PubMed Health⌕ Search

Biomedical subjects

J E Michalek

Publications and source records attributed to J E Michalek.

At least 19 recordsLinked to original sources
PubMed2001

Relation of serum tetrachlorodibenzo-p-dioxin concentration to diet among veterans in the Air Force Health Study with background-level exposure.

To examine the contribution of various foods to exposure to 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) in a background-exposed U.S. population, serum TCDD levels were examined in relation to diet as assessed by a standard diet assessment instrument among men with no known unusual exposure to TCDD. Our subjects were male veterans aged 42-76 yr who were in the unexposed comparison group in the Air Force Health Study, a study of the health effects of exposure to Agent Orange and herbicides in Vietnam. Food consumption was assessed by a 126-item food frequency questionnaire. Two hundred and ninety veterans who had both TCDD levels and diet assessed in 1992 were included. In general, associations between serum TCDD and consumption of foods in specific groups or nutrients, that is, meats and fats, were not evident. Among younger men, fish and chicken intake were associated with higher serum TCDD levels. The results suggest that no single food group accounts for a large proportion of variation in TCDD exposure in older U.S. men.

Adult↗
PubMed2001

Serum dioxin and cognitive functioning among veterans of Operation Ranch Hand.

We used the Halstead-Reitan neuropsychological test battery, the Wechsler adult intelligence scale-revised, the Wechsler memory scale, and the wide range achievement test to assess cognitive functioning among Air Force veterans exposed to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam war The index subjects were veterans of Operation Ranch Hand (N = 937), the unit responsible for aerial herbicide spraying in Vietnam from 1962 to 1971. A comparison group of other Air Force veterans (N= 1,052), who served in Southeast Asia during the same period but were not involved with spraying herbicides served as referents. Cognitive functioning was assessed in 1982, and dioxin levels were measured in 1987 and 1992. We assigned each Ranch Hand veteran to the background, low, or high dioxin exposure category on the basis of a measurement of dioxin body burden. Although we found no global effect of dioxin exposure on cognitive functioning, we did find that several measures of memory functioning were decreased among veterans with the highest dioxin exposure. These results became more distinct when we restricted the analysis to enlisted personnel, the subgroup with the highest dioxin levels. An analysis based on dioxin quintiles in the combined cohort produced consistent results, with veterans in the fifth quintile exhibiting reduced verbal memory function. Although statistically significant, these differences were relatively small and of uncertain clinical significance.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2001

Serum dioxin and peripheral neuropathy in veterans of Operation Ranch Hand.

We studied whether exposure to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam War is related to peripheral neuropathy. The index subjects were veterans of Operation Ranch Hand, the unit responsible for aerial herbicide spraying in Vietnam from 1962 to 1971. We report peripheral nerve function assessed in 1982, 1985, 1987, 1992 and 1997, nerve conduction velocities measured in 1982, and vibrotactile thresholds of the great toes measured in 1992 and 1997. We assigned each Ranch Hand veteran to one of three exposure categories named "background", "low" and "high", based on his serum dioxin level. Other than the bilateral vibrotactile abnormalities, we consistently found a statistically significant increased risk of all indices of peripheral neuropathy among Ranch Hand veterans in the high exposure category in 1997, and a statistically significant increased risk of diagnosed peripheral neuropathy, incorporating bilateral vibrotactile abnormalities of the great toes, in the high category in 1992. Restricting to the enlisted veterans did not alter these results. Cautious interpretation of these results is appropriate until the relationship between pre-clinical diabetes mellitus and peripheral neuropathy is further evaluated in future examinations.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2001

Serum dioxin and hepatic abnormalities in veterans of Operation Ranch Hand.

PURPOSE: We studied hepatic abnormalities and indices of hepatic function in relation to exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. METHODS: The prevalence of ever having liver disease through March 1993, and level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase (GGT), lactic dehydrogenase (LDH), alkaline phosphatase, and total bilirubin were examined according to serum dioxin levels. RESULTS: We found an increased risk of "other liver disorders" among veterans with the highest dioxin levels [adjusted odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.2 to 2.1], due primarily to increased transaminases or LDH (adjusted OR = 2.7, 95% CI 1.4 to 5.1) and to other nonspecific liver abnormalities (adjusted OR = 1.4, 95% CI 1.0 to 2.0). CONCLUSIONS: Whether the associations observed were causal is unclear from these data.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2000

Maximum likelihood estimation for longitudinal data with truncated observations.

We obtain maximum likelihood estimates of the parameters when the observations on the response variable in a repeated measures design are truncated above a cutpoint. The maximum likelihood equations are solved iteratively using an EM-like procedure. It is observed that these estimates have smaller mean squared error than recently proposed iterative weighted least-squares estimates. The results are applied to data arising from a study of dioxin elimination in Air Force veterans. Published in 2000 by John Wiley & Sons, Ltd.

Aerospace Medicine↗
PubMed2000

Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure.

Data from several epidemiologic studies suggest that exposure to unusually high amounts of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) increases the risk of diabetes mellitus, and experimental data suggest that the mechanism for this is decreased cellular glucose uptake. To investigate the dose-response relation more closely, we examined the association of serum dioxin level with prevalence of diabetes mellitus and with levels of serum insulin and glucose among 1,197 veterans in the Air Force Health Study who never had contact with dioxin-contaminated herbicides and whose serum dioxin level was within the range of background exposure typically seen in the United States (< or =10 ng/kg lipid). Compared with those whose serum dioxin level was in the first quartile (<2.8 ng/kg lipid), the multivariate-adjusted odds of diabetes among those in the highest quartile (> or =5.2 ng/kg lipid) was 1.71 (95% confidence interval = 1.00-2.91). The association was slightly attenuated after adjustment for serum triglycerides. Whether adjustment for serum triglycerides was appropriate, however, cannot be determined with available data. The association of background-level dioxin exposure with the prevalence of diabetes in these data may well be due to reasons other than causality, although a causal contribution cannot be wholly dismissed.

Blood Glucose↗
PubMed1999

Pharmacokinetics of TCDD in veterans of Operation Ranch Hand: 15-year follow-up.

Using multiple measurements from serum collected over 15 yr (in 1982, 1987, 1992, and 1997), the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 97 veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam, was estimated. The potential influences of age, percent body fat, and changes in percent body fat on the half-life estimate were also examined. The elimination rate of TCDD for these veterans was 0.0915 per year with 95% confidence interval 0.0844 to 0.0986 per year; the corresponding half-life estimate was 7.6 yr with 95% confidence interval 7.0 to 8.2 yr. The elimination rate decreased significantly with increasing body fat, but not with age or relative changes in percent body fat.

Adipose Tissue↗
PubMed1999

Serum dioxin and immunologic response in veterans of Operation Ranch Hand.

The authors studied immune response and exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) among veterans of Operation Ranch Hand, the US Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. A comparison group of Air Force veterans who served in Southeast Asia but were not involved in spraying herbicides was included. The authors studied delayed-type hypersensitivity skin test responses to Candida albicans, mumps, Trichophyton, and a bacterial antigen made from lysed Staphylococcus aureus. Lymphocyte measurements included total lymphocyte counts; T-cell (CD3, CD4, CD5, and CD8), B-cell (CD20), and NK-cell (CD16 and CD56) subsets; and expression of the activation antigen CD25 on CD3 T cells. The authors quantitated the serum concentrations of immunoglobulin (Ig)A, IgG, and IgM; examined sera for the presence of monoclonal immunoglobulins (M proteins); and looked for a broad range of autoantibodies (rheumatoid factor, antinuclear antibody, smooth muscle autoantibody, mitochondrial autoantibody, parietal cell autoantibody, and thyroid microsomal autoantibodies). They measured the level of dioxin in 1987 or 1992, extrapolated the result to the time of service in Vietnam, and assigned each veteran to one of four exposure categories: Comparison and three Ranch Hand groups (Background, Low, or High). Overall, the authors found no evidence of a consistent relation between dioxin exposure category and immune system alteration.

Antibodies, Antinuclear↗
PubMed1999

Serum dioxin and cancer in veterans of Operation Ranch Hand.

We studied cancer prevalence and exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. A comparison group of Air Force veterans who served in Southeast Asia during the same period and who were not involved with spraying herbicides was included. Comparison veterans were matched to Ranch Hand veterans on age, race, and military occupation. We measured dioxin in 1987 or 1992, extrapolated the result to the time of service in Southeast Asia, and assigned each Ranch Hand veteran to Background, Low, or High exposure categories. This study had low power to detect an effect for specific or rare cancers. The risk of cancer at sites other than the skin within 20 years of service was increased in the Low (odds ratio (OR) = 3.4, 95% confidence interval (CI) 1.5-8.0) and High (OR = 2.7, 95% CI 0.9-8.0) categories, but the pattern was inconsistent with another study, suggesting that the excess risk may not have been caused by dioxin exposure. Overall, we found no consistent evidence of a dose-response gradient and no significant increase in cancer risk in the High dioxin exposure category, the subgroup of greatest a priori interest.

Environmental Exposure↗
PubMed1999

Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.

The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögren's syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögren's syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events.

Administration, Oral↗
PubMed1999

Reduction of morning stiffness and improvement in physical function in fibromyalgia syndrome patients treated sublingually with low doses of human interferon-alpha.

One hundred and twelve fibromyalgia syndrome (FMS) patients were randomized into one of four demographically similar groups (n = 28/group). Sequential primary FMS patient volunteers were to receive daily sublingual placebo or interferon-alpha (IFN-alpha) at 15, 50, or 150 IU. After a screening evaluation, analgesic or sedative hypnotic medications were withdrawn. Two weeks later, daily IFN-alpha or placebo was initiated with follow-up evaluations at 2-week intervals ending with week 6. One primary, three secondary, and seven tertiary variables were assessed. Study outcome was based on improvement in the tender point index (TPI). The TPI did not improve with any IFN-alpha dose. However, significant improvement was seen in morning stiffness and in physical function with the 50 IU IFN-alpha (p < 0.01). None of the other outcome means changed significantly and no adverse events were attributable to IFN-alpha therapy.

Administration, Sublingual↗
PubMed1999

Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.

A clinical study was designed to utilize flow cytometric immunophenotyping and chromium release from cultured tumor target cells to characterize peripheral blood mononuclear leukocyte (PBML) subpopulations and natural killer activity in healthy normal controls (n = 18) and in patients with fibromyalgia syndrome (FMS) at baseline (n = 124) and again after 6 weeks of treatment with low-doses of orally administered human interferon-alpha (IFN-alpha). Volunteer subjects discontinued all analgesic and sedative hypnotic medications for 2 weeks prior to the baseline phlebotomy. Laboratory measures included a complete blood count; a phenotypic analysis of PBML by flow cytometry; and in vitro natural killer (NK) cell activity. After baseline blood sample collection, the FMS patients were randomized to one of four parallel treatment groups (n = 28/group) to receive sublingual IFN-alpha (15 IU, 50 IU, 150 IU), or placebo every morning for 6 weeks. The tests were repeated at week 6 to evaluate treatment effects. At baseline, FMS patients exhibited fewer lymphocytes and more CD25+ T lymphocytes than did normal controls. By week 6, the main significant and consistent change was a decrease in the HLA-DR+ CD4+ subpopulation in the 15 IU and 150 IU treatment groups. These data do not support an immunologically dysfunctional PBML phenotype among patients with FMS as has been observed in the chronic fatigue syndrome.

Administration, Sublingual↗
PubMed1999

Serum dioxin, insulin, fasting glucose, and sex hormone-binding globulin in veterans of Operation Ranch Hand.

We studied insulin, fasting glucose, and sex hormone-binding globulin (SHBG) in Air Force veterans exposed to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam War. The index subjects were veterans of Operation Ranch Hand, the unit responsible for aerial herbicide spraying in Vietnam from 1962-1971. Other Air Force veterans who served in Southeast Asia during the same period but were not involved with spraying herbicides served as comparisons. We assigned each Ranch Hand veteran based on his dioxin level to one of three exposure categories, named background, low, and high. Among nondiabetic veterans, we found the mean of the logarithm of insulin significantly increased in the high dioxin category. Additionally, in nondiabetic veterans the relation between SHBG and insulin interacted significantly with dioxin category on the log scale within strata defined by age and percent body fat. Among young (age, < or = 53 yr), lean (percent body fat, < or = 25%) nondiabetic veterans in the high category, the slope relating the logarithm of SHBG and the logarithm of insulin was significantly decreased. These findings suggest a compensatory metabolic relationship between dioxin and insulin regulation.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1998

Postservice mortality of US Air Force veterans occupationally exposed to herbicides in Vietnam: 15-year follow-up.

The US Air Force continues to assess the mortality of veterans of Operation Ranch Hand, the unit responsible for aerially spraying herbicides in Vietnam. The authors of this study found that the cumulative all-cause mortality experience of these veterans was not different from that expected (standardized mortality ratio (SMR) = 1.0). Overall, cause-specific mortality did not differ from that expected regarding deaths from accidents, cancer, or circulatory system diseases, but the authors found that there was an increased number of deaths due to digestive diseases (SMR = 1.7, 95% confidence interval (CI) 0.9-3.2). When analyzing by military occupation, they found an increase in the number of deaths caused by circulatory system diseases (SMR = 1.5, 95% CI 1.0-2.2) among enlisted ground personnel, the subgroup with the highest dioxin levels. Most of the increase in the number of deaths from digestive diseases was caused by chronic liver disease and cirrhosis, and more than half of the increase in the number of deaths from circulatory system diseases was a result of atherosclerotic heart disease. In the subgroup of Ranch Hand veterans who had survived more than 20 years since their military service in Southeast Asia, the authors found no significant increase in the risk of death due to cancer at all sites (SMR = 1.1) and a nonsignificant increase in the number of deaths due to cancers of the bronchus and lung (SMR = 1.3).

Aged↗
PubMed1998

Maximum (Max) and Mid-P confidence intervals and p values for the standardized mortality and incidence ratios.

The authors present algorithms to compute the confidence interval for a Poisson parameter (lambda) and the p value for testing the hypothesis that lambda is equal to a constant, which can be used to make inferences about the standardized mortality ratio and the standardized incidence ratio. The p value and confidence interval always agree, despite the discrete nature of the Poisson distribution. The authors also give simple equations to compute numeric approximations of the confidence limits that do not require the use of any probability distributions. An example based on data arising from a study of cancer incidence is given.

Algorithms↗
PubMed1998

Paternal dioxin, preterm birth, intrauterine growth retardation, and infant death.

We studied paternal exposure to Agent Orange and its dioxin contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) and preterm birth, intrauterine growth retardation, or infant death in veterans of Operation Ranch Hand, the unit responsible for spraying herbicides during the Vietnam war. A Comparison group of Air Force veterans who served in Southeast Asia during the same time period and who were not occupationally exposed to herbicides was included. We studied children conceived during or after the father's service in Southeast Asia and based exposure on paternal dioxin measured in 1987 or 1992 extrapolated to the time of conception of the child. We assigned each child to one of four exposure categories: Comparison and three Ranch Hand categories (Background, Low, High). Children in the High (relative risk = 1.3) and Background (relative risk = 1.4) categories were at increased risk of preterm birth. The risk of intrauterine growth retardation was not increased in any exposure category. The risk of infant death was increased in all Ranch Hand children, with the greatest increases in the High (relative risk = 4.5) and Background (relative risk = 3.2) categories. These patterns indicate that the increases in the relative risk of preterm birth and infant death may not be related to paternal dioxin level.

2,4,5-Trichlorophenoxyacetic Acid↗