Biomedical subjects
Publications and source records attributed to D Cookfair.
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Triple-antibody flow cytometry was used to search for distinctive populations of peripheral blood lymphocyte immunophenotypes in multiple sclerosis (MS). Using monoclonal antibodies to the cell surface markers CD3, CD4, and CD8, T cell subsets were quantified on a cohort of 31 MS patients (not treated with corticosteroids for at least 6 months), 30 healthy donors, and 14 patients with other autoimmune diseases (also corticosteroid treatment-free for at least 6 months). Untreated MS patients displayed a significantly greater population of CD3+CD4+CD8+ circulating T cells than healthy donors (P = 0.023). Patients with other autoimmune diseases displayed mean populations of CD3+CD4+CD8+ cells greater than normal donors and less than MS, but not significantly different from either. An additional 45 MS patients who had received corticosteroid therapy within the previous 6 months were phenotyped. Treatment of symptomatic MS with corticosteroids was associated with a smaller population of circulating CD3+CD4+CD8+ cells. Some MS patients have significantly greater numbers of peripheral blood T lymphocytes simultaneously expressing CD3, CD4, and CD8 surface markers than healthy donors and this population of cells may be reduced by corticosteroids treatment. This triple positive phenotype may be a manifestation of a systemic immune abnormality in MS.
We determined inter- and intrarater Kurtzke Expanded Disability Status Scale (EDSS) scoring agreement for four trained examining physicians who evaluated 10 clinically stable multiple sclerosis patients. These patients had previously been determined to have EDSS scores of 1.0 to 3.5 and were scheduled to participate in a funded clinical trial of intramuscular recombinant interferon-beta. Intrarater reliability was greater than interrater reliability for scoring the EDSS and all of its component functional systems scores (FSS). Specifically, individual examiners were able to reproduce three serial examination scores on the same patient on the same day (intrarater agreement) within 1.0 EDSS or 2.0 individual FSS points. Reproducible scoring across examiners (interrater agreement), however, could only be accomplished within 1.5 EDSS or 3.0 individual FSS points. Additionally, the interrater scoring variability in our patients is greater than that previously reported for patients with higher EDSS scores. We conclude that clinical trials that employ the EDSS as an outcome measure of treatment efficacy should include inter- and intrarater agreement data for all examining physicians. Most importantly, studies using a single examining physician to evaluate individual patients throughout the course of a clinical trial will require less change in the EDSS to reliably measure disease activity than will studies using more than one examining physician to evaluate individual patients throughout the trial.
The relationships between cigarette smoking, occupational exposures, dietary vitamin A and lung cancer is explored in a case-control study. The study is based on 1002 primary lung cancers among white men and 1119 white male controls between 35 and 79 years of age admitted to Roswell Park Memorial Institute from 1957 to 1965. Four hundred sixty-four lung cancer cases were classified as one of the three major histologic cell types: squamous, small cell, or adenocarcinoma. Each of the three main histologic types displayed a statistically significant trend of increasing risk associated with increasing consumption of cigarettes with the strongest relationship being seen for small cell carcinoma (odds ratio for 40+ pack-years = 17.5) and the weakest with adenocarcinoma (odds ratio for 40+ pack-years = 6.7). Increasing risk for squamous cell cancer was seen with increasing duration of exposure to all lung carcinogens, asbestos, and aromatic hydrocarbons. Small cell carcinomas were not associated with any of the occupational exposure categories studied with the exception of asbestos exposure in light smokers. Increasing risk of adenocarcinoma was seen with increasing duration of employment in occupations with potential exposure, but only for light smokers. Dietary vitamin A consumption did not confound the occupational associations. Hypotheses have been generated regarding interplay of risk factors in the etiology of different histologic subtypes of lung cancer. Studies of specific histologic types of lung cancer are needed to elucidate the role of various environmental and occupational risk factors.
After seven pediatric cases of chronic fatigue syndrome (CFS) were diagnosed in a farming community in upstate New York, a questionnaire regarding symptoms and potential risk factors of CFS was distributed to all students enrolled in the same school district. Twenty-one students with symptoms of CFS were identified. Two controls per case matched for age and sex were randomly selected from questionnaire respondents. Health status was verified for all subjects by telephone, and diagnosis of CFS was confirmed by a physician. Information was collected on the following factors: symptoms of CFS among other family members; history of allergy/asthma; consumption of raw milk, raw eggs, raw cheese, or raw meat; water supply; exposure to animals; home heating source; proximity to farmland/orchards; tick bite; blood transfusion; camping; and appendicitis. Logistic-regression analyses indicated that the best model (characterized by symptoms among other family members, recent ingestion of raw milk, and history of allergy/asthma) produced significant estimates of relative risk (P less than .05) of 35.9, 44.3, and 23.3, respectively, for the three factors (corrections were made for the effect of the other covariates). These data suggest that a combination of host and environmental factors, including an infectious agent or agents, are involved in the etiology of CFS.
Endogenous sex hormones seem to influence the risk of several common and debilitating diseases. With a view toward better understanding the effects of surgical removal of the ovaries and high-dose pelvic radiotherapy on plasma sex hormone levels, we measured estrogen and androgen concentrations cross-sectionally among 147 women who had been treated for cervical cancer 0.3-18.5 years previously. Pelvic radiotherapy (mean dose to ovaries, 50 Gy) and bilateral ovariectomy were associated with similarly reduced hormone concentrations relative to levels among nonirradiated women with intact ovaries, most of whom had had early-stage disease and were treated by hysterectomy. There was little evidence that radiotherapy in addition to ovariectomy further lowered concentrations below levels associated with ovariectomy alone, such as might be expected if radiation was suppressing adrenal endocrine function. Among women age 50 years or older at the time of blood drawing, the removal or irradiation of the ovaries was associated with approximately 45% lower concentrations of estradiol (mean ratio [MR], 0.55; 95% confidence interval [CI], 0.32-0.95) and testosterone (MR, 0.57; 95% CI, 0.32-0.99), and 25-30% lower concentrations of estrone (MR, 0.69; 95% CI, 0.44-1.09) and androstenedione (MR, 0.76; 95% CI, 0.47-1.23), relative to the hysterectomy-only group. Among women younger than 50, ovariectomy and radiotherapy, alone or in combination, were associated with 83% lower estradiol concentrations (MR, 0.17; 95% CI, 0.09-0.31), 46% lower estrone concentrations (MR, 0.54; 95% CI, 0.37-0.81), 23% lower androstenedione concentrations (MR, 0.77; 95% CI, 0.57-1.04), and 14% lower testosterone levels (MR, 0.86; 95% CI, 0.64-1.15).(ABSTRACT TRUNCATED AT 250 WORDS)