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Biomedical subjects

S Wallenstein

Publications and source records attributed to S Wallenstein.

At least 19 recordsLinked to original sources

A prospective study of bone loss in African-American and white women--a clinical research center study.

Although bone loss occurs universally with age, the incidence of age-related osteoporotic fractures varies widely among ethnic groups. In the U.S., age-adjusted hip fracture incidence is 50% lower in African-American than in white women. Adult African-American women also have higher bone mass, but it is not known whether this difference is entirely due to higher peak bone mass or also results from slower rates of bone loss. Rates of bone loss were measured prospectively in 122 white and 121 African-American healthy, nonobese, pre- and postmenopausal women. Bone density was measured at 6-month intervals over a mean of 3-4 yr using single and dual photon absorptiometry of the forearm (cortical bone) and spine (trabecular bone). Similar rates of premenopausal bone loss were documented in both white and African-American women. However, in early menopause, bone loss was faster in the white women in the forearm (-2.4%/yr in whites vs. -1.2%/yr in African-Americans; P = 0.045), with a similar trend in the spine (-2.2%/yr in whites vs. -1.3/yr in African-Americans; P = 0.27). In women more than 5 yr postmenopause, the rates of bone loss did not differ by ethnic group. Our results indicate that the higher bone mass in African-American women is largely due to the attainment of a greater peak bone mass by early adulthood. However, slower rates of bone loss in the early postmenopausal period may also contribute to the higher bone density of older African-American women. Although bone loss occurs in both groups, there are ethnic differences in bone loss rates which indicate that data derived from white women cannot be simply extrapolated to nonwhite populations. Ethnic group-specific data on the determinants of bone homeostasis are needed.

Adult

Increased incidence of HLA antigen B35 in patients with chronic lymphocytic leukemia.

We and others have reported an increased incidence of chronic lymphocytic leukemia (CLL) among Ashkenazi (ASH) Jews of European origin. We performed HLA Class I typing on all 50 CLL patients seen by us and compared them with 3886 controls consisting of healthy blood donors from the New York Blood Center. Thirty of our CLL patients were ASH Jews, 17 of whom (57%) expressed the B35 antigen compared with 462 ASH controls (26%). Seven (39%) of the CLL Caucasian patients expressed the B35 antigen compared with 305 (14.5%) of the Caucasian controls. Combining the information from the ASH Jews and the Caucasians the difference is highly significant, (p = 0.0001). The summary odds ratio was 3.7. These results indicate an increased incidence of the antigen B35 amongst ASH and Caucasian patients with CLL.

Adult

Clustering of attempted suicide: New Zealand national data.

BACKGROUND: The extent to which clusters of attempted suicides occur is a significant problem that is complementary to the current available research on the clustering of completed suicide. However, little systematic research on clusters of attempted suicides exists. The present study examines the extent and nature of clustering of suicide attempts. METHOD: The occurrence of clustering of attempted suicide was examined in nationwide data for all New Zealand hospitals, obtained from the New Zealand Health Statistics Services for the years 1988-1990. The Scan statistic and Knox procedure were employed for testing the significance of clusters in time and time-space, respectively. RESULTS: The analyses indicated that significant time clustering occurred in younger age groups, specifically among 15-19 and 20-24 year olds. The results could not be accounted for by seasonal variations in admissions. Age specificity of time-space clusters emerged, exhibiting a similar pattern to that reported for completed suicides in the US. CONCLUSIONS: The results suggest a similar underlying mechanism for the clustering of parasuicide and completed suicides and provide support for the existence of contagion of suicidal behaviour. The implications for prevention are discussed.

Adolescent

The natural history of thoracic aortic aneurysms.

Because improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 +/- 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 +/- 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (> 5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter)2.1; change in volume = 0.0356 (initial aortic volume)1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Incidence and timing of germinal matrix/intraventricular hemorrhage in low birth weight infants.

Incidence and time of onset of germinal matrix/intraventricular hemorrhage (GM/IVH) were prospectively ascertained in 1,105 infants weighing < or = 2,000 g at birth, a cohort comprising about 85% of all births of that weight born from September 1984 to June 1987 in the central New Jersey counties of Ocean, Monmouth, and Middlesex. Cranial ultrasonography was performed as nearly as possible to age 4 hours, 24 hours, and 7 days. Each scan was reviewed by two independent readers and, if necessary, a third; consensus was achieved on scan of first diagnosis of GM/IVH in 965 of the 1,079 infants with assessable scans. The cumulative incidence of GM/IVH in the first week of life was 24.6% (265/1,079). In the 965 infants with consensus diagnoses, the first scan, at 4.9 +/- 2.2 hours, yielded the highest incidence--10.6% (95/899). Incidence by the second scan (25.1 +/- 4.9 hours) was 6.0% (49/813), and by the third scan (7.2 +/- 0.8 days), 9.0% (64/715). The iterative algorithm for interval-censored data developed by Turnbull (J R Stat Soc [B] 1976;8:290-5) was used to estimate the most likely time of onset based on time of first diagnosis. From 34% to 44% of hemorrhages were present at the first opportunity to scan, which in these data was at age 1 hour. At least a third of GM/IVH in infants < or = 2,000 g appears to be of congenital or immediate postnatal onset.

Age Factors

Power of the scan statistic for detection of clustering.

The scan statistic is the maximum number of events in an interval of fixed length w as the subinterval moves over the entire time frame. Previous research derived the null distribution of the scan statistic under the conditional model which assumed that the total number of events was fixed, and under the unconditional model which let the total number of events be a random variable. This paper derives approximations for the power of the scan test for a pulse alternative. Under this alternative, the relative risk of disease on a subinterval (tau, tau + w), tau unknown, is theta-fold as high as it is for other subintervals of length w. Two sets of approximations are given for each model. The first approximation gives highly accurate results, but requires use of a personal computer. The second procedure can be performed on a hand-held calculator and appears very accurate for the cases examined.

Cluster Analysis

The power of the Mantel-Haenszel test for grouped failure time data.

The Mantel-Haenszel test for grouped failure time data (MHF test) compares the distribution of failure times in two cohorts followed for an interval of time when the data are collected in discrete subintervals. This paper derives approximations to the power of the Mantel-Haenszel test for arbitrary failure time distributions in the presence of censoring. The approximations are appropriate for both equal and nonequal odds ratios in the constituent tables, and can be used for arbitrary subdivisions of time. Four approximations are proposed. They differ from each other according to whether the parameter measuring treatment effect is an odds ratio or a difference in proportions, and whether the survival distributions are calculated under the null or alternative hypothesis. In addition, we demonstrate that when the hazards are constant, increasing the number of subintervals often produces only a negligible increase in the power of the MHF test. On the other hand, for arbitrary hazards and nonconstant hazard ratios, the choice of frequency and actual times of measurement can have important effects on power. Finally, the paper presents simple expressions for power under exponential failure and censoring models.

Biometry

Racial differences in pre- and postmenopausal bone homeostasis: association with bone density.

The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Genetics of autoimmune thyroid disease: lack of evidence for linkage to HLA within families.

Clinical and epidemiologic observations, including the association of Graves' disease (GD) and Hashimoto's thyroiditis (HT) with the HLA gene complex, support a role for specific disease-related genes in the development of autoimmune thyroid disease (AITD). The combination of HLA and immunoglobulin heavy chain allotypes (Gm) has previously been reported to be predictive of AITD in multiply affected Japanese families. We have investigated the immunogenetics of AITD in families in the United States. Twenty-seven pedigrees including 15 with GD, 8 with HT, and 4 with both HT and GD were immunogenetically typed and analyzed for population and within family disease associations. The majority of families (63%) were multiplex for AITD. HLA-DR3 was increased in affected family members with GD and HLA-DR5 was increased in affected family members with HT. Formal linkage analysis was applied to test for coinheritance of disease with the HLA locus within families. The LIPED computer program was used to calculate the probability of linkage in terms of the lod score. Evidence from linkage analysis was consistently against linkage of either GD or HT to the HLA region under various penetrances and different modes of inheritance. The combination of HLA and Gm was not found to be predictive of disease in 7 selected multiplex families with multigenerational instances of AITD. T cell function was also examined in 3 pairs of siblings genetically identical for HLA and Gm but discordant for disease expression. We found no evidence of a global T cell defect in the small number of patients examined. We conclude that whereas there is an association of AITD with the HLA region, our linkage analysis demonstrates that alleles of the HLA region are not cosegregating with either GD or HT within these families. Thus, whereas HLA may increase susceptibility to AITD, as shown by the existence of an HLA association, the major genetic influence on the inheritance of AITD must be at another locus.

B-Lymphocytes

A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction.

Immune function in normal pregnancy and the postpartum period remains poorly defined. We hypothesized that a comparative study between pregnant women with normal and abnormal immune function would further our understanding of the immune mechanisms of pregnancy. We chose to study a cohort of pregnant women at risk for the development of postpartum thyroid dysfunction (PPTD) as well as a group of normal controls. We chose PPTD as the model for abnormal immune function because of the relative ease of monitoring disease development and the relatively high prevalence for PPTD reported in earlier studies. Five hundred and fifty-two women were screened for the presence of thyroid autoantibodies in the first trimester of pregnancy. Thirty-three thyroid autoantibody-positive women and 28 thyroid autoantibody-negative women were followed prospectively throughout pregnancy and 6 months into the postpartum period. Lymphocyte subset analyses, thyroid function tests, and thyroid autoantibodies (antihuman thyroglobulin and antithyroid peroxidase) were performed at defined intervals. All patients were HLA serotyped. Normal pregnancy was principally characterized by decreased CD4+ T-cells and increasing CD8+ T-cells, causing a significant fall in the CD4+/CD8+ ratio in late pregnancy and into the postpartum period. Women who developed PPTD had 1) a higher CD4+/CD8+ ratio (P = 0.04), 2) activation of T-cells in the postpartum period (P = 0.02), and 3) significantly higher thyroid autoantibody titers (antihuman thyroglobulin, P = 0.02; antithyroid peroxidase, P = 0.0018). We found an overall incidence for PPTD of 8.8%. These data demonstrated that women who were thyroid autoantibody positive in the first trimester of pregnancy had a one in three chance of developing PPTD. We observed a significant fall in the T-cell helper/suppressor ratio in normal pregnant women, which was associated with distinct T-cell subset changes. This pregnancy-initiated T-cell regulation reflected an overall suppression of immune function. The development of PPTD was a frequent postpartum event in our population and was associated with a triad of immune markers: a reduction in the normal immune suppression of pregnancy (as indicated by higher T-cell helper/suppressor ratios), enhanced postpartum T-cell activation, and elevated thyroid autoantibodies. The reduction in the degree of immune suppression was, therefore, a major factor in the development of PPTD. Our results define immunological changes that occur in normal pregnancy and distinct immunological abnormalities necessary for the development of PPTD.

Autoantibodies

Nonparametric tests for interaction and group differences in a two-way layout.

Nonparametric tests of group differences and interaction across strata are developed in which the null hypotheses for these tests are expressed as functions of rho i = P(X > Y) + 1/2P(X = Y), where X refers to a random observation from one group and Y refers to a random observation from the other group within stratum i. The estimator r of the parameter rho is shown to be a useful way to summarize and examine data for ordinal and continuous data.

Drug Therapy

Calcium, vitamin D, and parathyroid hormone status in young white and black women: association with racial differences in bone mass.

The etiology of the racial disparity in bone mass and fracture rate is unknown. Since the PTH-vitamin D endocrine system is a major regulator of calcium metabolism and bone turnover, this cross-sectional study examined the relationship of radial and lumbar bone density to vitamin D metabolite and PTH concentrations and to calcium intake and excretion in 67 white and 70 black highly comparable, healthy, premenopausal women. Bone density at both radial and lumbar sites was higher in blacks than in whites. Serum 25-hydroxyvitamin D was slightly but not statistically significantly (P = 0.08), lower in blacks than in whites, but there were no racial differences in 1,25-dihydroxyvitamin D, PTH, or renal tubular maximum for reabsorption of phosphate. The mean 25-hydroxyvitamin D concentration in blacks was well within the normal range and was not associated with evidence of secondary hyperparathyroidism. There were no correlations of bone density to vitamin D or PTH concentrations. Although there were no racial differences in dietary intake of calcium and vitamin D or in sodium excretion, 24-h urinary calcium excretion was significantly lower in blacks than in whites, and calcium excretion was inversely associated with radial bone density. In contrast to previous reports, in healthy, normal weight, premenopausal black women there is no evidence of vitamin D deficiency or secondary hyperparathyroidism, suggesting that factors other than the vitamin D-PTH axis are responsible for racial differences in bone mass.

Adult

Cancer rates after the Three Mile Island nuclear accident and proximity of residence to the plant.

BACKGROUND: In the light of a possible link between stress and cancer promotion or progression, and of previously reported distress in residents near the Three Mile Island (TMI) nuclear power plant, we attempted to evaluate the impact of the March 1979 accident on community cancer rates. METHODS: Proximity of residence to the plant, which related to distress in previous studies, was taken as a possible indicator of accident stress; the postaccident pattern in cancer rates was examined in 69 "study tracts" within a 10-mile radius of TMI, in relation to residential proximity. RESULTS: A modest association was found between postaccident cancer rates and proximity (OR = 1.4; 95% CI = 1.3, 1.6). After adjusting for a gradient in cancer risk prior to the accident, the odds ratio contrasting those closest to the plant with those living farther out was 1.2 (95% CI = 1.0, 1.4). A postaccident increase in cancer rates near the Three Mile Island plant was notable in 1982, persisted for another year, and then declined. Radiation emissions, as modeled mathematically, did not account for the observed increase. CONCLUSION: Interpretation in terms of accident stress is limited by the lack of an individual measure of stress and by uncertainty about whether stress has a biological effect on cancer in humans. An alternative mechanism for the cancer increase near the plant is through changes in care-seeking and diagnostic practice arising from postaccident concern.

Bias

Comparison of severity of illness indicators in an intensive care unit.

Meaningful comparison of patient outcomes requires an assessment of the severity of illness for the patients being compared. The more severe the underlying illness, the worse the expected outcome. We studied several severity of illness indicators derived from different methodologies in a medical intensive care unit. We compared the Acute Physiologic and Chronic Health Evaluation II, the accepted benchmark indicator for intensive care units, with one complex indicator, Computerized Severity Score, and three simpler indicators, Comorbidity, McCabe-Jackson, and American Society of Anesthesiologists. We found that all correlated well with a comorbidity index. We conclude that the Acute Physiologic and Chronic Health Evaluation II, the Computerized Severity Score, and the McCabe-Jackson scoring systems appear to be comparable predictors of comorbidity in a medical intensive care unit. Selection of a severity indicator will depend on the resources available and the intended uses.

Aged

Within-mouth correlations for indicators of the host response in gingival crevicular fluid.

Gingival crevicular fluid was collected from multiple sites in patients with chronic adult periodontitis, and analysed for the lysosomal enzymes beta-glucuronidase and arylsulphatase, the cytoplasmic enzyme lactate dehydrogenase, total IgA, IgG and IgM and the protease inhibitor alpha 2-macroglobulin. The within-mouth (intraclass) correlation coefficients were calculated to describe the relationship between samples collected from individual patients. Data collected at baseline and 3 months after root planing and scaling were analysed, as was the change between examinations. Volume of crevicular fluid demonstrated the smallest intraclass correlation coefficient (0.16 at baseline, 0.12 at 3 months; 0.11 change), while probing depth and enzyme activity had moderate intraclass correlations (i.e. 0.36, 0.36, 0.26 for beta-glucuronidase). Immunoglobulin and alpha 2-macroglobulin activity in the fluid had the strongest correlations (i.e. 0.64, 0.57, 0.65 for IgG). The correlations for anatomically related teeth within a quadrant (molar, non-molar) were equivalent to or greater than the correlation for all samples within a mouth. Examined by tooth type, the intraclass correlations for volume of crevicular fluid, probing depth, beta-glucuronidase, arylsulphatase and lactate dehydrogenase were higher for non-molar teeth. In contrast, intraclass correlations for IgA, IgG, IgM and alpha 2-macroglobulin in samples from molar teeth were either equivalent to or greater than the correlations for non-molar samples. Calculation of intraclass correlation coefficients for such data can (1) indicate the degree of variability present in multiple samples of crevicular fluid collected from individual patients, (2) provide information about the source of host mediators in the fluid, and (3) help identify appropriate sampling strategies for the fluid.

Adult

Time-space clustering of teenage suicide.

The occurrence of time-space clusters was examined in national mortality data on suicide among adolescents aged 15-19 years obtained from the National Center for Health Statistics Mortality Detail Files for 1978-1984. The analyses indicated that overall significant time-space clustering occurred among 15-19 year olds. The authors thus believe that they have documented for the first time that outbreaks of suicide occur more frequently than expected by chance alone. The occurrence of suicide clusters among teenagers appeared to vary considerably by state and year of investigation. There is some indication that there has been an increase in teenage clusters in more recent years.

Adolescent

Suicide clusters: an examination of age-specific effects.

The age specificity of time-space clusters of suicide was examined using National Center for Health Statistics data for 1978-84. Significant clustering of suicide occurred primarily among teenagers and young adults, with minimal effect beyond 24 years of age. Clustering was two to four times more common among adolescents and young adults than among other age groups.

Adolescent

Use of the scan statistic to detect time-space clustering.

A test for time-space clustering is proposed based on the scan statistic, the maximum number of events in a 365-day period in each of several geographic units. The data under consideration should consist of the exact date and geographic unit for each event, and data should be available for several years for which the risk of disease can be assumed constant. The statistic is the ratio of the excess number of events summed over all the geographic regions, to the square root of the sum of the variances. This statistic is similar in construction to the Ederer-Myers-Mantel statistic (Biometrics 1964;20:626-38), but does not require that attention be limited to calendar years (January 1-December 31). Unlike other tests for time-space clustering, the scan statistic allows one to calculate measures of attributable risk and effect size. Data concerning adolescent suicide are used to illustrate the procedure. The tables and asymptotic formulas given for the mean and variance of the proposed statistic should be useful in the evaluation of both clustering in time and in time-space.

Adolescent