The risk of serious cardiac arrhythmias among cisapride users in the United Kingdom and Canada.

PURPOSE: Serious, although rare, ventricular arrhythmias and deaths have been reported in patients taking cisapride monohydrate. Without quantification of the risk involved, it is impossible to develop rational therapeutic guidelines. SUBJECTS AND METHODS: Arrhythmic events (sudden deaths and other events compatible with serious ventricular arrhythmias) were sought among 36,743 patients prescribed cisapride in the United Kingdom and Saskatchewan, Canada. Prescriptions and cases were identified from computerized medical claims data and physicians' office records. We compared rates of events between periods of recent cisapride use and nonrecent use, using cohort analysis. Potential confounding factors, including concomitant treatment with agents that inhibit CYP3A4 metabolism or that prolong the QT interval, were assessed in a nested case-control study. RESULTS: In the cohort analysis, the incidence of the arrhythmic events was 1.6 times greater (95% confidence interval [CI]: 0.9 to 2.9) in periods of recent use. With adjustment for clinical history, use of CYP3A4 inhibitors, and use of drugs that prolong the QT interval, the odds ratio for cisapride and cardiac outcomes was 1.0 (95% CI: 0.3 to 3.7). There was no identifiable increase in risk when cisapride was dispensed at about the same time as QT-prolonging drugs or CYP3A4 inhibitors. QT-prolonging agents were associated with a 2.5-fold increase in the risk of arrhythmic events (95% CI: 1.1 to 5.8). CONCLUSIONS: Serious rhythm disorders were not associated with cisapride use, although the upper confidence bounds do not rule out an increase in risk.

Lymphatic and haematopoietic cancer mortality in a population attending school adjacent to styrene-butadiene facilities, 1963-1993.

STUDY OBJECTIVE: To evaluate the risk of mortality from lymphatic and haematopoietic cancers and other causes among students. DESIGN: The study used school records, yearbooks, and Texas Department of Health records for the school years 1963-64 to 1992-93 to construct a cohort of 15,403 students. Three mortality databases were searched to identify deaths, and mortality rates in the cohort were compared with mortality rates from the United States and Texas. Computed standardised mortality ratios and 95% confidence intervals were used. SETTING: Eastern Texas high school adjacent to facilities that have been producing synthetic styrene-butadiene since 1943. MAIN RESULTS: 338 deaths were identified. The all causes standardised mortality ratio was 0.84 (95% confidence intervals 0.74, 0.95) for men and 0.89 (0.73, 1.09) for women. The standardised mortality ratio for all lymphatic and haematopoietic cancers was 1.64 (95% confidence intervals 0.85, 2.87) for men and 0.47 (0.06, 1.70) for women. The slight male excess in lymphatic and haematopoietic cancers was stronger among men who attended school for two years or less. CONCLUSIONS: The overall mortality from lymphatic and haematopoietic cancer among the students was little different from that of the United States as a whole. A moderate excess for men, predominantly among the shorter-term students, was offset by a deficit among women. These variations are compatible with random fluctuations; the overall pattern is not indicative of an effect of environmental exposure sustained while attending the high school.

Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome.

Systematic, prospective data regarding phenotypic features, including echocardiographic findings, in pediatric patients with the Marfan syndrome are lacking. In addition, limited and conflicting information exists regarding the impact of pharmacologic therapy on aortic growth rate in children. Fifty-three children and adolescents with the Marfan syndrome underwent physical examination, anthropometric evaluation, and echocardiography. The relation of pharmacologic therapy to aortic growth rate was examined in the 44 subjects in whom serial echocardiograms were recorded. Although boys and girls did not differ in ocular, skeletal, or cardiovascular manifestations, aortic dilatation tended to be more common in boys (86% vs 72%). Children with aortic dilatation at baseline (42 of 53 or 79%) were more likely to also have scoliosis and mitral prolapse (both p <0.005). The medicated patients had slower aortic growth than the unmedicated patients with regard to both absolute aortic growth rate (p <0.01) and aortic growth rate adjusted for age and body size (p <0.005). Nevertheless, major cardiovascular complications developed in 5 patients despite long-term pharmacologic therapy. In conclusion, beta-blocker and calcium antagonist therapy retards aortic growth rate in children and adolescents with the Marfan syndrome.

Overall mortality of cellular telephone customers.

Unlike mobile cellular telephones, in which the antenna is not part of the handset, a portable cellular telephone exposes the user's head to radio frequency energy transmitted from the antenna. This exposure has prompted concerns about potential biological effects, including brain cancer. As a first step in a record-based mortality surveillance of cellular telephone customers, we report on overall mortality of a cohort of more than 250,000 portable and mobile telephone customers during 1994. We found age-specific rates to be similar for users of the two types of telephones. For customers with accounts at least 3 years old, the ratio of mortality rates in 1994 for portable telephone users, compared with mobile telephone users, was 0.86 (90% confidence interval = 0.47-1.53).

Utility of telephone company records for epidemiologic studies of cellular telephones.

We conducted a survey of over 5,000 telephone users who were customers of one large cellular telephone company covering four major geographical areas. Our primary goal was to assess the utility of ascertaining information on telephone use and type from telephone company records. We compared information from 3,949 respondents with corresponding data from company billing records. We found that 48% of the account holders were sole users, and 69% were the primary user, meaning that they accounted for at least 75% of the use. Respondent reports of amount of telephone use were highly correlated with data on the billing record (r = 0.74). Respondent reports of telephone type were similarly correlated with data from the manufacturer (r = 0.92). We also inquired about telephone holding patterns, since these have implications for exposure. Most users reported favoring one side of the head when using the telephone, but the side of the head used was not strongly associated with handedness.

A five-year clinical experience with 112 Blalock-Taussig shunts.

In spite of recent advances in neonatal open repair for complex cyanotic heart disease, some patients require palliation with a systemic-to-pulmonary artery shunt. We report a 5-year experience (1985-1990) with 112 Blalock-Taussig shunts. Forty-six of the 92 patients had some variant of tetralogy of Fallot, with a wide spectrum of diagnoses in the remainder. The median age at surgery was 3 months. A classic Blalock-Taussig shunt was done in 26% (group I), and a 4- or 5-mm PTFE graft was utilized in the remainder (group II). The technical aspects of each of the procedures are reviewed. There were three early deaths in the entire group, none of them related to Blalock-Taussig shunt function. There was no incidence of early shunt insufficiency, bleeding, infection, limb ischemia, or pulmonary artery distortion. There was a 21% incidence of clinical congestive heart failure, seen somewhat more commonly in group I. The overall need for reshunting/open repair was similar in both groups, but there was a statistically longer interval between the initial Blalock-Taussig shunt and the second procedure in group I (21.6 vs 12.4 months). The Blalock-Taussig shunt remains a safe, reliable, and effective means of increasing pulmonary flow.

Congenital aortic regurgitation: natural history and management.

OBJECTIVES AND BACKGROUND: Congenital aortic regurgitation is rare as an isolated lesion. We describe seven children with no physical features of the Marfan syndrome in the patients or their families and no other cardiac lesions who had congenital valvular aortic regurgitation. METHODS: From 1954 to the present, seven children with auscultatory and physiologic characteristics of aortic regurgitation were evaluated for a total of 108 patient-years. We report on their natural history, clinical and laboratory findings, management and outcome. RESULTS: In five of the seven children congenital aortic regurgitation was diagnosed in infancy. In four, progressive severity of the regurgitation led to valve replacement at age 3, 10, 15 and 20 years, respectively, and to resection of an aneurysm of the ascending aorta in the 10-year old patient. Two patients had cystic medial necrosis on aortic biopsy. One of these patients died after reoperation for dissecting aneurysm of the thoracic aorta at 22 years of age; the other died after dissection and rupture of the ascending aorta at age 25 years. After obstructing pannus developed, the 3-year old patient underwent replacement of the St. Jude valve at age 10 years. The other three patients were asymptomatic at last follow-up at age 8, 10 and 20 years, respectively. CONCLUSIONS: Supportive management is recommended until it becomes necessary to intervene surgically when regurgitation becomes severe. The need for surgical treatment is indicated by the appearance of a diastolic thrill, left ventricular strain on the electrocardiogram or other evidence of left ventricular dysfunction on the echocardiogram or exercise stress testing by treadmill or radionuclide cineangiocardiography. Close follow-up of these patients is important to detect progression of aortic regurgitation, especially in the presence of cystic medial necrosis.

MR imaging of cardiac mass in Wegener granulomatosis.

Wegener granulomatosis is a disorder of unknown etiology characterized by a necrotizing granulomatous vasculitis that primarily affects the paranasal sinuses, lungs, and kidneys. It is usually a disease of adults with infrequent cardiac involvement. We report the unusual presentation of this disorder in an adolescent with a cardiac mass. The findings on two-dimensional echocardiography and MR imaging are discussed.

Unique variant of Taussig-Bing heart: double-outlet right ventricle with double ventricular septal defects and double overriding of great arteries.

A cyanotic, tachypneic newborn was diagnosed to have double-outlet right ventricle of the Taussig-Bing type. Cardiac failure did not respond to medical treatment or surgical palliation. Postmortem examination revealed two ventricular septal defects (VSDs), one a malalignment VSD in the membranous septum and adjacent tissue and the other in the anterosuperior part of the muscular septum. The D-malposed aortic root emerged mainly from the right ventricle, with aortic-mitral continuity. The larger posterolateral pulmonary root arose almost entirely from the right ventricle, confluent with the muscular VSD, and unrelated to the mitral valve. Its right ventricular aspect was obstructed by hypertrophied infundibulum. This unique malformation of the heart functioned as a double-outlet right ventricle of Taussig-Bing type. In addition, however, the malformation had elements of tetralogy of Fallot because of the malaligned VSD and hypertrophied conal musculature (although pulmonary flow was excessive), and also of complete transposition of the great arteries because of the arrangements of the two VSDs, which favored aortic flow from right ventricle and pulmonary blood flow from the left ventricle. Thus, a single heart presented similarities to three anatomic and functional entities.

Mortality from cancer of the colon or rectum among workers exposed to ethyl acrylate and methyl methacrylate.

Mortality from colon and rectum cancer has been reviewed in three cohorts working in 1933-1982 in two plants manufacturing and polymerizing acrylate monomers. The two cohorts with later dates of hire showed no excess mortality. In the earliest cohort, excess colon cancer seemed restricted to men employed extensively in the early 1940s in jobs entailing the highest exposures to vapor-phase ethyl acrylate (EA) and methyl methacrylate (MMA) monomer and volatile by-products of the EA/MMA polymerization process. The excess mortality appeared only some two decades after the equivalent of three years' employment in jobs with the most intense exposures. A smaller elevation in colon cancer mortality also appeared in a low-exposure group in the early cohort. Rectal cancer mortality was elevated in the same categories that showed excess rates of colon cancer death. Because of the lower rates, the rectal cancer results are more imprecise.

Clinical trial of single-dose intravenous gamma globulin in acute Kawasaki disease. Preliminary report.

Gamma globulin administered in a single dose of 1 g/kg of body weight intravenously caused prompt clinical improvement in 27 of 32 consecutive children with Kawasaki disease treated by the 12th day of illness. Response was equally good for the 20 children treated in the first week and the 12 treated in the second week. Fever and clinical signs abated within the first day after treatment, the mean white blood cell count normalized by 48 hours, and the sedimentation rate continued to be elevated for about 2 weeks, while the platelet count rose during the first 2 weeks after treatment and returned to normal approximately 1 month after treatment. Five children with incomplete relief needed more than the single dose before resolution of signs and symptoms occurred. Coronary aneurysms in 2 patients before treatment regressed by 2 weeks. No patient developed coronary aneurysms. No child had sequelae of Kawasaki disease at a follow-up of 2 to 31 months. We believe that although this was a one-arm, uncontrolled pilot study, the results suggest that this protocol provides a safe, flexible, and effective treatment for acute Kawasaki disease.

A comparison of thermodilution and pulsed Doppler cardiac output measurement in critically ill children.

To evaluate the pulsed Doppler cardiac output method as a noninvasive means for determining cardiac output in critically ill children, we performed paired pulsed Doppler and thermodilution cardiac output determinations in 17 critically ill children. Commercially available equipment, specifically designed for this purpose, was employed. Forty paired thermodilution and pulsed Doppler determinations were made. There was a significant correlation between the two measurements (pulsed Doppler = 0.84 thermodilution + 0.39; r = 0.79, p less than 0.01). The ranges of thermodilution measurements (1.02 to 6.26 L/min; median 2.77 L/min) and pulsed Doppler measurements (1.13 to 6.35 L/min; median 2.57 L/min) were not different (p = 0.25). However, differences between individual paired thermodilution and pulsed Doppler measurements were large (-3.13 to 2.03 L/min; median 0.12 L/min), and the percentage difference between individual paired thermodilution and pulsed Doppler measurements ranged from 0.41% to 102.5% (median 12.7%). A discrepancy of 15% or more between thermodilution and pulsed Doppler was encountered in 18 (45%) of 40 of paired measurements (95% confidence interval: 29% to 61%), and one fourth of the paired measurements differed by more than 25%. We conclude that, as employed in this study, pulsed Doppler cardiac output determination is not sufficiently representative of the thermodilution output to be employed for hemodynamic monitoring in critically ill children.

Epidemiologic aspects of Kawasaki disease in a Manhattan hospital.

Epidemiologic and clinical features of Kawasaki disease in 106 patients seen between 1980 and 1986 at The New York Hospital in midtown Manhattan were compared with those in large series from the United States, Canada, and Japan. Dissimilarities in our Kawasaki disease experience included ethnic heterogeneity of our patients (50% white, 18% black, 16% Hispanic, and 16% Oriental) and, in comparison with the Japanese experience, an older mean age (3 1/2 vs 1 1/2 years) with fewer children less than 2 years of age (32% vs 50% to 60%). In comparison with the general population of the geographic urban and suburban referral area for our hospital and in comparison with our general pediatric population, Oriental children with Kawasaki disease were overrepresented (16% vs 2%). More families of children with Kawasaki disease were members of the upper and middle class (73%) than were the population seen in general pediatrics (31.7%) at our hospital. Personal interviews with 63 families of children with Kawasaki disease and 63 control families with children paired for ethnic group, sex, and age revealed no epidemiologic differences except for use of rug shampoo within 1 month of onset in 16 episodes in 15 children with Kawasaki disease in 14 families (22% of families) compared with two families of control children (3%) (P less than .001).

Correlation of electrocardiographic and echocardiographic changes in Kawasaki syndrome.

To determine whether changes in ECGs correlated with abnormalities in echocardiograms in children with acute and convalescent Kawasaki syndrome, we undertook a retrospective analysis of 44 patients examined during the first 2 weeks of illness and followed for at least 6 months, 31 for longer than 1 year. We analyzed 360 ECGs, 282 echocardiograms, and clinical status. Results of echocardiography showed 18 children with myocardial dysfunction, pericardial effusion, and/or coronary arterial abnormalities (41%); 26 children had no abnormalities. All 18 of the former and all but 10 of the latter had abnormalities on serial ECGs that normalized on recovery. Thirty-four of 44 patients (77%) had ECG abnormalities. These abnormalities were most prevalent in the first month: 68% appeared in the first week, about 50% in the second to fourth weeks, 16% at 2 months, and 10% at 3 months. The type of ECG change did not predict the type of echocardiographic abnormality, except that low voltage of QRS was found only with pericardial effusion. The most frequent early changes were in T waves, which were flattened in 28 (64%). Later 12 patients had high, peaked, abnormal T waves. Prolonged PR interval occurred in 13 patients, seven of whom had echocardiographic abnormalities. Of six with prolonged QT interval, four had abnormal echocardiograms. The possibility of having an abnormal echocardiogram increased with the number of ECG changes: from 0 risk with no change to 37% for one, 47% for two, 80% for three, and 100% for four changes in serial ECGs. Both ECGs and echocardiograms are important in early and subsequent evaluation of these patients. Inasmuch as the ECGs showed abnormalities in 77% whereas echocardiograms showed changes in 41%, we believe that serial ECGs in comparison with prior tracings offer the more sensitive noninvasive indicator of pancarditis in young children during acute and convalescent Kawasaki syndrome.

Neonatal Staphylococcus epidermidis right-sided endocarditis: description of five catheterized infants.

Coagulase-negative staphylococci are important causes of bacteremia and focal infections in infants hospitalized in neonatal intensive care units. The medical records and echocardiograms of 58 newborns with persistent Staphylococcus epidermidis bacteremia who were hospitalized in the neonatal intensive care unit at The New York Hospital during the past 5 1/2 years were reviewed, and five infants were identified as having S epidermidis right-sided infective endocarditis. These episodes were associated with placement of umbilical venous catheters in the right atrium, slow resolution of bacteremia, and persistent thrombocytopenia. This experience suggests the role of endocardial trauma resulting from the placement of umbilical venous catheters in the pathogenesis of endocarditis. The increasing importance of coagulase-negative staphylococci as a cause of bacteremia in the newborn may explain the emergence of S epidermidis as an important cause of infective endocarditis in the neonatal intensive care unit. These cases underscore the potential severity of S epidermidis infection in the premature newborn.

Coronary artery involvement in Kawasaki syndrome in Manhattan, New York: risk factors and role of aspirin.

Since January 1980, 110 children having 113 attacks of Kawasaki syndrome were studied. Age at onset was 7 weeks to 12 years (mean 3 6/12 years, median 2 9/12 years); 77% were younger than 5 years of age; the male to female ratio was 1.8; racial distribution was 52% white, 19% black, 14% Hispanic, and 16% Asian. Protocol of management consisted of high-dose aspirin (100 mg/kg/d) until afebrile, and then 81 mg every day until free of coronary aneurysm. Two-dimensional echocardiograms were done weekly during the acute stage, at 2 and 6 months after onset, and yearly if a coronary abnormality was detected. At 1 month, 51 coronary arterial abnormalities were present in 25 patients. Risk factors for a coronary abnormality were duration of fever greater than or equal to 2 weeks, level of platelet count, marked elevation of ESR, and age younger than 5 years. No statistically significant difference in incidence of aneurysms was detected between patients on high-dose aspirin and those on medium-or low-dose aspirin.