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Biomedical subjects

E B Kaplan

Publications and source records attributed to E B Kaplan.

At least 19 recordsLinked to original sources

Chronic graft-versus-host disease and pulmonary function.

Pulmonary complications are a major cause of morbidity and mortality in bone marrow transplant recipients. Earlier series, consisting mainly of adults, have shown evidence of obstructive changes of pulmonary functions in association with chronic graft-versus-host disease (CGVHD). We longitudinally evaluated spirometry in 46 patients who received bone marrow transplants as children or as young adults to determine whether they had similar abnormalities. Group mean FEV1/FVC, and percent predicted FVC, FEV1, and FEF25-75 values did not demonstrate obstructive changes in association with CGVHD in this patient population. Our findings suggest that younger patients with CGVHD, as a group, may fare better than older bone marrow transplant recipients with CGVHD. However, due to small sample sizes, it cannot be conclusively stated that the pulmonary function parameters analyzed do not differ in the two patient groups.

Adolescent

Blood loss and replacement in total hip arthroplasty: a multicenter study. The Preoperative Autologous Blood Donation Study Group.

To determine blood loss, the number of transfusions, and the hemoglobin levels achieved in patients via transfusion in the course of total hip arthroplasty, 324 patient records from 1987 through 1989 were reviewed at three university and three community hospitals. Calculated blood loss was 3.2 +/- 1.3 units in primary procedures and 4.0 +/- 2.1 units in revision procedures (mean +/- SD). Of 777 red cell units transfused, 455 (59%) were autologous units. Transfused patients received 2.0 +/- 1.8 units for primary procedures and 2.9 +/- 2.3 units for revision procedures (mean +/- SD). The maximum number of units given to 95 percent of the transfused patients was 4 for primary procedures and 6 for revision procedures. The mean postoperative hemoglobin level after all transfusions was 103 to 110 g per L, regardless of patient age group of physical status, autologous donor status, or hospital. No difference in length of hospital stay was observed for patients less than 65 years old with hemoglobin concentrations of 80 to 139 g per L at discharge.

Aged

Interstitial pneumonitis, pulmonary fibrosis, and chronic graft-versus-host disease.

Pneumonopathies in association with graft-versus-host disease (GVHD) are known, but the evolution of biopsy-proven interstitial pneumonitis (IP) to pulmonary fibrosis as a major pulmonary manifestation in an individual patient with chronic GVHD has not been previously reported. We present a patient with chronic GVHD who developed IP and then pulmonary fibrosis. We suggest that IP with evolution to pulmonary fibrosis was a major pulmonary manifestation of chronic GVHD in this patient.

Adolescent

Ratings of personality change in patients being evaluated for memory disorders.

Caregivers of 35 mildly to moderately memory-impaired patients rated current and premorbid personalities with the NEO Personality Inventory. We then examined changes in the five domains of personality tapped by the NEO. There were significant changes in four of the five domains of normal personality functioning toward less conscientiousness, lower extraversion, higher neuroticism, and lower openness. The difference toward lower agreeableness was not significant when controlling for multiple comparisons. Spearman rank correlation coefficients indicated that changes in conscientiousness and vulnerability were not related to rated premorbid personality patterns and thus appear to describe shifts for all patients evaluated for memory disorders. These data suggest that personality inventories may be helpful in characterizing caregivers' observations of memory-impaired patients and thus represent a critical source of information for the clinician in charge of care.

Adult

Extensions to sib-pair linkage tests applicable to disorders characterized by delayed onset.

Extensions of the approach to sib-pair linkage tests developed by Haseman and Elston [Behav Genet 2:3-19, 1972] are proposed which incorporate information on age of onset and age at examination. Alternate sources for the age of onset corrections are described, including models for the estimation of parameters associated with the age of onset distribution. Simulation is used to examine the performance of the approach when applied to a dominant disorder of late onset for a range of recombination fractions ranging from very tight linkage to free recombination. For each set of genetic parameters, 2,000 samples of 50 four-member sibships were generated under a complete ascertainment model to investigate power and Type I error, and to compare variants of the proposed technique. Results with and without age-of-onset correction are compared to each other and to those obtainable if penetrance were complete, i.e., if there were no intervening age-of-onset phenomenon. Results from simulation studies show that significance probabilities are enhanced in the presence of linkage when age-of-onset extensions are used. The proposed methods are associated with acceptable levels of Type I error, and substantive gains in power are obtained when data related to age of onset and age at examination are incorporated into the analysis.

Age Factors

Biological and cultural sources of familial resemblance in plasma lipids: a comparison between North America and Israel--the Lipid Research Clinics Program.

Heterogeneity in determinants of familial resemblance of lipid and lipoprotein levels between populations in North America and Israel was investigated using path analysis. A common protocol, identical measurement techniques, and the same statistical procedures were used in the two samples. Both genetic (h2) and cultural (c2) determinants of inheritance were significant for all lipid variables in the two studies. Genetic and cultural heritability of total cholesterol (h2 = 0.61, c2 = 0.02), low-density lipoprotein cholesterol (h2 = 0.59, c2 = 0.02), and high-density lipoprotein cholesterol (h2 = 0.55, c2 = 0.06) did not differ significantly between North America and Israel, while there was a significant difference for triglyceride (h2 = 0.41, c2 = 0.07 in North America; h2 = 0.61, c2 = 0.05 in Israel). Secondary parameters of the path model describing intrafamilial environmental relationships differed between the two countries. In particular, there was a higher correlation between marital environments in Israel for all traits except triglyceride, and a larger effect of father's environment on offspring's environment in Israel for all traits. Within both populations, variation of plasma lipids and lipoproteins was mostly explained by genetic factors and random unmeasured environmental factors. The contribution of common family environment was found to be small, though statistically significant. This is probably due to homogeneity of the distribution of familial environmental determinants within both countries.

Cholesterol

Segregation analysis of low levels of high-density lipoprotein cholesterol in the collaborative Lipid Research Clinics Program Family Study.

Complex segregation analysis with the unified mixed model in white families from nine lipid research clinics was carried out to delineate the mode of familial transmission of plasma high-density-lipoprotein cholesterol (HDL-C). Three groups of families from the collaborative Lipid Research Clinics Program Family Study were assessed: 1,146 selected at random, 483 obtained through hypercholesterolemic probands, and 177 selected from the random sample because a number had low HDL-C, the sample sizes being 4,279, 1,807 and 735, respectively. The data were first transformed and adjusted for effects of covariates. Analyses were performed within clinic and selection strata and also pooled across clinics within strata. The results were consistent across strata and identified two major HDL-C clusters with means separated by approximately 3 SD. There was significant evidence of transmission of a major factor for low HDL-C, but transmission did not conform to Mendelian segregation expectations. There was also evidence of significant multifactorial transmission. Since low HDL-C levels are a major independent risk factor for coronary heart disease, the association of a major factor with familial aggregation of low HDL-C emphasizes the importance of detailed within-family sampling for low HDL-C after identifying a proband whose predominant dyslipoproteinemia is low HDL-C.

Cholesterol, HDL

The usefulness of preoperative laboratory screening.

We assessed the usefulness of routine laboratory screening of preoperative patients. Computer-readable laboratory, demographic, and discharge diagnostic data were assembled for 2,000 patients undergoing elective surgery over a four-month period, and randomly selected samples of patients were studied. Several tests ordered by protocol and performed by the laboratory at the time of admission were examined in these samples, including complete blood cell count, differential cell count, prothrombin time, partial thromboplastin time, platelet count, six-factor automated multiple analysis, and glucose level. Sixty percent of these routinely ordered tests would not have been performed if testing had only been done for recognizable indications, and only 0.22% of these revealed abnormalities that might influence perioperative management. Chart review indicated that these few abnormalities were not acted on nor did they have adverse surgical or anesthetic consequences. In the absence of specific indications, routine preoperative laboratory tests contribute little to patient care and could reasonably be eliminated.

Adolescent

The Collaborative Lipid Research Clinics Family Study: biological and cultural determinants of familial resemblance for plasma lipids and lipoproteins.

This paper reports on the biological and cultural determinants of total, LDL, and HDL cholesterol, and triglyceride (TC, LDL-C, HDL-C, TG) levels using a general linear model on randomly selected family data collected during 1975-1978 at nine North American Lipid Research Clinics. Initially, the analyses were clinic-specific to assess the importance of genetic and cultural transmission, marital resemblance, and other determinants of these traits and then were made jointly to identify the nature and sources of any heterogeneity between clinics. There was evidence of significant genetic and cultural factors for all traits in most clinics. Clinic heterogeneity was also significant, but excluding one clinic reduced the heterogeneity considerably. The genetic (h2) and cultural (c2) heritabilities for the remaining eight clinics were homogeneous with pooled estimates of h2 of .556 +/- .028, .539 +/- .028, .485 +/- .029, and .358 +/- .028, and of c2 of .029 +/- .006, .033 +/- .006, .075 +/- .008, and .089 +/- .009 for TC, LDL-C, HDL-C, and TG, respectively. Among the traits, HDL-C exhibited the most difference among clinics, and both HDL-C and TG showed the largest cultural heritability. The relevance of these and similar studies in a broader understanding of the determinants of plasma lipids and lipoproteins is discussed.

Cholesterol

A multivariate analysis of familial associations of lipoprotein levels in the Lipid Research Clinics Collaborative Family Study: I. Familial correlation and regression analyses.

In view of the complex, intraindividual relationships among different lipoprotein levels (LDL-C, HDL-C, and VLDL-C), multivariate methods aimed at assessing joint familial associations and their possible determinants were performed in the white, random sample component of the Collaborative Lipid Research Clinics Family Study data (1,336 families with 5,097 subjects). After appropriate transformations and covariate adjustments of the data, several kinds of correlation and regression analyses were performed, taking into consideration variable family size and possible age and clinic differences. The association patterns across clinics and age strata were found to be homogeneous for the vast majority of comparisons. The results of multivariate analyses (especially the significant association of each lipoprotein among biological relatives), the persistence of parental levels as the best predictors for the same lipoprotein levels among the offspring, and the essentially unchanged partial correlation estimates as compared to ordinary correlations suggest strong influence of factors specific to each lipoprotein in the familial associations. But the highly significant intraindividual correlations and the nonnegligible cross-correlations among relatives also suggest the additional presence of common underlying factors for the familial associations, especially between HDL-C and VLDL-C and to a lesser extent between LDL-C and VLDL-C. The issues stemming from these analyses and the directions for further analyses are discussed.

Cholesterol

Effects of storage temperature and pH on the stability of eleven beta-lactam antibiotics in MIC trays.

Microdilution MIC test trays containing 11 beta-lactam antibiotics in Mueller-Hinton broth at pH 7.31 or 6.80 were prepared and stored at 4, -10, -25, and -70 degrees C. The drugs tested were ampicillin, ticarcillin, mezlocillin, piperacillin, azlocillin, cefazolin, cefotaxime, moxalactam, cefoperazone, ceftriaxone, and imipenem. MICs for Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 were determined at weekly intervals for up to 1 year. The data from the MIC determinations showed the stability of antimicrobial activity over time to be -70 degrees C greater than -25 degrees C approximately 4 degrees C much greater than -10 degrees C. The relative stability at 4 degrees C as compared with that at -10 degrees C cannot be explained by desiccation, as determined by changes in broth sodium concentrations. The relative instability at -10 degrees C may have been caused in part by a temperature fluctuation, resulting in intermittent freezing and thawing of the antibiotics. Some of the drugs appeared to be more stable when diluted in broth at pH 6.80, but endpoints were more difficult to read. Cefazolin and cefoperazone were stable at all four storage temperatures. Cefotaxime, moxalactam, and ceftriaxone also were relatively stable. The other drugs showed moderately rapid to rapid deterioration at each temperature except -70 degrees C. Storage at -25 degrees C is suitable for up to 3 months for many, but not all, beta-lactams; -10 degrees C appears to be unsuitable. Storage at -70 degrees C is recommended.

Anti-Bacterial Agents

The Collaborative Lipid Research Clinics Program Family Study. II. Response rates, representativeness of the sample, and stability of lipid and lipoprotein levels.

The Collaborative Family Study (1975-1978), the third phase of the Lipid Research Clinics Program Population Studies, covers 2405 probands and 15,693 of their relatives from nine North American communities. This sample was examined for participation differences across race, sex, locality, educational level, and reason for selection. The participation rates were somewhat lower for blacks, younger age groups, and subjects with lower educational levels. The probands' reason for selection into the study had little impact on the participation of probands or relatives. Moreover, based on information gathered at earlier examinations on eligible Family Study probands, the cornary risk factor profile appeared to be similar among participants and nonparticipants . The available longitudinal lipid data on probands indicated general consistency in lipid levels within subjects over short periods of time, in cholesterol even more so than in triglycerides. Among age strata, the younger subjects showed the least intrapersonal stability, especially for triglycerides.

Adolescent

The Collaborative Lipid Research Clinics Program Family Study. III. Transformations and covariate adjustments of lipid and lipoprotein levels.

Several methods of transformation and covariate adjustment have been applied to the Collaborative Lipid Research Clinics Program Family Study data to facilitate analysis of lipid levels of examinees of different sex and age groups. After several exploratory analyses, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were logarithmically transformed, and triglycerides were transformed by the power -0.25. Two types of covariate adjustment procedures, the regression and Z score methods, were used. A modified regression method was developed and was found to be preferable to both simple cubic regression and the Z score method on theoretical and empirical grounds. Refinements in this method to correct for change in variance with age, and for the effect of socioeconomic status, seasonality, and anthropometric measures were made. Methodological issues connected with the transformation and adjustment procedures are discussed.

Adolescent

The Collaborative Lipid Research Clinics Program Family Study. IV. Familial associations of plasma lipids and lipoproteins.

Familial associations of total cholesterol, low density lipoprotein cholesterol, triglycerides, and very low density lipoprotein cholesterol were examined in a population-based random sample of 858 white and 73 black probands and their 4,027 white and 245 black relatives from nine North American Lipid Research Clinics. Correlations among biologic relatives were highly significant for total cholesterol and low density lipoprotein cholesterol and to a lesser extent for triglycerides and very low density lipoprotein cholesterol in whites. Correlations for spouses, however, were not significant, suggesting a stronger influence of genes than shared environment in the determination of these traits. Homogeneity of familial correlations across age strata, clinics, and racial groups was examined. In general, correlations were homogeneous across age strata and clinics, and there was no asymmetry in parent-offspring correlations by the sex of the parent or offspring. Racial differences in correlations were not significant except in four of 32 comparisons, with blacks showing weaker correlations than whites in those instances.

Adolescent

A five-generation family with sacral agenesis and spina bifida: possible similarities with the mouse T-locus.

In man, a malformation that recalls some of the defects associated with T/t mutants in the mouse is sacral agenesis. We report on a family with a high incidence of sacral malformation, ranging from a complete absence of the sacrum (SA), with or without spina bifida aperta, to a spina bifida occulta (SBO) that could only be detected by x-ray. The condition appeared in a man with four children who were all affect, and thereafter, to varying degrees, in 17 of his 28 descendants. Segregation analysis has been performed in this family, using the Elston and Stewart transmission probability model [1971]. The two traits (SA and SBO) were first studied separated and then together. A fully penetrant major dominant gene is show to cause SA. When the phenotypes SA and SBO are considered together, Mendelian transmission is rejected. This could be explained genetically by two alternative hypotheses: genetic heterogeneity or a dominant major gene transmitted in excess by heterozygotes (tau Aa A = 0.896), suggesting a segregation distortion property of an allele at a T-like locus.

Adult

Segregation analysis of congenital glaucoma: approach by two differential models.

To determine the mode of inheritance of congenital glaucoma, segregation analysis was performed using two different models: the transmission probability model and the mixed model. Whereas the latter, testing for monogenic inheritance in the presence of both monogenic and polygenic components, results in strong evidence for a major locus, the former, testing for Mendelian segregation at one locus, rejects this hypothesis. The differences in the results of these two models are discussed and are attributed to the underlying structure of each. Genetic heterogeneity of congenital glucoma is proposed.

Female