Olli S. Miettinen

Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study.

Among 3559 newborn infants with birth weight less than 1750 gm, 421 developing a hemodynamically significant patent ductus arteriosus were entered into a randomized trial to evaluate the role of indomethacin in the management of PDA. Indomethacin given concurrently with usual medical therapy at the time of diagnosis resulted in ductal closure in 79%, versus 35% with placebo (P less than 0.001). Indomethacin as backup to usual medical treatment resulted in similar closure rates. To assess overall effects through hospital discharge, three management strategies were compared. Although mortality did not differ significantly, infants given indomethacin only if usual therapy failed (strategy 2) had a lower incidence of bleeding than those to whom indomethacin was given with initial medical therapy (strategy 1) and lower rates of pneumothorax and retrolental fibroplasia than those to whom no indomethacin was administered, with surgery the only backup to medical therapy (strategy 3). Thus the administration of indomethacin only when medical treatment fails appears to be the preferable approach for the management of symptomatic PDA in premature infants.

Coffee and Myocardial Infarction

Abstract A positive association between coffee consumption and acute myocardial infarction was confirmed by analyses of data from a multipurpose survey of 12,759 hospitalized patients, including 440 with a diagnosis of acute myocardial infarction. As compared with those who drink no coffee, the risks of infarction among those drinking one to five and six or more cups of coffee per day are estimated to be increased by 60 and 120 per cent, respectively. This association could not be attributed to confounding by age, sex, past coronary heart disease, hypertension, congestive heart failure, obesity, diabetes, smoking or occupation, nor could it be explained by the use of sugar with coffee. There was no positive association between tea drinking and acute myocardial infarction. (N Engl J Med 289:63–67, 1973)

HYPERGLYCEMIA AND PLASMA LIPID LEVELS: A PROSPECTIVE STUDY OF YOUNG INSULIN-DEPENDENT DIABETIC PATIENTS

We explored the relation of plasma lipid levels to the degree of blood glucose control in young, insulin-dependent diabetic patients. Levels of total plasma cholesterol and triglyceride, of their lipoprotein subfractions, and of hemoglobin A, and fasting blood glucose were measured repeatedly over a one-year period in 105 patients. Lipid levels were also measured in 74 nondiabetic siblings. Increasingly poor control of diabetes, reflected by levels of hemoglobin A1 or of fasting blood glucose, was associated with statistically significant increases in total cholesterol (P less than or equal to 0.01), total triglyceride (P less than or equal to 0.007), and lipoprotein subfractions except for high-density lipoprotein cholesterol. Diabetic patients in best control had lipid levels similar to those in their nondiabetic siblings. These data on the relation of plasma lipid levels to diabetic control lend credence to the hypothesis that poor control of blood glucose is conducive to accelerated atherosclerosis in diabetes mellitus.

Risk of Myocardial Infarction in Relation to Current and Discontinued Use of Oral Contraceptives

In a hospital-based case-control study, we evaluated the rate of myocardial infarction in relation to discontinued as well as current use of oral contraceptives. We compared 556 women with infarction, 25 to 49 years old, with 2036 age-matched control subjects. For current users, the rate-ratio estimate was 3.5 (95 per cent confidence limits, 2.2 to 5.5). For past users 40 to 49 years of age, the magnitude of the rate ratio was related to the duration of use: for total durations of past use of less than five years, five to nine years, and 10 or more years, respectively, the rate-ratio estimates (with 95 per cent confidence limits) were 1.0 (0.8 and 1.4), 1.6 (1.1 and 2.5), and 2.5 (1.5 and 4.1). This trend was statistically significant (P less than 0.01). The findings suggest that an effect on the risk of myocardial infarction persists after the discontinuation of long-term use of oral contraceptives.

Recent and Past Use of Conjugated Estrogens in Relation to Adenocarcinoma of the Endometrium

It has been suggested that the reported association between estrogen use and endometrial cancer may have been biased because estrogens provoke uterine bleeding in women with otherwise asymptomatic disease. To evaluate this hypothesis we compared 149 patients with endometrial cancer and 402 control subjects with other conditions with reference to the time when they had last used conjugated estrogens. In women who had last used conjugated estrogens two or more years previously and who had taken them for at least five years, the rate-ratio estimate was 3.3 (95 per cent confidence interval, 1.4 to 8.0) relative to women who had never used them. Uterine bleeding, and hence the diagnosis of otherwise asymptomatic cancer, cannot be attributed to estrogen use that ceased in the distant past. Our results suggest that such use has a residual effect on the risk of endometrial cancer; this effect is not accounted for by biased selection of cases according to estrogen use.

Ebstein's anomaly: Clinical profile and natural history

Abstract The clinical features, cardiac catheterization data and natural history of 55 patients with Ebsteins anomaly are presented; 18 had a significant associated cardiac anomaly. The clinical features are usually clear-cut. Cardiac catheterization and angiography demonstrate downward displacement of the tricuspid valve, a large right atrium, no important elevation of the right ventricular pressures, decreased pulmonary blood flow and right to left shunt through the foramen ovale. Right ventricular outflow obstruction may be masked by the low level of pulmonary blood flow and resistance. Intracardiac electrocardiogram is usually diagnostic. The prognosis in these children is relatively poor in the presence of (1) complicating cardiac lesions, (2) more marked cyanosis and (3), to a lesser extent, extreme cardiomegaly. The appearance of congestive heart failure foretells early death ( In neonates presenting with Ebsteins anomaly the incidence of important associated cardiac anomalies is higher, and the clinical picture more variable because of the physiologic adjustments of birth. Cyanosis may be severe only to improve later. The electrocardiogram may show atypical features and exhibit the classic pattern within weeks. Radiographic cardiomegaly may be dramatically out of proportion to the apparent well-being of the infant. Surprisingly gross cardiomegaly is compatible with survival.

Decreased Risk of Endometrial Cancer among Oral-Contraceptive Users

A case-control study was carried out to assess the effects of OC (oral contraceptive) usage on the risk of endometrial cancer. The cases were chosen from an ongoing case-control surveillance program at the Drug Epidemiology Unit of Boston University Medical Center. 154 women with a diagnosis of endometrial cancer were compared with 525 controls as to OC usage. 1% of the cases and 2% of the controls had used sequential OCs, numbers too small for inclusion in the study. 6% of the cases and 13% of the controls had used combination OCs. The relative risk of developing endometrial cancer was found to be only .5 for women who had used combination OCs. This halved risk rate falls to .3 for use that lasted for 3 or more years. There was no evidence that the time of last use affected the reduced risk factor; i.e., the reduced risk appeared to persist for at least 5 years after discontinuation of OC use. This protection against endometrial cancer offered by combined OC use may begin to show up in incidence rates for the disease soon if the protective effect does indeed remain after usage.

Relation of Cigarette Smoking to Myocardial Infarction in Young Women

To examine the relation between myocardial infarction and cigarette smoking in young women, we investigated the smoking habits of women under the age of 50 who had survived a recent myocardial infarction. They had not been using oral contraceptives, and other identifiable risk factors were excluded. Among 55 such women and 220 control matched for age and area of residence, the proportions of cigarette smokers were 89 per cent and 55 per cent respectively (P less than 0.001). A dose-response relation was evident; among women smoking 35 or more cigarettes per day the rate of myocardial infarction was estimated to be some 20-fold higher than among those who had never smoked. This study demonstrates that cigarette smoking is a risk factor for myocardial infarction in young women who are otherwise apparently healthy.

Lung Cancers Diagnosed at Annual CT Screening: Volume Doubling Times

PURPOSE To empirically address the distribution of the volume doubling time (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP), first and foremost with respect to rates of tumor growth but also in terms of cell types. MATERIALS AND METHODS All CT screenings in I-ELCAP from 1993 to 2009 were performed according to HIPAA-compliant protocols approved by the institutional review boards of the collaborating institutions. All instances of first diagnosis of primary lung cancer after a negative screening result 7-18 months earlier were identified, with symptom-prompted diagnoses included. Lesion diameter was calculated by using the measured length and width of each cancer at the time when the nodule was first identified for further work-up and at the time of the most recent prior screening, 7-18 months earlier. The length and width were measured a second time for each cancer, and the geometric mean of the two calculated diameters was used to calculate the VDT. The χ(2) statistic was used to compare the VDT distributions. RESULTS The median VDT for 111 cancers was 98 days (interquartile range, 108). For 56 (50%) cancers it was less than 100 days, and for three (3%) cancers it was more than 400 days. Adenocarcinoma was the most frequent cell type (50%), followed by squamous cell carcinoma (19%), small cell carcinoma (19%), and others (12%). Lung cancers manifesting as subsolid nodules had significantly longer VDTs than those manifesting as solid nodules (P < .0001). CONCLUSION Lung cancers diagnosed in annual repeat rounds of CT screening, as manifest by the VDT and cell-type distributions, are similar to those diagnosed in the absence of screening.

Screening for lung cancer: the early lung cancer action approach

Suddenly, screening for lung cancer has become a hot topic. Researchers are initiating projects to study it; the public is demanding it; and medical institutions are offering it. The sudden activity is also prompting reconsideration of the still-nihilistic North American public policies on lung-cancer screening. Out of the Fourth International Conference on Screening for Lung Cancer, held in February 2001 and only 16 months after the first one, arose a unanimous recommendation to quickly publish the current protocol of the International Early Lung Cancer Action Program (I-ELCAP) initiated by a resolution of the third Conference. The purpose here is to do just that, though only upon first outlining the origins of this initiative and also specifying its aims and broadest principles.