Evaluation of the heart rate method to determine the daily energy expenditure in disease. A study in juvenile diabetics. Three different methods for the determination of the daily energy expenditure in disease were evaluated. The methods were based on a heart rate technique that caused the least possible interference with usual bahaviour of the patients. The study was performed on six juvenile diabetics in their homes and during a hospital stay of 3 weeks with sedentary as well as moderate physical activity. The daily energy supply derived from food analyses and urinary glucose losses, the body weight, and the total body potassium were followed. The three methods were: individual relationships between energy expenditure and heart rate with (method A) and without (method B) considering different body positions and the use of tabulated data on these relationships (method C). It was concluded that individual relationships had to be established and, furthermore, that these relationships must be determined within the whole activity area of the subjects. No consideration of the body position was found to be necessary. The blood glucose level had no influence on the energy expenditure or the heart rate. The activity of this group of diabetics was not significiantly different from what is normally expected for healthy subjects under similar conditions. The proposed heart rate method was found applicable in sedentary as well as physically active persons and would be possible to use in other patient groups.


Productivity and maximal oxygen consumption in sugar cane cutters. Vo2max and daily productivity (metric tons/day) have been measured in 46 sugar cane cutters 18 to 34 years of age. A multiple regression analysis demonstrated that productivity was simultaneously related to VO2max, height and body fat (r=0.685;P less than 0.001). The multiple regression equation was: productivity (tons/day)=0.81 VO2max-0.14 percent fat +0.03 height -1.96. The data indicate that productivity is affected indirectly by nutritional status through the influence of the latter on height, fat content and VO2max. The decrease in VO2max that occurs with age was similar to that reported in the literature. Evidence is presented that, as the worker ages, a higher percent VO2max has to be utilized to maintain productivity.


Body size and work output.

Body size and work output. The relationship between work output and anthropometric, biochemical, and socioeconomic varables was studied in 57 male industrial workers engaged in the production of detonator fuses. These workers were studied for 3 months and their daily work output was carefully measured. Work output was measured in terms of the number of fuses produced per day. Clinical and biochemical examination indicated that their current nutritional status was adequate. Among the parameters studied only body weight, height, and lean body weight were significantly correlated with work output. Body weight and lean body weight were significantly correlated (P less than 0.001) with work output even after removing the influence of height by partial correlation. Total daily work output was significantly higher (P less than 0.01) in those with higher body weight and lean body weight. The rate of work was also higher in the higher body weight group


Endurance training and body compostition of the elderly. Body composition was studied in subjects from the seventh decade of life (13 M, 25F), observations being made on recruitment and at selected points over a 1-year program of endurance training. As at younger ages, the women initially had more subcultaneous fat than the men, particularly over the limbs. In both sexes, excess weights (9.3 kg. M; 8.1 kg, F) and average skinfold radings (16.2 mm, M; 21.1mm, F) were greater than in younger adults. Edurance training (1 hr of supervised exercise, 150-200 kcal persession, nominal four sessions per week) progressively reduced skinfold readings, by an average of 1.6 mm at 7 weeks, by 2.4 dependent upon the intensity and the frequency of exercise undertaken by the individual. Total body potassium (40K determinations) agreed well with previous studies of older subjects. Body fat estimated form 40K showed a fair correlation with skinfold estimates of body fat (r=0.69, M; 0.93, F), but absolute precentages were higher by 40K(36.6%, M; 48.7%, F) than by subcutaneous fat measurements (20%, M;32% F). Body potassium increased by 4% over the year of training, 70% of this change, occurring between the 14th and the 52nd week of conditioning. Small gains were also recorded in arm circumference, grip strenght (R but not L) and knee extension force. Neutron activation data showed that both sexes had lower initial bone calcium counts than sedentary middle-aged adults. The sample as a whole showed no calcium loss over the year of training, but the group taking the least exercise did show a significant loss (P less than 0.05). Modest endurance training of an elderly population seems not only to correct loss of cardiorespiratory condition, but also to induce favorable changes in body fat and lean mass.


Defective local leukocyte mobilization in children with kwashiorkor. The Rebuck window technique was used to determine the functional integrity of the inflammatory response in nine children with kwashiorkor. The total numbers of leukocytes mobilized into skin abrasions were similar between kwashiorkor and control patients. However, children with kwashiorkor showed significantly delayed and decreased macrophage migration and increased polymorphonuclear leukocyte migration. These defects of leukocyte mobilization were corrected with nutritional repair.


Protein nutrition value of urea supplementation of opaque-2 corn for adolescent boys. The effect of urea supplementation on the protein nutritional value of a plant protein, opaque-2 corn, for adolescent boys was investigated. Seven 12- to 16-year-old boys were subjects for this 23-day study. The mean apparent nitrogen balance when 6 g of nitrogen from corn was fed and when 4 g of nitrogen from urea was added were + 0.63 and + 1.37 g/day, respectively. The improvement in nitrogen balance resulting from the addition of urea to a plant protein source suggested that urea may be used to partially supply the protein needs of growing boys.


Dietary folate intake and concentration of folate in serum and erythrocytes in women using oral contraceptives. Conflicting reports regarding the possible effect of oral contraceptives agents (OCA's) on folate status prompted us to evaluate the relationship between dietary folate intake and the concentration of folate in serum and erythrocytes among users and nonsuers of OCA's during two consecutive menstrual cycles. Twenty-two women (ages 19 to 28) had been on combination type OCA's for 4 months or more and a control group of 18 women (ages 18 to 29) had not used OCA's for at least 6 months prior to this study. The serum folate levels were lower in the OCA users than in the controls and the difference was statistically significant on day 5 of the menstrual cycle (P less t-an 0.05) but not on day 20. However, the differences in the erythrocyte folate levels and dietary folate intakes were not statistically significant between the two groups of subjects. There was a consistently higher degree of correlation between serum folate and folate intake among the control women than among the OCA users. Hematological parameters such as hemoglobin, hematocrit, mean corpuscular volume, mean corpusclar hemoglobin, mean corpuscular hemoglobin concentration and red cell count were similar in the two groups. It is concluded that the use of OCA's produces significantly lower serum folate levels during the first week of the menstrual cycle in spite of adequate folate intake.


The effects of an oral contraceptive on plasma growth hormone and glucose tolerance in two strains of rats. Effects of an oral contraceptive on plasma growth hormone and glucose tolerance were studied in two strains of rats, Sprague-Dawley, a normal strain, and BHE, a carbohydrate-sensitive strain. Ethynyl estradiol and norgestrel, combined in a dose representative of the clinical preparation of Ovral were given for 21 days. Plasma growth hormone was measured following sodium pentobarbital stimulation. In both strains fasting blood glucose levels were unchanged following oral contraceptive therapy, however, a strain difference in response to a glucose load was found. With contraceptive steroid treatment, Sprague-Dawley rats developed an impaired tolerance to glucose during the latter part of the glucose tolerance test. BHE control animals had an abnormal response to a glucose load which improved with oral contraceptive therapy. No significant correlation between growth hormone changes and changes in glucose tolerance during contraceptive steroid treatment were observed. Both strains of rats receiving oral contraceptives gained less weight than their controls, however, the difference was statistically significant only in the Sprague-Dawley strain.


Sucrose sensitivity of patients with coronary artery disease. Various loads of simple carbohydrates were fed to 148 patients with known coronary-artery disease (CAD) for 4 days in the Clinical Research Center. The 148 patients were grouped according to the diet regimen tested-sucrose (low and high), glucose, and fructose. A high-sucrose diet was fed to 29 control subjects. Diets containing 2 g of simple carbohydrate (predominantly either sucrose or glucose) per kilogram of body weight per day had no significant effect on fasting plasma glucose, serum triglycerides, or serum free fatty acids. However, diets containing 4 g of simple carbohydrate (predominantly sucrose) or 2 g fructose per kilogram of body weight per day produced a significant rise in serum triglycerides with decreases in fasting plasma glucose and free fatty acids. Serum cholesterol diminished in all the diet groups, probably because of the decrease fat and cholesterol intakes. The increase of serum triglycerides in CAD patients receiving simple carbohydrate at the 4-g/kg rate was significantly greater than in the normal control subjects fed the same diet, suggesting a sensitivity of CAD patients to this stimulus. No significant correlation could be demonstrated between changes in serum triglycerides and the extent of CAD (one, two, or three vessels) as determined from coronary angiograms.


Effect of carbohydrate restriction and high carbohydrates diets on men with chemical diabetes. The influence of low carbohydrate (CHO) diets, starvation, and high CHO diets on glucose tolerance tests (GTT) and plasma insulin response of men with chemical diabetes was studied. The GTT and insulin responses of these seven lean diabetic men were unchanged when the carbohydrate content of the diet was reduced from 44 to 20% of calories. After a 48-hr fast a significant deterioration of the GTT was observed in these diabetic men but the percentage change was identical to that reported previously for normal men. Thus these studies indicate that changes in glucose mtes are quite similar to those reported previously for normal men. The fasting plasma glucose values of seven lean and four obese men with chemical diabetes were significantly lower after one week on a 75% CHO diet than values on a 44% CHO diet. The 75% CHO diet also was accompanied by slight improvements in the oral and intravenous GTT and by slightly lower plasma insulin responses. The improvement in glucose metabolism on high CHO diets appears to results from increased insulin sensitivity. Serum triglyceride values were approximately 55% higher on the 75% CHO diet than values on the 44% CHO diet for the 11 men but these differences were not statistically significant. These studies support previous observations and suggest that high CHO diets may be beneficial in the management of certain diabetic patients. However, further studies are required to determine the long-term effects of high CHO diets containing natural foods on the glucose and lipid metabolism of diabetic patients.


Metabolic responses to exhaustive exercise in racing sled dogs fed diets containing medium, low, or zero carbohydrate. Eighteen racing sled dogs were assigned to three diets containing protein, fat, and carbohydrate in proportions as follows: diet A, 39:61:0; diet B, 32:45:23; and diet C, 28:34:38 on an available energy basis. The dogs were studied through a 28-week training period and subjected to three special tests, the first after 12 weeks training, the second at 24 weeks, and the third 4 weeks later. Overnight fasting, resting blood samples were taken before exercise, then about 5 or 30 min after exercise in the first 2 tests, or 1,5...30 min after exercise in the third test. Negligible changes in the red cell indices or serum concentrations of total protein, sodium, and urea indicated that there were no major water shifts. Significant decrements were found in serum concentrations of albumin (3% of resting value), calcium (4%), magnesium (13%), and inorganic phosphorus (39%). Significant increments were found in serum concentrations of creatinine (50%) and activities of glutamic-pyruvic and glutamic-oxalacetic transaminases (31 and 52%, respectively). None of the above variables showed differences between diets, exercise bouts, or time after exercise. Significant decrements in plasma cholesterol (D, mg/100 ml) were linearly related to the initial concentration (I mg/100 ml); D - 0.161 I - 17 mg/100 ml. Hyperglycemic responses were exhibited by 14 dogs in the 3rd test, including five dogs on diet A. Resting plasma glucose concentrations, peak values after exercise, and removal rates were the same in dogs fed all three diets. Blood lactic acid concentrations were linearly related to plasma glance (two from each group) had significantly higher peak lactic/glucose ratios tthan the six "worst" dogs, but there was no significant difference between diets in other measures of glucose or lactic acid. Plasma concentrations of free fatty acids, acetoacetic acid and 3-OH-butyric acid reached a maximum 10 min after exercise. Peak values and mean increments of free fatty acids were highest in dogs fed diet A. Also, mean free fatty acid increment was significantly higher in the six best dogs than in the six worst. An enhanced ability to mobilize body fat should confer an advantage in a dog subjected to prolonged strenous exercise in which fatty acid oxidation accounts for most of the oxygen consumption.


Hematological and metabolic responses to training in racing sled dogs fed diets containing medium, low, or zero carbohydrate. In a 28 week study, 18 racing sled dogs were trained to maximal fitness in 12 weeks, sustained through a racing season of 12 weeks, followed by gradual of training of 4 weeks. The dogs were fed a predominantly cereal diet prior to the study; experimental diets containing more chicken and meat by products were introduced from the 2nd to the 4th week of training. On an energy basis, the diets contained protein, fat, and carbohydrate in the proportions of 39:61:0 (diet A), 32:45:23 (diet B), and 28:34:38 (diet C). Blood samples were taken at rest just before the start of training, at 6, 12,24 and 28 weeks; 33 variables were measured on most samples. The results were subjected to analysis of variance. No adverse effects were observed in dogs fed the extreme diet A. Significant relationships to training were shown by serum glutamic oxaloacetic transaminase, creatinine, packed cell volume, calcium, hemoglobin, and globulin. Serum cholesterol concentration increased with the introduction of the higher protein-fat diets; the high concentrations attenuated with time but rose again when training was abated. Dogs on diet A maintained higher serum concentrations of albumin, calcium, magnesium, and free fatty acids during the racing season than did dogs fed diets B or C. They also exhibited the greatest increases in red cell count, hemoglobin concentration, and packed cell volume during training. High values of red cell indices were not sustained through the racing season in dogs fed diet C. In addition to attributes already widely appreciated, viz. a higher energy density an digestibility, the carbohydrate-free, high-fat diet A appeared to confer advantages for prolonged strenuous running in terms of certain metabolic responses to training.


Vitamin status of older women.

Vitamin status of older women. A study of the nutritional vitamin status of older women included 46 patients in nursing homes and 24 residents of private homes. The age range was 62 through 99 years. Calculated values for the mean daily caloric and vitamin intakes indicated that vitamin A and thiamin were the vitamins that compared less favorably with the Recommended Dietary Allowances. Values for vitamin A and C in sera and for thiamin, riboflavin, and N-methyl nicotinamide excretion were compared with standards of adequacy, Vitamin A values in sera of 14% of all subjects were "deficient" or "low". All serum ascorbic acid levels were "acceptable". Thiamin and riboflavin concentrations in urine of 17 and 15% of the subjects, respectively, were "deficient" or "low". Except for one subject, all N-methyl nicotamide values were "acceptable". In general, values for caloric and vitamin intakes and for corresponding levels of vitamins in sera or urine of patients in nursing homes did not differ significantly from analogous values obtained for subjects in private homes. The effect of age and income and education level are discussed.


Preparation and use of a quality control hemolysate for microchromatographic determinations of hemoglobin A2. Compared with other methods for determining hemoglobin A2 (Hb A2) levels, the new microchromatography procedures are fast, easy laboratory technics useful for quantitating Hb A2 that can be readily monitored for quality control of results. A reliable method for preparing a stable hemolysate control for monitoring the accuracy and precision of Hb A2 microchromatographic procedures is described. The recombination of purified hemoglobin fractions in known concentrations and the addition of potassium cyanide and carbon monoxide produce a control solution that gives stable hemoglobin A2 values for at least 40 weeks. Variability among six reference laboratories was small.


Fibrinogen Seattle: a qualitatively abnormal fibrinogen in a patient with tetralogy of Fallot. A dysfibrinogen was detected in the plasma of a 14-year-old asymptomatic Caucasian boy who had tetralogy of Fallot. The mutant molecular species could be traced through four generations in an autosomal dominant type of inheritance pattern. Nine of 14 family members were found to have the coagulopathy. Following laboratory and clinical evaluation, the proband underwent radical repair of the cardiac defect without incident. This variant is tentatively designated fibrinogen Seattle pending further characterization.


A computer program to record technical data in leukapheresis and plateletpheresis procedures. A computer program for the recording of data and calculation of results from leukapheresis and plateletpheresis procedures is described. It provides a printout of cell yields and other results for each procedure, as well as an updated list of donors and phereses. The data are kept on tape, accessible for periodic statistical analysis. While primarily set up for use with Haemonetics (intermittent-flow centrifugation) equipment, the program is adaptable for other systems.


Evaluation of a high-resolution electrophoresis system. A high-resolution electrophoresis system (Panagel) is evaluated by comparing the results with Microzone electrophoresis and with quantitation of individual protein fractions by the radial immunodiffusion technic and by the SMA system. The high-resolution electrophoresis showed a higher percentage of gamma globulin and a lower percentage of albumin than the Microzone system, with the alpha-1, alpha-2, and beta globulins being similar in quantity. The eight protein fractions studied: albumin, alpha-1 antitrypsin, alpha-2 macroglobulin, haptoglobin, beta-lipoprotein, C3 complement, and gamma globulin, correlated very well with the corresponding components in the various methods used. The normal values of the protein fractions were determined.


Effect of pulmonary tuberculosis on blood concentrations of copper and zinc. An investigation of copper and zinc concentrations in active cases of pulmonary tuberculosis (TB) was undertaken. Whole-blood, plasma, and erythrocyte concentrations of copper and zinc were determined for TB patients and controls using atomic absorption spectrophotometry. Elevated whole-blood and plasma copper concentrations or depressed whole-blood and plasma zinc concentrations, or both, were characteristic of the TB patients. In most cases, however, the high copper concentrations and low zinc concentrations did not occur concurrently. The whole-blood and plasma copper/zinc concentration ratios were also significantly elevated in the TB patients.


Screening hospital patients for hepatitis B surface antigen. A survey of adult patients admitted to a general hospital showed that 1.5% had hepatitis B surface antigen in the blood and 22% had hepatitis antibody. The majority of patients with hepatitis B did not have clinical hepatitis and would not have been recognized without screening all hospital admissions for hepatitis B antigen. The question of routine screening is discussed in relation to the risk of acquiring hepatitis.


Evaluation of the API 20C for identification of yeasts. The API 20C reactions were compared with the results of conventional methods for identifying yeasts using 45 strains. There was a 98% (44/45) correlation between the two methods in the identification of the yeasts. Individual fermentation tests ranged from 89 to 100% correlation, with an average agreement of 96.7%. The assimilation tests ranged from 85 to 100% correlation, with an overall agreement of 97.3%. The two methods had 91% agreement for cycloheximide resistance. The results of this limited study indicate that the API 20C may prove to be an acceptable substitute for conventional carbohydrate fermentation and assimilation tests.


Systematic evaluation of the World Health Organization classification of salivary gland tumors: a clinicopathologic study of 366 cases. In an evaluation of the WHO classification of salivary gland tumors, 339 major and 27 minor salivary gland tumors were examined, these being all available cases seen at The New York Hospital during the years 1948-1968. The clinical records were examined and follow-up data (average 8.7 years) were obtained in 88% of cases. The relative incidences of sites and tumor types were similar to those in previously reported series. The WHO classification was found to be applicable to this group of tumors with the following exceptions: (1) cases of chronic sialedenitis, and lymphomas presenting primarily as salivary gland masses (4.1% of all cases in this series), do not appear in this classification but frequently present problems to the pathologist and ought to be included in any subsequent revision; (2) the histologic concept of "differentiation" was not helpful in predicting the outcome of cases of mucoepidermoid tumor and acinic-cell tumor; (3) some confusion, possibly justified, still exists between poorly differentiated acinic-cell tumors and adenocarcinomas; (4) a high frequency of atypical histologic types was encountered among the minor salivary gland tumors, suggesting that this group might benefit from separate treatment. Adequate surgical excision of the primary lesion was again found to play a decisive role in the eventual clinical result. In conclusion, the WHO classification of salivary gland tumors proved to be a practical guide for the categorization of the vast majority of this group of lesions.


Bilateral nephromegaly and multiple pulmonary cysts. A newborn female infant with marked bilateral renal enlargement resulting from an absolute increase in renal parenchymal mass is described. The number of renal lobes was increased and there was persistent subcapsular glomerulogenesis. In addition, the lungs manifested delayed maturation and contained multiple small cysts. Although the renal growth disturbance resembled that sometimes found in hemihypertrophy and the Beckwith syndrome, the associated pulmonary lesions and the absence of other anomalies make this patient distinctive.


Unilateral salpingitis due to Enterobius vermicularis. A case of perforated unilateral salpingitis in which Enterobius vermicularis ova were identified in the inflammatory process is reported. Arguments for considering the parasite to be of etiologic significance in the production of the pathologic changes and clinical symptoms are presented. The infrequent occurrence of symptoms associated with ectopic localization of Enterobius vermicularis is emphasized by a review of the literature.


Nutritional benefits from federal food assistance: a survey of preschool black children from low-income families in Memphis. Approximately 4,000 preschool black children from low-income families in South Memphis participated for three years in a supplementary food program sponsored by the US Department of Agriculture. Part of this group received additional benefit from food stamps, day-care centers, and an infant-feeding program. We evaluated the effects of this participation in 250 children selected randomly from the enrollment list of the supplemetary program. Each child was examined for height, weight, head circumference, and levels of hemoglobin, serum iron, and vitamins A and C. The data were then compared with those from a similar survey in the same area conducted three years before. The results of this comparison indicate considerable improvements in height and weight and a reduction in the incidence of anemia and in the numbers of children with low plasma vitamin A levels. In the absence of other recognizable intervening factors, we conclude that federal food assistance programs were primarily responsible for the observed nutritional improvements.


Management criteria, recording of performance, and peer review of tonsillopharyngitis. As part of a national study to formulate criteria for chart audit of quality assurance of child health care, criteria were developed for diagnosis and management of tonsillopharyngitis. These criteria were validated by pediatricians and family physicians in academic medicine and in practice. They were judged relevant to the medical care process and patient outcome by both. The selected criteria were also recommended by the majority of two large physician groups for use in peer review. In the first three phases of the study most of these criteria were said to be performed and recorded by a majority of physicians. However, in the fourth (community) phase, when charts of 166 primary-care physicians were actually audited, documentation was so poor that peer review by chart audit would be impractical at present.


Echocardiography in cystic fibrosis.

Echocardiography in cystic fibrosis. Echocardiograms were obtained for 25 patients with cystic fibrosis (CF) and 20 controls to evaluate this technique as a means of assessment of right ventricular changes in patients with CF. Right ventricular anterior wall thickness per square meter of body surface (RVAW/sq m) and right ventricular internal dimension per square meter of body surface (RVID/sq m) were compared with other techniques for detection of cor pulmonale. Significant correlations existed between both RVAW/sq m and RVID/sq m and the forced vital capacity, forced expiratory volume in one second, midmaximal expiratory flow rate, clinical score of severity of disease, and roentgenographic score of pulmonary involvement. The RVAW/sq m was slightly more sensitive than RVID/sq m; RVAW/sq m thickness on echocardiogram in vivo compared well with actual measurements at autopsy in five patients. No correlations were found between echocardiography and electrocardiograms, vectorcardiograms, thoracic index, or cardiothoracic ratio.


The atrial septal defect-patent ductus arteriosus complex. Both atrial septal defect and patent ductus arteriosus are common isolated lesions, each accounting for approximately 10% of the total incidence of congenital heart diseases. Yet, the combination of these defects, without other significant cardiac lesions, is infrequent. We review the clinical and pathologic data on 16 patients with this combination of defects, including cardiac catheterization data on eight patients. In patients with this combination, we found an unusually high incidence of severe pulmonary hypertension, multiple noncardiac anomalies, mental retardation, and early mortality.


Rickets in children receiving anticonvulsant drugs. Biochemical and hormonal markers. Forty-one epileptic children, aged 2 to 16 years, receiving combinations of phenobarbital, phenytoin, and primidone, and 39 control children were studied. The epileptics demonstrated slight but significant reductions in serum calcium, phosphorus, and 25-hydroxyvitamin D concentrations, and a significant increase in serum alkaline phosphatase values. No significant difference in serum immunoreactive parathyroid hormone levels was noted. Further analysis of the data revealed that patients whose drug therapy included primidone had the lowest serum levels of calcium and 25-hydroxyvitamin D. They had also received the largest number of drugs for the longest duration, and had serum phenobarbital levels that were significantly higher than those of other patients. The minimal degree of vitamin D deficiency in our epileptic children contrasts with the results of other investigations and warrants emphasis. The reasons for this difference are not apparent.


Ludwig angina in childhood.

Ludwig angina in childhood. Two patients had Ludwig angina. Prompt recognition of this once common, but now rare, clinical entity is essential to save the life of the patient.


Cardiovascular abnormalities in the Beckwith-Wiedemann syndrome. Twelve of 13 patients with Beckwith-Wiedemann syndrome were found to have cardiovascular abnormalities: congenital heart disease in 7 of the 12 and isolated cardiomegaly in the others. No specific type of cardiac abnormality predominated.


Reye syndrome without initial hepatic involvement. We report Reye syndrome in an 11-year-old boy whose first symptoms were generalized convulsions and coma without clinical or laboratory evidence of liver disease. Serum glutamic oxaloacetic transaminase and lactate dehydrogenase (LDH) values increased strikingly on the third day after the onset of coma. These enzymatic changes were associated with prolongation of prothrombin time. A rise in blood ammonia concentrations began on the fourth day of coma. The diagnosis of Reye syndrome was confirmed by a liver biopsy and at autopsy. This case demonstrates that encephalopathy in Reye syndrome can develop prior to detectable hepatic involvement, and suggests that factors unrelated to generalized liver damage may occasionally play a role in the pathogenesis of this obscure disorder.


Clotrimazole: intermittent therapy in chronic mucocutaneous candidiasis. Long-term intermittent therapy with the orally administered antifungal agent, clotrimazole, has not been reported previously. On the basis of experiences with our patient we propose that this is an effective way of treating chronic mucocutaneous candidiasis with a minimum of side effects.


Menstrual epileptoid psychosis in an adolescent girl. An adolescent girl with a previous history of trance-like states and a strong family history of epilepsy developed a pattern of recurrent brief psychotic episodes. These episodes seemed to coincide with her monthly menstrual periods, and after four to seven days of bizzare, catatonic behavior, she would return to a normal state. These episodes have been virtually eliminated by maintenance of a therapeutic blood level of phenytoin. The case is discussed in the light of the complex interrelationship of seizures, menstrual hormonal changes, and behavior.


Pediatric evaluation of children with school problems. A practicing pediatrician participated in the evaluation of 21 children with school dysfunction. Diagnoses were coded according to a scheme that included (1) clinical psychiatric syndrome, (2) intellectual level, (3) associated or etiological factors, and (4) academic achievement level. Other members of the team included the school principal, guidance counselor, teacher, nurse, psychologist, social worker, and speech pathologist. The 21 consecutive evaluations were carried out during a 15-month period, comprised 1.5% of the school-age children in the suburban pediatric practice, and accounted for 0.54% of the author's office appointments during the study period. The problems encountered included conduct disorders, specific learning disabilities, mild mental retardation, and seizure disorders. It is suggested that pediatricians may need additional training to participate effectively in this area of school health.


The return of Boston exanthem. Echovirus 16 infections in 1974. Although the "Boston exanthem" has been seen rarely over the past 20 years, in the summer of 1974 we identified ten children, aged 1 week to 7 years with echovirus 16 infections. Seven of the children had rashes, and in four, the illness suggested roseola infantum. Five of these children were neonates, all with illnesses severe enough to mimic sepsis. In addition information obtained on echovirus 16 isolations occurring in 1974 elsewhere in the country showed an additional 27 isolations from eight states. It is postulated that more outbreaks of the Boston exanthem or other echovirus 16 illnesses will appear during the next several years, before the virus again "disappears".


Mummies that I have known. A pediatrician's venture in the field of paleopathology. We describe the activities of a pediatrician in the field of medical archeology. Having pioneered the use of electron microscopy in the examination of Egyptian mummified tissue, we also describe some of the exciting pathological findings from various autopsies of ancient Egyptian mummies. These findings give us a glimpse of disease and death in ancient Egypt and of the evolution of these diseases as they affect man today.


Pancreatitis following the intraductal injection of partially purified enterokinase in dogs. Experimental pancreatitis (PT) is induced by proximal and distal duodenal closure in the bile-duct-ligated dog, by causing duodeno-pancreatic reflux of lumenal secretions. It has been postulated that trypsin and enterokinase (EK) in the secretions activate trypsinogen within the pancreas, producing PT. There is supporting evidence for trypsin, but EK has not previously been investigated. To determine whether EK alone could cause PT, we injected saline suspensions of partially purified EK, and other test materials, into the duct of Wirsung of dogs and after 24 hr examined their pancreases and estimated the increment in serum amylase. Following 0.5% EK, both PT and hyperamylasemia (HA) ensued; HA without PT occured when EK was inactivated by heat, administered with trypsin inhibitor (TI), or administered in more dilute solution. Injection of TI or of hog gastric mucin likewise leads to HA but not to PT. It is concluded that the PT observed was due to EK activity, and that therefore EK could contribute to the production of PT observed was due to EK activity, and that therefore EK could contribute to the production of PT in the closed-duodenal-loop model. The HA observed in the absence of PT is unexplained but appears to be related to the colloidal properties of the materials injected.


Increased lithogenicity of  bile on fasting in normal subjects. The effect of fasting on bile lithogenicity was studied in 19 normal men and 22 normal women. The molar percentages of bile acid, phospholipid, and cholesterol, determined after random overnight fasts of 9, 12, and 16 hr, were plotted on triangular coordinates. The molar percentage of cholesterol increased in both men and women. Analysis using Admirand and Small's criteria for cholesterol saturation revealed that 4.50% of normal women were lithogenic at 9.1 hr and 54.5% at 16.5 hr (P less than 0.005). A similar trend in men was not significant. The mean values for both sexes were lithogenic at 16 hr only. Lithogenic bile was present in 4 men and 1 woman at 9 hr fasting and became more lighogenic with longer fasting. Analysis using the criteria of Hegardt and Dam revealed an increased proportion of both sexes moving into the metastable-labile and supersaturated zones on fasting, again with significant changes for women (P less than 0.01). The duration of fasting is important in interpreting the presence of lithogenic bile; although more pronounced in women, both sexes showed increased cholesterol saturation in bile with fasting.


Antral gastrin concentration in upper-gastrointestinal disease. Antral gastrin concentration (AGC) was measured in prepyloric mucosa specimens obtained by forceps biopsy during endoscopic examination of 174 clinic and hospital patients. AGC in 32 patients who had normal endoscopic findings, the control group, varied widely from 2 to 38.6 ng gastrin/mg tissue. The mean AGC of the control patients was 14.2 +/- 1.4 (mean +/- 1 SE) ng gastrin/mg tissue. AGC was similar to control values in 18 patients with duodenal ulcer, 14.7 +/- 2.1; 12 patients with a pyloric channel or antral ulcer, 16.4 +/- 3.5; and 48 patients with miscellaneous diagnoses, 14.3 +/- 1.5. AGC was significantly less than control values in 13 patients with a ulcer in the body or fundus of the stomach, 5.9 +/- 1.5, and 4 patients with the Zollinger-Ellison syndrome, 4.9 +/- 2.4. AGC was significantly greater than in control values in 16 patients with gastritis, 25.8 +/- 4.3;22 patients with esophagitis, 23.2 +/- 3.0; and 9 patients with gastric atrophy and fasting serum hypergastrinemia 44.6 +/- 12.3. In group of 77 of these patients with heterogeneous diagnoses, meal-stimulated 3-hr integrated gastrin output was directly related to AGC (r = 0.47, P less than 0.001). In a group of 106 patients AGC was inversely related to histalogstimulated maximum acid output. The correlation was very weak (r = -0.20) but significant (P less than 0.05).


Amyloidosis and inflammatory bowel disease. Surprisingly little has been written about the association of amyloidosis with inflammatory bowel disease. On reviewing the literature it appears that there is a correlation between amyloidosis and Crohn's disease, but little definitive evidence of such a relationship with ulcerative colitis could be found. No specific features emerge as aetiological factors in the amyloidosis of inflammatory bowel disease. The amyloidosis may arise after only a short duration of bowel disease, and there is evidence that the association may be commoner than is realized. The need for a prospective systematic search in a large number of patients with inflammatory bowel disease is emphasized.


Cholinergic inhibition and release of gastric following insulin injection in duodenal ulcer before operation and after complete and incomplete vagotomy. In 50 duodenal ulcer patients acid and gastrin secretory responses were determined in the fasting state and after insulin hypoglycemia. Completeness of vagotomy was assessed by multiple criteria. In all three groups of patients studied, i.e., the unoperated, the incomplete and the complete vagotomy groups, and initial gastrin inhibition was observed, the inhibition being minimal, moderate, adn exaggerated, respectively. This inhibitory phase was followed by a significant rise in gastrin the unoperated and the incomplete vagotomy groups, the rise being significantly higher in the latter. This rise was insignificant in those with complete vagotomy. The evidence suggests the presence of both an inhibitory and a releasing mechanism for gastrin release. The ratio of basal serum gastrin to postinsulin gastrin separates complete and incomplete vagotomy without overlap.


Three-dimensional reconstruction of jejunal biopsy in tropical sprue. There is a lot of diversity in the observations on jejunal histology between light and discretion microscopy in tropical sprue. In order to compare the light and dissection microscopic appearances, a three-dimensional model of the villous pattern was constructed after a study of 350 serial sections of jejunal biopsy from a patient with tropical sprue. There was considerable variation in the morphological appearance of the villi in different sections. The changes seen varied from mild to partial villous atrophy. Broad synechia and bridge formation between adjoining villi due to fusion was frequently observed. It is postulated that the process of fusion of villi may be partly responsible for the development of features of partial villous atrophy seen in jejunal biopsies in tropical sprue. Normal jejunal pattern reported by some workers in patients with tropical sprue could possibly be due to inadequate sampling of the total biopsy piece.


Effect of bethanechol on gastroesophageal reflux. In this study we determined the acute effect of bethanechol (5 mg SC) on gastroesophageal reflux (GER) and lower esophageal sphincter pressure (LESP) in 27 patients with symptomatic esophagitis. The effect of bethanechol on esophageal acid clearance was also determined in 7 of the patients. Intraluminal pH monitoring prior to bethanechol administration demonstrated free or stress-induced reflux episodes in 18 of the 27 patients. Following bethanechol (1) LESP increased significantly, (2) GER diminished or ceased in many of the patients, and (3) acid clearance times decreased significantly. Some individuals, however, continued to reflux despite LESP elevation to 30 mm Hg or more. This latter finding suggests that LESP alone is not the sole factor governing LES competency. Other factors such as improved esophageal emptying may also contribute to the beneficial therapeutic effect of bethanechol in patients with heartburn.


Myoelectrical and mechanical activity of stomach and intestine in hypothyroid dogs. Myoelectrical activity was studied in normothyroid and hypothyroid Labrador dogs in the resting state, following injection of pentagastrin, bethanechol chloride, and after feeding. Hypothyroidism was produced by total thyroidectomy and chronic treatment with thiouracil. Electrodes were surgically implanted over the serosa of the stomach, duodenum, jejunum, and ileum and used for repeated recording of myoelectrical activity of gastrointestinal muscles. A strain gauge was implanted over the gastric antrum and served to record mechanical activity of the stomach. As compared with control dogs, hypothyroid animals showed (a) decreased frequency of electrical control activity of the stomach and jejunum, (b) decreased occurrence of electrical response activity (spike potentials) following stimulation, and (c) decreased mechanical response to the same stimulants, ie, pentagastrin, bethanechol chloride, and food.


Automated high-speed analysis of gastrointestinal myoelectric activity. The value of myoelectric recording in the gastrointestinal tract has been limited by the difficulty of analyzing the prolonged recordings which are required to demonstrate integrated physiological activity. This problem has been solved by the use of a tape recording system with accelerated replay, originally developed for cardiac monitoring. Rapid replay not only reduces the time required for data retrieval but also increases the frequency of the recorded signals to allow electronic separation of fast and slow wave activity for on-line conversion into digital pulses suitable for computer analysis. The technique is illustrated by the analysis of an imperfect prolonged multichannel recording of cannine gastrointestinal myoelectric activity, demonstrating some of the possibilities for data analysis and error detection inherent in the system.


Cholestatic liver disease associated with diphenylhydantoin therapy. Possible pathogenic importance of altered bile salt metabolism. A ten-year-old boy persented with a prolonged cholestatic liver disease 5 weeks after starting diphenylhydantoin therapy. The initial phase of his illness was characterized by hepatocellular damage with swollen liver cells and centrilobular cholestasis. Severe hyperlipoproteinemia with eruptive xanthomata developed within 3 weeks of his initial jaundice. The second phase of his illness was characterized by portal tract inflammation with bile ductular proliferation and chronic cholestasis gradually resolving over a period of 15 months. It is postulated that diphenylhydantoin sensitivity produced swollen hepatocytes with hypertrophy of the smooth endoplasmic reticulum, reducing hepatic sinusoidal blood flow and the clearance of secondary bile salts. A fall in clearance of lipoproteins, including the cholesterol precursor of primary bile acid synthesis, may have been responsible for a reduction in serum bile acid concentration. High levels of serum lithocholic acid, largely unsulfated presumably due to decreased hepatic uptake, may have produced the prolonged second phase of this illness when histological changes resembled that seen in experimental animals following lithocholic acid administration.


Remarkably large, benign esophageal tumor. Difficulties in diagnosis. A patient with a leiomyoma of the esophagus is reported because it reached extraordinary size before becoming symptomatic and caused some difficulty in diagnosis despite its large size. Diagnosis was made with the fiberoptic esophagoscope after standard roentgenograms and rigid esophagoscopy were inconclusive. The tumor was removed through a cervical incision. Attention is called to the potential fatal outcome of these lesions.


1976 Harvey A.K. Whitney lecture: the peril of deprofessionalization. It is argued that American pharmacy is in great peril of being deprofessionalized, and that hospital pharmacy practice offers the best hope for restoring public confidence in the profession. Pharmacists are criticized for a failing sense of mission and a waning dependence on knowledge. It is observed that pharmacy has diminished control over practitioner education. Various threats to the professional association of hospital pharmacists, and the need for ethical codes enforced by the profession are discussed. The concept of an American School of Hospital Pharmacy is supported. Hospital pharmacists are urged to become drug experts; it is suggested that pharmacists in hospitals be required to develop expertise in specific categories of drugs. It is concluded that pharmacy must use its drug knowledge effectively to avoid the peril of deprofessionalization.


Conceptual framework for drug usage review, medical audit and other patient care review procedures. The following concepts are discussed: (1) quality assurance programs, (2) drug usage review, (3) utilization review, (4) peer review, (5) medical audit, (6) patient care audit and (7) medical care evaluation studies. A framework within which all types of hospital quality assurance mechanisms can be constructed is proposed and their interrelationships are described. The pharmacist's particpiation in the hospital's overall quality assurance program is stressed in two main areas-drug usage review, performed jointly with the medical staff, and quality assurance of pharmaceutical services, a peer review function of the pharmacy profession. These services are primarily drug distribution and control, drug information, clinical pharmacy, continuing education, and other pharmacy and pharmacist functions. Both functions may be viewed as parts of the pharmacy audit, one of several patient care audits within the facility. Pharmacists in skilled nursing facilities have quality assurance responsibilities similar to those of hospital-based pharmacists.


Drug usage screening criteria.

Drug usage screening criteria. Screening criteria for adult use of 40 drugs and pediatric use of 10 drugs are presented. The reasons for presenting the criteria are to (1) document the specific screening criteria applied in a number of drug usage review studies, (2) provide a starting point for other groups wishing to develop criteria for drug usage review and (3) seek comments to be used in improving the criteria.


Integration of pharmacy into the computerized problem-oriented medical information system (PROMIS)--a demonstration project. The integration of pharmacy into the computerized problem-oriented medical information system (PROMIS) at the Medical Center Hospital of Vermont is discussed. Practioners who generate and retrieve information communicate directly with the computer without intermediary personnel. Touch-screen cathode-ray tube terminals are used for data input. Under PROMIS, the pharmacist has two new resources which better integrate his services into total patient care: (1) the ability to directly access online patient data in the pharmacy, and (2) the ability to directly couple online current drug information to a specific patient's computerized medical record in the pharmacy. The PROMIS solutions to pharmacy problems in drug ordering, drug distribution and drug therapy audit are discussed; In a demonstration project on a 20-bed unit, PROMIS made the medical record readily available to all health care providers, reduced reliance on memory, preserved the logic of medical action, and provided feedback loops for corrective action in everyday medical practice. Also discussed are user acceptance of the system, effect on pharmacy staffing, and implications for pharmacy.


Model for the development of rural pharmaceutical services. The Central Pharmacy of Presbyterian Medical Services (PMS) a nonprofit corporation operating a rural comprehensive health care system in New Mexico, is discussed. PMS Central Pharmacy provides pharmaceutical services to a 34-bed acute care hospital and 24 widely scattered clinics for ambulatory patients. The financial base, administration, development of a formulatory, purchasing, prepackaging of medications, and consulting services of the PMS Central Pharmacy are described. Central Pharmacy acts as a drug wholesaler for PMS; the gross margin between acquisition cost and average wholesale price covers 90% of the cost of the pharmacy operation. In addition, the clinics pay a fee and travel expenses for pharmacist consultation. Seven clinics employ drug technicians who are trained and supervised by Central Pharmacy. It is concluded that this system may serve as a model for the development of pharmaceutical services in other rural areas or in poverty-stricken urban areas.


Successful oral anticoagulant therapy in a patient with short bowel syndrome. The case of a 41-year-old male with a history of multiple emboli and short bowel syndrome who was successfully anticoagulated with sodium warfarin is described. The prothrombin times were stabilized in a therapeutic range with warfarin doses of 5.0 mg -7.5 mg daily. The pharmacokinetics of warfarin suggests that absorption is high in the proximal intestine. The successful use of sodium warfarin in the patient substantiates this finding and demonstrates that short bowel does not necessarily preclude the use of warfarin for anticoagulation. It is suggested that patients with short bowel syndrome may be successfully anticoagulated with oral products; however, careful monitoring of each patient's prothrombin time is necessary because of the variability and extent of bowel loss.


Estimation of drug dosage regimens with a pharmacokinetic slide rule. A pharmacokinetic slide rule to facilitate the computations based on relatively simple pharmacokinetic principles involved in the development of individualized drug dosage regimens is described. The calculations are based on the assumption that the body can be conceived as a one-compartment open model with drug elimination proceeding by apparent first-order kinetics. Examples are presented (1) to illustrate the clinical application of a slide rule to compute the time-course of drug in the body, (2) to calculate steady-state maximum and minimum levels, and accumulation during multiple dosage and (3) to estimate appropriate maintenance doses and intravenous infusion rates.


Sodium and potassium levels in antacids. The current sodium and potassium levels of commercial antacid products is reported; many of these products have been reformulated recently. The clinical importance of sodium and potassium content of antacids is discussed.


Levels of 5-hydroxymethylfurfural in dextrose injection. The levels of the degradation product, 5-hydroxymethylfurfural (5-HMF), in Dextrose Injection USP were determined by spectrophotometry. A freshly prepared solution of dextrose (1 g/2 ml) had a 5-HMF level of 0.10 mug/ml. The level in 50% dextrose injection, within 24 hours of manufacturing, was 0.72 mug/ml. The level of 5-HMF in 50% dextrose injection, after storage for four years at 70 F, was 5.80 mug/ml. Data are reported also for 10% fructose injection. It is concluded that limits for 5-HMF levels in commercially available solutions can be established. It is recommended that a quantitative procedure for determining this impurity be included in quality control testing of dextrose injection.


Benign monoclonal gammaglobulinemia and glomerulonephritis. Serum protein electrophoresis revealed a monoclonal gammopathy in three patients who presented with glomerulonephritis. Other features of myeloma were not found. Clinical manifestations of glomerulonephritis included marked proteinuria and significant hematuria. Rate of progression of renal failure was variable. Morphologically, glomerulonephritis was characterized by diffuse proliferative lesion with predominant mesangial involvement. Immunoglobulins and complement were found deposited in the mesangium. Immunoglobulins deposited in the glomeruli were found to consist exclusively of the circulating monoclonal IgG in one patient. Immunoglobulins eluted from the glomeruli of another patient consisted of immunoglobulin (IgM) which had electrophoretic mobility similar to that of the monoclonal spike in the serum. Selective deposition of monoclonal immunoglobulins in the glomeruli indicated that an active process was involved in their glomerular localization and that the monoclonal immunoglobulins may have had a role in the pathogenesis of glomerulonephritis in these patients.


Graded exercise testing in patients with sinus node dysfunction. Serial measurements of heart rate and oxygen uptake were obtained before and during maximal upright graded bicycle stress testing in 16 patients, 10 to 77 years old (mean 46 years), with sinus node dysfunction; five had permanent and two had temporary demand ventricular pacemakers. In 15 patients, including those with pacemakers, maximal exercise was performed before and after the intravenous administration of 1 mg atropine. Maximal exercise was terminated because of cerebral symptoms in seven (three had effort-induced tachyarrhythmias and one had autonomic insufficiency), fatigue in five (one had effort-induced heart block), heart failure in three and angina pectoris in one. With maximal exercise, patients with sinus node dysfunction were unable to obtain maximal heart rates or oxygen uptakes comparable to age- and sex-matched control subjects. Additionally, maximal oxygen uptake did not differ significantly between patients with or without pacemakers even when ventricular pacing rates were increased (two instances). The administration of atropine increased the resting heart rate, but the maximal heart rate and oxygen uptake achieved during maximal exercise did not differ significantly from those obtained before the administration of atropine in the patient and control groups. Physically active patients with sinus node dysfunction have diminished exercise capacity due in part to cardiac arrhythmia, latent or overt cardiac failure, or autonomic dysfunction.


Multifactor evaluation of the determinants of ischemic electrocardiographic response to maximal treadmill testing in coronary disease. Despite widespread use of treadmill stress in the detection of coronary disease, detailed information relating the important features of coronary pathoanatomy to the ischemic response noted on the electrocardiogram is lacking. Accordingly, 91 consecutive patients undergoing graded maximal exercise tests (MEXT) who were found to have clinical stenosis (larger than or equal to 75 per cent luminal narrowing) of at least one of the three major coronary arteries on coronary arteriography were evaluated. Positive MEXT was defined as larger than or equal to 0.1 mV horizontal or downsloping S-T segment depression larger than or equal to 0.08 second beyond J point. Over-all sensitivity of positive MEXT was 59 of 91 (65 per cent) patients; 11 of 26 (42 per cent) with single vessel stenosis, 20 of 30 (66 per cent) with two vessel disease and 28 of 35 (80 per cent) with three vessel disease. In patients with two vessel disease, the frequency (p less than 0.05) of positive MEXT was greater in those with (15 of 21;71 per cent) than in those without (five of nine; 55 per cent) stenosis of the left anterior descending artery. Concerning the site of intravessel stenosis, the frequency of positive MEXT was greater (p less than 0.05) with stenosis proximal to the left anterior descending artery in patients with one vessel disease. Quantification of total numbers of intra- and intervessel stenoses revealed 2.7 stenoses in the 59 patients with positive MEXT in contrast (p less than 0.01) to 1.9 in 32 patients with negative MEXT. Similarly, graded luminal narrowing index of severity of total stenoses per patient was 9.9 in those with positive MEXT compared (p less than 0.01) to 6.1 in those with negative MEXT. The poststenotic myocardial perfusion index, estimated by graded distal vessel opacification per major vessel disease, was only 1.5 in those with positive MEXT contrasted (p less than 0.01) to 2.4 in those with negative MEXT. These data indicate that sensitivity of positive MEXT in patients with coronary disease is most closely determined by the number of major coronary vessels involved, the total number of major vessels stenosed, the severity of total stenoses and poststenotic distal vessel perfusion. Less important factors are the precise site of intravessesl stenosis and the specific major coronary artery involved, although stenosis proximal to the left anterior descending artery favored positive MEXT. Unimportant variables were the quality of collateral vessels, ventricular function and prior inferior infarction. Angina occurred more frequently in those with positive MEXT, and marked degree of positive MEXT indicated stenosis proximal to the left anterior descending artery.


Control of breathing during methadone addiction. Chemical control of breathing was studied before and after the administration of the daily dose of methadone in 14 former heroin addicts who were enrolled in a methadone maintenance program and taking 60 to 100 mg/day. Two major groups were identified: group 1 in which subjects (n=6) had taken the drug for less than two months, and group 2 in which the subjects (n=6) had taken the drug from eight to 43 months. Prior to the daily dose of methadone, the levels of arterial carbon dioxide tension were significantly higher and ventilatory response to hypoxia significantly lower in group 1 than in group 2. Ventilatory responses to carbon dioxide (CO2) were also lower in group 1, but the difference was not statistically significant. Following the daily dose of methadone, the subjects in group 1 manifested significant reductions of ventilation and arterial oxygen tension, significant increases in arterial carbon dioxide tension and significant depressions of ventilatory responses to both CO2 and hypoxia in comparison to values before the administration of methadone. In contrast, subjects in group 2 manifested only a significant decrease in ventilatory responsiveness to hypoxia with no change in ventilation, arterial blood gas tensions or ventilatory responsiveness to CO2 following the daily dose. Two intermediate subjects (five and seven months) behaved as long-term subjects with regard to arterial carbon dioxide tension and CO2 responses but as short-term subjects with regard to responsiveness to hypoxia. Thus, during the first two months of methadone maintence, there is continual alveolar hypoventilation due to depression o both central (CO2) and peripheral (hypoxia) chemoreception. After five months, alveolar hypoventilation is abolished as the CO2-sensitive chemoreflex acquires full tolerance to methadone at the maintenance dose level. In contrast, tolerance of the hypoxia-sensitive chemoreflex is developed more slowly and is never complete.


The clinical features of submassive and massive pulmonary emboli. Clinical findings in 167 patients with angiographically established pulmonary emboli were analyzed in detail. The clinical symptoms and physical findings in this group were compared with the findings in 160 patients (diagnosis established by angiography) from an earlier similar study. The observations from this, the largest known group of patients with documented pulmonary emboli that has been studied and reported on, revealed that many of the "classic signs and symptoms" occurred infrequently. Most patients in this study had prognostic value. The data from this study demonstrate that no clinical findings are specific for the diagnosis of pulmonary emboli, but the absence of isolated frequently occurring signs and symptoms should mitigate against the presence of pulmonary emboli.


The clinical assessment of roentgenographically atypical pulmonary sarcoidosis. We studied 89 patients in whom the clinical diagnosis of sarcoidosis was supported by the findings on tissue biopsy. A chest roentgenogram in 14 of the patients showed one of the following atypical features: large pulmonary nodules, an alveolar parenchymal pattern or a pleural effusion. Diagnoses of infection, malignancy or vasculitis were suggested by interpretations of atypical chest roentgenograms in eight of these 14 patients. Nonspecific and misleading clinical information contributed. The diagnosis of sarcoidosis was corroborated by extrathoracic tissue biopsies in 11 of the 14 patients. Over an average observation period of 38 months, the 14 patients remained classified as having sarcoidosis. This suggests that an extrathoracic tissue biopsy, whose findings are consistent with sarcoidosis, is often sufficient to support a clinical diagnosis of some forms of roentgenographically atypical pulmonary sarcoidosis.


Bone marrow necrosis associated with a Mucor infection. Peripheral blood cytopenia due to documented marrow necrosis is an unusual occurrence. This report describes a diabetic patient who presented with profound anemia and thrombocytopenia. Extensive bone marrow necrosis was demonstrated. He had a large renal cyst that contained hyphae later identified as Mucor species. It is postulated that the marrow necrosis was a direct or indirect result of Mucor infection. The phenomenon of bone marrow necrosis in reviewed.


True and false aneurysms of the left ventricle following myocardial infarction. Anterolateral myocardial infarction resulted in the formation of both true and false aneurysms in a 75 year old man in whom severe congestive heart failure subsequently developed as the false aneurysm became progressively larger. Left ventriculography detected and quantified both aneurysms, and demonstrated reasonable function of the remaining volume-overloaded left ventricle. Resection of both aneurysms was accomplished with marked relief of symptoms. The literature on false aneurysm is reviewed, and the dilemma posed by the need to recognize false aneurysms before they become symptomatic or rupture is discussed.


Partial hypopituitarism and possible hypothalamic involvement in sarcoidosis: report of a case and review of the literature. A 20 year old patient with generalized sarcoidosis is described. Sudden cessation of growth, and failure of development of secondary sex characteristics were noted at age 16. Tests of hypothalamic-pituitary function documented a deficiency of growth hormone and adrenocorticotropin reserve. The patient has osteolytic lesions in the calvarium of his skull, a previously unreported finding in patients with hypopituitarisim seconary to sarcoidosis. This is the 29th reported case of sarcoidosis and hypopituitarism, and the first in which growth hormone deficiency is documented. The literature pertaining to sarcoidosis and hypopituitarism, and sarcoid involvement of the skull is reviewed.


Acute myelofibrosis and malignant hypercalcemia. A 33 year old man presented with symptoms of one week's duration; he had a serum calcium of 22.5 mg/dl and a markedly hypercellular bone marrow. Despite therapy with saline diuresis, furosemide mithramycin, total parathyroidectomy and corticosteroids, symptomatic hypercalcemia was poorly controlled. Inappropriate serum parathyroid hormone (PTH) levels were found before and after parathyroidectomy whereas assays of the peripheral blood for osteoclast-activating factor and prostaglandin E (PGE2) were negative. An elevated leukocyte alkaline phosphate level, the inability to aspirate marrow, the marked generalized hyperplasia of all hematopoietic marrow elements, the focal accumulations of blastic cells and increasing reticulin fiber formation led to the diagnosis of acute myelofibrosis. A single course of cytosine arabinoside and thioguanine therapy was followed by profound hyperphosphatemia, hypocalcemia and death. The rarity of hypercalcemia with myeloproliferative disorders is documented by a review of the world literature, and the possible mechanism for hypercalcemia in this patient is discussed.


Hemoglobin SC, SS/GPhiladelphia and SOArab diseases diagnostic importance of an integrative analysis of clinical, hematologic and electrophoretic findings. Hemoglobin studies are presented on two children in whom electrophoretic analysis of hemolysates at alkaline pH initially suggested the diagnosis of hemoglobin SC disease. In both patients the course of the disease was unusually severe, blood smears contained irreversibly sickled cells, and crystal formation did not occur when red cells were incubated in 3 per cent sodium chloride solution. Each of these findings is inconsistent with the interpretation of the electrophoretic patterns. Family studies demonstrated that one of the patients had sickle cell anemia and was also a carrier of an alpha chain variant; citrate agar electrophoresis at pH 6.2 of the second child's hemolysate revealed that the "C-like" hemoglobin was not hemoglobin C. Tryptic peptide analyses of the nonhemoglobin S fractions showed that the first child has SS/GPhiladelphia disease and that the second child has SOArab disease. These observations emphasize the importance of integrating the clinical and hematologic data with the results of electrophoretic procedures in order to define precisely the hemoglobin abnormality in patients with sickling disorders.


Mitral valve prolapse due to coronary artery disease. Controversy exists concerning the etiologic role of coronary artery disease in the prolapsing mitral valve leaflet syndrome. A 35 year old man with progressive coronary artery disease is described. Auscultation before and after his first myocardial infarction revealed only a fourth heart sound; subsequently left ventricular cineangiography demonstrated normal anatomy and function of the mitral valve, despite extensive wall motion abnormalities. Six months later he experienced another myocardial infarction after which the typical mid-systolic click, late systolic murmur of mitral valve prolapse developed. A second left ventricular cineangiogram at this time revealed mid-systolic mitral valve prolapse and mitral regurgitation. This patient's course indicates that myocardial damage from coronary artery disease can cause mitral valve prolapse in patients with preexisting redundant mitral valve tissue.


Minimum protection factors for respiratory protective devices for firefighters. Carbon monoxide and oxygen concentrations were measured in seventy-two structural fires using a personal air sampler carried by working firefighters. In a total sampling time of 1329 minutes the carbon monoxide concentration exceeded 500 ppm approximately 29 percent of the time. The maximum carbon monoxide concentration was 27,000 ppm and in 10 percent of the fires, the maximum concentration exceeded 5500 ppm. Only six runs indicated oxygen concentrations less than 18 percent. On the basis of these exposure data, a minimum protection factor of 100 is proposed for breathing apparatus for structural firefighting.


Automatic systems for monitoring vinyl chloride in working atmospheres. During the past two years, Union Carbide Corporation (UCC) has developed completely automatic systems for monitoring 0-25 ppm vinyl chloride monomer (VCM) in working atmospheres and for processing the data obtained. Each system includes a process gas chromatograph, a sampling system capable of monitoring up to 19 points and data processing equipment. The data systems compute and print out statistical summaries on shift, daily and monthly bases and estimate the maximum exposure to VCM for each job. These systems are now essential operating tools at several UCC production units.


Ergonomics technology.

Ergonomics technology. Many aspects of NASA's research programs and projects focus on the working environment of man. Ergonomics research has a broader application of technological spinoffs. This paper describes these research efforts and may have implications for environmental control in industry.


A relation between heat of adsorption and breakthrough time for low concentrations of organic vapors in air passing a bed of charcoal at room temperature. The concentration of pollutants in the breathing zone of exposed persons can be determined by adsorption of the pollutants. Condition is that during sampling the pollutants which have to be determined are trapped. A simple model has been developed which predicts with fair accuracy the amount of adsorbent necessary to trap the pollutant molecules which have to be determined.


A system for labeling and control of toxic materials in a large research facility. For large industrial and research operations, maintaining reasonable control of all toxic materials used in their operations can be a formidable task. A system utilizing cards has been developed which serves a dual purpose - informing the user regarding hazards of a particular material and also facilitating appropriate workplace surveillance during its use. Selected data is printed on the card. The card contains a label which the user detaches and affixes to the container. This label classifies the material according to flammability, toxicity, reactivity and special properties on a 0 through 4 hazard rating system.


Results of trace arsenic analyses performed by various laboratories. Personal monitor filter cassettes were spiked with a known amount of arsenic and sent to various laboratories in the public and private sectors for analysis. Results and methods of analysis are discussed in light of proposed arsenic standards. Comparison indicates a high degree of analytical precision and accuracy are lacking.


A comparative analysis of the relationship between organizational climate and job satisfaction of medical technologists. This study  examines the quality of the total workplace enviroment (organizational climate) as a correlate of six dimensions of job satisfaction for a sample of 344 medical technologists. The main focus is upon comparisons of administrators versus nonadministrators, hospital laboratory personnel versus nonhospital laboratory personnel, and men versus women. Various dimensions or organizational climate were found to be important correlates of job satisfaction, and similarities and differences between the units of analysis are noted. Also discussed are the implications for the managers of medical technologists.


Evaluation of the Honeywell ACS 1000.

Evaluation of the Honeywell ACS 1000. The Honeywell ACS 1000, an automated computerized scanning system, is evaluated against the recommended manual method for WBC differentials. Over 400,000 data points were gathered by both methods during an 11-month study, employing routine peripheral blood smears and critically characterized control preparations. These data were found to exhibit an effective increase in throughput, precision, comparable accuracy, and a reduction in operator fatigue. In addition, the instrument demonstrates application to the improvement of quality control, teaching, and continuing education.


A behaviorally anchored rating scale for the evaluation of student performance. A behaviorally anchored rating scale for the clinical performance of medical technology students was developed from expected behaviors and critical incidents using retranslation by a number of independent judges. The scale and discussion of the results indicate the behaviors which are expected of medical technology students by a variety of medical technology educators.


Cortisol levels in amniotic fluid in prostaglandin F2alpha-induced midtrimester abortion. Cortisol concentrations in amniotic fluid and maternal plasma were determined by a competitive protein-binding assay in 14 patients in the midtrimester of pregnancy before and after intra-amniotic administration of prostaglandin F2alpha. Samples were obtained at three-hour intervals until abortion or until the fetal heartbeat ceased. The mean plasma levels of cortisol increased from 324 +/- 173 ng. per milliliter at hour 0 to 524 +/- 272 ng. per milliliter at 6 hours (the peak elevated value). In amniotic fluid, the mean levels of cortisol increased from 4.71 +/- 2.5 ng. per milliliter to a maximum at 9 hours of 10.24 +/- 2.5 ng. per milliliter. We concluded that at 16 to 20 weeks' gestation the fetoplacental unit is capable of responding to prostaglandin F2alpha instillation by increased levels of cortisol in the amniotic fluid.


Gonadotropin, prolactin, and steroid hormone levels after discontinuation of oral contraceptives. Serum levels of LSH, LH, estradiol, progesterone, and prolactin were measured daily for 2 months in six women after discontinuation of combination oral contraceptives. The initial LH peak occurred from 21 to 28 days after ingestion of the last tablet. Apart from variable prolongation of the follicular phase in the first postcontraceptive cycle, the patterns and levels of all hormones were indistinguishable from those found in normal ovulatory subjects. These results indicate that after a variable brief interval following discontinuation of oral contraceptive steroids, their suppressive effect on the hypothalamic-pituitary-ovarian axis disappears. This initial recovery results in completely normal endocrine function.


Rat mammary deoxyribonucleic acid synthesis during the estrous cycle, pregnancy, and lactation in relation to mammary tumorigenesis: its implication for human breast cancer. Rat mammary DNA synthesis is greatly reduced during late pregnancy and lactation; this corresponds to the decreased incidence of induced mammary tumors by chemical carcinogens during these periods. The protective effects of pregnancy and lactation against mammary tumorigenesis of rats and human subjects may be explained by the prolonged phases of mitotic rest encountered during pregnancy and lactation.


Vitamin B6 treatment of gestational diabetes mellitus: studies of blood glucose and plasma insulin. Thirteen women with late pregnancy gestational diabetes mellitus were tested with an intravenous glucose tolerance test and both blood glucose and plasma insulin levels were measured. Each woman was then treated with 100 mg. of vitamin B6 per day for 2 weeks and the intravenous glucose tolerance test was then repeated. There was a statistically significant improvement in the glucose tolerance curve after the vitamin B6 treatment, with a lowering of blood glucose levels at all points on the curve except for the 5 minute value. This glucose effect occurred despite an unchanged or lowered plasma insulin level. These results suggest that a relative deficiency in vitamin B6 is associated with some cases of gestational diabetes mellitus and that the replacement of this vitamin improves the metabolic state. The low vitamin B6 levels appear to alter metabolic pathways which result in a lowering of the biologic activity of endogenous insulin.


Bacterial growth inhibition by amniotic fluid. VII. The effect of zinc supplementation on bacterial inhibitory activity of amniotic fluids from gestation of 20 weeks. Twenty human amniotic fluids obtained from gestations of 20 weeks' duration supported bacterial growth. Nine of the 20 fluids could be made inhibitory by adjusting the phosphate to zinc ratios of the fluids to less than 200 mug per milliliter. These fluids contained the phosphate-sensitive bacterial inhibitor previously, but the fluids contained sufficient phosphate to inactivate the antibacterial system. The remaining 11 amniotic fluids did not contain the peptide component of the phosphate-sensitive bacterial inhibitor and could not be made inhibitory by adjusting the phosphate to zinc ratio to less than 200 mug per milliliter. The data obtained suggested synthesis of the peptide component may occur at a gestational age of approximately 20 weeks. The peptide may indirectly be detected in fluids by determining whether antibacterial activity is obtained when the phosphate to zinc ratio of the fluids is adjusted to less than 200 mug per milliliter.


Serum progesterone and estradiol-17beta levels in premature and term labor. A total of 30 to 50 per cent of premature labors occur without identifiable predisposing conditions. To evaluate the hormonal status of these pregnancies, serum progesterone (P) and estradiol (E2) were measured by radioimmunoassay singly in 60 premature labor patients and serially in 19 normal pregnancies. Premature labor patients as a group have significantly lower P and E2 levels than controls. Pregnancies complcated by idiopathic premature labor (IPL) (p less than 0.01), premature labor secondary to abruptio-marginal separation (A-MS) (p less than 0.05), and premature rupture of membranes (PROM) (p less than 0.05) have significantly lower P levels than controls. Patients with IPL and A-MS have significantly lower P levels (p less than 0.01) than PROM patients. No significant change in P or E2 occurs immediately prior to normal term labor. Conclusions are that (1) premature labor patients have significantly lower Pand E2 levels than controls, (2) the degree of P depression varies according to the type of premature labor and (3) IPL is characterized by premature labor with no identifiable predisposing factors.


Prolactin and hypertension.

Prolactin and hypertension. Progesterone (2.5 mg per kilogram) caused sustained hypertension in rabbits. When the same dose of progesterone was administered together with prolactin (1.25 mg. per kilogram), there was no increase in the blood pressure. In rabbits with progesterone-induced hypertension, the addition of prolactin caused a sharp drop in blood pressure. It is suggested that prolactin acts by reducing the sensitivity of the blood vessels to circulating pressor substances and further that a reduced prolactin response may be the cause of heightened sensitivity to pressor substances observed in pre-eclampsia.


The supine hypertensive test as a predictor of incipient pre-eclampsia. The supine hypertensive test was performed on 178 primigravidas. This prospective study demonstrated that the test is a true predictor of patients at risk of developing pre-eclampsia-eclampsia.


Roll-over test.

Roll-over test. One hundred randomly selected nulliparous, normotensive women were subjected to the roll-over test between 28 and 32 weeks' gestation. Twenty-five women had a positive test. Thirteen of those 25 women developed pre-eclampsia requiring magnesium sulfate therapy. Eight had transient hypertension during labor requiring no therapy. Four had no evidence of hypertension during pregnancy. A false-positive rate for the 25 women with a positive roll-over test was 16 per cent. Seventy-five women had a negative roll-over test. Sixty-eight of those women had no evidence of hypertension of pregnancy. Seven had evidence of transient hypertension during labor requiring no therapy. A false-negative test was present in 10 per cent of the 75 patients with a negative roll-over test. In no case did a patient with a negative test develop pre-eclampsia. The roll-over test is recommended as a routine test for every pregnant patient between 28 and 32 weeks' gestation for the early diagnosis of hypertension of pregnancy.


Effects of behavioral and medical variables on fetal growth retardation. Cigarette smoking, indulging in certain drugs, restricting maternal weight gain in pregnancy, failing to obtain sufficient prenatal care, undertaking pregnancy at too early or too advanced on age, and being underweight for height at conception have in the past been identified with either increased premature births or births of term infants with fetal growth retardation. Each of these seven variables contains an element of maternal choice and has therefore been labeled by us as a behavioral variable. The combined group of mothers having these seven behavior variables was compared to a smaller group of mothers with medical complications and to a control group of mothers with neither behavioral nor medical variables. In the control group, there was a remarkably low incidence of premature births under 37 weeks (1 per cent), of term infants who had short body lengths at birth for their fetal ages (1.4 per cent), and of low-birth-weight infants (1 per cent). As the number of seven behavioral variables increased from none to three or more per pregnancy, the incidences of premature births, of short-for-dates term infants, and of low-birth-weight infants increased proportionately and significantly. The incidences of these seven behavioral variables, occurring either singly or in combination, were inverse to the mothers' socioeconomic status. However, the incidences of premature births, of growth-retarded term infants, and of low-birth-weight infants were high among mothers who had two or more behavioral variables in their pregnancies regardless of the mothers' socioeconomic status. The group of mothers with behavioral variables in comparison to the smaller group of mothers with medical complications had lower incidences but higher absolute numbers of premature infants, of growth-retarded term infants, and of low-birth-weight infants. Mothers who had medical complications as well as behavioral variables had more growth-retarded term infants than mothers with medical complications alone.


The volumetric growth of the human placenta: a longitudinal ultrasonic study. Twelve patients were examined by ultrasound at biweekly intervals from 23 weeks of menstrual age until term. Placental volumes were calculated with four ultrasonic placental cross sections. In 10 patients placental volume reached its maximum well before the end of pregnancy. The conclusion is drawn that the human placenta stops growing before the end of pregnancy.


Mechanical and metabolic effects of insulin on newborn lamb myocardium. The effects of insulin on myocardial contractility (MC) and metabolism were studied in 18 newborn lambs. Cardiac work and rate were kept constant. Following insulin (80 units, intravenously), contractility increased and remained elevated for 1 hour. This was not prevented by beta blockade or glucose infusion. Myocardial extraction and uptake of glucose and nonesterified fatty acid (NEFA) increased, the arterial concentration of both decreased. But after glucose fell to less than 20 per cent of control, uptake of both glucose and NEFA declined as did MC. It is concluded that in the neonate insulin increases MC as well as substrate uptake.


Human fetal respiratory arrhythmia.

Human fetal respiratory arrhythmia. The association of human fetal respiration with the fetal heart rate was studied in 13 pregnant patients between Weeks 34 and 41 of pregnancy. Fetal respiration was recorded with the use of a tocodynamometer. Fetal heart rate was recorded with the use of ultrasound and abdominal fetal electrocardiogram monitoring devices. The results documented the presence of human fetal respiratory arrhythmia. An increase in fetal heart rate was seen during fetal "inspiration" followed by a decrease during "expiration." The possible mechanisms of the respiratory arrhythmia are discussed.


Topical progesterone in treatment of vulvar dystrophy: preliminary report of five cases. Topical progesterone was used in five cases of chronic vulvar dystrophy which were confirmed by biopsy. Good results were obtained in three of the cases through the sole use of topical progesterone. In one case, topical testosterone was substituted for the progesterone, and it was not as effective. The concomitant use of estrogen vaginal cream was required in order to achieve maximum results in another case due to the presence of senile vaginitis. The apparent failure of the progesterone preparation to achieve satisfactory results in a diabetic patient could possibly be explained by the presence of neurodermatitis.


A conformer for the reduction of facial burn contractures: a preliminary report. Based on the theory and principles of splinting in the reduction of burn contractures, a facial conformer was fabricated with satisfactory results and further surgery was averted. The facial skin softened and regained pliability and function, thus the lower eyelids were restored to their normal position, which allowed full closure and prevented further drying of the cornea and conjunctiva.


A finger device for obtaining satisfactory voiding in spinal cord-injured patients. Anal sphincter stretch is a technique or procedure that recently has been found effective in overcoming the problem of ineffective voiding caused by detrusor-sphincter dyssynergia in some cases and for patients with upper motor neuron lesions. This technique was made available to quadriplegic patients when a fabricated device worn over the patient's finger was used. Four C7 quadriplegics have been able to achieve consistently acceptable amounts and residual volumes when voiding.


Bioethics: occupational therapy attitudes toward the prolongation of life. A comprehensive array of bioethical issues have emerged from advances in biological technology. This report assesses the views of individuals at three occupational therapy levels concerning one such issue: The option of painless death for the incurable. A battery of measures used to study beliefs in occupational therapy students included an item dealing with euthanasia. Item analysis revealed that the mean response to the euthanasia item by groups of occupational therapy juniors, seniors, and supervising clinicians from two schools indicated approval of voluntary painless death for the incurably ill. The article concludes with a discussion of the inclusion of bioethical issues in occupational therapy educational programs.


Nonsterile self-intermittent catheterization for male quadriplegic patients. Individuals with cervical lesions at C6-7 level are capable of performing self-intermittent catheterization if they are deemed appropriate candidates for this type of bladder management by a urologist, and if they are provided with adaptations to help them compensate for limitations in hand function. The purpose of this paper is to present methods used at one university medical center for evaluating a quadriplegic patient's ability to manage self-intermittent catheterization, and to describe the adaptive devices needed for this form of independent bladder management.


Clothing adaptations: the occupational therapist and the clothing designer collaborate. An occupational therapist and a clothing designer collaborated in solving the dressing problem of a child with multiple amputations. The dressing problems were identified and solutions for clothing adaptations relating to sleeves, closures, fasteners, fit, and design were incorporated into two test garments. Evaluation of the garments was based on ease in dressing and undressing, the effect on movement and mobility, the construction techniques, and their appearance. A description is given of the pattern adjustments, and considerations for clothing adaptations or selection or both are discussed. These clothing adaptations can be generalized to a wider population of handicapped persons.


Congenital absence of the radius: the occupational therapist and a new orthosis. Congenital absence of the radius (radial club hand) is a relatively common and disabling limb deficiency characterized by dislocation of the hand and carpus from the single forearm bore, the ulna. An understanding of the clinical-pathologic anatomy and consequent disruption of hand mechanics enables the orthopedic surgeon and the occupational therapist to formulate a team approach to this birth defect that can result in maximum functional capability for the child. The role of the occupational therapist and a specific therapy program for early stimulation and achievement of hand function are described. Orthotic support of the arm is indispensable to successful management. The design and fabrication of a dynamic upper-extremity orthosis for radial club hand is presented.


Primary myocardial disease in the cat. A model for human cardiomyopathy. Thirty-four cats with primary myocardial disease were studied. The cats were divided into two groups, depending on the clinical, hemodynamic, angiocardiographic, and pathologic findings. Group A consisted of those cats with hypertrophic cardiomyopathy and Group B consisted of those cats with congestive cardiomyopathy. Similarity in the characteristics of cardiomyopathy in the human cat was found. Both Group A and Group B consisted predominantly of mature adult male cats. The most common presenting signs were dyspnea and/or thromboembolism, systolic murmurs with gallop rhythms on auscultation, cardiomegaly with (Group A) or without (Group B) pulmonary edema, abnormal electrocardiograms, elevated left ventricular end diastolic pressures, and angiocardiographic evidence of mitral regurgitation with left ventricular concentric hypertrophy (Group A) or left ventricular dilatation (Group B). Some cats in Group A also had evidence of left ventricular outflow obstruction. The principal pathologic findings in these cats were left atrial dilatation, symmetric hypertrophy or asymmetric septal hypertrophy of the left ventricle (Group A), and dilatation of the four cardiac chambers (Group B). Aortic thromboembolism was commonly observed in both groups. These clinical and pathologic findings indicate that cardiomyopathy in the cat is similar to the two most common forms of cardiomyopathy in the human (hypertrophic cardiomyopathy, with and without obstruction, and congestive cardiomyopathy).


Morphology of a naphthalene-induced bronchiolar lesion. Nonciliated bronchiolar epithelial (Clara) cells are selectively damaged by intraperitoneal administration of naphthalene. We examined these changes using light microscopy, transmission electron microscopy, and scanning electron microscopy. Naphthalene administration causes the Clara cells to expand and exfoliated shortly thereafter. Following exfoliation the remaining ciliated cells show morphologic abnormalities, including cilia loss and ballooning of remaining cilia. Upon regeneration of the Clara cells the ciliated cells gradually return to their normal appearance. One possible explanation for these findings is that the Clara cell secretions directly affect the physiologic state of the surrounding ciliated cells.


Separation of proximal tubule cells from suspensions of rat kidney cells in density gradients of Ficoll in tissue culture medium. Rat kidneys were disaggregated with 0.25% trypsin. Cell were separated by velocity sedimentation in a previously described isokinetic gradient, by isopycnic sedimentation, and by velocity sedimentation followed by isopycnic sedimetation. In some fractions from the isokinetic gradient, 71.8+/-2.4+ of the nucleated cells contained histochemically demonstrable alkaline phosphatase (HDAP); in semithin sections, 62.7+/-2.3% of these cells had brush borders. The correspondence between fractions enriched for cells with HDAP and fractions enriched for brush border suggested that HDAP might be a suitable marker for rat proximal tubule cells. These cell constituted 46.5+/-2.6% of the nucleated cells in the starting sample suspension of kidney cells, and 81.9+/-2.7% of nucleated cells in the purified fractions from the gradients. More than 98% of nucleated cells in these fractions excluded typan blue. Following isopycnin centrifugation, the purest fractions contained 87.3+/-1.5% nucleated cells with HDAP, 9.6+/-2.5% nucleated cells iwithout HDAP, and 3.1+/-2.5% red blood cells. These proximal tubule cells had densities of 1.036 to 1.052 g/ml. With rate-zonal separation followed by isopycnic separation, the purest gradient fraction contained 93.0+/-1.9% nucleated cell with HDAP, 6.0+/-2.3% nucleated cells with HDAP, and 1.0+/-0.9% red blood cells. These proximal tubule cells sedimented a density of 1.041 g/ml. More than 98% of these cells excluded trypan blue.


Immune adherence in renal glomeruli. Complement receptor sites on glomerular capillary epithelial cells. Several very recent reports have indicated the presence of receptor sites for the third component of complement in human but not other vertebrate renal glomeruli. The present study constitutes a demonstration that the glomerular capillary epithelial cell bears this receptor, detectable with either EAC complexes (EAC1423b) or fluores ceinated zymosan-C3 (ZC3b) complexes, Fresh, unfixed frozen sections of normal or diseased human kidneys, mechanically isolated human glomeruli, dissociated glomerular cells, and glomeruli and golmerular cells maintained in tissue culture were examined with various EAC complexes or ZC3b and examined by phase light microscopy, fluorescence microscopy, or transmission and scanning electron microscopy. Clearly, by scanning electron microscopy it was determined that glomerular capillary epithelial cells bind the immune-adherence EAC indicator cells. Because glomeruli or glomerular epithelial cells did not bind E, EA, EACI, EAC14, or EAC142 but did bind EAC1423b or ZC3b, it is concluded that C3b (activated bound fragment of the third component of complement) is responsible for the immune-adherence reaction in glomeruli. Preliminary examination of diseased renal biopsies indicates that sclerotic glomeruli, focal segmental sclerotic or proliferative glomerular capillary lesions, and proliferative epithelial crescents are immune-adherence negative. Furthermore, a clear or consistent inverse relationship between glomerular capillary deposits of C3 which presumably might block epithelial C3 receptor sites, and immune-adherence reactivity with EAC in vitro was not as evident in this study as reported previously by other investigators. Nevertheless, it is still attractive to conceive that glomerular C3 receptor sites might be responsible for binding of antigen-antibody-complement complexes and formation of immune-complex deposits, at least on the epimembranous (subepithelial) surface of glomerular capillary walls. Inability to demonstrate this immune-adherence phenomenon in glomeruli of other vertebrate animals suggests among other things that more investigation is necessary before ascribing a unique or universal significance to the C3 receptors identified in human glomeruli.


The human atherosclerotic plaque.

The human atherosclerotic plaque. The fibrous plaque is regarded as the vascular lesion most characteristic of atherosclerosis. The notion that these lesions develop from mural thrombi has received considerable support, and there is also much support for the idea that plaques form as a reaction to mechanical or chemical damage to the endothelium. As an alternative to these two hypotheses, Benditt and Benditt have suggested that plaques represent monoclonal proliferation of altered smooth muscle cells similar to leiomyomas. Evidence in favor of this suggestion has been obtained using tissues from human black females who are heterozygous for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). In such individuals, as a result of random inactivation of the X-chromosome during embryogenesis, all normal tissues contain both the A and B isoenzymes of G6PD, when assayed electrophoretically, whereas plaques and other lesions suspected of being of monoclonal origin contain predominantly one isoenzyme. A certain proportion of fatty streaks also show a single G6PD isoenzyme pattern, suggesting that some fatty streaks act as the foreunners of the fibrous plaque.


Response to injury and atherogenesis.

Response to injury and atherogenesis. We postulate that the lesions of atherosclerosis arise as a result of some form of "injury" to arterial endothelium. This injury somehow results in alteration in endothelial cell-cell attachment or endothelial cell-connective tissue attachment, so that forces such as those derived from the shear in the flow of blood result in focal desquamation of endothelium. This is followed by adherence, aggregation, and release of platelets at the sites of focal injury. During the process of release, a mitogenic factor is secreted from the platelets which, together with plasma constituents, gains entry into the artery wall, resulting in focal intimal proliferation of smooth muscle cells. This  intimal proliferation is accompanied by the synthesis of new connective tissue matrix proteins and often by the deposition of intracellular and extracellular  lipids. Studies in cell culture of arterial smooth muscle have demonstrated that the principle mitogen present in blood serum is a platelet-derived factor that is present in all whole blood sera and missing in serum derived from platelet-free plasma. In the absence of the platelet factor, smooth muscle cells are quiescent in culture. This platelet mitogen is also active in vivo, since experimentally produced lesion of atherosclerosis induced mechanically by diet or by homocystine can be prevented if platelets are missing, as in thrombocytopenia, or if platelet function is impaired as a result of the use of platelet inhibitors such as dipyridamole. These studies point to the key role of the platelet in the stimulation of intimal smooth muscle proliferation that leads to the development of lesions of atherosclerosis.