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Biomedical subjects

K Belanger

Publications and source records attributed to K Belanger.

At least 19 recordsLinked to original sources

Phase I study of Aplidine in a dailyx5 one-hour infusion every 3 weeks in patients with solid tumors refractory to standard therapy. A National Cancer Institute of Canada Clinical Trials Group study: NCIC CTG IND 115.

BACKGROUND: Aplidine is a cyclic depsipeptide isolated from the marine tunicate Aplidium albicans. METHODS: This phase I study of Aplidine given as a 1-hour i.v. infusion daily for 5 days every 3 weeks was conducted in patients with refractory solid tumors. Objectives were to define the dose limiting toxicities, the maximal tolerated dose, and the recommended phase II dose. RESULTS: Thirty-seven patients were accrued on study. Doses ranged from 80 microg/m(2) to 1500 microg/m(2)/day. Eleven patients received more than three cycles of Aplidine. Dose-limiting toxicities occurred at 1500 microg/m(2) and 1350 microg/m(2)/day and consisted of nausea, vomiting, myalgia, fatigue, skin rash and diarrhea. Mild to moderate muscular pain and weakness was noted in patients treated with multiple cycles with no significant drug related neurotoxicity. Bone marrow toxicity was not observed. The recommended dose for phase II studies was 1200 microg/m(2) daily for 5 days, every 3 weeks. Pharmacokinetic studies performed during the first cycle demonstrated that therapeutic plasma levels of Aplidine are reachable well below the recommended dose. Nine patients with progressive disease at study entry had stable disease and two had minor responses, one in non-small cell lung cancer and one in colorectal cancer. CONCLUSIONS: Aplidine given at a dose of 1200 microg/m(2) daily for 5 days, every 3 weeks is well tolerated with few severe adverse events. This schedule of Aplidine is under evaluation in phase II studies in hematological malignancies and solid tumors.

Adolescent↗

The influence of air conditioning, humidity, temperature and other household characteristics on mite allergen concentrations in the northeastern United States.

BACKGROUND: Information about the influence of housing and occupant characteristics on mite allergen concentrations is crucial to determine which methods could be used to decrease exposure of susceptible subjects. OBJECTIVES: To identify housing and occupant characteristics that are associated with mite allergen concentrations in house dust collected from living rooms and mattresses. METHODS: We collected dust samples from 750 homes in the northeastern US. The influence of various characteristics on concentrations of mite allergens (Der p 1 and Der f 1) was studied using multiple linear regression analysis. RESULTS: Some characteristics, like absence of air conditioners, the presence of mold or mildew, and a lower temperature were consistently associated with higher concentrations of both mite allergens in dust from all sampling locations. However, none of these factors changed Der p 1 or Der f 1 concentrations by more than a factor of 2. People of white ethnic background had roughly two times higher mite allergen concentrations, while family income, family size, and education level only marginally influenced mite allergen concentrations. CONCLUSIONS: Various housing characteristics have some influence on mite allergen concentrations, and could possibly be used to decrease exposure of susceptible subjects. However, only a limited percentage of the variation in mite allergen concentrations was explained by these characteristics.

Air Conditioning↗

Phase II study of troxacitabine (BCH-4556) in patients with advanced and/or metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE: A multi-institution phase II study was undertaken by National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of intravenous troxacitabine (Troxatyl; Shire Pharmaceuticals Plc, Laval, Quebec, Canada), in patients with renal cell carcinoma. PATIENTS AND METHODS: Between June 1999 and March 2000, 35 patients (24 male) with a mean age of 60 years who had advanced and/or metastatic disease were treated with troxacitabine given as an intravenous infusion over 30 minutes at a dose of 10 mg/m2 intravenously, once every 3 weeks. RESULTS: Of the 33 of 35 patients evaluable for response, there were two confirmed partial responses, 21 patients had stable disease (median duration, 4.4 months), and 10 patients had progressive disease. Eight patients remained stable for more than 6 months, of whom six remain free of progression. The most common drug-related nonhematologic toxicities observed were skin rash (77.1%), hand-foot syndrome (68.6%), alopecia (51.4%), fatigue (51.4%), and nausea (57.1%). Out of a total of 145 cycles of treatment, 98 were given without steroid premedication, whereas 47 cycles were given with steroid premedication. Without premedication, skin rash occurred in 37% of cycles compared with 26% when steroids were given prophylactically. CONCLUSION: Troxacitabine given at a dose of 10 mg/m2 once every 3 weeks was well tolerated in patients with metastatic renal cell cancer, with common toxicities being a moderate to severe granulocytopenia and skin rash. Steroid premedication may reduce the frequency and severity of the skin rash. Our current study suggests that the nucleoside analog troxacitabine may have modest activity against renal cell carcinoma; however, larger studies are required to confirm this.

Aged↗

The relation between fungal propagules in indoor air and home characteristics.

BACKGROUND: Questionnaires are commonly used in epidemiologic studies to obtain information about house characteristics in order to predict the household aeroallergen exposure levels. However, the reliability of the predictions made with the questionnaires has not been evaluated. To address this issue, we compared objectively measured fungal propagules including the most frequently isolated mold genera (i.e., Alternaria, Aspergillus, Cladosporium, Penicillium, etc.) in a large sample of homes and compared these measured values to the questionnaire-determined household characteristics. METHODS: As part of a prospective cohort study on the relation between residential allergen exposure and development of asthma in neonates, fungal air samples were collected from infant bedrooms and main living areas in 1000 homes in the Northeast USA, from December 1996 to January 1999. A Burkard portable air sampler was used in combination with DG-18 and MEA agars. A questionnaire was used to obtain information on host and house characteristics that may have an impact on the presence of fungal propagules in the air. This included information on observation of moisture problems (e.g., water leakage or damage, and mold or mildew growth), ventilation and heating facilities, building age and type, number of occupants, annual household income, presence of pets and pests, cleaning regimens, etc. RESULTS: The number of CFU/m3 air collected on MEA was significantly higher than on DG-18 (means, respectively, 1033.5 and 846.0 CFU/m3) (P < 0.0005). However, there was no significant difference between the numbers of CFU/m3 air collected from the main living area and from the infant bedroom. There was only a very weak relationship between the house characteristics, as described by questionnaire, and the presence of fungal propagules in indoor air. Only the temperature, relative humidity, season, and cats inside homes had a statistically significant impact on the presence of fungal propagules in indoor air. CONCLUSION: The presence of fungal propagules in indoor air cannot be reliably predicted by home characteristics. Actual measurements are required for fungal exposure assessment, and the use of only one medium to collect samples in one location in a home might be adequate to represent residential levels of fungi in indoor air.

Air Microbiology↗

Risk factors for asthma prevalence among urban and nonurban African American children.

Urban residence is a risk factor for asthma. We examined multiple risk factors simultaneously among African American children. We interviewed 2409 African American mothers of newborns who had at least 1 child at home under 18 years of age. Sixteen percent reported at least 1 child with physician-diagnosed asthma. Significantly associated with an asthmatic child were maternal asthma and allergies, maternal cigarette smoking, a humidifying device, and a gas range or oven in the home. Urban residence was related to asthma but became nonsignificant once other factors were controlled for. Asthma associated with urban residence may be explained by identifiable factors.

Black or African American↗

Maternal caffeine intake and intrauterine growth retardation.

This study estimates the effect of maternal caffeine consumption throughout pregnancy on fetal growth. We studied 2,714 women who delivered a liveborn infant between 1988 and 1991. Detailed information regarding coffee, tea, and soda drinking during the first and third trimesters of pregnancy was obtained. Average caffeine intake during month 1 of pregnancy was higher than for month 7 (72.4 vs 54.0 mg per day). Consumption of >300 mg caffeine per day during month 1 (adjusted odds ratio = 0.91; 95% confidence interval = 0.44--1.90) and during month 7 (adjusted odds ratio = 1.00; 95% confidence interval = 0.37--2.70) was not associated with intrauterine growth retardation. There was little evidence for any effect modification due to cigarette smoking on the caffeine associations. This study provides evidence that antenatal caffeine consumption has no adverse effect on fetal growth.

Adult↗

NCIC-CTG phase II study of gemcitabine in patients with malignant glioma (IND.94).

PURPOSE: We conducted a phase II multicentre study of gemcitabine in patients with anaplastic astrocytoma and glioblastoma multiforme at first relapse. PATIENTS AND METHODS: Patients with anaplastic astrocytoma or glioblastoma multiforme receiving a stable dose of steroids and ECOG performance status < or = 3 were eligible for this study at the time of first relapse. One adjuvant chemotherapy regimen was permissible. Patients received gemcitabine 1000 mg/m2 i.v. weekly x 3, repeated on a four-weekly cycle. RESULTS: Of 20 patients enrolled, 15 were evaluable for response, 19 for non-hematological toxicity and 18 for hematological toxicity. Seven patients had anaplastic astrocytoma (AA) and twelve glioblastoma multiforme (GBM). Age ranged from 28-71 years (median 50). Fifteen patients discontinued therapy due to disease progression. The median number of cycles administered was 1 (range 1-11); only two patients received more than three cycles. Hematologic toxicity was acceptable and no grade 4 toxicity was seen. One patient developed Pneumocystis pneumonia and eventual pulmonary embolism; one died of gastric hemorrhage related to steroid therapy. No objective responses were seen. Nine patients had stable disease (median duration 2.7 months, range 0.9-11.2). CONCLUSIONS: Gemcitabine given in this dose and schedule seems well tolerated but is not active in patients with recurrent high-grade gliomas.

Adult↗

Environmental tobacco smoke exposure and small-for-gestational-age birth.

The aim of this analysis was to examine the effect of environmental tobacco smoke exposure on the risk of small-for-gestational-age (SGA) birth. The study population included 2,283 nonsmokers from a nested cohort study undertaken in southern Connecticut from 1988 to 1992. The duration and intensity of exposures incurred at multiple locations during the third trimester of pregnancy were measured by postpartum interview. The effect of exposure on birth weight and on incidence of SGA birth was assessed by multivariate logistic and linear regression. An estimated 26.5% of the women had been exposed to environmental tobacco smoke for at least 1 hour per week during the third trimester. The median duration of exposure among the exposed over all locations was 5 hours per week. The adjusted odds ratio for SGA birth in exposed mothers compared with unexposed mothers, using a dichotomous exposure variable, was 0.82 (95% confidence interval: 0.51, 1.33). The adjusted birth weight difference associated with exposure was -1.2 g (95% confidence interval: -43.3, 41.0). No effect of environmental tobacco smoke exposure on fetal growth was seen in this relatively homogeneous upper middle class group of women exposed at low levels. This is reassuring for women exposed at low levels, but it does not exclude the possibility of an effect in women exposed to higher levels of environmental tobacco smoke.

Adult↗

Healthy women's PEF variations with ambient summer concentrations of PM10, PM2.5, SO42-, H+, and O3.

The relationship between ambient air pollution and daily change in peak expiratory flow (PEF) was studied in a sample of 473 nonsmoking women (age 19 to 43 yr) in Virginia over summers 1995- 1996. Daily 24-h averages of particulate matter (PM2.5 and PM10), fine particulate sulfate (SO42-) and strong acid (H+), hourly ozone (O3), and select meteorologic variables (e.g., temperature) were collected at a regional outdoor monitoring site. Subjects took PEF measurements twice daily for a 2-wk period using a standard MiniWright peak flow meter. Concurrent measures for summer periods of 24-h PM2.5 (micrograms/m3) ranged from 3.5 to 59.7; H+ (nmol/m3) from 0 to 250; maximal daily 8-h average O3 (ppb) from 17.0 to 87.6. Morning PEF decrements were significantly associated with H+ and PM2. 5. An increase of 50 etamol/m3 of H+ and 10 micrograms/m3 of PM2.5 related to decreases of 0.89 (95% CI = 0.21 to 1.57) and 0.73 (95% CI = 0.07 to 1.38) L/min in morning PEF, respectively. Ozone was the only exposure related to evening PEF with 5-d cumulative lag exposure showing the greatest effect; 7.65 L/ min (95% CI = 2.25 to 13.0) decrease per 30 ppb O3 increase. Separate physiologic effects were observed for summer ambient concentrations of two different pollutants (PEF decrements related to PM2.5 in morning and O3 in evening) at concentrations below the new U.S. EPA 24-h ambient air quality standard for PM2.5 and 8-h standard for O3.

Adult↗

Correlates of residential wiring code used in studies of health effects of residential electromagnetic fields.

The home wiring code is the most widely used metric for studies of residential electromagnetic field (EMF) exposure and health effects. Despite the fact that wiring code often shows stronger correlations with disease outcome than more direct EMF home assessments, little is known about potential confounders of the wiring code association. In a study carried out in southern Connecticut in 1988-1991, the authors used strict and widely used criteria to assess the wiring codes of 3,259 homes in which respondents lived. They also collected other home characteristics from the tax assessor's office, estimated traffic density around the home from state data, and interviewed each subject (2,967 mothers of reproductive age) for personal characteristics. Women who lived in very high current configuration wiring coded homes were more likely to be in manual jobs and their homes were older (built before 1949, odds ratio (OR) = 73.24, 95% confidence interval (CI) 29.53-181.65) and had lower assessed value and higher traffic densities (highest density quartile, OR = 3.99, 95% CI 1.17-13.62). Because some of these variables have themselves been associated with health outcomes, the possibility of confounding of the wiring code associations must be rigorously evaluated in future EMF research.

Adult↗

Spontaneous abortion and exposure to electric blankets and heated water beds.

We conducted a prospective study (N = 2,967) to evaluate the relation of spontaneous abortion with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. At interview, 61.5% of women were at less than 12 weeks gestation, and 38.5% were between 13 and 16 weeks; thus, very early pregnancy losses would have been excluded. Information regarding exposure to electric beds was obtained for the month of conception and the 7 days before interview. Electric blanket use at conception was associated with an increased risk of spontaneous abortion in the unadjusted analysis [relative risk (RR) = 1.84; 95% confidence interval (CI) = 1.08-3.13], but adjustment for other factors reduced the risk slightly [odds ratio (OR) = 1.74; 95% CI = 0.96-3.15]. Heated water bed use was not associated with an increased risk of spontaneous abortion at conception (OR = 0.59; 95% CI = 0.33-1.07) or at interview (OR = 0.63; 95% CI = 0.36-1.12). Measures of dose response (daily use, hours of use, or temperature setting) were not associated with increased risk. Wire code data were obtained for the first, or only, house lived in during pregnancy. Women living in homes classified as "very high" or "ordinary high" current configuration were not at greater risk than women living in homes with buried wires. Nor was there any trend for increased risk of spontaneous abortion by wire code category. This study does not support the hypothesis that use of electric beds or residence in a high current configuration home increases the risk of spontaneous abortion; however, it indicates that electric blanket use at the time of conception and in early pregnancy may be associated with a slight increase in risk of pregnancy loss.

Abortion, Spontaneous↗

Pilot phase I-II study on 5-aza-2'-deoxycytidine (Decitabine) in patients with metastatic lung cancer.

5-Aza-2'-deoxycytidine (5-AZA-CdR, Decitabine) is a nucleoside analog and an active drug for the therapy of acute leukemia. The incorporation of 5-AZA-CdR into DNA blocks DNA methylation and can result in the activation of specific genes, such as tumor suppressor genes. This novel mechanism of action of 5-AZA-CdR stimulated our interest in its potential for cancer therapy in patients with lung cancer. Using a colony assay we observed that 5-AZA-CdR showed a potent antineoplastic effect against two human lung carcinoma cell lines. The objective of this preliminary phase I-II study was to evaluate the toxicity and clinical efficacy of 5-AZA-CdR in patients with stage IV non-small cell lung carcinoma. There were 15 patients that entered the clinical study. For nine assessable patients that received 5-AZA-CdR by a single 8 h i.v. infusion of 200-660 mg/m2 for one or more cycles, the median survival duration was 6.7 months, with three patients surviving more than 15 months. The steady-state plasma concentration of 5-AZA-CdR during the infusion was estimated in some patients and was in the same range that produced activation of a tumor suppressor gene in human lung tumor cell lines as reported by other investigators. The major side effect of 5-AZA-CdR was hematopoietic toxicity which required a 5-6 week recovery period before the next cycle of therapy. This study suggests that 5-AZA-CdR may have some clinical activity against metastatic lung carcinoma using this type of dose schedule.

Adult↗

Maternal caffeine consumption and spontaneous abortion: a prospective cohort study.

We investigated the relation between caffeine beverage consumption and spontaneous abortion in 2,967 pregnant women planning to deliver at Yale-New Haven Hospital in 1988-1992. We evaluated coffee, tea, and soda drinking in the first month of pregnancy in interviews before the end of the sixteenth week of gestation. We obtained information on 98.2% of the pregnancies (including 2,714 singleton livebirths and 135 spontaneous abortions). As compared with abstention from caffeine beverages (coffee, tea, and soda), the adjusted odds ratios for spontaneous abortion associated with consumption of 1-150, 151-300, and > 300 mg caffeine daily were 0.81 [95% confidence interval (CI)) = 0.54-1.20], 0.89 (95% CI = 0.48-1.64), and 1.75 (95% CI = 0.88-3.47), respectively. Drinking > or = 3 cups of tea or coffee was associated with elevated risks of spontaneous abortion (adjusted odds ratio = 2.33, 95% CI = 0.92-5.85; and adjusted odds ratio = 2.63, 95% CI = 1.29-5.34, respectively). These results, if replicated, suggest that some ingredient (or correlate) of tea or coffee may account for some of the observed association of caffeine with spontaneous abortion. In this study, caffeine consumption is more strongly related to spontaneous abortion than alcohol or cigarette use in early pregnancy.

Abortion, Spontaneous↗

Asthma among Puerto Rican Hispanics: a multi-ethnic comparison study of risk factors.

For a study of childhood asthma we interviewed 9,276 mothers during 1993-1994, ascertaining whether they had asthmatic children younger than 18 yr of age and asking about genetic and environmental risk factors for asthma. Independent risk factors for asthma in 7,776 children were: Hispanic and African American ethnicity, maternal history of asthma, lower socioeconomic status (SES) of the mother, and the presence of a cigarette smoker in the household. Hispanic ethnicity was also a strong risk factor for asthma in the mother. The prevalence of asthma among children of Hispanic (mainly Puerto Rican) mothers with one or more children older than 9 mo of age was 18.4%, for blacks it was 1 1.3%, and for non-Hispanic whites it was 7.4%. The marked increased risk for asthma in children of Hispanic mothers was not explained by SES or maternal age. In addition, increased risk for asthma in these children was not associated with higher reporting of environmental tobacco smoke (ETS) exposure. In this study of asthma in primarily Puerto Rican Hispanics, the risk of physician-diagnosed asthma as reported by mothers was significantly associated with Hispanic ethnicity, and it was not confounded by SES or active smoking in the home.

Adolescent↗

Occupationally related magnetic field exposure and male subfertility.

OBJECTIVE: To determine whether there is an association between occupationally related magnetic field exposure, as estimated in milligauss (mG), and male subfertility. DESIGN: Nested case-control study using three defined case groups and one standard control group. SETTING: Yale New Haven Hospital Infertility Clinic, New Haven, Connecticut. PATIENTS, INTERVENTIONS: Male partners of couples seeking diagnosis and care at the infertility clinic. Men included in the analysis had complete first semen analysis and interview information. Subjects for this investigation consisted of case groups for motility (n = 177), morphology (n = 135), and concentration (n = 172); controls included men normal on all three parameters (n = 304). MAIN OUTCOME MEASURES: Laboratory confirmation in semen analysis of poor morphology, inadequate motility, and low concentration. Comparisons of occupational magnetic field exposure categories are made between case groups and controls. RESULTS: The odds of high job exposure category to magnetic fields (> 3 mG [> 0.3 muT]) for morphology cases were odds ratio (OR) = 0.6, for motility cases OR = 1.1, and concentration cases OR = 1.0 as compared with controls. No significant association was demonstrated for medium exposure (> 2 to 3 mG) among all case groups. Multivariate adjustment for selected risk factors did not substantially change estimates of risk. CONCLUSIONS: A lack of association between occupationally related categories of magnetic field exposure and male subfertility, as evaluated by morphology, motility, and concentration, has been demonstrated. These findings do not substantiate theories of deleterious effects to male reproductive health from magnetic fields.

Adult↗

Exposure to electromagnetic fields during pregnancy with emphasis on electrically heated beds: association with birthweight and intrauterine growth retardation.

Several animal and human studies indicate that fetal growth may be retarded following exposure to electromagnetic fields (EMF). We conducted a prospective study (N = 2,967) to evaluate the relation of birthweight and fetal growth retardation with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. A "nested" study design allowed monitoring of exposure at different stages of pregnancy using both direct and indirect methods. We assessed EMF exposure using personal monitors, home measurement, video display terminal use, and wire code. Exposure to EMF during pregnancy, either at conception, at < or = 16 weeks, or in the third trimester, showed no important relation to risk of low birth-weight or fetal growth retardation. This result was the same whether we used subjective measures of exposure or direct measurement. Use of video display terminals at home or work, exposure to > or = 2.0-milligauss fields as measured by home or personal monitors, and home wire code were unrelated to the reproductive outcomes studied. A time-weighted analysis of electric bed use, which accounted for strength of EMF exposure and hours of use, also showed evidence of no meaningful increase in risk. None of the exposure measures showed a dose response relation to risk. We conclude that risk of low birth-weight and intrauterine growth retardation is not increased after electrically heated bed use during pregnancy.

Adult↗

Human exposure to magnetic fields: a comparative assessment of two dosimeters.

Two types of dosimeters for measuring human exposure to 60 Hz magnetic fields were compared. Fifty adults wore the single-axis, wrist model AMEX (average magnetic field exposure system) and the triple axis, hip-pocket or pouch model AMEX-3D meters for 2 days. Ninety-six percent of the tests were accomplished without apparent dosimeter failure. The average root mean square magnetic flux density measurements with the AMEX-3D (mean = 0.10 microT, S.D. = 0.07, range = 0.03-0.31) were significantly higher than with the AMEX meter (mean = 0.07 microT, S.D. 0.05, range = 0.02-0.27 microT) (t test, P < 0.01). There was substantial correlation between the AMEX and the AMEX-3D measurements (Pearson's correlation coefficient = 0.65, P < 0.01) but poor concordance (Intraclass correlation coefficient = -0.25). These results suggest that there is a wide variation in exposure to extremely low frequency magnetic fields in the population. Magnetic field measurements with the AMEX-3D are nearly always higher than with the AMEX dosimeters. Caution is advised when comparing magnetic field measurements made with different types of dosimeters.

Adult↗