output was high (172 +/- 64 meq/24 hours). These data reveal no evidence for major roles of PRA, circulatory volume and free peripheral catecholamines in the maintenance of benign essential hypertension. Essential hypertension with low PRA is usually not a hypervolemic state, but it may reflect diminished adrenergic activity, factors associated with aging and effects of a high systemic pressure. High PRA in benign essential hypertension may be at least partly a consequence of hypovolemia resulting from high blood pressure-induced sodium diuresis.


Bacteremic hemophilus influenzae pneumonia in adults. A report of 24 cases and a review of the literature. Twenty-four cases of Hemophilus influenzae pneumonia diagnosed by positive blood or pleural fluid cultures are compared to 43 cases previously reported in the literatrue. Frequently associated illnesses in both series include alcoholism, chronic airways obstruction and preceding respiratory tract infection. Moderate temperature elevation and slight leukocytosis were common on admission in both groups. Chest roentgenograms in our series revealed both bronchopneumonia (75 per cent) and lobar consolidation (38 per cent). Pleural disease occurred frequently, with two empyemas noted on admission and nine additional effusions developing during therapy. Treatment of choice was ampicillin. All five patients who did not receive ampicillin died, whereas 16 to 19 who received this drug survived. High mortality (33 per cent) in our series may be attributed to the advanced age of the patients and the presence of associated illnesses. In addition, a 10 year review suggests a true increase in the incidence of H. influenzae pneumonia in adults.


Hematopathology and Pathogenesis of the X-linked recessive lymphoproliferative syndrome. Subtle immunodeficiency to infectious agents including measles virus and ten Epstein-Barr virus (EBV) has been described in the X-linked recessive lymphoproliferative syndrome. This syndrome has affected six male cousins and possibly another boy. Three brothers died of an infectious mononucleosis syndrome, in a maternal cousin agammaglobulinemia developed three years after infectious mononucleosis, and two half-brothers of the Duncan kindred died of lymphoma of the brain and intestinal tract, respectively. In three of the boys, unusual measles viral infections had developed. Paramyxovirus-like particles suggestive of measles virus were seen at necropsy in the atrophic lymphoid tissue of two boys. Also, numerous plasma cells were seen in the brains, visceral organs and the thymus glands, and thymic-dependent lymphocytes were sparse in lymph nodes and spleen. The abnormal lymphopoiesis in the syndrome probably results from a subtle immunodeficiency, and concurrent measles and EB virus infections.


Concentrative transport in human renal biopsy specimens. In vitro concentrative transport to tritiated p-aminohippuric acid (3H-PAH) was evaluated in renal biopsy specimens from human subjects by section freeze-dry autoradiography. Renal cortical tissue obtained by percutaneous needle biopsy (23 of 27 tissue specimens) was incubated in vitro using a modified renal cortical slice technic. Following incubation in medium containing 3H-PAH, the biopsy fragment was snap-frozen, and section freeze-dry autoradiographs were prepared. The autoradiographs demonstrated cellular accumulation of 3H-PAH by proximal tubules of human kidney in vitro and suggest that PAH transport is uphill across the luminal as well as the antiluminal membrane. The number of proximal tubules which accumulate 3H-PAH in vitro diminishes as renal failure progresses. Cellular accumulation of PAH, however, was not impaired by heavy proteinuria, and appeared not to be related to the underlying glomerular histologic diagnosis. The frequency of proximal tubules showing 3H-PAH uptake in the cortex varied directly with the glomerular filtration rate and inversely with the degree of interstitial involvement. Proximal tubules which maintain the ability to accumulate 3H-PAH are clustered in fewer regions of the cortex in patients with reduced glomerular filtration rates. This observation is consistent with the view that residual renal function is renal failure arises from a few relatively normal nephrons rather than from a more uniformly damaged population of nephrons.


"Masked" 21-hydroxylase deficiency of the adrenal presenting with gynecomastia and bilateral testicular masses. An infertile 27 year old man with precocious puberty is described. He presented in adulthood with unilateral and then bilateral gynecomastia, and subsequently testicular tumors developed. An early diagnosis of congenital adrenal hyperplasia would have avoided unnecessary surgery. Initial detailed metabolic evaluation led to the erroneous diagnosis of 11-hydroxylase deficiency because of the presence of an unusual steroid (21-desoxycortisol) in serum which was falsely reported as an increased 11-desoxycortisol (compound S). The observed low urinary pregnanetriol measurements would have supported this diagnosis. Subsequent specific measurements of 21-desoxycortisol established its presence in the serum and its major metabolite, tetrahydro-21-desoxycortisol, in the urine. The unique features in this case of 21-hydroxylase deficiency alert the physician to its unusual clinical presentation and the pitfalls that may be encountered when evaluating adrenal steroidogenesis.


Hyperphosphatermia and hypocalcemia accompanying rapid cell lysis in a patient with Burkitt's lymphoma and Burkitt cell leukemia. Hyperphosphatemia, hypocalcemia and acute oliguric renal failure resulting from uric acid nephropathy developed in a patient with Burkitt's lymphoma and Burkitt cell leukemia after effective chemotherapy. A review of other reported cases in which the patients had similar metabolic abnormalities is presented, and the pathophysiology is discussed. The clinical setting in which these metabolic developments are most likely to occur is defined, and an approach for their prevention and management is presented.


Sustained hypertension after section of the glossopharyngeal nerve. A case of sustained hypertension produced by unilateral section of the glossopharyngeal nerve is reported. Special tests revealed baroreceptor dysfunction. The hypertension was responsive to propranolol therapy. Review of  the literature revealed no other documented cases of sustained hypertension although transient hypertension is common.


Right atrial myxoma with right to left shunting and mitral valve prolapse. A 58 year old black man presented with progressive dyspnea and persistent systemic arterial hypoxemia. Initial hemodynamic evaluation revealed mitral valve prolapse and evidence for isolated right to left shunting, presumed to be extracardiac. A detailed pulmonary evaluation disclosed normal volume and flow parameters with a mild reduction of the single breath carbon monoxide diffusing capacity. An open lung biopsy disclosed no abnormalities. Radionuclide studies of the heart, however, suggested the possibility of a filling defect in the right atrium, and echocardiography enforced the impression of a mass in the right atrium, subsequently demonstrated by superior vena cava angiography. Our report outlines the use of multiple diagnostic tools in difficult situations and stresses the importance of right atrial  myxoma in the differential diagnosis of isolated right to left shunting