Effects of dynamic and isometric exercise on the radionuclide-determined regurgitant fraction in aortic insufficiency.

Twenty-five patients with aortic insufficiency and eight asymptomatic control subjects underwent radionuclide ventriculography at rest and during dynamic and isometric exercise to clarify the mechanisms for preservation of exercise capacity in aortic insufficiency. Regardless of symptomatic state or severity of regurgitation, patients with aortic insufficiency had no significant increase in left ventricular ejection fraction or relative left ventricular end-diastolic volume during dynamic or isometric exercise. The radionuclide stroke count ratio (ratio of left ventricular to right ventricular stroke counts) progressively decreased in patients with aortic insufficiency from 2.98 +/- 1.14 (mean +/- 1 standard deviation) at a mean heart rate at rest of 69.6 beats/min to 2.48 +/- 0.59 (p = not significant [NS]) at a mean submaximal bicycle exercise heart rate of 129 beats/min and to 1.97 +/- 0.57 (p less than 0.005) at a mean maximal bicycle exercise heart rate of 145 beats/min. The decrease in stroke count ratio with bicycle exercise was significantly related to the severity of valvular regurgitation at rest (p less than 0.005). Although achieving lower bicycle exercise heart rates and comparable diastolic blood pressures, symptomatic patients had a lower mean stroke count ratio compared with asymptomatic patients with aortic insufficiency, suggesting that an elevation left ventricular diastolic pressure significantly decreased the regurgitant fraction in symptomatic patients during bicycle exercise. In patients with aortic insufficiency, the mean heart rate (92 beats/min) was significantly lower with isometric exercise than during the submaximal stage of bicycle exercise (129 beats/min). However, diastolic blood pressures, left ventricular diastolic counts and ejection fractions were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of cardiac and pulmonary complications related to elective abdominal and noncardiac thoracic surgery in geriatric patients.

PURPOSE: Major cardiac and pulmonary complications associated with abdominal and noncardiac thoracic surgery are a common cause of mortality and serious morbidity in elderly patients. We postulated that a simple, inexpensive bicycle exercise test could provide objective documentation of cardiopulmonary reserve and, therefore, predict perioperative pulmonary as well as cardiac complications. PATIENTS AND METHODS: Prior to elective surgery, 177 patients aged 65 years or older had assessment of the clinical history, results of physical examination, electrocardiogram, chest radiograph, blood chemistries, pulmonary function test findings, supine exercise test results, Dripps classification, and Goldman cardiac risk factors. Observations in patients with and without major perioperative cardiac and/or pulmonary complications were compared using univariate analysis followed by a multivariate logistic regression procedure. RESULTS: Major perioperative complications were pulmonary in 24 patients, cardiac in 25 patients, and either cardiac or pulmonary in 39 patients. By multivariate analysis, inability to perform two minutes of supine bicycle exercise raising the heart rate above 99 beats/minute was the best predictor of perioperative pulmonary, cardiac, and combined cardiopulmonary complication (p less than 0.0005). Among 108 patients who were able to achieve these exercise criteria, cardiac or pulmonary complications occurred in 10 patients (9.3%), with one death (0.9%). Among 69 patients unable to exercise satisfactorily, cardiac or pulmonary complications occurred in 29 patients (42%), with five total deaths (7.2%). CONCLUSION: Objective measurement of exercise capacity by supine bicycle ergometry appears to be of clinical value for preoperative risk stratification for both pulmonary and cardiac complications prior to major elective abdominal or noncardiac thoracic surgery in elderly patients.

Radioiodine-131 therapy for well-differentiated thyroid cancer--a quantitative radiation dosimetric approach: outcome and validation in 85 patients.

For almost five decades, 131I treatment of thyroid cancer has been based empirically on administered activity rather than on actual radiation doses delivered. In 1983, we defined radiation dose thresholds for successful treatment. This report is concerned with the subsequent validation of those thresholds in 85 patients. The successful ablation of thyroid remnants occurred after a single initial 131I administration in 84% of inpatients and in 79% of outpatients when treatment was standardized to a radiation dose of at least 30,000 cGy (rad). Administered activities low enough to permit outpatient therapy could be used in 47% of the patients. Lymph node metastases were treated successfully in 74% of patients with a single administration of 131I calculated to deliver at least 8,500 cGy (rad). For athyrotic patients with nodal metastases only, success was achieved in 86% of patients at tumor doses of at least 14,000 cGy (rad). These success rates are equal to or better than those reported with empiric methods of 131I administration. The individualized treatment planning selectively allocates hospitalization and higher exposures to 131I to those patients who require them.

Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo.

Rhenium-186 (tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that simultaneously localizes in multiple skeletal metastases in patients with advanced cancer. A single intravenous administration of 30-35 mCi (1110-1295 MBq) is associated with a prompt, significant relief of osseous pain in about 80% of such patients. The efficacy of this new compound was evaluated further by utilizing a double-blind crossover comparison with 99mTc-methylene diphosphonate (MDP) as a radioactive placebo. The new rhenium compound resulted in a significantly (p less than 0.05) greater decrease in pain than did treatment with the radioactive placebo. Rhenium-186(Sn)HEDP appears to be a useful new compound for the palliation of painful skeletal metastases.

Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases.

Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.

Statistical issues in risk assessment of reproductive outcomes with chemical mixtures.

Establishing the relationship between a given chemical exposure and human reproductive health risk is complicated by exposures or other concomitant factors that may vary from pregnancy to pregnancy. Moreover, when exposures are to complex mixtures of chemicals, varying with time in number of components, doses of individual components, and constancy of exposure, the picture becomes even more complicated. A pilot study of risk of adverse reproductive outcomes among male wastewater treatment workers and their wives is described here. The wives of 231 workers were interviewed to evaluate retrospectively the outcomes of spontaneous early fetal loss and infertility. In addition, 87 workers participated in a cross-sectional evaluation of sperm/semen parameters. Due to the ever-changing nature of the exposure and the lack of quantification of specific exposures, six dichotomous variables were used for each specific job description to give a surrogate measure of exposure. Hence, no quantitative exposure-response relationships could be modeled. These six variables were independently assigned by two environmental hygienists, and their interrater reliability was assessed. Results are presented and further innovations in statistical methodology are proposed for further applications.

Diagnostic chelation challenge with DMSA: a biomarker of long-term mercury exposure?

Chelation challenge testing has been used to assess the body burden of various metals. The best-known example is EDTA challenge in lead-exposed individuals. This study assessed diagnostic chelation challenge with dimercaptosuccinic acid (DMSA) as a measure of mercury body burden among mercury-exposed workers. Former employees at a chloralkali plant, for whom detailed exposure histories were available (n = 119), and unexposed controls (n = 101) completed 24-hr urine collections before and after the administration of two doses of DMSA, 10 mg/kg. The urinary response to DMSA was measured as both the absolute change and the relative change in mercury excretion. The average 24-hr mercury excretion was 4.3 microg/24 hr before chelation, and 7.8 microg/24 hr after chelation. There was no association between past occupational mercury exposure and the urinary excretion of mercury either before or after DMSA administration. There was also no association between urinary mercury excretion and the number of dental amalgam surfaces, in contrast to recent published results. We believe the most likely reason that DMSA chelation challenge failed to reflect past mercury exposure was the elapsed time (several years) since the exposure had ended. These results provide normative values for urinary mercury excretion both before and after DMSA challenge, and suggest that DMSA chelation challenge is not useful as a biomarker of past mercury exposure.

Parathyroid hormone and calcitriol changes in normal and insulin-dependent diabetic pregnancies.

In pregnancy, an increase in serum calcitriol and parathyroid hormone concentrations has been reported in several studies, though the increase in parathyroid hormone remains controversial. In magnesium deficiency states, parathyroid hormone and calcitriol secretion may be decreased. Because magnesium deficiency may occur in insulin-dependent diabetic patients, mainly because of urinary magnesium losses, we hypothesized that serum parathyroid hormone and calcitriol do not increase in the diabetic pregnancy. We studied, in a prospective longitudinal manner, 35 nondiabetic and 199 insulin-dependent diabetic pregnancies. In diabetic women, the goals of glycemic control were fasting blood glucose below 100 mg/dL and postprandial blood glucose less than 140 mg/dL. Serum magnesium, calcium, parathyroid hormone (whole molecule; ie, 1-84 fragment), and calcitriol were measured three times: 1) 8-12 weeks, 2) 22-28 weeks, and 3) 32-38 weeks' gestation. In normal women, serum parathyroid hormone did not change significantly over pregnancy, and a wide scatter of values was observed. Serum calcitriol increased significantly with advancing gestation. In diabetic women, serum parathyroid hormone had a narrow scatter, but values were within the low-normal range. During the third trimester there was no increase, and even a decrease, in serum calcitriol concentrations. Diabetics had, throughout pregnancy, significantly reduced serum magnesium concentrations when compared with controls. Their serum calcium and ionized calcium concentrations were similar to those of controls, except in the third trimester, when diabetic women had significantly lower serum calcium and ionized calcium concentrations than controls. We speculate that mineral metabolism abnormalities in diabetic pregnancies might be due to relative magnesium and/or insulin deficiency.

Low-grade vesicoureteral reflux. Variability in grade on sequential radiographic and nuclear cystograms.

Paired voiding cystourethrogram (VCU) and nuclear cystogram (NC) studies in 68 children with vesicoureteral reflux (VUR) were analyzed to determine the variability of VUR on sequential studies. Sequential paired examinations included 82 studies where a VCU was followed by a repeat VCU study and 128 studies where a VCU was followed by a NC study. Grade I VUR on the initial VCU was difficult to duplicate on repeat cystography, regardless of the follow-up modality. When the initial VCU showed no VUR, 20% of follow-up studies demonstrated VUR. Follow-up VCU and NC studies showed similar results in detecting increases and decreases in the grade of VUR. Low-grade VUR may be intermittent, and clinical therapeutic decisions should take this variability into account.

Warfarin vs aspirin for symptomatic intracranial stenosis: subgroup analyses from WASID.

The WASID trial showed no advantage of warfarin over aspirin for preventing the primary endpoint of ischemic stroke, brain hemorrhage, or vascular death. In analyses of selected subgroups, there was no definite benefit from warfarin. Warfarin reduced the risk of the primary endpoint among patients with basilar artery stenosis, but there was no reduction in stroke in the basilar artery territory or benefit for vertebral artery stenosis or posterior circulation disease in general.

A model for variability in arteriographic reading.

We propose a class of models for the joint cumulative distribution function (c.d.f.) of the values of two independent readings of percentage stenosis from a coronary arteriography. We show that these models are identifiable and that a certain subclass has unique consistent estimators for the parameters in question. We obtain these estimates for a data set from a substudy of the Coronary Artery Surgery Study (CASS).

Human health effects of 2,4,5-T and its toxic contaminants.

A clinical epidemiologic study was conducted to determine the long-term health effects of workplace exposure to the process of manufacturing the herbicide (2,4,5-trichlorophenoxy)acetic acid including contaminants such as 2,3,7,8-tetrachlorodibenzo-rho-dioxin. The population consisted of two cohorts: 204 clearly exposed and 163 not exposed. Among the exposed, clinical evidence of chloracne persisted in 55.7%. None of the not exposed experienced chloracne development. An association was found between the persistence of chloracne and the presence and severity of actinic elastosis of the skin. There is an association between exposure and the history of gastrointestinal tract ulcer. Pulmonary function values among those who were exposed and who currently smoked were lower than those who were not exposed and who currently smoked. The data assembled in the study indicate no evidence of increased risk for cardiovascular disease, hepatic disease, renal damage, or central or peripheral nervous system problems.

Daily variation of serum unconjugated estriol and estetrol in normal pregnancy.

Serum unconjugated estriol and estetrol were assayed daily in seven nondiabetic, uncomplicated third-trimester pregnancies to define the daily variation of these compounds. When compared to the mean of the three preceding days' values, or to the highest mean of three consecutive daily values previously obtained in a pregnancy, daily estriol and estetrol values fell greater than or equal to 40% on 1.2 and 0% of occasions, respectively. Isolated estriol values represented falls of greater than or equal to 40% from previously obtained single estriol values on 2% of occasions, and no isolated estetrol values fell greater than or equal to 40% from any other isolated values obtained in a given pregnancy. These results define the stability of daily serum estriol and estetrol in late-gestation normal pregnancy, although they emphasize the large variability encountered when comparing isolated estriol values.

Social and biological factors in relation to survival among black vs. white women with breast cancer.

Longer survival for white women than black women with breast cancer has been observed even when relative survival rates are used and stage at diagnosis is controlled. This study compared prognostic factors in relation to survival for 144 white women and 67 black women with breast cancer diagnosed 1969 to 1979 and identified through the tumor registry. Data were obtained from medical records, the registry, death certificates, and pathology files. Median survival was 7.5 years for whites, vs. 5.6 years for blacks. Significant differences between races were also observed for histological type and grade of tumor, presenting symptoms, and health status at diagnosis. Although Cox multiple regression analyses showed pathological stage at diagnosis and number of positive nodes to be the best predictors of survival in both whites and blacks, the differences in histological type observed in this sample merits further research; blacks have fewer well-differentiated tumors, the type associated with positive estrogen receptors and with better survival.

Polycythemia, hypomagnesemia, and hypocalcemia in infants of diabetic mothers.

Hypomagnesemia (serum magnesium concentration, less than 1.5 mg/dL [0.62 mmol/L]) and hypocalcemia (serum calcium concentration, less than 8 mg/dL [2.00 mmol/L]) have been reported in polycythemic infants, as well as in infants of diabetic mothers (IDMs). These latter infants are at risk for neonatal polycythemia (venous hematocrit, greater than or equal to 65% [0.65]). We tested the hypothesis that neonatal polycythemia in IDMs is associated with increased serum calcitonin concentration, hypomagnesemia, and hypocalcemia. Serum magnesium and calcium concentrations were measured at 24 and 72 hours of age in 76 IDMs; serum calcitonin concentration was measured at 24 hours of age. Peripheral venous spun hematocrit was measured between 2 and 4 hours of age. The rates of hypomagnesemia and hypocalcemia were similar in polycythemic and nonpolycythemic IDMs (0% vs 9% and 56% vs 49%, respectively). The serum calcitonin concentration was similar in both groups. There was no correlation between hematocrit and the serum magnesium or calcium concentration; a significant association existed between hypocalcemia and hypomagnesemia.

Kinetics of zinc absorption by the rat jejunum: effects of adrenalectomy and dexamethasone.

Effects of dexamethasone and adrenalectomy on the kinetics of jejunal 65Zn uptake and absorption were studied in the anesthetized adult rat. The jejunal lumen was perfused in situ with 5 mM glucose in 150 mM saline containing 65Zn and [14C]polyethylene glycol as volume marker. Over the 30-min perfusion period, the rate of net 65Zn removal from the perfusate was biexponential due to the establishment of a return flux to the lumen. An open two-compartment model satisfactorily describes these observations: (formula; see text) Dexamethasone (2 mg/kg ip 7 h before perfusion) increased k12 by 75% (P less than 0.0002) and decreased k20 by 45% (P less than 0.04). Both effects were independent of adrenalectomy. Mathematical simulations using the compartmental model and experimentally determined kinetic constants predicted that transfer of 65Zn into the body should be enhanced by adrenalectomy and retarded by dexamethasone administered to adrenalectomized rats. Dexamethasone and adrenalectomy thus differentially affect Zn uptake and absorption in this system, suggesting a possible adrenocortical hormone involvement in the regulation of Zn absorption. These changes are apparently not mediated via metallothionein.

Serum unconjugated estriols in insulin-dependent diabetic pregnancies: normative data and clinical relevance.

The purpose of this study was to establish normative reference values for serum unconjugated estriol (E3) concentrations in insulin-dependent diabetic pregnancy. There were 1973 samples analyzed in 63 diabetic pregnancies not complicated by fetal distress and/or neonatal asphyxia. These samples were compared with 867 samples collected in 25 pregnancies complicated by fetal distress and/or neonatal asphyxia and 103 samples collected in seven nondiabetic, uncomplicated pregnancies. E3 values were found to be significantly higher in diabetic compared with nondiabetic healthy gravid women, correlating with infant birthweight. The percent change of daily E3 values from the highest previous 3 days mean (maximum mean) was 1 +/- 27% (mean +/- SD). The 95% confidence limit for this percent change indicates that a decrease of 52% or more is theoretically seen in 2.5% of the observations. Using the traditional decrease of 40% currently used in the literature, there were false-negative and false-positive predictions of fetal distress and/or neonatal asphyxia at rates unacceptable for patient management. The use of E3 determinations in combination with nonstress test-contraction stress test did not improve the predictability of this latter test. Serum E3 determinations are of little clinical value in the management of insulin-dependent diabetic pregnant women.

Hypothesis testing with the similarity index.

Multilocus DNA fingerprinting methods have been used extensively to address genetic issues in wildlife populations. Hypotheses concerning population subdivision and differing levels of diversity can be addressed through the use of the similarity index (S), a band-sharing coefficient, and many researchers construct hypothesis tests with S based on the work of Lynch. It is shown in the present study, through mathematical analysis and through simulations, that estimates of the variance of a mean S based on Lynch's work are downwardly biased. An unbiased alternative is presented and mathematically justified. It is shown further, however, that even when the bias in Lynch's estimator is corrected, the estimator is highly imprecise compared with estimates based on an alternative approach such as 'parametric bootstrapping' of allele frequencies. Also discussed are permutation tests and their construction given the interdependence of Ss which share individuals. A simulation illustrates how some published misuses of these tests can lead to incorrect conclusions in hypothesis testing.

Frequency and patterns of abnormality detected by iodine-123 amine emission CT after cerebral infarction.

Single photon emission computed tomography (SPECT) was performed in 31 patients with cerebral infarction and 13 who had had transient ischemic attacks, using iodine-123-labeled N,N,N'-trimethyl-N'-(2-hydroxyl-3-methyl-5-iodobenzyl)-1,3-propanediamin e (I-123-HIPDM) as the radiopharmaceutical. SPECT scans were compared with computed tomographic (CT) scans. SPECT was as sensitive as CT in detecting cerebral infarction (94% vs. 84%). The abnormalities were larger on the SPECT scans than on the CT scans in 19 cases, equal in seven, and smaller in five (SPECT abnormalities greater than or equal to CT abnormalities in 86% of cases). Fifteen of 30 patients with hemispheric infarction had decreased perfusion (decreased uptake of I-123-HIPDM) to the cerebellar hemisphere contralateral to the cerebral hemisphere involved by the infarction (crossed cerebellar diaschisis). Nine of these 15 patients had major motor deficits, while only one of the 15 without crossed cerebellar diaschisis had a major motor deficit.

Prediction of coronary artery disease in a population of insulin-requiring diabetic patients: results of an 8-year follow-up study.

To identify predictors of clinical coronary artery disease, 110 insulin-requiring diabetic patients with no symptoms suggestive of cardiac disease and with a normal resting ECG underwent metabolic and noninvasive cardiovascular screening including a history and physical examination, exercise ECG, M-mode echocardiography, and chemical laboratory testing. During a median follow-up interval of 100 months, 14 of these patients had clinical evidence of coronary artery disease consisting of acute myocardial infarction, sudden cardiac death, or anginal chest pain with angiographic documentation of occlusive coronary artery disease. Baseline variables that were univariately predictive of subsequent clinical coronary disease included age, peak treadmill heart rate, and retinal neovascularization. According to multivariate analysis the peak treadmill heart rate was the single most important predictor of subsequent development of clinical coronary disease. A treadmill ECG result that was either abnormal or inconclusive because of failure to achieve 90% of predicted maximal heart rate identified each patient in whom clinical coronary artery disease developed within 50 months after entry testing. Thus the entry treadmill ECG provided prognostic information not available from the history and physical examination results, but little further prognostic information was provided after the first 50 months of follow-up, suggesting the need for serial testing.