Isocaloric exchange of dietary starch and sucrose in humans. I. Effects on levels of fasting blood lipids. For 6 weeks, 10 men and nine women aged 35 to 55 consumed each of two diets in a cross-over design. The diets were comprised of identical natural foods with 30% of the calories as either sucrose or cooked wheat starch. Carbohydrate, fat and protein supplied 43, 42, and 15% of the calories, respectively. Of the calories 10% were eaten at breakfast (7:00 to 8:30 AM) and 90% at dinner (4:30 to 6:30 PM). Initial body weights were essentially maintained. Total serum lipids, triglycerides, and total cholesterol levels were significantly higher when the subjects consumed the sucrose diet than when they consumed the starch diet. Increases associated with the sucrose diet were greatest for triglycerides (33.0%). In a subgroup of nine subjects with triglyceride levels above the normal range, sucrose feeding increased triglyceride levels 45.2%. Triglycerides and pre-beta lipoproteins were significantly higher in males than in females. Pre-beta lipoproteins were 32% higher when the subjects consumed sucrose than when they consumed starch. For alpha and beta lipoproteins, small, nonsignificant increases were associated with sucrose feeding. Serum free fatty acids were not affected by diet. These results indicate that the consumption of sucrose can increase blood lipids that are considered to be risk factors in heart disease and that males and carbohydrate-sensitive individuals may be more susceptible than others to the effects of sucrose.


Triglyceride integrated concentrations: effect of variation of source and amount of dietary carbohydrate. The effect of changes in the amount of dietary carbohydrate (45 or 65% of total energy) and in the source of carbohydrate (sucrose or corn syrup) on plasma triglyceride and cholesterol concentrations was studied in eight healthy males. Subjects ingested each of the four formula diets for 10 days in a latin square sequence. Diet-induced response was assessed by measurement of plasma lipid concentrations in blood obtained after overnight fast and by measurement of the mean plasma lipid concentrations--designated the integrated concentration--of blood obtained by 24 hr continuous blood withdrawal. The fasting plasma triglyceride concentration increased significantly during ingestion of the high carbohydrate diet (P less than 0.005) but was not significantly influenced by the source of carbohydrate calories. The 45% carbohydrate diets induced larger meal associated plasma triglyceride variation than 65% diets. Sucrose-containing diets induced significantly higher plasma triglyceride integrated concentrations than corn syrup diets, whether provided as 45% (P less than 0.05) or 65% (P less than 0.005) of total energy. Diet-induced changes in fasting or integrated plasma cholesterol concentration were minimal.


The effects of vitamin C, vitamin B6, and vitamin B12 supplementation on the breast milk and maternal status of well-nourished women. The effects of vitamin supplements and/or diet on the levels of vitamin C, vitamin B6, and vitamin B12 in milk and blood of lactating women were determined. At the end of gestation, subjects were divided into two lactation groups: supplemented (10 subjects) and nonsupplemented (seven subjects). Milk samples were collected from 5 to 7 days and 43 to 45 days postpartum. Fasting blood samples were drawn at 8 and 46 days postpartum for vitamin C, B6, and B12 status measurements. Dietary records of all foods consumed by the subject were kept for 4 days at 1 and 6 weeks postpartum. The vitamin B6 level in breast milk of the unsupplemented group of mothers was significantly lower (P less than 0.05) than the supplemented group of women at 5 to 7 days postpartum. Vitamin B12 concentration in milk of nonsupplemented mothers at 43 to 45 days postpartum was significantly lower (P less than 0.05) than the supplemented group of women at 43 to 45 days postpartum. None of the milk values or the maternal blood levels measured in the women was less than published norms for vitamin C, vitamin B6, and vitamin B12.


The effects of ascorbic acid and flavonoids on the occurrence of symptoms normally associated with the common cold. A controlled study was made of the effects of natural orange juice, synthetic orange juice, and placebo in the prevention of the common cold; both natural and synthetic orange juices contained 80 mg of ascorbic acid daily. Three-hundred sixty-two healthy normal young adult volunteers, ages 17 to 25 years, were studied for 72 days with 97% of participants completing the trial. There was a 14 to 21% reduction in total symptoms due to the common cold in the supplemented groups that was statistically significant (P less than 0.05). Ascorbic acid supplementation also increased the number of "episode-free" subjects. However, the clinical usefulness of the results does not support prophylactic ascorbic acid supplements in the well-nourished adult. The results in this study with both natural and synthetic orange juice of physiological content of ascorbic acid, are similar to those obtained using a "megadose" of ascorbic acid.


Integumentary loss of calcium.

Integumentary loss of calcium. Integumentary calcium loss was studied in 16 healthy young men. The daily loss by the 16 ambulatory but relatively sedentary young men in 52 determinations of 6-day periods each was 8.7 +/- 1.9 mg/m2 per day (average 15.8 mg/man per day). The amount lost was not influenced by calcium intake (0.1 to 2.3 g/day). In contrast to urinary calcium excretion, which is directly related to protein intake, there was no significant change in integumentary calcium loss with varying protein intakes (1 to 96 g nitrogen per day). No compensatory relationship between urinary and integumentary calcium excretion was noted. During strenuous exercise calcium loss increased to an average of 25 mg in 40 min. There was no compensatory decrease in urinary excretion on the day of strenuous exercise. It was also noted that integumentary calcium loss was not affected by general calcium balance.


A two-reservoir energy model of the human body. A macroscopic two-reservoir model relating body weight, exercise, basal metabolism, and food intake is developed from the principle of the conservation of energy. A feature of this model is that it can account for changes in aqueous fluids. Experimental data on subjects undergoing a semistarvation diet are fit by the adjustment of a single parameter. The effects of changes in the activity level on the equilibrium body weight and the variation of the equilibrium body weight in individuals of different food utilization efficiencies are considered. The hypothesis that over-eating may lead initially to a volume displacement of aqueous fluids by fat is demonstrated by application of the model to experimental data; this hypothesis obviates paradoxical results suggested by single reservoir concepts.


Compressibility of skinfolds and the measurement of subcutaneous fatness. Compressibility of subcutaneous fat thickness when measured with skinfold calipers was investigated in 65 white American youths. Compression of skinfolds was determined relative to measurements of subcutaneous fat thickness from radiographs at each of seven sites. There is statistically significant heterogeneity among sites in skinfold compression, with skinfolds on the medial and lateral calf being the least compressible of those measured. There is little statistically significant sex difference in skinfold compression in the present sample and, within the range concerned, there were no significant correlations between skinfold compressibility and age. When compressibilities of the seven skinfolds were intercorrelated within individuals, statistically significant average correlations were obtained, indicating that individuals tend toward similar degrees of skinfold compressibility among sites. This communality of skinfold compression within individuals is such that, at least in male youth, there are significant differences among individuals in the average compressibility of the seven skinfolds.


Evidences suggestive of no intestinal nitrogen fixation for improving protein nutrition status in sweet potato eaters. Total of seven teenagers and two adults were given sweet potato diets that supplied slightly below requirement levels of protein for 32 (experiment 1) or 53 days (experiment 2) in two separate experiments. In experiment 1 and during the first 36 days of experiment 2, nitrogen (N) balance studies with the teenagers were conducted with 0.67 and 0.71 g of protein per kilogram of body weight, respectively. Results of the N balances including skin N loss were -0.5 mg N/kg per day in experiment 1 and -3.2 mg N/kg per day in experiment 2. Two adults were given 0.63 g/kg of protein and gave average N balance of +6.0 mg N/kg per day (experiment 2), however, one of them had a slightly negative cumulative N balance if miscellaneous N losses were included in calculation. Plasma urea N of both teenagers and adults decreased significantly from 8 to 11 to 2 to 3 mg/100 ml in experiment 2. After 32 or 53 days on the sweet potato diets, the plasma free amino acid pattern of the teenager subjects showed abnormality. Furthermore, the subjects were easier to get fatigue by physical exercise, and took longer nap due to sleepiness during the latter days of the experiments. Thus, although the mean hemoglobin, hematocrit, plasma total protein, and plasma albumin levels were within the normal ranges, the protein nutrition status of the teenagers and one of the two adults was considered to be not normal. The results suggested that intestinal N-fixation that was proposed by several investigators to occur in sweet potato eaters probably did not occur. The subjects' feces were examined in vitro for the ability of N-fixation with negative results. During the last 17 days of experiment 2 the effect of excess calorie on N balance was examined.


Postgraduate training in ambulatory pediatrics. Program evaluation. Ambulatory pediatric, adolescent medicine, and child development fellowship programs listed in the Ambulatory Pediatric Association (APA) newsletter were surveyed to gather information about the programs for prospective fellows, to develop a descriptive summary, and to determine the extent to which programs adhere to APA guidelines. Number and types of positions offered, criteria for admission to programs, program educational objectives and activities, and career choice of graduates were examined for the 73 programs offering 132 fellowship positions in 1976 to 1977. In general, APA guidelines were followed. Programs emphasized patient care experience in contrast to health care administration, research, and teaching.


Current pediatric roles in child abuse and neglect. Many pediatricians are being called on to undertake expanded roles in the field of child abuse and neglect, whether as a practicing pediatrician, a hospital-based child abuse consultant, or as a child protection team pediatrician. The practicing pediatrician must consider the diagnosis of child abuse and neglect, confirm the diagnosis, report all suspected cases to child protective services, hospitalize any abused child who needs protection, and provide preventive services. The hospital-based child abuse consultant should provide consultation to primary physicians, report seriously injured cases for the primary physician or surgeon, provide expert medical testimony on difficult to prove cases, teach house staff and medical students about child abuse and neglect, and improve treatment services for abused children who are hospitalized. The child protection team pediatrician will usually become involved in the broader problem of improving team decision making and the interagency system that deals with child abuse and neglect.


Selected chronic disease 'risk factors' in two elementary school populations. A pilot study. Ninety-five first-grade elementary school students (aged 5 to 6 years) in two New York City area schools participated in a pilot test of a chronic disease primary prevention program stressing nutrition, antismoking, and physical activity. Program components included a health knowledge questionnaire; measurement of height, weight, skin-fold thickness, total serum cholesterol level, and blood pressure; and a modified Harvard step test of pulse rate recovery after exercise and subsequent classroom health education. The proportion of students with test values higher than specified critical levels was much greater in school M compared with school S. These measures will be repeated after one year to determine the feasibility and potential effectiveness of certain classroom health education activities.


Training in developmental pediatrics. How practitioners perceive the gap. Ninety-seven randomly selected, board-certified pediatricians in five New England states were interviewed by two physicians to explore attitudes toward previous training and current sources of knowledge in developmental pediatrics. Formal training in development was rated as inadequate by 79%, of residency experience was viewed as highly valuable by only 30%, and 47% rated medical school as having no value. Although clinical experience was reported as a valuable source of knowledge by 99% of the sample, almost two thirds did not regard it as an adequate substitute for formal training. Frequent interdisciplinary communication was reported, and professional contacts were described as a highly valuable ongoing source of knowledge. Social class and size of practice did not correlate with differences in consultation patterns. A part-time longitudinal clinical experience for further education was preferred by 97%. Improved training with greater interdisciplinary content is needed.


Physician's responsibility to parents after death of an infant. Beneficial outcome of a telephone call. The effectiveness of a telephone call to the parents after the death of an infant has been assessed. Eleven parents who had received no formal contact after the death of their infant were interviewed at the hospital eight to 25 weeks (mean, 18 weeks) after than crisis. Eighteen other parents whose infants died were called three to 19 days (mean, nine days) after the death. The call lasted 26 minutes (range, 15 to 40 minutes). These parents were also interviewed at the hospital at nine to 27 weeks (mean, 15 weeks) after the death. Nine different problems were evaluated. Three of the 18 families who received a call had ten moderate or major problems compared with the 36 moderately severe or major problems in all 11 control families. This study documents the beneficial outcome of a telephone call in ameliorating emotional problems in the parents.


Trisomy in the distal end of the long arm of chromosome 3. A condition clinically similar to the Cornelia de Lange syndrome. A patient had a trisomy for the distal portion of the third chromosome. The major clinical features were failure to thrive, profound mental retardation, dysmorphic head shape, a short nose, anteverted nares, long eyelashes, synophrys, characteristic mouth, and short stature. The similarities between the clinical picture and the Cornelia de Lange syndrome are very striking.


Toxicity of amphotericin b in children with cancer. The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.


Zollinger-Ellison syndrome with Marden-Walker syndrome. Association of two rare diseases in a 5-year-old girl. A 5-year-old girl had the symptom of vomiting for four years. Gastric analysis showed elevated basal acidity unaffected by betazole stimulation. Roentgenographic examinations of the upper gastrointestinal tract showed two ulcers in the lesser curvature of the stomach. Fasting serum gastrin values were remarkably elevated and a calcium infusion test resulted in noticeable increases in serum gastrin levels. These data were consistent with the Zollinger-Ellison syndrome. In addition, the patient demonstrated such anomalies as retarded physical and mental development, kyphoscoliosis, median cleft palate, joint contracture and unusual facies due to blepharophimosis, and malformed low-set ears. These clinical features were in accord with the Marden-Walker syndrome. To our knowledge, the present case presents the first case of the combination of these two rare entities in the literature.


Familial asymmetric crying facies. Its occurrence secondary to hypoplasia of the anguli oris depressor muscles. Asymmetric crying facies is a common neonatal problem with multiple causes. Asymmetric crying facies occurred in a newborn, secondary to familial hypoplasia of the anguli oris depressor muscle. The differential diagnosis of asymmetric crying facies should include this genetic cause.


Lead poisoning without encephalopathy. Effect of early diagnosis on neurologic and psychologic salvage. Medical and psychological status of 166 patients previously treated for lead poisoning and of 22 sibling controls were evaluated. Maximum blood lead levels ranged from 40 to 471 microgram/dL. Eighteen patients had definite symptoms, 32 had questionable symptoms, and 116 were asymptomatic. No patients developed seizures, other neurological sequelae, or abnormal nerve conduction velocity. No statistically significant relationship was found between blood lead concentration (PbB) and subsequent intellectual function. The mean IQ of the patient cohort was 87, approximately at the 50th percentile for inner-city schoolchildren in Chicago. Detection prior to encephalopathy and prompt detoxification were effective in preventing or minimizing sequelae despite high PbBs.


Nutritive value of elemental formula with reduced osmolality. The osmolality of an elemental formula was reduced from 627 to 338 mOsm/kg H2O by replacing dextrose with corn syrup solids, reducing the content of casein hydrolysate, and replacing a portion of the medium-chain triglycerides with corn oil. In three convalescent malnourished infants, the protein quality of the formula was compared at isonitrogenous levels with that of a casein-sucrose-vegetable oil formula and was found to be at least as high: in all three nitrogen retention was higher than during a preceding casein period, and in one of the three it was also higher than during a following casein period. The levels of postprandial plasma amino acids suggested that threonine might be the first-limiting amino acid. Four severely malnourished infants received the formula as their only food during initial rehabilitation. The formula was well tolerated and supported satisfactory weight gain, linear growth, and serum protein regeneration.


Clinical and physiological manifestations of bronchiolitis and pneumonia. Outcome of respiratory syncytial virus. The physiological abnormalities and clinical correlates of 32 infants consecutively hospitalized with lower respiratory tract disease from respiratory syncytial virus (RSV) were studied in an attempt to characterized the infant most at risk for the acute and long-term complications of RSV infection. Arterial oxygen saturation (Sao2) determinations were obtained daily by means of an ear oximeter. On admission all infants were hypoxemic with a mean Sao2 of 87% (range, 74% to 95%). The mean of the lowest Soa2 recorded during their hospitalization was 85.5% (range, 53% to 96%). The hypoxemia improved little during hospitalization but showed improvement three to seven weeks later. The severity of the hypoxemia correlated significantly with the duration of viral shedding, occurrence of apnea, respiratory rate, age, and percentage of immature neutrophils. Clinical severity did not correlate with the degree of hypoxemia.


Transient respiratory depression of the newborn. Its occurrence after succinylcholine administration to the mother. A baby born after a cesarean section experienced transient respiratory depression. The mother had a postsuccinylcholine apnea caused by homozygosity for the atypical allele for serum pseudocholinesterase; the baby was heterozygous for this allele and the usual allele for serum pseudocholinesterase. The possible relationship between the genotype of the baby and the respiratory difficulty at birth is raised.


Rose bengal sodium I 131 studies in infants with suspected biliary atresia. Twenty-eight infants suspected of having biliary atresia were studied with radionuclide imaging and quantitation of liver activity clearance using rose bengal sodium I 131. Scanning the abdomen for the presence or absence of gut radioactivity was a sensitive indicator of complete biliary obstruction. Absence of gut radioactivity correctly predicted biliary atresia in all 11 infants proved to have that diagnosis. Biliary atresia was excluded by the presence of gut radioactivity in 13 of 17 infants with other forms of neonatal juandice. When present, gut activity was identifiable within 24 hours after injection. Serial tests improved specificity. Plotting the rate of clearance of liver activity did not aid diagnosis.


Congenital glomerulosclerosis and nephrotic syndrome in two infants. Speculations and pathogenesis. The incidental finding of hyalinized glomeruli in otherwise normal infant kidneys is referred to as congenital glomerulosclerosis. Two infants had extensive glomerulosclerosis manifested by nephrotic syndrome, severe oliguria, and progressive renal failure. Both patients were believed to have had intrauterine infections. These two cases have unequivocally identified congenital glomerulosclerosis as one of the causes of nephrotic syndrome in infancy. In addition, they suggest that extensive glomerulosclerosis in some cases may be a result of congenital infections.


Noonan's syndrome. IQ and specific disabilities. The IQ of eight male patients with Noonan's syndrome, aged 13 to 26 years, ranged from 64 to 127, with a median of 102. The full IQ masked the possible presence of specific verbal or praxic (visual-constructional) disability. There was no verbal/praxic disparity in three cases; there was substantial verbal disability in one case; and there was major praxic disability in four cases, three unrelated to vision and one accounted for by severe visual impairment. Ostensible general mental retardation in Noonan's syndrome should always be further evaluated for specific disability. Academic placement should then be arranged accordingly.


Coagulation studies in infants of diabetic mothers. Coagulation studies on 17 infants of diabetic mothers were compared with 11 control infants. Only minor differences were noted, including lower platelet counts in the former group. On the basis of these findings, the increased thrombotic tendency in diabetic progeny cannot be attributed to altered hemostasis.


Surgical management of ileosigmoid fistula in Crohn's disease. Seventeen cases with Crohn's disease and ileosigmoid fistula were reviewed. They have been subdivided into four groups according to the anatomic site and extent of disease. Seven patients had disease localized to the terminal ileum and a fistula to normal sigmoid. Five were treated by ileocolic resection and simple of the sigmoid fistula (group I. All seven cases with concomitant sigmoid involvement had a double resection (group II). Two patients with diffuse ileocolitis (group III) had subtotal colectomy and ileostomy. One case (group IV) had left-sided colonic disease with a fistula to normal ileum and was treated with a double resection. In six patients, a temporary ileostomy was performed to protect the anastomoses. Forty-seven percent of patients had granulomatous involvement at only one end of the fistula. Resection of the diseases bowel and simple closure of the fistula can be performed safely in most patients in this group.


Responses of serum gastrin and gastric acid output before and after bilioenteric by-pass in the dog and man. Responses of serum gastrin and gastric acid output levels were studied in four dogs before and after a bilioenteric by-pass. Serum gastrin levels during bombesin infusion were measured in eight patients submitted to Roux-en-Y hepatocholangiojejunostomy. No change was observed in acid secretion from the main stomach or from the Heidenhain pouch in dogs following biliojejunostomy. The peak acid output, however, occurred significantly earlier after diversion of bile from the duodenum. Serum gastrin levels decreased significantly in dogs after bilioenteric by-pass and in the operated patients compared with normal subjects. The possible role played by bile in the release of duodenal gastrin is hypothesized.


Isolated granulomatous disease of the stomach. Report of three cases presenting as incidental findings in gastrectomy specimens. Three cases of isolated granulomatous disease of the stomach are reported. Other granulomatous diseases were ruled out on the basis of clinical and histological studies. These cases differ from those previously described in having only mucosal granulomas which were discovered as incidental findings in stomachs removed for peptic ulcers. Perigastric lymph node involvement by granulomas was present in one of three cases.


Tuberculosis of the duodenum.

Tuberculosis of the duodenum. At present, tuberculosis of the intestinal tract is rare in the United States. When gastrointestinal disease is seen, 85--90% of cases involve the ileocecal area. A case of tuberculosis of the duodenum unassociated with pulmonary disease is described. Although fiberoptic enndoscopy, abdominal ultrasonography and computerized axial tomography were used, the diagnosis required laprotomy with biopsy. The clinical manifestations, diagnostic investigations and treatment of the 49 previously reported cases of duodenal tuberculosis are also reviewed.


Specificity of serum amylase and amylase creatinine clearance ratio in the diagnosis of acute and chronic pancreatitis. In 31 patients with pancreatitis, the amylase to creatinine clearance ratio (CACR) was significantly greater than for controls (10.7 +/- 1.7 vs. 2.6 +/- 0.3, P less than .001). Sixteen pancreatitis patients with serum amylase (SAm) within the normal range had a mean CACR significantly greater than that of 19 hospital control patients with normal SAm (9.2 +/- 1.5 vs. 3.0 +/- 0.4, P less than .001). For control patients a highly significant inverse correlation between SAm and CACR was observed. No relationship was detected between these parameters for pancreatitis patients. The results suggest that the CACR may be of aid in establishing the diagnosis of pancreatitis even in patients without hyperamylasemia.


A case of meglumine iodipamide hepatotoxicity. There have been only two reports of severe hepatotoxic reaction caused by meglumine iodipamide. Lately we experienced such a reaction in an 66-year old female with chronic intrahepatic cholestasis. After drip infusion cholangiography was performed by infusing 40 ml. of 50% meglumine iodipamide (Biligrafin) intravenously, the patient developed nausea and abdominal pain. Her serum transaminase rose to more than 2,000 K-A units on the third day and gradually returned to normal by the 18th day. The macrophage migration inhibition test of her blood was positive for meglumine iodipamide. Accordingly some delayed type of hypersensitivity in the above reaction could be considered. When a larger amount than a recommended dose of meglumine iodipamide is infused in cholangiography, a severe hepatotoxic reaction might be induced, especially in icteric cases.


Pancreatic pseudocyst simulating an intrahepatic mass. A case of pancreatic pseudocyst is presented which mimicked an intrahepatic mass both after selective hepatic arteriography and isotope (99m Tc-S-Co) evaluation of the liver. A previous upper gastrointestinal series and ultrasonograhpy had seemed to accurately establish the diagnosis of pancreatic pseudocyst. A pancreatic pseudocyst may pose as an intrahepatic mass lesion and this entity should be recognized as a pitfall in nuclear imaging of the liver.


Caroli's disease. Clinical presentation simulating carcinoma of the pancreas. A patient with Caroli's disease (intrahepatic biliary duct dilatation), presenting when he was middle-aged with symptoms of painless jaundice and weight loss suggesting carcinoma of the head of the pancreas, is described. The world's literature of Caroli's disease is reviewed and this patient's unusual presentation is put into perspective.


Two cases of complicated intestinal lipoma. Review of small intestinal lipomas. Two cases of solitary small intestinal lipoma are presented. One occured in the duodenum as a submucosal pedunculated polyp with a bleeding ulcerated surface. This was diagnosed by means of the fiberoptic duodenoscope (Olympus D1G2). The second involved a large massive submucosal lipoma which formed the leading edge of an intussusception resulting in small bowel obstruction. A brief review of the pathology, complications, symptoms, radiographic diagnosis and treatment of small intestinal lipomas is given.


Transient subcutaneous granulomatosis of the upper extremities in Crohn's disease. Skin lesions occur fairly commonly in patients with Crohn's disease of the colon (14%). Erythema nodosum and pyoderma gangrenosum are the most frequently recognized. Granulomatosis of the skin, continuous with bowel involvement, has been reported. Involvement of the subcutaneous tissue, discontinuous with intestinal disease, is unusual and we wish to report a case of Crohn's disease of the colon complicated by infraepidermal perivascular granulomas of the forearms. The lesions disappeared spontaneously.


The radiology corner. Segmental lymphangiectasia of the small bowel. A case of intestinal lymphangiectasia, limited to a small segment of jejunum, is reported. This finding reflects part of the spectrum of generalized dysplasia of the lymphatic system. A discussion of the pathogenesis, pathophysiology and roentgen features of intestinal lymphangiectasia as part of a systemic disorder is presented.


An outbreak of influenza aboard a commercial airliner. A jet airliner with 54 persons aboard was delayed on the ground for three hours because of engine failure during a takeoff attempt. Most passengers stayed on the airplane during the delay. Within 72 hours, 72 per cent of the passengers became ill with symptoms of cough, fever, fatigue, headache, sore throat and myalgia. One passenger, the apparent index case, was ill on the airplane, and the clinical attack rate among the others varied with the amount of time spent aboard. Virus antigenically similar to A/Texas/1/77(H3N2) was isolated from 8 of 31 passengers cultured, and 20 of 22 ill persons tested had serologic evidence of infection with this virus. The airplane ventilation system was inoperative during the delay and this may account for the high attack rate.


Effect of parental cigarette smoking on the pulmonary function of children. The authors have investigated the effects of parental smoking patterns on the pulmonary function of children in East Boston, Massachusetts. A crude inverse dose-response relationship was observed between the level of FEF25--75% predicted of children who never smoked and the number of smoking parents in the household. Compared to children with two non-smoking parents, the level of FEF25--75% predicted was 0.156 and 0.355 standard deviation units lower for children with one and two currently smoking parents, respectively. An additional decline in level of FEF25--75% predicted was observed for children who themselves had smoked. Smoking children with two smoking parents had an average FEF25--75% predicted level which was 0.355 standard deviation units lower than non-smoking children with two smoking parents. These data not only confirm that cigarette smoking by young children and teenagers has direct measurable effects on their pulmonary function, but also show that cigarette smoking by parents has a measurable effect on the pulmonary function of their children which is independent of any direct use of cigarettes by the children.


Identifying a susceptible subgroup: effects of the Pittsburgh air pollution episode upon schoolchildren. Pulmonary function test results on 224 parochial schoolchildren collected during and after the Pittsburgh air pollution episode of November 1975 were reanalyzed to determine whether a small subgroup of susceptible children could be defined. Individual regressions of three-quarter second forced expiratory volumes (FEV.75) and forced vital capacities (FVC) on time over the six-day study period were calculated, and the distributions of individual slopes for the four exposed and two control schools were compared. Excesses of strong upward trends in the exposed areas would suggest effects of suspended particulate air pollution by indicating significant improvement following the episode. A highly statistically significant excess of strong upward trends in the FVC among exposed students was observed, and was consistent by sex and by school within sex. Approximately 10--15% of the students appear susceptible to an average impairment of about 20% of the FVC. The findings are limited by the small number of subjects with strong post-episode upward trends in the FVC, and by lack of validation by replication of the study design, but do suggest that episode levels of suspended particulates induce lung damage, and that this may occur only in a small susceptible subgroup. Children with low baseline pulmonary function values, histories of asthma, or with acute respiratory symptoms immediately following the episode were not found to be especially susceptible to these effects of suspended particulates.


Temporal and regional variation in hysterectomy rates in the United States, 1970--1975. Regional hysterectomy rates in the United States for 1970 and 1975 have been estimated from a one per cent sample of hospital discharges. All rates have been corrected for the number of women truly at risk, that is, with uteri intact, and regional and age-specific estimates of uterine prevalence in 1975 are provided. The rates rose by one-third in 1970-1975, with the increase taking place nearly uniformly over all ages below 65 years. Rates were greatest for 40--44-year-old women, but in 1970 there was a secondary peak for women between the ages of 65 and 69 years. That peak disappeared with rising rates for younger women in 1975. For women under age 35 years, the hysterectomy rate in the South was three times higher than that in the Northeast.


Cancer of the corpus uteri: increasing incidence in the United States, 1970--1975. Incidence rates of cancer of the corpus uteri have been estimated from a one per cent sample of hospital discharges in the United States for the years 1970--1975. Among postmenopausal women, rates rose sharply in 1970--1975, while for younger women there was little net change. There were substantial regional variations in incidence, which were largest between the ages of 65 and 69 years. All rates have been corrected for the numbers of women in each region and age group with uteri intact.


Work activity and fatal heart attack studied by multiple logistic risk analysis. A group of 3975 San Francisco longshoremen in cohorts classified annually by work activity (WA) was followed for fatal heart attack (FHA) over a 22-year period. In 57,632 person-years of follow-up, 410 men died from heart attack. A multi-factor logistic analysis was used to study work energy output adjusted for age, race, systolic blood pressure, smoking, body mass index, glucose intolerance and EKG status as predictors of FHA. After adjustment for these factors, men with a high WA of 7 kcal/min above basal metabolism at the beginning of a yearly follow-up period had a FHA rate about one-half the rate for men in the lowest WA category of 1 kcal/min above basal metabolism (p = 0.0003). In addition, the predictability of average WA during the four years preceding a yearly follow-up period was isolated to see if the lower risk associated with high WA derives from selective factors. After adjustment for factors described above and also for rate of change in WA used to represent selective factors, subjects with WA of 7 kcal/min still had about one-half the FHA rate observed for men at the lowest WA level (p = 0.0006). The findings from these and other phases of the analysis are consistent with the hypothesis that a substantial protective effect against FHA results from vigorous physical exertion.


Antibody against hepatitis A in seven European countries. I. Comparison of prevalence data in different age groups. Using a solid phase radioimmunoassay, antibody to hepatitis A virus (anti-HAV) was determined in 3890 sera from populations in seven European countries. Prevalence of anti-HAV was lowest in Scandinavian countries and highest in Greece and France. Antibodies were found in 77 (13%) of 602 blood donors in Sweden, in 29 (17%) of 175 blood donors and women taking birth control pills in Norway, in 273 (39%) of 700 blood donors in Switzerland, in 262 (52%) of 505 blood donors in Holland, in 365 (55%) of 661 accident patients in West Germany, in 452 (75%) of 600 blood donors in France and in 530 (82%) of 647 persons in Greece. Prevalence of anti-HAV increased with age in all populations tested, indicating nearly total exposure to HAV in persons over 19 years of age in Greece and in persons over 39 years of age in West Germany, Holland and France. Antibody was found more frequently in rural than in urban populations in Greece and Switzerland. Calculation of the age-specific incidence of HAV infections suggests a remarkable decline in the exposure rate in the last few decades.


Hypertension among Aleuts.

Hypertension among Aleuts. Surveys of Aleuts on St. Paul Island, Alaska, in 1966 and 1976 found a prevalence of hypertension as high as any reported in the United States. The rate remained high over the 10-year period. Preliminary data from other Aleut villages on the Aleutian Chain indicate that a high prevalence of hypertension may be widespread in this region. Etiologically genetic factors, obesity, and a high salt intake are all present. In addition, an exceedingly high level of cadmium content was found in seal livers, a dietary staple. Isolated locations such as St. Paul provide natural laboratories for possibly elucidating the complex etiology of this disease.


Laterality of breast cancer in families. A new method for analyzing concordance for a binary variable in extended pedigrees was developed to study tumor laterality in families with high incidence of breast cancer. It was found that related breast cancer patients in 15 high-risk Midwestern US families did not have their tumors on the same side more frequently than would be expected by chance. This finding is in contrast to previous studies in London and Denmark that reported a significant concordance for tumor laterality in related breast cancer patients. This result may reflect an increasing incidence of sporadic breast cancer in genetically susceptible families or, alternatively, independent determination of cancer susceptibility and tumor laterality.


Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976--1977. Because of an increase in the number of reports of Guillian-Barre syndrome (GBS) following A/New Jersey influenza vaccination, the National Influenza Immunization Program was suspended December 16, 1976 and nationwide surveillance for GBS was begun. This surveillance uncovered a total of 1098 patients with onset of GBS from October 1, 1976, to January 31, 1977, from all 50 states, District of Columbia, and Puerto Rico. A total of 532 patients had recently received an A/New Jersey influenza vaccination prior to their onset of GBS (vaccinated cases), and 15 patients received a vaccination after their onset of GBS. Five hundred forty-three patients had not been recently vaccinated with A/New Jersey influenza vaccine and the vaccination status for 8 was unknown. Epidemiologic evidence indicated that many cases of GBS were related to vaccination. When compared to the unvaccinated population, the vaccinated population had a significantly elevated attack rate in every adult age group. The estimated attributable risk of vaccine-related GBS in the adult population was just under one case per 100,000 vaccinations. The period of increased risk was concentrated primarily within the 5-week period after vaccination, although it lasted for approximately 9 or 10 weeks.


Five-year analysis of adenovirus 8 antibody levels in an industrial community following an outbreak of keratoconjunctivitis. Serum hemagglutination-inhibition (HI) antibody titers were monitored for five years with samples from 79 keratoconjunctivitis patients with type 8 adenovirus (AV-8) infection. Geometric mean antibody titers declined from 1:161 at the peak of the epidemic to 1:56 after five years. Computerized analysis of the decline in geometric mean antibody titer indicates that most patients will have a serum HI titer of 1:25 by 10 years after their clinical infection. These residual antibody levels and the consistent failure to document re-infection with AV-8 suggest that recurrent episodes of keratoconjunctivitis are caused by adenovirus serotypes other than type 8.


Acquaintance networks among leukemia and lymphoma patients. A case-control study of clustering through acquaintanceship among lymphoma and leukemia patients was conducted for the years 1967 through 1972 in Orleans County, New York. Twenty lymphoma and 17 leukemia cases met criteria for inclusion in the study. Data on acquaintanceship linkage were gathered from the source cases and controls, and from their acquaintances yielding a data base of 13,409 unique individuals linked by acquaintance. Three different analyses were carried out: a statistical analysis of linkage via intermediaries of case pairs in comparison with control pairs; a computer simulation of disease transmission from selected source cases to selected targets and controls based on the acquaintance data; and a secondary attack rate type analysis. The first two types of analysis yielded statistically significant case-control differences at the .05 level. The third method also yielded a positive result but was not subject to quantitative hypothesis testing. An additional conclusion is that these epidemiologic methods for disease with long induction periods merit further study.


Gross differences observed in the placentas of smokers and nonsmokers. Gross placental characteristics of 7651 smokers and nonsmokers are compared in light of the previous finding that placentas of smokers are heavier for the weight of their fetuses than are those of nonsmokers. Subchorionic fibrin deposits and placental calcification are more prevalent in the placentas of smokers than in those of nonsmokers. While mean placental weights and placental weight distributions for light and heavy smokers combined do not differ from those of nonsmokers, other placental measurements do differ. Smokers have thinner, rounder placentas than nonsmokers and the distance from the edge of rupture of the membranes to the placental margin is reduced among smokers. These findings are discussed in relation to placental changes observed at high altitudes and complications of pregnancy that differ for smokers and nonsmokers.


Increased risk of thrombosis due to oral contraceptives: a further report. In a previously reported case-control study of the relationship between oral contraceptives and thromboembolism, there were 461 cases and 1302 controls, individually matched on age, race, marital status, hospital, and date of admission. Initially, the control patients had not been matched with the cases for the presence or absence of six factors thought to predispose to or precipitate thromboembolic disease. The present paper reports the effects of taking into consideration these factors in the controls. Two methods of analysis (matched set, and logistic regression) gave closely similar results. Where the case series consisted of idiopathic cases, the revised estimate of the relative risk was reduced from 7.2 to 4.7 by these procedures; for predisposed cases, it was increased from 1.2 to 2.2. The explanation suggested in the previous report for the failure to find an increased risk for cases with predisposition receives support from these findings. Variation in the relative risk was examined for four separate diagnostic categories: venous thrombosis alone, pulmonary embolism alone, venous thrombosis and pulmonary embolism together, and myocardial infarction. The relative risk estimates were greater than unity for each thrombosis category for both predisposed and non-predisposed cases. The relative risk was not found to vary significantly according to age or smoking status.


Drug utilization and reported adverse reactions in hospitalized children. An intensive drug surveillance program has been developed to study the clinical effects of drugs in hospitalized children. This program collects information on drug exposures and the occurrence of adverse clinical events. The 1669 children monitored to date received an average of 7.6 drugs during an average hospital stay of 8.4 days. A group of specified adverse clinical events, whether or not drug attributed, occurred in 45.7% of the patients; drug-attributed events (adverse drug reactions) occurred in 16.8%. Both drug use and reported adverse reactions tended to increase with age, except that newborns received many drugs but had the lowest reported adverse reaction rates. Newborns, however, had the highest rate of adverse events not attributed to drugs, suggesting that perhaps some of these latter events include presently unrecognized adverse drug reactions.


Assessment of the association between habitual salt intake and high blood pressure: methodological problems. Despite the finding in cross-cultural comparisons that habitual sodium intake correlates with levels of blood pressure, similar studies from within population groups have yielded inconsistent results. The data presented in this report indicate that in industrialized societies the high degree of intra-individual variability of sodium intake, compared to much smaller inter-individual differences, may obscure potential biological correlations. A quantitative statistical method is presented to assess and minimize the effect of the large intra-individual variation in daily urinary sodium excretion.


Evidence for a hybrid hexosaminidase isoenzyme in heterozygotes for Sandhoff disease. Patients with Sandhoff disease have less than 5% of normal levels of serum or tissue hexosaminidase activity. They are thought to have a defect in the structural gene for the beta chain of hexosaminidase (HEX). Heterozygotes for Sandhoff disease have approximately 50% of the total serum HEX activity of normals and more than 75% of the HEX is heat-labile. In normals, only 55%--65% of serum HEX is heat-labile. Serum HEX separates into three forms on DEAE cellulose chromatography: HEX A, a tetramer of 2 alpha and 2 beta chains, and HEX I and B composed solely of beta chains. The DEAE chromatograms from normals and Sandhoff heterozygotes did not differ in the relative distribution of HEX activity between peaks. In normals, the HEX A peak was heat-labile (60 degrees C for 9 min), but HEX I and B were heat-stable. In Sandhoff heterozygotes, however, HEX I and B were only 50%--53% heat-stable. This suggests the heterozygotes synthesized a hybrid enzyme containing both mutant and wild-type beta chains for HEX. The mutant beta chain renders the isoenzyme less stable to heating.


Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology. Enzyme assays of skin fibroblasts from five children with familial hyperlysinemia from unrelated families are added to the previous report of three children from two unrelated families. In all instances there was a deficiency in lysine-ketoglutarate reductase, saccharopine dehydrogenase, and saccharopine oxidoreductase activities. To complete the studies on the enzymes associated with familial hyperlysinemia, saccharopine oxidoreductase was partially purified from human liver and characterized. The activity did not separate from that of lysine-ketoglutarate reductase or saccharopine dehydrogenase. A simple screening test for familial hyperlysinemia is described based on the evolution of 14CO2 from lysine-14C by skin fibroblasts. The test differentiated, without overlap, seven patients with familial hyperlysinemia from control subjects. The relation of the two genetic entities involving lysine degradation, familial hyperlysinemia and saccharopinuria, is discussed. It is suggested that familial hyperlysinemia, type I, be applied to patients with major defects in lysine-ketoglutarate reductase and saccharopine dehydrogenase, and that familial hyperlysinemia, type II, to be used to designate patients in whom significant amounts of lysine-ketoglutarate reductase are retained. The nomenclature would be consistent with that of an analogous disease, orotic aciduria.


Triple-spot proteins in two-dimensional gel electrophoresis. A triple-spot pattern of polypeptides occurring in two-dimensional gel electrophoresis of proteins is described. The presence of a mutant protein, Pc 1 Duarte, which results in a splitting of all three polypeptides, is evidence that they are produced by the same gene. This pattern is seen in about 1% of the proteins from a variety of sources. Typically, about 50% of the protein occurs as a single major spot, the remainder occurring as two polypeptides with an additional negative charge and slightly different molecular weight. The reproducibility of this pattern implies a functional significance which is presently unknown. The implication of this configuration for patterns seen by one-dimensional gel electrophoresis is discussed.


Hemolytic anemia due to pyruvate kinase deficiency: characterization of the enzymatic activity from eight patients. We have studied the red cell pyruvate kinase (PK) variants from eight patients representing five families with pyruvate kinase deficiency-associated hemolytic anemia. The kinetic properties, electrophoretic mobilities, and immunological reactivity with anti-normal red cell pyruvate kinase were determined. The patients differ in the severity of their clinical condition and in the molecular properties of their red cell pyruvate kinase variants. The most seriously affected patient (PK Beaverton) has no electrophoretically demonstrable red cell isozymes. The activity present is due to the M2 isozyme, however red cell isozyme can be detected immunologically. PK Molalla and PK Lake Oswego are thermolabile variants with normal kinetic parameters. PK Molalla, in addition, has altered electrophoretic mobility. PK Multnomah and PK Milwaukie have decreased affinity for the substrate phosphoenolpyruvate, and PK Multnomah also has altered electrophoretic mobility. PK Coos Bay shows electrophoretic variation and a slightly decreased affinity for phosphoenolpyruvate consistent with an increased modulating effect of fructose-1,6-diphosphate.


Maternal effects on fingertip dermatoglyphics. Significantly larger variation between sibships within families of male MZ twins than between sibships within families of female MZ twins, indicative of maternal influences, was found for 10 of 41 dermatoglyphic fingertip variables. Of these, five were thumb-related with the effect primarily on the thumb radial and ridge count (larger of radial and ulnar count). These same variables were previously found to have unequal variances in MZ twins of known placental type, and the results indicate maternal influences in singletons as well as twins for these variables. Although the total ridge count (TRC), previously shown to differ in MZ twins of known placental type (paralleling the thumb radial and ridge counts) did not reach significance, the trend indicated that the observed thumb changes may be reflected in the TRC as well. Little finger pattern type and ulnar counts also showed less variability in families of female MZ twins, but the interpretation is complicated by the concomitant differences in mean squares within-sibships for these little finger variables.


Drug therapy for Reye's syndrome.

Drug therapy for Reye's syndrome. The pathogenesis, biochemical defects, pathophysiology, clinical and laboratory symptoms, and treatment of Reye's syndrome are reviewed. The etiology of the syndrome is unknown, but it appears to be a viral interference with basic biochemical processes. Increased intracranial pressure is one of the most lethal aspects of the disease; cerebral edema often ensues. Physiologic and pharmacologic methods of treating cerebral edema, including the use of osmotically active agents (mannitol, urea and glycerol), corti-costeroids and potent diuretics are reviewed. Correction of the biochemical abnormalities with enzyme and nutritional factor replacement is discussed. Intensive supportive care, including maintenance of fluid and electrolytes, reduction of intracranial pressure and elective endotracheal intubation, is the mainstay of treatment.


Lidocaine infusions: effect of duration and method of discontinuation on recurrence of arrhythmias and pharmacokinetic variables. The effect of abrupt versus gradual discontinuation of lidocaine hydrochloride infusion on the incidence of recurrent ventricular arrhythmia and on lidocaine pharmacokinetics was studied. Twenty-nine patients with documented myocardial infarction receiving no other antiarrhythmic drugs and having no evidence of congestive heart failure, liver disease or renal failure were randomly assigned to one or two groups: Group 1--lidocaine infusion was abruptly discontinued after a course of therapy, and Group 2--lidocaine infusion was tapered over a three-hour period. Lidocaine blood levels were measured at the abrupt discontinuation of an infusion or the initiation of tapering and three hours later. Cardiac rhythms were monitored until patients were transferred from the coronary care unit. Three of 18 patients in Group I and two of 11 patients in Group 2 had recurrent ventricular arrhythmias at least 12 hours after idocaine infusion was stopped. The duration of infusion did not correlate with the recurrence of ventricular arrhythmia. In patients infused with lidocaine for 36 hours or less, apparent body clearance was significantly faster than that in patients infused with lidocaine for longer than 36 hours (p less than 0.01). There was no difference in the incidence of recurrent ventricular arrhythmias when comparing abrupt cessation of lidocaine with three-hour tapering. Lidocaine infusion rates may have to be decreased after 36 hours to avoid accumulation of the drug.


Improved methods for estimating initial heparin infusion rates. Two methods of calculating heparin infusion rates for patients with venous thrombotic disease were compared; one method was based on a one-compartment pharmacokinetic model, the other on patient weight. Sixty-eight patients with presumed thromboembolic disease were started on continuous i.v. heparin sodium (porcine) using an infusion pump. Patients were divided into two groups--the infusion rate of Group I was based on patient weight (77 units/kg/4 hrs) and the infusion rate of Group 2 was determined by a pharmacokinetic equation based on a one-compartment heparin model. Heparin effect was measured by an activated partial thromboplastin time (APTT). The initial heparin infusion rate for Group 1 (4,784 +/- 672 units/4 hrs) was significantly greater (p less than 0.039, two-sample t-test) than that for Group 2 (4,413 +/- 779 units/4 hrs), but the variances of the rates were not significantly different (p = 0.40, ratio of variance F-test). Both methods for estimating initial heparin infusion rates gave mean APTT values in the center of the therapeutic range, but the variance in the APTTs of Group 2 patients was significantly smaller (p = 0.004) than that of Group 1. The pharmacokinetic model was more precise and reliable. This model should be valuable for insuring heparin's therapeutic effect without exposing patients to the potential risk of hemorrhage.


Pharmacist involvement in a deferoxamine education program for patients with Cooley's anemia. A program to train patients with Cooley's anemia to self-administer deferoxamine via an intermittent infusion pump is described. A pharmacist provides the patient and his family with indepth information on the disease and on deferoxamine dosage, preparation, subcutaneous administration, stability, storage, side effects and precautions. Patients are trained by the pharmacist in aseptic technique and in use and maintenance of the intermittent infusion pump. The patient education program allows patients with Cooley's anemia to receive their daily deferoxamine therapy without the neef for frequent hospitalization.


Pharmacy internship: patient care experience through nursing service. A pharmacy internship that offers graduated levels of hospital experience, with an emphasis on nursing assistant and medication administration programs, is described. Students work full time in the summer and part time during the academic year in the three-year program. The progression of duties is as follows: nursing assistant; inpatient drug distribution and control; sterile and nonsterile product production; patient education, monitoring and medication history-taking activities; drug information services; and medication administration. Interns are selected by the pharmacy department and trained and supervised by the nursing staff in nursing assistant and medication aide roles. The program provides the pharmacy department with a highly trained corps of interns who understand and appreciate the full range of systems required to deliver patient care and provides interns with patient-oriented work experiences valuable in their future roles as pharmacists.


Method for evaluating drug information systems. A method for evaluating drug information systems is described. The method measures both qualitative and quantitative performance. For the categories, "Basic Therapeutic Information", and "Commercial and Investigational Product Information," specific data that should be present are identified; evaluated systems are searched for these data related to a standard sample of 122 drugs. Systems are also searched for the presence of any information relating to these drugs in the categories, "Applied Clinical Research Information" and "Nonclinical Laboratory Research Information". In addition, systems are searched for the presence of 215 drug-drug interactions and 244 drug-laboratory test interferences. Using relative weights that have been assigned to the content statistics, an aggregate measure of system's content is determined. The method also measures annual cost of operating a system. The application of the method to two drug information systems is discussed briefly.


Sucrose as a sweetener for activated charcoal. The efficacy of sucrose as a flavor for activated charcoal was studied. In vitro adsorption of sucrose (in Simulated Gastric Fluid, USP, without pepsin) to activated charcoal, and of a 1-g/liter sodium salicylate solution to a 1:1 mixture of sucrose and activated charcoal and to plain activated charcoal, was measured spectrophotometrically. In vitro adsorption of sucroses to activated charcoal was minimal. Sucrose reduced in vitro adsorption of sodium salicylate to activated charcoal by only small amounts. For example, at a ratio of 4 g activated charcoal to 1 g sodium salicylate, sucrose reduced salicylate adsorption to activated charcoal from 99% to 95%. A 1:1 sucrose-activated charcoal preparation provides sufficient flavor without substantial loss of adsorbance.


Therapeutic problem solving: a systematic approach. A systematic approach to therapeutic problem solving is discussed. Therapeutic problem solving includes defining the problem, assessing possible solutions to the problem and choosing the best solution (therapy). The thought processes specific to drug therapy include: (1) choice of agent, (2) evaluation of benefit versus risk ratios, and (3) determination of dosage. Once treatment has been initiated, the problem-solving process shifts to reassessing the patient, monitoring and readjusting therapy, and anticipating new problems related to therapy. An algorithm is provided to demonstrate a thought sequence for solving therapeutic problems. To assure that no important consideration has been neglected, it is useful to develop a pattern of thought that may be applied to each therapeutic situation.


Using pharmacokinetics in drug therapy. IV: Consideration in applying pharmacokinetic and pharmacodynamic estimates to antihypertensive dosage regimens. A theory explaining the pharmacokinetics of drugs with direct and rapidly reversible pharmacologic effects is reviewed, and the application of this theory to individualizing dosage regimens for antihypertensive drugs is discussed. In a few studies, investigators have correlated, under controlled conditions and in a small number of patients, the pharmacokinetic variables needed to individualize minoxidil and clonidine dosage regimens with clinical responses (mean arterial blood pressure). The potential clinical application of these correlations to other antihypertensive drugs was studied by retrospectively analyzing diastolic and mean arterial blood pressure data reported in 26 published studies of seven antihypertensive drugs. The wide interpatient variation recorded in the dose-response plots derived from the published data yielded pharmacodynamic values of little reliability or predictive value in individualizing antihypertensive dosage regimens. Use of retrospective data analysis for obtaining the necessary pharmacokinetic values to individualize antihypertensive dosage regimens is discouraged.


Relapsing polychondritis in a Latin American man. The first known reported case of relapsing polychondritis in a Latin American man is presented. The 35-year-old man, demonstrating auricular chondritis, arthritis, nasal cartilage involvement, episcleritis and respiratory tract chondritis, was admitted to the hospital and treated with 60 mg of prednisone daily, prednisolone acetate 1% ophthalmic drops every waking hour and homatropine hydrobromide 5% ophthalmic drops twice daily. After discharge from the hospital, he received 30 to 60 mg of prednisone daily and prednisolone acetate 1% ophthalmic drops twic daily for about 18 months. A permanent trachestomy was placed, azathioprine, 150 mg daily, was given and prednisone dosage was tapered to 25 mg daily when the patient subsequently was hospitalized for colapsed airway and Cushing's syndrome. The classic symptoms, pathogenesis and treatment of the disease are reviewed. Systemic corticosteroids are the drugs of choice in relapsing polychondritis, with immunosuppressive drugs, azathioprine in particular, being used as adjuvants to lower steroid dosage requirements and to achieve greater control of symptoms in patients with the severe progressive disease. Treatment of the disease with dapsone alone is promising and may offer an alternative to high-dose steroids and immunosuppressive therapy.


Lepromatous leprosy masquerading as disseminated tuberculosis. A patients with disseminated leprosy is described. A 57 year old man from Cuba presented with fever and pancytopenia. Bone marrow aspirate showed numerous acid-fast bacilli and a liver biopsy specimen contained multiple granulomas. The patient was considered to have tuberculosis and was treated with isoniazid and rifampin, with initial clinical improvement, only to have the fever recur and to show deterioration in hematologic and hepatic function. Failure to grow M. tuberculosis suggested a diagnosis of leprosy which was proved by skin biopsy. How lepromatous leprosy can masquerade as disseminated tuberculosis is discussed.


Nitrofurantoin: another cause of drug-induced chronic active hepatitis? A report of a patient with HLA-B8 antigen. Nitrofurantoin, an agent used extensively in chronic urinary tract infections, is rarely incriminated as a hepatotoxin. In this 27 year old women chronic active hepatitis first developed during exposures to nitrofurantoin, and she later suffered exacerbations. Earlier reported cases are reviewed which describe a spectrum of hepatotoxic reactions. This patient has HLA-B8, an antigen associated with autoimmune forms of chronic active hepatitis. It is postulated that the antigen may be associated with liver injury initiated by drugs such as nitrofurantoin.


Morphologic, biochemical and physiologic alterations in a case of idiopathic hypoalbuminemia (analbuminemia). A patient with idiopathic hypoalbuminemia is described. A study of albumin kinetics demonstrated slowed albumin degradation suggesting low albumin synthesis. Morphologic observation of hepatocellular alterations suggested decreased protein synthesis. The intra- and extravascular space was low with an abnormally large postural shift of intravascular fluid into the extravascular compartment. Disturbances in the concentration of plasma lipids and of several plasma proteins were detected. The effect of albumin infusion on these physiologic and biochemical abnormalities suggests that most occurred as a secondary response to the hypoalbuminemic state. Evaluation of the patient's kindred revealed no members with hypoalbuminemia.


Testicular sarcoidosis.

Testicular sarcoidosis. A 20 year old black man presented with shortness of breath, hilar adenopathy, monoarticular arthritis, polydipsia and polyuria, and bilateral testicular masses. Transbronchial biopsy revealed noncaseating granulomas consistent with sarcoidosis. Subsequent work-up demonstrated hypothalamic dysfunction, and joint fluid analysis was consistent with sarcoid arthropathy. Concern over the possibility of a testicular neoplasm led to right testicular biopsy which revealed noncaseating granulomas consistent with testicular sarcoidosis. A short course of steroid therapy resulted in clinical improvement and complete resolution of the remaining left testicular mass.


Acute myelofibrosis in progressive systemic sclerosis. Report of a case developing during long term chlorambucil therapy and discussion of pathogenetic factors. A case of acute myelofibrosis occurring in the course of long-term chlorambucil therapy for cardiac manifestations of progressive systemic sclerosis (PSS) is reported. Although hematologic malignancies have been known to develop consequent to long-term use of alkylating agents, and bone marrow suppression is well known, acute myelofibrosis has not, to our knowledge, been reported as a complication of this therapy, nor has any specific myeloproliferative syndrome been described consequent to such therapy in a patient with PSS. As abnormal fibroblastic proliferation is central to both PSS and myelofibrosis, it may be speculated that the patient with scleroderma may be predisposed to this particular expression of hematologic dyscrasia. The roles of fibroblastic proliferation, and immunologic and vascular factors in these two illnesses are currently poorly understood.


Vasculitis and Sjögren's syndrome with IgA-IgG cryoglobulinemia terminating in immunoblastic sarcoma. Generalized lymphadenopathy and other manifestations of Sjögren's syndrome developed in a 68 year old woman with a long history of systemic vasculitis and arthralgia. An unusual immunologic feature was hypogammaglobulinemia and immunoglobulin A (IgA) monoclonal immunoglobulinemia with mixed IgA-IgG cryoglobulin. At autopsy, the histopathologic findings were compatible with immunoblastic sarcoma. The monoclonal IgA protein, found in serum, pleural and pericardial fluids, showed rheumatoid factor activity. Immunocytes from the immunoblastic sarcoma were found to be the source of the monoclonal IgA protein.


Familial recurrent rhabdomyolysis due to carnitine palmityl transferase deficiency. Muscle carnitine palmityltransferase (CPT) activity was very low (0 to 14 per cent of controls) in two brothers with a syndrome of recurrent rhabdomyolysis and myoglobulinuria. In isolated muscle mitochondria the majority (87.5 per cent) of total measurable CPT enzyme activity could be attributed to external membrane CPT with severe deficiency of inner membrane CPT. By contrast, control mitochondria demonstrated a 1:1 distribution of external membrane CPT to inner membrane CPT. Thus, myoglobinuria may be due to a genetic defect of lipid metabolism in skeletal muscle, with inner membrane CPT deficiency presenting the same clinical features as external membrane CPT deficiency.


Diagnosis and localization of pheochromocytoma. Detection by measurement of urinary norepinephrine excretion during sleep, plasma norepinephrine concentration and computerized axial tomography (CT-scan). The feasibility of differentiating patients with pheochromocytoma from other hypertensive patients by measuring urinary excretion rates of norepinephrine during sleep, a period of physiologic suppression of norepinephrine release, was investigated. The mean excretion rates of norepinephrine in 248 normal subjects and in 109 patients with essential hypertension were 1.03 +/- 0.03 and 1.12 +/- 0.06 (SEM) micrograms/hour, respectively, whereas the lowest excretion rate among the six patients with pheochromocytoma was about seven times higher. Plasma norepinephrine concentration in patients with pheochromocytoma was also consistently above the range observed in both normotensive and hypertensive subjects. CT scan correctly identified the same tumors visualized by selective arteriography. It is suggested that the usefulness of these approaches will provide simpler means of screening and detecting pheochromocytoma.


Essential hypertension in black and white subjects. Hemodynamic findings and fluid volume state. Systemic hemodynamics (cardiac output, intraarterial pressure, total peripheral resistance) and intravascular volume (plasma volume and red cell mass) were measured in a population of 126 black and white patients, 51 with borderline hypertension and 75 with established essential hypertension. The findings were compared with those in 29 age-matched normotensive control subjects of both races. The white patients with established hypertension demonstrated a faster heart rate than the black patients (less than 0.05); this difference was more pronounced during upright tilt (p less than 0.02). No significant difference in cardiac index, total peripheral resistance, plasma volume or total blood volume was found between the two racial populations. Cardiac index correlated directly with plasma and total blood volume in black patients (r = 0.32, p less than 0.05) and white patients (r = 0.35, p less than 0.001) as well as in the whole study population (r = 0.36, p less than 0.001). The regression lines were similar in the two races. Further, a negative correlation was observed between the total peripheral resistance and plasma volume (r = -0.31, p less than 0.001) or total blood volume (r = -0.34, p less than 0.001), and it was similar in both races (blacks r = -0.48, p less than 0.01; whites r = -0.25, p less than 0.05). Age correlated significantly with total peripheral resistance in the white patients (r = 0.35, p less than 0.001) and in the total study population (r = 0.28, p less than 0.001). We conclude that, for every given age or level of arterial pressure, systemic hemodynamics are similar for the black and white patients with essential hypertension. These data, therefore, do not support the clinical impression that basic pathophysiology and hypertensive vascular disease are different in the black patient with essential hypertension.


The value of edema fluid protein measurement in patients with pulmonary edema. Alveolar fluid and plasma proteins were analyzed in 24 patients with florid pulmonary edema, in 21 of whom pulmonary capillary wedge pressure (Pcw) was also measured. In all patients with Pcw less than 20 mm Hg, the edema fluid to plasma protein ratio exceeded 0.6; the mean edema fluid to plasma protein ratio in the four patients with cardiogenic edema (increased Pcw) was 0.46. In the 21 patients in whom full data were available, the net intravascular filtration force (Pcw - plasma colloid osmotic pressure) was less than -4 mm Hg, the value at which (according to others) pulmonary edema should occur, in only 10. When the interstitial colloid osmotic pressure, approximated by the osmotic pressure of edema fluid protein, was added, the net filtration force became positive in 17 of 21 patients. Comparison of the protein concentrations of edema fluid and plasma aids in the diagnostic separation of increased permeability from high hydrostatic pressure edema and adds to our understanding of the relative osmotic and hydrostatic forces that contribute to pulmonary edema when the alveolar-capillary membrane is damaged.


Community-acquired acinetobacter pneumonia. Acinetobacter calcoaceticus var anitratus, a nonfermentative grampnegative bacillus, has been infrequently reported as a cause of community-acquired pneumonia. In this paper we describe the course of six recent patients with community-acquired, bacteremic pneumonia due to this organism and review the six previously reported cases. Our experience suggests this organism is a more common cause of community-acquired pneumonia than previously thought. Acinetobacter pneumonia occurs in older persons with chronic disease, especially alcoholism. It is a fulminant illness with respiratory distress, hypoxemia, leukopenia and shock. Chest roentgenograms reveal a lobar or bronchopneumonic infiltrate which often becomes bilateral within 24 hours of admission to the hospital. Pleural effusions are common. The mortality rate is 43 per cent. Factors that predict a fatal outcome are granulocytopenia, empyema and therapy with inappropriate antibiotics. Therapy with appropriate antibiotics, especially carbenicillin and an aminoglycoside, increases survival.


Transfer factor therapy in the Wiskott-Aldrich syndrome. Results of long-term follow-up in 32 patients. Thirty-two patients with the Wiskott-Aldrich syndrome have been treated with transfer factor provided by this laboratory. Apparent clinical benefit was observed in 44 per cent of them. The mean age of the patients who showed clinical benefit was significantly greater than that of the patients who showed no benefit. Conversion of immunologic reactivity correlated with clinical benefit. Thirteen of the patients who received transfer factor are alive, and 17 have died (43 per cent survival). Clinical benefit was correlated with survival. The median survival was greater than five years in the patients who showed clinical benefit, whereas it was 18 months in those who did not show clinical benefit. We conclude that transfer factor caused conversion of immunologic parameters, apparent clinical benefit and prolonged survival in some, but not all, patients with the Wiskott-Aldrich syndrome.


Abnormal regulation of antidiuretic hormone in idiopathic edema. Idiopathic edema is characterized by impaired water excretion, particularly in the upright posture. Indirect evidence has shown that antidiuretic hormone is involved in this disease. For this reason, we measured urinary arginine vasopressin by radioimmunoassay before and during water loading (15 ml/kg) in 10 normal women and in 10 subjects with idiopathic edema in both the supine and upright postures. Daily sodium intake was 100 meq. Renin and aldosterone were concomitantly investigated, and abnormally high values were observed both in the recumbent and upright postures. Basal values for urinary arginine vasopressin were identical in control subjects and in patients with idiopathic edema. The water load significantly reduced urinary arginine vasopressin in normal women in both positions, but in those with idiopathic edema only in the supine position. In those with idiopathic edema, assumption of the upright posture was accompanied by a transient decrease in glomerular filtration, a major decrease in osmolar clearance and no decrease in urinary arginine vasopressin after water loading. Significant correlations were established between urinary arginine vasopressin and osmolar or volemic parameters in normal women, but these correlations were not found in those with idiopathic edema in either position. Arginine vasopressin regulation was abnormal in idiopathic edema, and this hormone was believed to play a part in the pathogenesis of this disease.


Survival after recovery from acute myocardial infarction. Two and five year prognostic indices. A prognostic index for two year survival following recovery from acute myocardial infarction has been verified in an independent group of 105 patients. Five variables comprise the index: systolic blood pressure level on admission, highest blood urea nitrogen level in the cardiac care unit; atrial arrhythmias in the cardiac care unit; angina pectoris for more than three months or a previous myocardial infarction; and more than one ventricular ectopic beat per hour recorded on an 8 hour dynamic electrocardiogram during convalescence just prior to hospital discharge. One hundred twenty-six patients have also been followed for five or more years, and we now report a five year prognostic index. Discriminant analysis indicates that the same five variables, although weighted differently, continue to be significant for prognostic assessment and may be utilized in the identification of patients at high and lower risk.


Hypertrophic hepatic osteoarthropathy. Clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature. Twenty patients with biopsy proved liver disease, and roentgenologic features of hypertrophic osteoarthropathy have been studied, and the literature has been reviewed. The syndrome is a rare association of many chronic liver diseases, including primary biliary cirrhosis, bile duct carcinoma, benign bile duct stricture, chronic active hepatitis, posthepatitic cirrhosis and alcoholic cirrhosis. Patients may be asymptomatic, although bone pain, arthralgia or arthritis may be presenting symptoms. Ninety per cent of the patients are clinical jaundiced at the time of diagnosis, and 95 per cent have digital clubbing. The distal tibia and fibula are the first bones to become involved, although wrist, foot bones, femurs, hand bones and humeri may be affected in order of frequency. There is no correlation between the presence of esophageal varices or surgical portacaval shunts and the extent of the syndrome, neither is there a correlation with the degree of liver function impairment. Serum calcium and phosphate levels are normal, as is urinary hydroxyproline and estrogen excretion. There was no evidence to implicate elevated levels of growth hormone or overdosage of vitamin A. Although the majority of patients tested had mild arterial hypoxemia, increased cardiac output and evidence of right to left shunting, these were also present in disease-matched control subjects without osteoarthropathy. For screening purposes, patients with chronic liver disease and clubbing should have roentgenologic studies of the lower tibias and fibulas, to select those patients suitable for a more extensive skeletal survey.


How to be less invasive.

How to be less invasive. Unless cardiac output is reduced, alveolar ventilation can be monitored without arterial blood gas analysis by estimating arterial carbon dioxide tension (PaO2) from rebreathing measurement of mixed venous carbon dioxide tension (PvCO2) (PaCO2 = 0.8 PvCO2). If cardiac output is reduced, the PvCO2 - PaCO2 difference increases, reflecting the increased venoarterial carbon dioxide (CO2) content difference (Fick principle). A reduction in cardiac output can thus be quantified without catheterization of the central circulation by measuring both PaCO2 and PvCO2. The significance of such a reduction in cardiac output for oxygen (O2) delivery to tissues is determined by calculation of mixed venous O2 saturation (SvO2), using the inter-relationship of CO2 production to O2 consumption. With normal arterial oxygenation (SaO2) and hemoglobin concentration, PaCO2 less than 0.8 PvCO2 - 12 implies a reduction in cardiac output such that SvO2 is less than 33 per cent, which indicates inadequate O2 delivery to tissues. Ear oximetry and rebreathing measurement of PvCO2 are simple, noninvasive, bedside techniques.


Marrow granulocyte reserves in black Americans. Hydrocortisone-induced granulocytosis in the "benign" neutropenia of the black. The bone marrow granulocyte reserves of nine black patients with "benign" neutropenia were estimated by measuring the maximum neutrophil increment after the administration of hydrocortisone. Thirty control subjects, including 16 black and 14 white adults, were also studied. The mean neutrophil increment in the black patients with neutropenia was significantly less than that in the control subjects. The mean increment in the black control was also significantly less than that in the white control subjects. Four of the 16 black control subjects had neutrophil counts below 2,000/microliter; if these four are excluded from the analysis, the difference between the black and white control subjects is no longer significant. These data suggest that there is a subpopulation of healthy black adults with neutrophil counts below 2,000/microliter with reduced marrow granulocyte reserves as tested by corticosteroids. Bone marrow aspirates in four of the neutropenic patients showed normal cellularity and myeloid maturation suggesting that the lower increments are due to a difference in granulocyte release rather than to a difference in granulocyte production.


Anaerobic bacterial meningitis.

Anaerobic bacterial meningitis. Anaerobic meningitis occurred in four patients in whom anaerobic bacteria had not been suspected as a possible cause. The predisposing conditions were typical of those seen in patients previously reported to have this infection and included chronic otitis media with mastoiditis, chronic sinusitis, recent craniotomy and abdominal trauma. Two of the patients had undergone immunosuppression (immunosuppressed patients); a compromised immune system may facilitate the development of anaerobic meningitis in patients with the appropritate underlying conditions. Head and neck neoplasms, head trauma, suppurative pharyngitis and laminectomy wounds are additional situations in which anaerobic meningitis occurs. Anaerobic bacterial meningitis probably occurs more often than is recognized. The cerebrospinal fluid should be transported and cultured anaerobically when meningitis develops in a patient with a predisposing condition.


Corynebacterium pseudotuberculosis. A new cause of infectious and eosinophilic pneumonia. A 28 year old veterinary medical student experienced spiking fever, cough, peripheral blood eosinophilia and an eosinophilic pulmonary infiltrate. Corynebacterium pseudotuberculosis was isolated from a transtracheal aspirate and bronchoscopy washings. C. pseudotuberculosis, a pathogen responsible for lymphadenitis in livestock, has never been reported to cause pneumonia in man. In the four cases of C. pseudotuberculosis previously reported, lymphadenitis was the chief clinical presentation. In our patient specific antibodies against the isolated C. pseudotuberculosis developed but not against the other corynebacteria. With erythromycin therapy, the peripheral blood eosinophilia and IgE anti-C. pseudotuberculosis titer decreased whereas the IgG titer continued to increase.


Fever and pulmonary thromboembolism.

Fever and pulmonary thromboembolism. Fever patterns associated with pulmonary thromboembolism have not been well characterized. Upon review of 35 consecutive patients with angiographically documented pulmonary emboli, fever was present in 24 patients; and in 20, it was attributed solely to pulmonary thromboembolism. Analysis of these cases indicates that high fever (temperature greater than 39 degrees C) due to pulmonary thromboembolism may occur early, and low-grade fever may continue for a week or more. Fever persisting beyond six days, however, especially with temperatures over 38.5 degrees C, should not be ascribed to pulmonary thromboembolism unless other causes have been carefully excluded. If the clinical setting and patient's findings are consistent with pulmonary thromboembolism, one should not be deterred from presumptively making this diagnosis and initiating therapy because of the presence of high fever.


Dysautonomia in mitral valve prolapse.

Dysautonomia in mitral valve prolapse. Many of the clinical features of patients with mitral valve prolapse can logically be attributed to abnormal autonomic neural function. Accordingly, we have studied heart rate and blood pressure response to a standardized Valsalva maneuver and postural test in 44 untreated patients with demonstrated mitral valve prolapse. Fifteen healthy subjects of similar age served as controls. The directional changes of blood pressure and heart rate were similar in control subjects and patients in both tests, but patients differed from control subjects by their widely oscillating heart rate during the upright posture, and their exaggerated and prolonged bradycardia during the recovery phase of the Valsalva maneuver and following their return to recumbency in the postural test. This bradycardia persisted for 30 to 90 seconds after blood pressure returned to control values. Patients also showed a greater respiratory variation of R-R interval, which became especially marked during the adjustment to changes of posture. We postulate an abnormal central modulation of baroreflexes as the best explanation for the dysautonomic responses of symptomatic patients with prolapsed mitral valves.


Renal stones in Wilson's disease.

Renal stones in Wilson's disease. Fifty-four patients with Wilson's disease were studied with regard to renal stones. Seven of the 45 patients (16 per cent) who underwent roentgenographic procedures of the urinary tract had unequivocal evidence of renal stones. In four of the seven patients with Wilson's disease who had renal stones, the stones were discovered at the time or before the diagnosis of Wilson's disease was made. Of the several possible factors that may predispose patients with Wilson's disease to renal stone formation, the renal tubular acidosis pattern of abnormality in acid-base excretion is probably the most significant. In general, patients with renal stones and unexplained neurologic, bony or hepatic abnormalities should be screened for Wilson's disease by slit-lamp examination, determination of serum copper and ceruloplasmin concentrations, and urinary excretion of copper, particularly if they have relatively alkaline urine.


Articular manifestations of polymyositis and dermatomyositis. Nine patients with polymyositis or dermatomyositis associated with arthritis without antinuclear antibodies have been studied. In eight patients a mildly inflammatory nonerosive arthritis occurred coincident with early manifestations or before the appearance of symptomatic muscle disease. Hands, wrists and knees were prominently involved. This arthritis responded to corticosteroids given for the myositis. One patient had erosive arthritis and periarticular calcifications associated with acute inflammation that seemed to diminish with colchicine therapy. Synovial biopsy specimens showed surface fibrin deposition, focal loss of lining cells and mild inflammation--findings similar to those in scleroderma. By electron microscopy tubuloreticular structures were found in vascular endothelium in synovium, as in other tissues in polymyositis. All patients surprisingly had pulmonary manifestations suggesting the possibility that the condition in this group of patients may represent a distinctive subset of polymyositis.


Antibody response to infection in multiple myeloma. Implications for vaccination. We report the humoral immune response of a patient with multiple myeloma to rapidly successive episodes of meningococcal and pneumococcal meningitis. Specific antibody responses included a high bactericidal titer (1:640) against the infecting meningococcus and a sharp increase (from 198 to 8,097 ng/ml antibody nitrogen) in antibody to the type-specific capsular polysaccharide of the infecting pneumococcus. These data, showing the production of protective antibodies against the two pathogens, suggest that some patients with multiple myeloma might also respond to appropriately administered bacterial vaccines. This fact should be ascertained because vaccination could potentially reduce the high rate of bacterial infections associated with this disease.


Rapid onset of emphysema associated with diffuse parenchymal disease. In experimental models pulmonary emphysema may be produced in hours to days; however, in human subjects emphysema commonly develops over a period of many years. In this report we document a case of severe emphysema which developed in less than six months in association with an unexplained illness characterized by dyspnea, hypoxemia and bilateral lung parenchymal disease. There was no hereditary predisposition. The diffuse alveolar injury syndrome must be considered as a potential cause of alveolar disruption.


Legionnaires' disease. A cause of severe abscess-forming pneumonia. In two previously well nonsmokers fatal pneumonia developed with extensive abscess formation. Legionnaires' bacillus was the only pathogen isolated. These cases indicate that Legionnaires' bacillus is capable of causing extensive necrosis of the lung.


Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation. A 51 year old woman sustained ventricular fibrillation while receiving perphenazine and protriptyline. After successful resuscitation and clinical stabilization, cardiac electrophysiologic studies were performed before and after the administration of each of these medications. Perphenazine widened the ventricular echo zone and facilitated induction of short salvoes of ventricular tachycardia (repetitive ventricular response). Protriptyline also widened the ventricular echo zone and allowed easy induction of long runs of ventricular tachycardia. Both psychotropic agents increased the incidence of ventricular dysrhythmias in this patient. The electrophysiologic study is a useful technique in determining the interaction between psychotropic drugs and life-threatening arrhythmias; it may provide a means of identifying the patients with cardiac disease in whom administration of these agents may be fatal.


Virus myocarditis: a critique of the literature from clinical, electrocardiographic, and pathologic standpoints. Concurrent viral infection and myocarditis presumably indicate viral myocarditis. The electrocardiographic and pathologic changes developing during acute infection may, however, result from changes not produced by the infection itself, eg, fever, tachycardia, ischemia, potassium depletion, vitamin deficiencies, drugs. This qualification should be remembered in the evaluation of all alleged virus myocarditis. Viral infection seems to prefer the very young. Its localization in the heart is favored by general or local hypoxia, perhaps thus explaining a predilection for the subendocardium. It may be influenced by the strain of the organism or by the hormonal or immunologic state of the host. Intrauterine infection of the fetus with rubella, mumps, and perhaps coxsackievirus can induce congenital cardiac defects. The role of virus infection in precipitating acute myocardial infarction deserves further study. The value of treatment, including steroids, nonsteroidal immunosuppressive agents, and "antiviral" agents is not yet established.


Turner's syndrome and carbohydrate metabolism. I. Impaired insulin secretion after tolbutamide and glucagon stimulation tests: evidence of insulin deficiency. Tolbutamide (25 mg/kg: maximum 1 mg) intravenously (IV) and glucagon (0.03 mg/kg; maximum 1 mg) intramuscularly (IM) were given sequentially to 12 untreated girls with XO-Turner's syndrome (ages 6.5 to 17.0 years) and to ten female siblings (ages 8.0 to 16.7 years) to evaluate blood sugar (BS), plasma free fatty acids (FFA), serum immunoreactive insulin (IRI), and growth hormone (IRGH) responses to these insulinogenic secretagogues in order to appreciate any differences of genotypes on carbohydrate metabolism within identical family backgrounds. Seven of 12 patients with Turner's syndrome (58%) but none of the siblings were 20% or more overweight for height. There was a family history of diabetes mellitus in 7 to 12 patients (58%). The results showed significant elevations of mean FFA levels and decreased mean IRI responses to both insulinogenic stimuli without differences in mean BS or serum IRGH responses in the Turner's syndrome patients when compared to the controls. Three of 12 patients (25%) had abnormally elevated and prolonged blood sugar responses to IM glucagon. These findings show a significant incidence of abnormal carbohydrate and lipid metabolism and insulin deficiency in untreated patients with XO-Turner's syndrome when compared to normal female siblings and implicate this chromosomal defect in the impaired insulin secretion.


Turner's syndrome and carbohydrate metabolism. II. Parotid salivary insulin concentration in normal subjects and in patients with gonadal dysgenesis. Ten children with XO gonadal dysgenesis and ten control siblings (CS) had sequential IV tolbutamide and IM glucagon tests to ascertain serum and salivary insulin concentrations, to confirm the presence of parotid salivary insulin and to determine if these concentrations were of diagnostic value in the diagnosis of insulin deficiency. After tolbutamide, peak serum insulin concentrations were lower in the patients with Turner's syndrome (TS) than in control siblings (58 +/- 10 vs 90 +/- 15 microU/ml) and fractional areas under insulin curves were significantly lower in the patients with Turner's syndrome at 10 to 15 minutes (TS: 240 +/- 16 microUmin/ml; CS: 340 +/- 46 microU-min/ml, P less than 0.05) and at 15 to 30 minutes (TS: 562 +/- 62 microU-min/ml; CS: 884 +/- 128 microU-min/ml, P less than 0.05). After glucagon, peak serum insulin concentrations were significantly lower in Turner's syndrome than in control siblings(P less than 0.02, at 45 minutes) and fractional areas under insulin curves were also lower in TS than in siblings at 30 to 45 minutes (TS: 1,062 +/- 185 microU-min/ml; CS: 2,189 +/- 402 microU-min/ml, P less than 0.02). Basal salivary immunoreactive insulin (IR) concentrations were similar in both groups: TS: 4.8 +/- 2.1 microU/min; CS: 2.1 +/- 0.4 microU/min. Peak salivary IRI concentrations after tolbutamide were 13.8 +/- 4.7 microU/min in Turner's syndrome and 8.8 +/- 1.8 microU/ml in control siblings. Peak salivary IRI values in Turner's syndrome and in control siblings after glucagon were 26.8 +/- 10.1 and 13.4 +/- 2.1 microU/min, respectively. While significant differces in insulin secretion in serum were detected in the two patient groups, no differences were noted between groups when salivary insulin concentrations were compared. These data confirm serum insulin deficiency in gonadal dysgenesis, the presence of immunoreactive insulin in parotid saliva, and suggest the possibility that extrapancreatic insulin synthesis could occur in the parotid gland.


Modern management of the breech delivery. Retrospective review of 457 breech deliveries failed to reveal a significant improvement in neonatal mortality and morbidity rates for those delivered by cesarean section vs. vaginal delivery. A slight but insignificant improvement in salvage was found for the 1,000 to 1,500 gram weight category when delivery was by cesarean section. Most of the deaths in the less than 1,500 gram breech presentation were associated with hyaline membrane disease or congenital defects incompatible with life and sepsis rather than directly related to the manner of breech delivery.


Carbohydrate metabolism in porphyria cutanea tarda. Porphyria cutanea tarda (PCT) has a known increased incidence of diabetes mellitus and hepatic involvement. We investigated glucose tolerance and glucoregulatory hormone alterations in seven patients with PCT and correlated these results with hepatic histology by percutaneous liver biopsy. Abnormal glucose tolerance was observed in six of the seven patients (87%). Fasting serum insulin levels were normal range, and normal glucose and growth hormone responses to standard, exogenous intravenous insulin were observed. Fasting serum glucagon and urine free cortisol levels were normal in those patients in whom they were measured. While varying degrees of abnormalities were found on histopathologic exam of the liver biopsies, no patient met the criteria for cirrhosis, and none of the patients demonstrated abnormal levels of insulin counterregulatory hormones commonly seen in cirrhosis. Thus, liver disease may not be the sole cause of the observed glucose intolerance and hyperinsulinemia in PCT patients.


Vaginal breech delivery or cesarean section. In 579 singleton breech deliveries the total perinatal mortality rate was 10.4% and the corrected perinatal mortality rate was 0.67%. There were 452 babies delivered vaginally (78.1%) and 127 delivered by cesarean section (21.9%). The perinatal mortality rate was very high in the premature breech delivery and in the low-birth-weight infant. Cesarean section should be used to avoid a traumatic vaginal delivery and it should be used more liberally in the mature breech, but it is unlikely that cesarean section rates in excess of 50% will significantly reduce the perinatal mortality mortality rate. More information is required as to whether extending the indications for cesarean section in the low-birth-weight infant will further reduce the perinatal mortality rate.