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Biomedical subjects

Pierre Douville

Publications and source records attributed to Pierre Douville.

8 recordsLinked to original sources

Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial.

Randomized trials have shown, unexpectedly, that supplementation with selenium or vitamin E is associated with a reduction of prostate cancer risk. We assess whether a supplementation with low doses of antioxidant vitamins and minerals could reduce the occurrence of prostate cancer and influence biochemical markers. The SU.VI.MAX trial comprised 5,141 men randomized to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years. Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrollment and at the end of follow-up from 3,616 men. Cox regression models were used to estimate the hazard ratio and related 95% confidence interval of prostate cancer associated with the supplementation and to examine whether the effect differed among predetermined susceptible subgroups. During the follow-up, 103 cases of prostate cancer were diagnosed. Overall, there was a moderate nonsignificant reduction in prostate cancer rate associated with the supplementation (hazard ratio = 0.88; 95% CI = 0.60-1.29). However, the effect differed significantly between men with normal baseline PSA (< 3 microg/L) and those with elevated PSA (p = 0.009). Among men with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements (hazard ratio = 0.52; 95% CI = 0.29-0.92). In men with elevated PSA at baseline, the supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (hazard ratio = 1.54; 95% CI = 0.87-2.72). The supplementation had no effect on PSA or IGF levels. Our findings support the hypothesis that chemoprevention of prostate cancer can be achieved with nutritional doses of antioxidant vitamins and minerals.

Adult↗

Estimation of heparin leak into the systemic circulation after central venous catheter heparin lock.

BACKGROUND: Although most catheter problems in haemodialysis are related to infection or clotting, bleeding associated with the heparin lock is of clinical importance especially during peri-operative conditions. The objective of this in vitro study is to estimate the volume of heparin that may leak into the circulation immediately after performing a catheter lock. METHODS: Different volumes (ml) of a dextrose solution were used to perform a catheter lock on haemodialysis catheters. The tip of the catheter was placed in a test tube containing water for a pre-specified period. The final concentrations of dextrose in the test tube were used to determine the volume of solution that leaked from the catheter. RESULTS: When the total lumen volume was filled, the catheter leak was estimated to be 0.59+/-0.03 and 0.71+/-0.04 ml after 15 and 25 s, respectively. There was a continuous leak of 1.23+/-0.41, 2.20+/-0.34 and 3.38+/-0.23 ml at 5, 15 and 30 min, respectively, after performing a catheter lock on a catheter with a total lumen volume of 4.5 ml. The catheter leak was significantly reduced when only 3.7 ml of solution was used to fill the total lumen volume of 4.5 ml. CONCLUSION: The present study demonstrates a significant early and late leakage from the catheter that occurs after performing a catheter lock. When applied to heparin, the volume of the unwanted catheter leak may result in adverse clinical events, especially following haemodialysis sessions and during peri-operative periods. However, these results are hypothesis-generating, and clinical studies are necessary to evaluate the efficacy of underfilling.

Catheters, Indwelling↗

Insulin-like growth factor binding protein 2: an androgen-dependent predictor of prostate cancer survival.

BACKGROUND: Evidence suggests that the insulin-like growth factor (IGF) family is important in prostate cancer. We evaluate the ability of IGF markers to predict biochemical recurrence-free survival (bRFS) following radical prostatectomy (RRP). METHODS: Preoperative sera from 141 patients undergoing RRP were analyzed for IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3. A multivariate Cox model was created to assess the ability of these markers to predict bRFS. Preoperative covariables included: biopsy Gleason score, clinical TNM stage, serum PSA and neoadjuvant hormonotherapy. Kaplan-Meier curves were stratifying by IGF cutpoints (determined by ROC analysis) and hormonotherapy status. RESULTS: Average follow-up was 6.92 years, median PSA was 6.9 ng/ml and 85.1% of patients had cT2NxM0 disease. 49 patients experienced a PSA failure. Average levels of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 were 156.5 ng/ml, 48.1 ng/ml, 396.8 ng/ml and 3303.7 ng/ml, respectively. IGFBP-2 was an independent predictor of PSA failure. Patients treated with neoadjuvant ADT (n=71) and whom had high IGFBP-2 levels experienced a 5-year bRFS that was better than those with low IGFBP-2 levels (77.7% vs. 53.3%). Patients without neoadjuvant ADT whom had high IGFBP-2 levels had a 5-year bRFS that was worse than those with low IGFBP-2 levels (64.5% vs. 82.7%). CONCLUSIONS: Preoperative IGFBP-2 predicts post-radical prostatectomy bRFS and is independent of stage, Gleason score and PSA. Increased IGFBP-2 is associated with better survival in patients with neoadjuvant hormonotherapy but worse survival in those without, suggesting a dramatic switch in function of this protein dependent on the presence or absence of androgens.

Adenocarcinoma↗

Problems with the estimation of urine protein by automated assays.

OBJECTIVES: Most clinical laboratories replaced their manual precipitation techniques for the determination of urinary protein with automated dye binding assays or benzethonium chloride-turbidimetric assays. Few studies have validated these assays for the measurement of urinary proteins in the normal range. DESIGN AND METHODS: This study compares four automated assays for the measurement of urinary protein to a manual Ponceau S/TCA precipitation assay. We evaluated the linearity, the precision, the analytical sensitivity, the accuracy and the recovery of different proteins for each assay. RESULTS: All assays showed good linearity with the theoretical concentration of albumin present in the sample. The coefficient of variation was below 10% at a concentration of 0.142 g/L. However, the manual Ponceau S/TCA assay demonstrated superior analytical sensitivity. Accuracy determinations showed a variable positive bias and poor correlations at concentrations below 0.1 g/L when compared to the Ponceau S/TCA assay. Small molecular weight peptides particularly affected the pyrogallol red assays but other urinary components also interfered with the automated assays. CONCLUSIONS: Most automated assays show high imprecision and poor accuracy for the measurement of urinary protein in the normal range. The Ponceau S/TCA offers a precise and accurate manual alternative to these automated assays.

Albuminuria↗

Nonfasting non-high-density lipoprotein cholesterol is adequate for lipid management in hemodialysis patients.

BACKGROUND: Guidelines for the management of dyslipidemia in patients with chronic kidney disease are based on results from the fasting lipid profile, which can be difficult to obtain from patients on an afternoon or night dialysis schedule. The present study tests the hypothesis that nonfasting non-high-density lipoprotein (HDL) cholesterol (total cholesterol-HDL cholesterol) results are similar to fasting non-HDL results as a basis for the management of dyslipidemia in hemodialysis patients. METHODS: Forty-eight long-term hemodialysis patients with a mean age of 63.6 years (42% with diabetes, 54% administered statins) participated in this study. For the lipid profile, blood samples were drawn after a 12-hour overnight fast (fasting) and again in a nonfasting state before the subsequent hemodialysis session. Data were analyzed by using paired t-test and regression analysis. RESULTS: Non-HDL cholesterol values were nearly identical regardless of whether the patient was fasting (r2 = 0.995). Only 2 patients (4%) had a nonfasting triglyceride (TG) level greater than 500 mg/dL (> 5.6 mmol/L), which would have required confirmation after an overnight fast. Non-HDL values had the greatest level of correlation (absolute relative difference, 5.7%). When comparing the subgroup of patients with a TG level less than 200 mg/dL (< 2.3 mmol/L), nonfasting non-HDL cholesterol values identified 3 additional patients compared with fasting calculated low-density lipoprotein cholesterol for whom lipid-lowering therapy would have been introduced according to current guidelines. CONCLUSION: In our study, non-HDL cholesterol levels were equivalent whether evaluated in the fasting or nonfasting state. We recommend that nonfasting non-HDL cholesterol level be used for the management of dyslipidemia in hemodialysis patients without imposing a 12-hour fast period.

Adolescent↗

A prospective study of the insulin-like growth factor axis in relation with prostate cancer in the SU.VI.MAX trial.

Several epidemiologic studies have examined with diverging results the relationships between circulating levels of insulin-like growth factors (IGF) and of IGF-binding proteins (IGFBP) and prostate cancer risk. We assessed the association of prediagnostic plasma levels of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and subsequent occurrence of prostate cancer in a case-control study nested in the SU.VI.MAX trial. The SU.VI.MAX study was a primary prevention trial testing a daily supplementation with low-dose antioxidant vitamins and minerals in male and female middle-aged volunteers in France. One hundred prostate cancer cases were diagnosed among 4,855 SU.VI.MAX participants over a 9-year follow-up period. For each case, four age-matched controls were selected randomly. Frozen baseline plasma samples were used to measure IGF-I, IGF-II, IGFBP-2, and IGFBP-3. Conditional logistic regression was used to assess the association between these four biochemical markers and prostate cancer risk. After controlling for the intervention group in the trial and the other IGF axis variables, the odds ratios and 95% confidence interval (95% CI) comparing the upper quartile to the baseline quartile were 1.83 (95% CI, 0.85-3.95), 1.05 (95% CI, 0.35-3.18), 0.79 (95% CI, 0.39-1.58), and 0.42 (95% CI, 0.12-1.52) for IGF-I, IGF-II, IGFBP-2, and IGFBP-3, respectively. More suggestive associations for IGF-I and IGFBP-3 were observed with advanced and aggressive cancers. Our results are consistent with those of some previous prospective studies and suggest that IGF axis variables are not long-term predictors of the occurrence of prostate cancer.

Antioxidants↗

Functional tests for primary aldosteronism: value of captopril suppression.

With the introduction of more simple screening tests such as the aldosterone/renin ratio, the detection rate of primary aldosteronism has increased considerably. Until now, no reference values have been available for reporting the aldosterone/renin ratio using plasma aldosterone values expressed in SI units (pmol/L) and plasma active renin (ng/L) measured by immunoradiometric assay. We studied 153 subjects who had either normal blood pressure, essential hypertension, or primary aldosteronism. Essential hypertensive patients usually have aldosterone/renin (pmol/L/ng/L) ratios below 100, whereas ratios for patients with primary aldosteronism are above 140. Results that fall between 100 and 140 suggest a need for repeat testing. Patients with elevated aldosterone/renin ratios require confirmatory testing to demonstrate nonsuppressive autonomous aldosterone production. To this end, salt loading is widely used, but this approach may be contraindicated in patients with severe hypertension. The captopril suppression test appears as effective as salt loading in confirming a diagnosis of primary aldosteronism. In addition, the captopril test is safe, well tolerated, and cost-effective.

Aldosterone↗