Biomedical subjects

D V Dawson

Publications and source records attributed to D V Dawson.

At least 37 records · Page 2Linked to original sources

PubMed1997

A new test statistic for linkage applied to bipolar disorder and marker D18S41.

We applied a new test statistic for linkage that removes the traditional assumption of equal female (theta f) and male (theta m) recombination fractions by testing Ho: theta f + theta m = 1 vs. HA: theta f + theta m < 1 to GAW10 Problem 1. Specifically we reanalyzed the reported possible linkage between a suggested susceptibility locus for bipolar affective disorder and marker D18S41 on chromosome 18 [Stine et al., 1995]. We used penetrance functions fitting the description of those used by Stine et al. [1995] assuming a continuous age-dependent logistic distribution. Maximum likelihood marker allele frequencies were estimated assuming Hardy-Weinberg equilibrium. Results from the traditional lod-score analyses do not strongly support the existence of linkage between the disease locus and marker D18S41. Similarly, the new test statistic for linkage failed to provide evidence in support of linkage. This was true whether dominant or recessive models of inheritance were assumed, and whether the analyses included all available pedigrees or were confined to paternally transmitted pedigrees. The appreciable difference found between our lod scores and those obtained by Stine et al. [1995] can be attributed to differences in the assumptions made regarding the age-dependent penetrance function, the marker allele frequencies, or both.

Alleles↗

PubMed1997

Modeling age of onset and residual familial correlations for the linkage analysis of bipolar disorder.

We applied regressive modeling to the data described by Stine et al. [1995] and further explored the possible linkage of bipolar disorder to marker D18S41 on chromosome 18. We performed analyses to determine age-dependent penetrance functions that best fit the data and that allow for residual familial correlations. Specifically, we introduce here a simple method to allow for a sibling correlations. that is not due to segregation at the linked locus, and then extend the results of Stine et al. [1995] by using the best fitting "regressive" model of this kind as input into a lod score linkage analysis. Although a formal segregation analysis was not attempted, a surprising finding was that, except for doubtful linkage to D18S41, there is little evidence for genetic transmission of bipolar disorder in these families.

Age of Onset↗

PubMed1996

Factors predicting change in prescription and nonprescription drug use in a community-residing black and white elderly population.

The current study identifies characteristics that predict change in use of prescription and nonprescription drugs over a period of 3 years. A modified health care services use model was applied to information obtained from a probability-based sample of black (n = 1778) and white (n = 1446) community-resident elderly, interviewed in 1986-1987 and 1989-1990. Analysis was by means of logistic and ordinary least-squares regression, with sample weights and design effects taken into account. The number of users and average number of prescription drugs used increased over the 3 years, and was best predicted by extent of prior drug use, older age, white race, poorer health, and number of health care visits. Conversely, nonprescription drug use declined significantly, and was best predicted by prior use, white race, and female gender. The reduced use of prescription drugs by blacks as compared to whites is of concern, suggesting that attention is needed to assure equitable access to prescription drugs.

Black or African American↗

PubMed1996

Is medication use by community-dwelling elderly people influenced by cognitive function?

To determine whether medication use differs by cognitive status among community dwelling elderly, a survey was made of a stratified random sample of 4110 black and white participants, aged 65 or older from the Duke Established Populations for Epidemiologic Studies of the Elderly in five adjacent urban and rural counties in the Piedmont area of North Carolina. Main outcome measures were usage of prescription medications, non-prescription medications, and medicines within therapeutic classes in the previous 2 weeks as determined during an in-home interview; and total number of prescription and non-prescription medicines used in the previous 2 weeks. Multivariate analyses, using weighted data adjusted for sampling design, were conducted to assess the association between drug use patterns and cognitive status, as assessed by the Short Portable Mental Status Questionnaire, while adjusting for demographic, health status, and access to health care factors. Participants with cognitive impairment (13.7% of sample) were less likely to use any prescription medications (Adjusted OR = 0.66, 95% CI = 0.48-0.90) or any non-prescription medications (Adjusted OR = 0. 71, 95% CI = 0.56-0.89) than cognitively intact subjects. Both groups took a similar number of prescription and non-prescription medications. Those who were cognitively impaired were less likely to take analgesics (Adjusted OR = 0.66, 95% CI = 0.52-0.83), but were more likely to take central nervous drugs (Adjusted OR = 1.55, 95% CI 1.18-2.04) than those who were cognitively intact. We conclude that drug use patterns by community-dwelling elderly people differ with cognitive status. Future research needs to examine medication use by specific causes of cognitive impairment.

Activities of Daily Living↗

PubMed1996

Microglia are not exclusively associated with plaque-rich regions of the dentate gyrus in Alzheimer's disease.

The functional significance of microglia found in neuritic plaques in Alzheimer's disease (AD) remains a source of controversy. In the present study, we explored the anatomic relationships between microglia and neuritic plaques in order to determine the potential role of microglia in plaque formation. We chose to study the molecular layer of the hippocampal dentate gyrus, a brain region where plaques have a strong tendency to line up parallel to the adjacent granule cell layer. We found that ferritin-labeled microglia were indeed most numerous in the same distinct band as plaques, but that microglia were relatively more common in the outer molecular layer. The distribution of microglia was more variable than that of plaques. Overall, microglial cell distribution was a relatively poor predictor of plaque distribution, particularly when cases were considered individually. Thus, there must be multiple triggers for microglial cell activation and accumulation in the AD brain, triggers which do not all necessarily lead to neuritic plaque formation.

Aged↗

PubMed1996

Predictors of outcome of epilepsy surgery: multivariate analysis with validation.

PURPOSE: To identify predictors of outcome of epilepsy surgery, using the Duke experience, applying multivariate analysis and validation techniques. To compare the results of different modeling algorithms. Few previous studies have reported multivariate analysis, or validated their results. METHODS: Records of 116 patients with focal resections for intractable epilepsy from January 1, 1980 through June 30, 1989 were analyzed. Primary outcome variable was patient's condition in second postoperative year: seizure free (except auras), or not. Three predictors of biologic interest were specified a priori for confirmatory analysis. Additional predictors were considered within exploratory analysis. Logistic regression techniques were applied to assess relations with pre- and postoperative predictors. Internal validity was assessed by repeated random selection of training and validation samples, used in conjunction with bootstrap techniques. RESULTS: By using multivariate analysis, percentage of epileptic EEG activity arising from the site of resection and either imaging localization or lack of use of invasive monitoring were the only statistically significant preoperative predictors for good outcome at 2 years. Presence of seizures within 2 months of surgery was a significant postoperative predictor for a poor outcome. Adding more variables did not result in significantly improved models. Use of validation techniques reduced the degree of optimism in the predictive value of the models. CONCLUSIONS: Pooling of data from multiple institutions is needed to attain the large sample sizes needed for multivariate analysis with validation.

Adolescent↗

PubMed1996

Interleukin-2 receptor levels in sera of patients with rheumatoid arthritis treated with sulfasalazine, parenteral gold, or placebo.

OBJECTIVE: To evaluate the associations of soluble serum interleukin-2 receptor (sIL-2R) levels in patients with rheumatoid arthritis (RA) with clinical and laboratory measures of disease activity and the predicted response to therapy. METHODS: sIL-2R levels were determined by ELISA in 137 patients with RA, not previously treated with 2nd line therapy. Patients were enrolled in a prospective, randomized, placebo controlled trial of sulfasalazine (SSZ) versus gold sodium thiomalate (GSTM), sponsored by the Cooperative Systematic Studies of Rheumatic Diseases. Using correlation analysis and regression modeling, the clinical utility of sIL-2R as a measure of disease activity and predictor of outcome was assessed. RESULTS: 91 women and 46 men with a mean age of 51 +/- 13 years and mean duration of disease of 64 +/- 78 months participated in this study. The mean sIL-2R level in all patients with RA was markedly elevated (980 +/- 589 U/ml) compared with that in healthy control subjects (446 +/- 196 U/ml; p = < 0.0001). There was no correlation between the sIL-2R levels and the joint pain/tenderness count, either at study entry or completion. There were significant positive correlations between the baseline sIL-2R and baseline erythrocyte sedimentation rate (ESR) and between the change in sIL-2R and the change in ESR. Both a multiple linear regression model and a multiple logistic regression model showed that baseline sIL-2R levels were not predictive of clinical outcome. CONCLUSION: sIL-2R levels are significantly elevated in patients with active RA and correlate positively with ESR. However, these results indicate that in patients with early RA, sIL-2R levels are neither associated with standard disease activity criteria nor predictive of the response to therapy with SSZ or GSTM, even after controlling for the simultaneous effects of other important clinical variables.

Adult↗

PubMed1995

Predominant infiltration of rejecting human renal allografts with T cells expressing CD8 and CD45RO.

Subsets of T cells have been identified by the expression of different isoforms of CD45. Some T cells expressing CD45RA (gp220) have been characterized as "naive" in their response to antigens including alloantigens, whereas T cells expressing CD45RO (gp180) have been characterized as "memory" T cells. To examine the potential association between kidney allograft rejection and infiltration with these subsets, immunohistologic labeling of serial frozen sections from 17 nonrejecting and 18 rejecting kidney transplant biopsies was performed. Biopsies were selected on the basis of unambiguous clinical pathological diagnosis, no antirejection therapy within 1 month before biopsy, and enough tissue available for immunohistologic labeling. Sections were labeled for CD3, CD4, CD8, CD45RA, and CD45RO, and slides were evaluated in a masked manner. The numbers of cells were counted in 10 (400x) high power fields (HPF) in each section. The medians of average cell counts were significantly higher in the rejecting compared with nonrejecting group for CD3+, CD4+, CD8+, CD45RA+, and CD45RO+ T cells in both diffuse and aggregate patterns of infiltration. However, the numbers of infiltrating cells per HPF in rejecting grafts were most striking for CD8+ and CD45RO+ cells: 16/18 rejecting vs. 1/17 nonrejecting cases had more than 5 CD8+ cells/HPF. Likewise, 17/18 rejecting vs. 1/17 nonrejecting cases had more than 5 CD45RO+ cells/HPF. In both cases, the difference was most striking for cells infiltrating in a diffuse versus aggregate pattern. Significantly higher CD45RO+ to CD45RA+ ratios were observed in rejecting versus nonrejecting groups, both in the diffuse and aggregate patterns. Within the rejecting cases, the CD45RO+ to RA+ ratio was significantly higher in diffuse versus aggregate patterns of infiltration (P < 0.0002). These results indicate that a significant increase in CD8+, CD45RO+, and the ratio of CD45RO+ to CD45RA+ T cells in a diffuse pattern of infiltration is most characteristic of clinical renal allograft rejection.

Biopsy↗

PubMed1995

Extended HLA profile of an inbred isolate: the Schmiedeleut Hutterites of South Dakota.

HLA-A, -B, -C, -DR, and -DQ typings of the Schmiedeleut Hutterites of South Dakota were collected as part of an ongoing genetic-epidemiologic study of HLA and fertility. A total of 1,082 individuals, including 852 married adults representative of the reproductive population of this isolate, were characterized for five-locus HLA haplotypes. HLA-A1, A2, A3, and A24 accounted for 75% of observed HLA-A alleles and HLA-B27, B35, B51, and B62 accounted for 55% of observed HLA-B alleles. S-leut Hutterites are derived from 68 or fewer ancestors. However, only 48 ancestral HLA haplotypes were observed and nine of these accounted for over 52% of the observed haplotypes. Measures of two-locus linkage disequilibrium derived from these haplotypes indicated that one-third to half of the observed HLA-A/B, B/DR, and A/DR allele combinations exhibited highly statistically significant linkage disequilibrium. Allele and haplotype frequencies did not differ between males and females. Recombination rates of 0.004% and 0.005% between HLA-A and -C and between HLA-B and -DR, respectively, were observed. This HLA profile points out a paucity of HLA alleles and haplotypes in this population and marked linkage disequilibrium among the HLA alleles that are present.

Alleles↗

PubMed1995

Reliability of the Rey-Osterrieth Complex Figure in use with memory-impaired patients.

Rater reliability was evaluated for the system most widely used to assess copy and recall of the Rey Complex Figure: the Osterrieth (1944) 18-item scoring system. The study sample consisted of 95 subjects (49 males, 46 females), most of whom were elderly individuals (M = 59.83, SD = 15.21 years) suffering from memory impairment. Four raters rated copy and delayed-recall protocols, and three raters re-rated the protocols after an interval of 3 months. Results revealed excellent inter- and intra-rater reliability coefficients (.85-.97) for total scores. However, reliabilities for the 18 individual items ranged from poor (.14) to excellent (.96). Differences in both reliability and level of subject performance were observed as a function of item and conditions of copy versus recall. It is concluded that the Osterrieth scoring system supports excellent reliability in use with memory-impaired patients using total scores. Nevertheless, individual-item reliability would benefit from enhancement, for example, via amplified delineation of relevant decision criteria.

Adult↗

PubMed1994

Ascertainment models incorporating effects of variable age of onset.

In pedigree analysis, nonrandom sampling, or ascertainment through affected persons, occurs commonly, making it necessary to adjust appropriately for the ascertainment procedure in order to secure the correct interpretation of results from genetic analysis. Ascertainment models for dichotomous phenotypes are considered for disorders characterized by variable age of onset, particularly considering those instances where the probability of ascertainment may be influenced by the age of onset of the disorder. For a variety of theoretical and practical reasons, sigmoidal functions appear to be well suited to the modeling of occurrence of a binary event, such as proband status. Relevant ascertainment models incorporating a modified exponential ascertainment function having such a sigmoidal form are described, together with associated modifications to the likelihood for the ascertained pedigree. Alternative parameterizations and methods for obtaining initial estimates are also discussed.

Age of Onset↗

PubMed1994

Behavior problems of young girls with fragile X syndrome: factor scores on the Conners' Parent's Questionnaire.

Mothers of 60 girls with fragile X [fra(X)] and 58 controls were asked to fill out the Conners' Parent's Questionnaire to determine if this commonly used checklist would detect behavior problems in young girls with fra(X). The mean T-scores were significantly different between the 2 groups of girls on 5 of the 6 factors on the Conners' Parent's Questionnaire and the girls with fra(X) had mean T-scores that were above the average range on both the Anxiety factor and the Hyperactivity Index factor. Significantly more girls had T-scores greater than 70 (> 98th centile) on 3 of the 6 factors. Twenty-three percent of the girls had T-scores greater than 70 on the Anxiety factor and 38% of the girls had T-scores greater than 70 on the Hyperactivity Index factor. This study suggests that some behavior problems will be reported frequently in young girls with fra(X) and should not be difficult for clinicians to detect.

Adolescent↗

PubMed1994

Interleukin-2 receptor levels in the sera of rheumatoid arthritis patients treated with methotrexate.

OBJECTIVE: To evaluate the association of the level of soluble serum interleukin-2 receptor (sIL-2R) with disease activity and response to therapy in patients with rheumatoid arthritis (RA). METHODS: The sIL-2R levels of 148 patients with refractory RA were determined by enzyme-linked immunosorbent assay. This parameter was correlated with other clinical observations obtained during a prospective, randomized, placebo-controlled trial of methotrexate, sponsored by the Cooperative Systematic Studies of Rheumatic Diseases consortium. Using statistical modeling, the usefulness of sIL-2R as a measure of disease activity and a predictor of outcome was evaluated. RESULTS: The mean sIL-2R level in all RA patients was markedly elevated compared with that in normal control subjects, and decreased significantly during the trial. There was no correlation of the sIL-2R level and the joint pain/tenderness count either at study entry or study end. There was a significant correlation of the sIL-2R level and the erythrocyte sedimentation rate, both at study entry and study end. A multiple linear regression model showed that treatment with methotrexate, but not the sIL-2R level or the change in sIL-2R level, predicted a change in joint count. A stepwise multiple logistic regression model defined no significant predictive information for outcome for the level of sIL-2R at study entry. CONCLUSION: After controlling for the simultaneous effects of other important clinical variables, the level of sIL-2R does not appear to predict the response to methotrexate in patients with refractory RA. Further analysis of cohorts of patients with earlier RA needs to be performed.

Adult↗

PubMed1994

Caregiver ratings of personality change in Alzheimer's disease patients: a replication.

Caregivers of 26 patients with Alzheimer's disease (AD) rated current and premorbid personality patterns with the NEO Personality Inventory. Results replicated previous findings on the degree of change reported in a previous group of patients with mixed memory disorder diagnoses. After a diagnosis of AD, the patients were rated as significantly more neurotic, less extraverted, less open, and less conscientious. There were no rated differences of changes in the personality domain of Agreeableness. These results strengthen the usefulness of caregiver ratings of personality change of patients with memory problems who cannot be useful informants on their own behalf.

Aged↗

PubMed1994

Swallowing in Alzheimer's disease.

Using a prospective case series design, we examined the incidence of oropharyngeal swallowing abnormalities in 25 patients with moderate or severe Alzheimer's disease by videofluoroscopy. Aspiration occurred in 6 of 25 (28.6%). Only four patients showed unequivocally normal performance. Exploratory statistical analyses showed that swallowing abnormalities associated significantly with duration of dementia, eating dependency, and abnormal oral praxis. We observed a trend toward a higher incidence of aspiration in patients with more severe dementia. We conclude that oropharyngeal swallowing abnormalities, including aspiration, are more prevalent in patients with Alzheimer's disease than in normal elderly individuals.

Aged↗

PubMed1994

A follow-up survey of clinical practices for the use of heparin, warfarin, and aspirin.

OBJECTIVE: To determine whether anticoagulation practices have changed when heparin and warfarin are used to treat cerebrovascular disease, and to determine the dosage of aspirin used to treat carotid territory transient ischemic attacks (TIAs). BACKGROUND: A 1987 study documented that neurologists and neurology house officers were using excessive amounts of heparin and warfarin. Recent studies have demonstrated the efficacy and safety of low-intensity anticoagulation for preventing strokes, but no data are available on how these findings have affected the treatment practices of clinicians. DESIGN/METHODS: Questionnaires were sent to neurology staff at 10 medical centers. The questions dealt with the use of heparin, warfarin, and aspirin in stroke/transient ischemic attack patients. The nonparametric Wilcoxon rank sum test was used for analyzing the responses. RESULTS: Ninety-three physicians responded compared with 52 in the prior study. Most (56 of 92; 61%) did not use an IV heparin bolus. The mean partial thromboplastin time (PTT) was 55 seconds, which was significantly less than the mean PTT of 62 seconds (p = 0.006) in the prior study. The mean prothrombin time (PT) fell to 16.0 seconds (range, 12.5 to 20.0) compared with a mean of 19.9 seconds (range, 15.0 to 27.0; p < 0.001) in the earlier study. There was a significant fall in the mean PT ratio from 1.74 (range, 1.20 to 2.25) to 1.49 (range, 1.12 to 2.50; p < 0.001). Most respondents used 325 mg qd of aspirin for treating TIAs. CONCLUSIONS: At the centers studied, neurologists and neurology house officers are using less intense anticoagulation when treating stroke patients now than in 1986. This concurs with recent studies demonstrating the efficacy and safety of low-intensity anticoagulation in some clinical settings. The use of 325 mg/d of aspirin is common, although the data supporting its efficacy compared with higher doses are unclear.

Anticoagulants↗

PubMed1994

Do young boys with fragile X syndrome have macroorchidism?

OBJECTIVE: Macroorchidism is one of the most well-described clinical characteristics of men with fragile X syndrome, but little information has been available regarding macroorchidism in prepubertal boys with fragile X. The purpose of this study was to learn whether macroorchidism is a characteristic of fragile X syndrome in prepubertal boys. METHODS: Clinical assessments were performed on 73 boys, 2.2 to 10.2 years, in whom fragile X either had been diagnosed or who had been referred for fragile X evaluations because of developmental delays. As part of these assessments, we measured testicular volumes using Prader orchiometer beads to find out if macroorchidism occurs before the onset of puberty. RESULTS: From 2.2 through 7 years, boys with fragile X have significantly larger mean testicular volumes than boys without fragile X, but macroorchidism (> or = 4.0 mL or > or = 2 times normal) only occurred in 1 of 27 boys with fragile X. From 8 to 10 years, all our patients with fragile X had clinically enlarged testicles (> or = 3.75 mL), and 7 of 9 boys with fragile X had macroorchidism (> or = 4.0 mL). The testicular volumes of control subjects were all < or = 3.0 mL. CONCLUSIONS: These findings suggest that macroorchidism occurs in some prepubertal boys with fragile X, but in this series it did not occur until age 6 and usually did not occur until after age 8.

Child↗

PubMed1993

The pattern and phenotype of T-cell infiltration associated with human liver allograft rejection.

Although transplant biopsy remains the best means for assessing liver allograft dysfunction, the presence and degree of rejection often is difficult to determine by current histologic criteria. The added diagnostic and prognostic value of examining liver allograft biopsy specimens by immunopathologic methods, such as phenotyping inflammatory cell infiltrates, has been inconclusive. To examine the value of assessing the phenotype and location of T-cell infiltrates we compared findings in 20 liver transplant biopsy specimens obtained from patients undergoing allograft rejection with those in 20 biopsy specimens from patients with no evidence of rejection. Serial frozen sections from all biopsies were labeled by immunoperoxidase techniques using monoclonal antibodies to identify cells expressing CD3, CD4, CD8, CD45RA, and CD45RO. As expected, the median of average cell infiltrates was higher in the rejecting versus nonrejecting group for each cell phenotype and region. However, statistical comparisons indicated that only some combinations of cell phenotype and location were significantly greater in the rejecting versus nonrejecting groups. The median number of portal CD3+ T cells per high-power field was increased in the rejecting versus nonrejecting groups (15.15 v 5.00 cells/high-power field; P < .01). This primarily was the result of a significant increase in CD8+ cells (7.15 v 1.55 cells/high-power field; P < .0001). Examination of cells expressing CD45 isoforms also revealed a suggested increase (P < .04) in CD45RO+ "memory" but not in CD45RA "naive" T cells infiltrating portal areas. In lobular areas cell infiltrates of any examined phenotype were not significantly increased in the rejecting versus nonrejecting groups. These findings indicate that during liver allograft rejection the most characteristic changes involve an increase in T cells infiltrating the graft in portal regions and suggest that human liver allograft rejection preferentially involves memory CD8+ T cells directed at portal structures.

Antigens, CD↗