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Biomedical subjects

G Howe

Publications and source records attributed to G Howe.

At least 19 recordsLinked to original sources
PubMed2006

Post-Chernobyl thyroid cancers in Ukraine. Report 2: risk analysis.

On April 26, 1986, the worst nuclear reactor accident to date occurred at the Chornobyl (Chernobyl) power plant in Ukraine. Millions of people in Ukraine, Belarus and Russia were exposed to radioactive nuclides, especially (131)I. Since then, research has been conducted on various subgroups of the exposed population, and it has been demonstrated that the large increase in thyroid cancer is related to the (131)I exposure. However, because of study limitations, quantified risk estimates are limited, and there remains a need for additional information. We conducted an ecological study to investigate the relationship between (131)I thyroid dose and the diagnosis of thyroid cancer in three highly contaminated oblasts in Northern Ukraine. The study population is comprised of 301,907 persons who were between the ages of 1 and 18 at the time of the Chornobyl accident and were living in 1,293 rural settlements in the three study oblasts. Twenty-four percent of the study population had individual thyroid dose estimates and the other 76% had "individualized" estimates of thyroid dose based on direct thyroid measurements taken from a person of the same age and gender living in the same or nearby settlement. Cases include 232 thyroid cancers diagnosed from January 1990 through December 2001, and all were confirmed histologically. Dose-response analyses took into account differences in the rate of ultrasound examinations conducted in the three study oblasts. The estimated excess relative risk per gray was 8.0 (95% CI = 4.6-15) and the excess absolute risk per 10,000 person-year gray was estimated to be 1.5 (95% CI = 1.2-1.9). In broad terms, these estimates are compatible with results of other studies from the contaminated areas, as well as studies of external radiation exposure.

Adolescent↗
PubMed2005

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Dose-Response Relationship, Drug↗
PubMed2005

Iodine excretion in regions of Ukraine affected by the Chornobyl Accident: experience of the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases.

Urinary iodine concentrations were measured in 11,926 subjects who are participants in the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident. Measurements were made in two time periods corresponding to the first and second thyroid screening cycles (1998-2000, 2001-2003). These time periods fall before and after initiation of a government program to increase iodine sufficiency. Median urinary iodine concentrations did increase in the later time period compared to the earlier [47.5 microg/L, 95% confidence interval (CI) 46.5-48.9 microg/L versus 41.7 microg/L, 95% CI 40.4-42.5 microg/L], but levels remained in the mild-to-moderate iodine deficiency range as defined by the World Health Organization (WHO), indicating the need for further efforts at iodination. In both time periods, urinary iodine levels were found to vary by place of residence and were lower in rural compared to urban areas. Iodine status needs to be considered when evaluating risk of thyroid cancer and other thyroid diseases.

Adolescent↗
PubMed2003

A biopsychosocial model of pain and depression in rheumatoid arthritis: a 12-month longitudinal study.

OBJECTIVE: To cross-validate a biopsychosocial model using physical disability, helplessness and passive coping to predict depression and pain in rheumatoid arthritis (RA). METHODS: Clinical and psychological measures were collected from 157 RA patients at three time points over a period of 12 months. Path analysis was used for cross-sectional and longitudinal prediction of depression and pain. RESULTS: Helplessness and passive coping were found to be significant mediators of the relationship between the physical disability and future depression and pain. Cross-sectionally, the predictive model could account for 52-94% of the variance of pain and 37-71% of the variance of depression. Longitudinally, the predictive model could explain 29-43% of the variance of pain and 21-33% of the variance of depression. CONCLUSIONS: These results suggest that physical disability, helplessness and passive coping have a significant impact on the levels of pain and depression experienced by RA patients.

Adaptation, Psychological↗
PubMed2000

Diet and benign ovarian tumors (United States).

OBJECTIVES: The relation between benign ovarian tumors (BOTs) and nutrients, primarily dietary fat, was examined using case-control data. METHODS: 746 cases were diagnosed from 1 January 1992 to 31 December 1993. The 404 age- and hospital frequency-matched community controls were identified by random digit dialing. Six hundred seventy-three cases and 351 controls provided dietary information. RESULTS: The risk of BOTs was elevated for the highest vs. lowest quartile of intake of total, vegetable, saturated, monounsaturated, and polyunsaturated fat. The corresponding age-, hospital-, total energy-, and body mass index-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) are 1.3 (0.9-1.9), 1.7 (1.2-2.5), 1.2 (0.8-1.8), 1.3 (0.9-1.8), and 1.6 (1.1-2.3). After adjustment for polyunsaturated fat, the risk of BOTs only remained elevated for vegetable fat (highest vs. lowest quartile OR and 95% CI = 1.4 (0.8-2.3)). Elevated risks were observed for higher intakes of polyunsaturated fat with endometrioid, serous, and teratoma tumors. Higher intakes of vegetable fat, adjusted for polyunsaturated fat, increased the risk of endometrioid, mucinous, and serous tumors. Only the risk of serous BOTs was consistently lower for higher intakes of micronutrients, with the strongest reduction observed for sources of vitamin A. Estimates were not confounded by non-nutrient covariates. CONCLUSIONS: Polyunsaturated and vegetable fat may increase the risk of BOTs, while vitamin A may lower the risk of serous BOTs; however, these findings and lack of associations for other nutrients should be replicated.

Adolescent↗
PubMed2000

Epstein-Barr virus RNA detection and glandular differentiation in nasopharyngeal carcinoma: report of 2 cases.

Most tumors arising in the nasopharynx are either squamous cell carcinoma or so-called undifferentiated carcinoma of the nasopharyngeal type. Primary adenocarcinomas of the nasopharynx are rare, and glandular differentiation in undifferentiated carcinoma of the nasopharyngeal type has not been reported to date. We report 2 cases of undifferentiated carcinoma of the nasopharyngeal type that show distinct glandular differentiation by light microscopy, histochemistry, immunohistochemistry, and ultrastructure. Both tumors showed equal positivity for Epstein-Barr virus latent membrane protein and in situ hybridization for Epstein-Barr virus genome in the undifferentiated areas of the tumor and those featuring glandular differentiation.

Adenocarcinoma↗
PubMed1999

Use of rituximab and irradiated donor-derived lymphocytes to control Epstein-Barr virus-associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation.

Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is an uncommon but potentially fatal complication of allogeneic stem cell transplantation. We report here two patients who underwent T cell-depleted mismatched-related stem cell transplantation for hematologic malignancies and required aggressive post-transplant immunosuppression for graft-versus host disease (GVHD). Both patients subsequently developed markedly elevated EBV-DNA titers in association with monoclonal, light chain-restricted B cell populations in the blood. Although immunosuppressive medications were rapidly tapered, neither patient could receive potentially curative therapy with unmanipulated donor-derived lymphocyte infusions (DLI) because of the substantial risk of severe GVHD. Therefore, both patients received repeated courses of rituximab, an anti-CD20 monoclonal antibody, in combination with irradiated DLI. This therapeutic strategy resulted in normalization of the elevated EBV-DNA titers and disappearance of the monoclonal B cell populations. Our results suggest that rituximab and possibly irradiated DLI played an important role in controlling early EBV-LPD in these two patients and may be an effective alternative therapeutic strategy for patients who develop EBV-LPD post transplant and are unable to receive unmanipulated DLI.

Adult↗
PubMed1997

Estimating lung cancer mortality from residential radon using data for low exposures of miners.

Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the "action level" suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures.

Air Pollutants, Radioactive↗
PubMed1996

Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases.

PURPOSE: To determine the clinicopathologic features of lymphoproliferative disorders (LPD) that occur in the setting of methotrexate (MTX) therapy for rheumatic diseases (RD) and to define the relationship between the presence of Epstein-Barr virus (EBV) in tumor cells and the response of LPD to MTX withdrawal. PATIENTS AND METHODS: In addition to nine new cases, we analyzed 28 cases previously reported in the literature of LPD in patients receiving MTX for RD. In addition to MTX, immunosuppressive therapy included corticosteroids in 19 patients, azathioprine in three, and cyclosporine in one. Extranodal disease was identified in 16 patients, but none had CNS involvement. Pathologic findings included five cases of Hodgkin's disease and seven low-grade lymphomas. The remaining patients had intermediate or aggressive lymphomas. In situ hybridization studies (ISHS) for EBV-RNA transcripts were positive in 12 of 27 patients (44%). RESULTS: Among 37 patients, 16 were initially observed after MTX withdrawal without additional antitumor therapy. Six achieved a spontaneous complete remission (CR), three had a partial response (PR), one had a minimal response, and six had no response to MTX withdrawal. Of 10 responding patients, EBV was detected by ISHS (n = 6) or polymerase chain reaction (PCR) (n = 2); one patient had a CR despite the absence of EBV by PCR and one had a CR but did not have viral assays performed. Only one of six patients with negative EBV by ISHS or PCR responded to MTX withdrawal. CONCLUSION: MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies are required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX.

Adult↗
PubMed1996

Epidemiology of gastric cancer.

The incidence of gastric cancer varies widely by country and population, with higher rates among the lower socioeconomic groups. Although the most common cause of cancer death in the United States in 1930, its incidence has decreased dramatically during the past 60 years. Most populations show a 2-1 ratio for male to female gastric cancer cases, and a higher incidence rate among United States blacks than whites. Although rates have generally decreased, there has been a dramatic increase in the incidence of gastric cancer in the cardia. Diet has been the most studied risk factor for gastric cancer. Of particular interest have been N-nitroso compounds derived from the consumption of preserved, smoked, and cured foods. An inverse association with the consumption of fruits and vegetables has also been consistently demonstrated, though the specific nutrient(s) that this represents has been unclear, although ascorbate and beta-carotene have been intensively studied. Among nondietary factors, substantial evidence has accumulated for an increased risk with Helicobacter pylori infection. Other exposures which have been fairly consistently associated with gastric cancer include cigarette smoking, partial gastrectomy, radiation exposure, family history, pernicious anemia, blood group A, certain occupational exposures, and Epstein-Barr virus.

Age Factors↗
PubMed1996

Lymphomatoid granulomatosis of the skin and lung. An angiocentric T-cell-rich B-cell lymphoproliferative disorder.

OBJECTIVE: To test the recent hypothesis that lymphomatoid granulomatosis (LYG) is a clonal B-cell proliferative process related to Epstein-Barr virus (EBV). BACKGROUND AND DESIGN: Historically, LYG has been classified as an angiocentric T-cell lymphoproliferative disorder. To further characterize LYG in the skin, we analyzed for EBV RNA in lymphocytes using in situ hybridization, coupled with colabeling for B-cell and T-cell markers. Clonality of lymphocytes was assessed by polymerase chain reaction using primers for immunoglobulin heavy chain genes and T-cell receptor beta and gamma genes. SETTING: Academic referral center. PATIENTS: In a 5-year retrospective review, we identified 4 patients with classic clinical and pathologic features of LYG in skin and lung, and tissue available from both sites. MAIN OUTCOME MEASURES: The presence or absence of EBV RNA and clonal gene rearrangements in cutaneous and pulmonary lesions of LYG. RESULTS: Biopsy specimens of skin and lung in all patients revealed angiocentric infiltrates predominantly composed of T lymphocytes. Epstein-Barr virus RNA was identified in the skin of 1 patient and the lung of 3 patients, and was restricted to B cells. Polymerase chain reaction revealed clonal immunoglobulin heavy chain gene rearrangements and no clonal rearrangement of T-cell receptor genes in skin and lung tissue of all patients. CONCLUSIONS: At least some examples of LYG in the skin and lung are characterized by a clonal proliferation of B lymphocytes, some of which contain EBV RNA. The B cells are typically scarce and may be obscured by striking angiocentric T-cell infiltrates.

Adult↗
PubMed1995

Biosynthesis of cytochrome f in Chlamydomonas reinhardtii: analysis of the pathway in gabaculine-treated cells and in the heme attachment mutant B6.

Chlamydomonas reinhardtii uses two c-type cytochromes for photosynthetic electron transfer: the thylakoid membrane-bound cytochrome f of the cytochrome b6f complex and the soluble cytochrome c6. Previously, a class of photosynthesis-minus, acetate-requiring mutants was identified which were deficient in both c-type cytochromes, and biochemical analyses of cytochrome c6 biosynthesis in these strains indicated that they were each blocked at the step of heme attachment to apocytochrome c6. In order to demonstrate that the deficiency in cytochrome f results from the same biochemical and genetic defect, cytochrome f biosynthesis was examined in the B6 mutant (a representative of this phenotypic class) and in spontaneous suppressor strains derived from B6. Pulse-radiolabeling experiments show that B6 synthesizes a form of cytochrome f that is rapidly degraded in vivo. This polypeptide is membrane associated and migrates with an electrophoretic mobility identical to that of standard apocytochrome f produced in vitro but slightly greater than that of standard holocytochrome f produced in vivo by wild-type cells. These findings suggest that the B6 strain is unable to convert apocytochrome f to holocytochrome f and that apocytochrome f is unstable in vivo. In the suppressed strains, accumulation of both holocytochrome f and holocytochrome c6 is restored. One suppressor mutation (strain B6R) displays uniparental inheritance whereas another (B6T3) displays Mendelian inheritance. In both cases, the three phenotypes, photosynthesis-plus, b6f+ and cyt c6+ co-segregate in genetic crosses. This study therefore confirms that the dual cyt b6f-/cytc6- deficiency in B6 results from a single mutation that affects a step in holocytochrome formation that is common to the biosynthetic pathways of both plastidic c-type cytochromes. The study also confirms that pre-apocytochrome f synthesis, processing and association with the membrane is not dependent on heme attachment. Synthesis of cytochrome f does, however, appear to be dependent on heme availability. In cells depleted of tetrapyrrole pathway intermediates by gabaculine treatment, cytochrome f synthesis was significantly reduced. Since gabaculine treatment did not affect the stability of cytochrome f nor the accumulation of cytochrome f-encoding transcripts, the reduction is attributed to post-transcriptional regulation of preapocytochrome f synthesis via a pathway that is sensitive to the availability of heme or a tetrapyrrole pathway intermediate.

Animals↗
PubMed1995

Reproducibility and validity of a food-frequency questionnaire designed for use in girls age 7 to 12 years.

This study focused on a food-frequency questionnaire (FFQ) designed to measure nutrient intake in girls aged 7 to 12 years, inclusive. The instrument's reproducibility and validity were assessed using food records (FRs) as gold standards of measurement. Log-transformed nutrient intake estimates were compared from two FFQs and between FFQs and FRs. Intraclass correlation coefficients measuring the reproducibility of the FFQ ranged from 0.11 (starch) to 0.69 (fiber). Intraclass correlation coefficients measuring agreement between FFQ and 14l-day FR data varied between 0.15 (starch) and 0.68 (vitamin B2) for the first, and between 0.06 (starch) and 0.95 (vitamin B1) for the second FFQ. FFQs were in the best agreement with FRs for the following nutrients: fiber, vitamin B1, vitamin B2, vitamin C, and beta-carotene. Joint classifications revealed that overall, 36% of subjects were similarly categorized by FFQ and FR, and 70% of those in the lowest or highest FR quartiles were were found in the lowest or highest FR quartiles were found in the lowest or highest two FFQ quartiles, respectively.

Ascorbic Acid↗
PubMed1995

Radon-exposed underground miners and inverse dose-rate (protraction enhancement) effects.

Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution.

Humans↗
PubMed1995

Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries.

Studies of the mortality among nuclear industry workforces have been carried out, and nationally combined analyses performed, in the U.S., the UK and Canada. This paper presents the results of internationally combined analyses of mortality data on 95,673 workers (85.4% men) monitored for external exposure to ionizing radiation and employed for 6 months or longer in the nuclear industry of one of the three countries. These analyses were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly gamma, radiation. The combination of the data from the various studies increases the power to study associations between radiation and specific cancers. The combined analyses covered a total of 2,124,526 person-years (PY) at risk and 15,825 deaths, 3,976 of which were due to cancer. There was no evidence of an association between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic lymphocytic leukemia (CLL)--the cause of death most strongly and consistently related to radiation dose in studies of atomic bomb survivors and other populations exposed at high dose rates--was significantly associated with cumulative external radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other specific types of cancer studied, a significant association was observed only for multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was attributable primarily to the associations reported previously between this disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The excess relative risk (ERR) estimates for all cancers excluding leukemia, and leukemia excluding CLL, the two main groupings of causes of death for which risk estimates have been derived from studies of atomic bomb survivors, were -0.07 per Sv [90% confidence interval (CI): -0.4, 0.3] and 2.18 per Sv (90% CI: 0.1, 5.7), respectively. These values correspond to a relative risk of 0.99 for all cancers excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative protracted dose of 100 mSv compared to 0 mSv. These estimates, which did not differ significantly across cohorts or between men and women, are the most comprehensive and precise direct estimates of cancer risk associated with low-dose protracted exposures obtained to date. Although they are lower than the linear estimates obtained from studies of atomic bomb survivors, they are compatible with a range of possibilities, from a reduction of risk at low doses, to risks twice those on which current radiation protection recommendations are based.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗