Non-Hodgkin's lymphoma among electric utility workers in Ontario: the evaluation of alternate indices of exposure to 60 Hz electric and magnetic fields

OBJECTIVES—To examine associations between non-Hodgkin's lymphoma (NHL) and exposures to 60 Hz magnetic and electric fields in electric utility workers with a series of indices that capture a variety of aspects of field strength.
METHODS—The study population consisted of 51 cases of NHL and 203 individually matched controls identified from within a cohort of male electric utility workers in Ontario. Odds ratios were calculated for several exposure indices with conditional logistic regression models. Aspects of exposure to electric and magnetic fields that were modelled included: the percentage of time spent above selected threshold field intensities, mean transitions in field strength, SD, and the arithmetic and geometric mean field intensities.
RESULTS—For the most part, there was a lack of an association between exposure indices of magnetic fields and the incidence of NHL. Subjects in the upper tertile of percentage of time spent above electric field intensities of 10 and 40 V/m had odds ratios of 3.05 (95% confidence interval (95% CI) 1.07 to 8.80) and 3.57 (1.30 to 9.80), respectively, when compared with those in the lowest tertile. Moreover, the percentages of time spent above these electric field thresholds were significant predictors of case status over and above the association explained by duration of employment and the arithmetic or geometric mean exposure.
CONCLUSIONS—These data suggest that exposures above electric field threshold intensities of 10 and 40 V/m are important predictors of NHL. Consequently, the findings support the hypothesis that electric fields may play a promoting part in the aetiology of this cancer. Further occupational studies that include assessment of exposure to electric fields and measures of field strength above similar threshold cut off points are needed to confirm these findings.


Keywords: non-Hodgkin's lymphoma; electric fields; magnetic fields     

Visual acuity and visual field development after cryocoagulation in infants with retinopathy of prematurity

Visual development was studied in 10 very-low-birth-weight infants (less than 1500 g) with retinopathy of prematurity (ROP) stage 3+ who had been treated with cryocoagulation in both eyes. Binocular visual acuity (acuity cards method) and binocular visual fields (kinetic perimetry) were assessed repeatedly in the first year of life. At 12 months corrected age, visual acuity was normal in seven and impaired in three infants, who appeared to be severely myopic. Normal visual fields were found in eight infants at this age. The results indicate that cryotherapy in cases of ROP stage 3+ does not interfere with visual acuity development. The effect on visual field development needs further investigation.     

Healthcare,race and diversity: time to act

Nearly 40 years after the enactment of civil rights legislation in the United States and following a generation of multicultural policy in Canada, the vast majority of nurses in both countries are still female and white. But while nursing remains starkly segregated by gender, it is hardly alone among the health professions in its under-representation of visible minorities. Physicians and other caregivers find themselves in similar positions--they do not always reflect the communities and patients they serve.     

Lung structural remodeling and pulmonary hypertension after myocardial infarction: complete reversal with irbesartan

OBJECTIVES: The severity of pulmonary hypertension associated with heart failure carries a poor prognosis. The lungs are very sensitive to the constrictive and proliferative effects of angiotensin-II and could represent a preferential target for this peptide. METHODS: Rats with large myocardial infarcts or sham surgery received the angiotensin-II receptor antagonist irbesartan (40 mg/kg/day) or vehicle for 2 or 8 weeks (n=5 to 8 for each group). Hemodynamic and morphometric measurements were obtained followed by immunohistochemistry, immunofluorescence analysis and electron microscopic characterization of lung sections. RESULTS: The infarct groups developed progressive pulmonary hypertension and right ventricular hypertrophy with elevated left ventricular filling pressures (all P<0.01). Despite similar infarct size, filling pressures were lower (P<0.01) while pulmonary hypertension and right ventricular hypertrophy were completely normalized by irbesartan. Isolated lungs pressure-flow relationships were identical at 2 weeks. At 8 weeks it was steepest and shifted upward in the infarct group (P<0.001), and completely normalized by irbesartan. Lung weight doubled after infarct with no evidence of pulmonary edema and was also normalized by irbesartan. Important lungs structural remodeling evidenced by collagen and reticulin deposition, thickening of the alveolar septa and proliferation of cells with ultrastructural characteristics of myofibroblasts (pericytes) were identified after infarct. CONCLUSIONS: After large myocardial infarct there is important pulmonary structural remodeling in which myofibroblasts (pericytes) proliferation may play an important role. This initially protective mechanism against high filling pressures could eventually contribute to the development of pulmonary hypertension and right ventricular hypertrophy. Future studies are needed to determine if angiotensin-II directly modulates pulmonary remodeling after myocardial infarct.     

Absence epilepsy with onset before age three years: a heterogeneous and often severe condition

PURPOSE: The classification of epilepsies and epileptic syndromes recognizes three syndromes with typical absences [TA, i.e., childhood and juvenile absence epilepsies (CAE and JAE), and epilepsy with myoclonic absences (EMA), none of which is characterized by onset in early childhood]. Although several other forms of absence epilepsies have been described recently, none concerns infants and very young children, and little is known about the nosology and prognosis of early-onset absences. METHODS: We retrospectively selected all cases with onset of absences as the only or major seizure type before age 3 years and >/=2 years of follow-up among cases newly referred between 1986 and 2002. Neuropsychological assessments (generally IQ measure), behavior patterns, and schooling situations were reviewed for each child. RESULTS: We found 10 patients (7 F, 3 M). No child had sensory or motor deficits: neuroimaging was performed in nine and was normal in eight, with aspecific findings in one. Only two could be characterized as CAE and EMA, respectively, both with seizure control and a good cognitive outcome. Among the remaining eight cases, four had a fairly homogeneous presentation with predominantly brief absences and clearly asymmetric interictal EEGs. All eight had neuropsychological and/or behavioral difficulties. Three had full seizure control, and five, persisting absences, with a follow-up ranging between 2 years 8 months to 9 years 4 months; only one child was older than 12 years. CONCLUSIONS: Great heterogeneity exists among absence epilepsies of early onset, which are rare conditions. Only a few patients can be categorized into well-known syndromes. The overall prognosis is poor. Early onset of absences is uncommon, and multicenter studies should help clarify the nosology and prognosis.     

The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver.

Polymorphisms in UGT1A9 were associated with reduced toxicity and increased response to irinotecan in cancer patients. UDP-glucuronosyltransferase (UGT) protein expression, glucuronidation activities for 7-ethyl-10-hydroxycamptothecin (SN-38), and probe substrates of the UGT1A9 and UGT1A1 were measured in 48 human livers to clarify the role of UGT1A9 variants on the in vitro glucuronidation of SN-38. Genotypes were assessed for UGT1A9 (-2152C>T, -275T>A, and -118T(9>10)), three novel UGT1A9 variants (-5366G>T, -4549T>C, and I399C>T), and UGT1A1 (-53TA(6>7), -3156G>A, and -3279T>G). Of all the variants, the UGT1A9 I399C>T was associated with the most dramatic change in SN-38-glucuronide (SN-38G) (2.64-fold; p = 0.0007). Compared with UGT1A9 I399C/C, homozygous I399T/T presented elevated UGT1A1 and UGT1A9 proteins and higher glucuronidation of UGT1A9 and UGT1A1 substrates (p < 0.05). The very low linkage disequilibrium (r(2) < 0.19) between UGT1A9 I399 and all the other UGT1A1 and UGT1A9 variants suggests a direct effect or linkage to unknown functional variant(s) relevant to SN-38 glucuronidation. The UGT1A9 -118T(9/10) was also linked to alteration of SN-38 glucuronidation profiles in the liver (p < 0.05) and was associated with higher UGT1A1 protein (p = 0.03). However, UGT1A9 -118T(10) appears to have low functional impact as a result of the lack of correlation with UGT1A9 protein levels and a modest 1.4-fold higher reporter gene expression associated with the -118T(10) allele in HepG2 cells (p = 0.004). In contrast, the UGT1A9 -5366T, -4549C, -2152T, and -275A, associated with higher UGT1A9 protein (2-fold; p < 0.05), have no influence on SN-38G. Despite limitations resulting from sample size, results indicate that UGT1A9 I399 and -118T(9/10) may represent additional candidates in combination with UGT1A1 promoter haplotypes for the prediction of SN-38 glucuronidation profile in vivo.     

金龙胶囊配合辨证用药治疗中晚期恶性肿瘤40例

1临床资料2003-12/2004-10采用北京建生药业生产的金龙胶囊配合辨证用药治疗中晚期癌症40例.Karnofsky评分≥40分,预计生存期>2 mo.     

Prediction of cyclosporine clearance in liver transplant recipients by the use of midazolam as a cytochrome P450 3A probe

BACKGROUND: Interindividual differences in the kinetics of cyclosporine (INN, ciclosporin) result in part from variations in the activity of cytochrome P450 3A (CYP3A). The biotransformation of midazolam to 1'-hydroxymidazolam is also catalyzed by CYP3A. The objective of this study was to examine the usefulness of midazolam as a CYP3A probe to predict cyclosporine clearance. METHODS: Twenty-six stable liver transplant recipients receiving immunosuppressive therapy with oral cyclosporine (Neoral) were studied. Midazolam (0.015 mg/kg) was administered intravenously and a blood sample was obtained 1 hour later. The plasma concentration of midazolam and 1'-hydroxymidazolam was measured by gas chromatography-mass spectrometry. Blood concentration of cyclosporine was measured by a fluorescence polarization assay. Cyclosporine clearance was calculated as daily dose divided by trough level. RESULTS: There were large interindividual variations in cyclosporine clearance and in midazolam metabolism. Cyclosporine blood levels correlated poorly with dose (r = -0.016). However, there was a significant correlation between cyclosporine clearance and the plasma concentration of 1'-hydroxymidazolam (r = 0.559; P < .001) or the midazolam/1'-hydroxymidazolam plasma concentration ratio (r = 0.668; P < .001). CONCLUSION: Heterogeneity in CYP3A activity contributes to interpatient differences in cyclosporine dosage requirements after liver transplantation. Midazolam metabolism correlated with cyclosporine clearance, but it accounted for only about 40% of the variability in the apparent oral clearance of cyclosporine and this relationship is not tight enough to be useful in the prediction of cyclosporine dosage requirements in the clinical setting.     

Distribution of inorganic and methylmercury among tissues in mink (Mustela vison) and otter (Lutra canadensis)

Total mercury and methylmercury concentrations were measured in brain, kidney, liver, and fur from several mink and otter collected in south-central Ontario. There was a large range in concentrations of both total and methylmercury. The percentage of the total mercury present as methylmercury varied among the various tissues; however, the percentage mercury found as the methyl form was relatively constant within a given tissue for all tissues in mink but highly variable in otter. For both species the highest percentage of methylmercury was found in the brain, whereas the lowest percentage was found in the kidneys for the otter and in the fur for the mink. Comparison of mercury concentrations in otter reveals that animals with higher body fat have higher mercury concentrations. Measurements of mercury in fur can be used as a general indicator of internal tissue concentrations.