Associations between ambient air pollution and daily mortality among persons with congestive heart failure

We conducted a mortality time series study to investigate the association between daily mortality for congestive heart failure (CHF), and daily concentrations of particles and gaseous pollutants in the ambient air of Montreal, Quebec, during the period 1984-1993. In addition, using data from the universal Quebec Health Insurance Plan, we identified individuals >/=65 years of age who, one year before death, had a diagnosis of CHF. Fixed-site air pollution monitors in Montreal provided daily mean levels of pollutants. We regressed the logarithm of daily counts of mortality on the daily mean levels of each pollutant, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, weather variables, and other gaseous and particle pollutants. Using cause of death information, we did not find any associations between daily mortality for CHF and any air pollutants. The analyses of CHF defined from the medical record showed positive associations with coefficient of haze, the extinction coefficient, SO(2), and NO(2). For example, the mean percent increase in daily mortality for an increase in the coefficient of haze across the interquartile range was 4.32% (95% CI: 0.95-7.80%) and for NO(2) it was 4.08% (95% CI: 0.59-7.68%). These effects were generally higher in the warm season.     

Geriatric nephrology and urology literature

Publications Received

Geriatric nephrology and urology literature     

Pre-operative kinetic parameter determination of colorectal adenocarcinomas. Prognostic significance

BACKGROUND: The aim of this study was to test the prognostic value of pre-operative assessment of tumour kinetics in colorectal adenocarcinoma. METHODS: The study of tumour kinetics was performed using an in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed using flow cytometry. This procedure enables calculation of the in vivo S-phase fraction labelling index (LI), the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). Disease-free survival curves were calculated by a Kaplan-Meier method. The statistical significance between curves was tested by the log rank test. A multivariate analysis was performed using the Cox's proportional hazards model to determine the effect of pathological staging (lymph node involvement), ploidy and kinetic parameters. RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy. In univariate analysis, lymph node involvement, labelling index > 10% and Tpot < 5 days were associated with poor prognosis, with P= 0.0006, 0.049 and 0.029 respectively; no significant differences were found in Ts (P = 0.214), and ploidy (P= 0.095). In multivariate analysis, lymph node involvement, ploidy and Tpot were found to be independent factors of colorectal cancer prognosis (P= 0.028, 0.032 and 0.035 respectively) in all tumours. Tpot was considered a independent prognostic factor in diploid tumours (P= 0.047) but not in aneuploid tumours (P= 0.345). CONCLUSIONS: These results suggest that kinetic parameters determined by pre-operative biopsies of colorectal adenocarcinoma represent a prognosis factor, independent of pathological staging, particularly in diploid tumours.     

Multidrug resistance genes (MRP) and MDR1 expression in small cell lung cancer xenografts: relationship with response to chemotherapy

Intrinsic or acquired drug resistance is a major limiting factor of the effectiveness of chemotherapy. Increased expression of either the MRP gene or the MDR1 gene has been demonstrated to confer drug resistance in vitro. In this study, we examined MRP and MDR1 gene expression in a panel of 17 small cell lung cancers (SCLC) xenografted into nude mice from treated and untreated patients using an RT-PCR technique. For some of them, the outcome of the corresponding patients was known and we related MDR1/MRP expression with the xenograft response to C′CAV (cyclophosphamide, cisplatin, adriamycin and etoposide) combined chemotherapy. Fifteen (88%) of the 17 cases of SCLC were found to be positive for either MDR1 or MRP. MRP gene expression was present in 12 (71%) of 17 cases, whereas MDR1 gene expression was detected in eight (50%) of 16 cases. For six SCLC, the survival duration of patients differed, with three patients surviving for more than 30 months after therapy. Among these six tumours, five expressed MRP and/or MDR1. These six xenografts responded to the C′CAV treatment but a significant rate of cure was obtained in only three cases. No obvious relationship was observed between the response to this treatment and MRP or MDR1 expression. However, the remarkably high levels and frequency of MRP expression in some SCLC samples indicate that future developments in chemotherapy of this tumour type should anticipate that drugs which are substrates of MRP may be of limited effectiveness.     

Polymyositis and dermatomyositis: short term and longterm outcome, and predictive factors of prognosis.

OBJECTIVE: To assess short term and longterm outcome of polymyositis (PM) and dermatomyositis (DM), and predictive variables of PM/DM course. METHODS: The medical records of 77 consecutive patients with PM/DM were reviewed. The criteria for PM/DM diagnosis were based upon Bohan and Peter criteria. RESULTS: Thirty-one patients (40%) achieved remission of PM/DM, whereas 33 (43%) improved and 13 (17%) worsened their clinical status. Short term recurrences of PM/DM (during tapering of therapy) occurred in 36 patients and longterm recurrences (after discontinuation of therapy) in 9 patients. PM/DM were associated with both decreased functional status and quality of life at longterm followup: (1) only 52% of patients considered to be in remission experienced a return to previous normal activities; and (2) 45% of the other patients with nonremitting PM/DM still had a marked reduction of activities (as shown by the disability scale of the Health Assessment Questionnaire). Overall mortality was as high as 22%, and the main causes of death were cancer and lung complications. Factors associated with PM/DM remission were younger age and shorter duration of clinical manifestations prior to therapy initiation. Variables associated with poor outcome of PM/DM were older age, pulmonary and esophageal involvement, and cancer. CONCLUSION: Our series shows both high morbidity and mortality related to PM/DM, emphasizing that management of PM/DM patients at an early stage is required. Lung complications (i.e., aspiration pneumonia due to PM/DM related esophageal dysfunction and ventilatory insufficiency) were one of the main causes of death in our series, indicating that investigating for subclinical esophageal and lung impairment should become an integral part of initial PM/DM evaluation. The presence of poor prognostic factors should prompt both close followup and aggressive therapy in patients with PM/DM.     

Lipid infusion lowers sympathetic nervous activity and leads to increased β-cell responsiveness to glucose

We investigated the possible involvement of the autonomic nervous system in the effect of a long-term elevation of plasma free fatty acid (FFA) concentration on glucose-induced insulin secretion (GIIS) in rats. Rats were infused with an emulsion of triglycerides (Intralipid) for 48 hours (IL rats). This resulted in a twofold increase in plasma FFA concentration. At the end of infusion, GIIS as reflected in the insulinogenic index (ΔI/ΔG) was 2.5-fold greater in IL rats compared with control saline-infused rats. The ratio of sympathetic to parasympathetic nervous activities was sharply decreased in IL rats relative to controls. GIIS was studied in the presence of increasing amounts of α- and β-adrenoreceptor agonists and antagonists. The lowest concentrations of the α2A-adrenoreceptor agonist oxymetazoline, which were ineffective in control rats, reduced GIIS in IL rats. At the dose of 0.3 pmol/kg, GIIS became similar in IL and control rats. The use of β-adrenoreceptor agonist (isoproterenol) or antagonist (propranolol) did not result in a significant alteration in GIIS in both groups. GIIS remained as high in IL vagotomized rats as in intact IL rats, indicating that changes in parasympathetic tone were of minor importance. Altogether, the data show that lipid infusion provokes β-cell hyperresponsiveness in vivo, at least in part through changes in α2-adrenergic innervation.