Objectives: To assess the additive benefit of combining an al-blocker and a Sa-reductase inhibitor. Methods: This European, randomized, double-blind, multicenter trial involved 1.051 patients with lower urinary tract symptoms related to benign prostatic hyperplasia. Patients received sustained release (SR) alfuzosin (n = 358), a selective alpha(1)-blocker given at a dose of 5 mg twice daily without dose titration; finasteride (n = 344), 5 mg once daily, or both drugs (n = 349), for 6 months. Primary efficacy criteria were symptomatic improvement (International Prostate Symptom Score: I-PSS) and maximum flow rate (Q(max)). Safety was assessed by monitoring adverse events. Results: Symptomatic improvement was significantly higher from the Ist month of treatment with SR alfuzosin, alone or in combination; mean changes in I-PSS versus baseline at end-point were -6.3 and -6.1, respectively, compared with -5.2 with finasteride alone (SR alfuzosin vs. finasteride, p = 0.01; combination vs. finasteride, p = 0.03). The percentages of patients with a decrease in I-PSS of at least 50% were 43, 42 and 33% for SR alfuzosin, the combination and finasteride, respectively (SR alfuzosin vs. finasteride, p = 0.008; combination vs. finasteride, p = 0.009). In the overall population, increases in Q(max) were greater with SR alfuzosin and the combination, compared with finasteride alone after 1 month of therapy, but changes at end-point were similar in the three treatment groups. In those 47% of patients likely to be obstructed (baseline Q(max) <10 ml/s), however, mean increases in Q(max) were significantly higher with SR alfuzosin, alone or in combination, whatever the visit. Finasteride, alone or in combination, significantly impaired sexual function. The incidence of postural symptoms was low and similar in the three treatment groups. Conclusion: In this 6-month trial, SR alfuzosin was more effective than finasteride, with no additional benefit in combining both drugs.

OBJECTIVES:To assess the efficacy and safety of a sustained-release (SR) formulation of alfuzosin, a selective alpha(1)-blocker, in patients with symptomatic benign prostatic hyperplasia (BPH).METHODS:A total of 390 men were randomly assigned to receive SR-alfuzosin (n = 194), 5 mg twice daily without dose titration, or placebo (n = 196) for 12 weeks. Of the patients included, 47% had concomitant cardiovascular disease, mainly hypertension or coronary heart disease.RESULTS:SR-alfuzosin significantly improved urinary symptoms versus placebo assessed using the I-PSS (-31 vs. -18%, p = 0.007) and Boyarsky (-30 vs. -16%, p < 0.001) scores, with a direct correlation between both scores. Maximum flow rate increased significantly with SR-alfuzosin (+2.4 ml/s, i.e. +29%) compared with placebo (+1.1 ml/s, i.e. +14%, p = 0.006). Residual urine was also significantly reduced with SR-alfuzosin. Overall, SR-alfuzosin was as well tolerated as placebo. Nine patients dropped out for adverse events with SR-alfuzosin (4.6%) and 14 (7.1%) with placebo. The incidence of vasodilation-related events (dizziness, postural symptoms, headache) with SR-alfuzosin (3.1%) was similar to that of placebo (3.6%). No first-dose effect was observed compared with placebo. The reduction in supine blood pressure with SR-alfuzosin was minor (< or = 5 mm Hg), both in normotensive and hypertensive patients.CONCLUSION:SR-alfuzosin is an effective treatment of symptoms related to BPH that shows a good safety profile in normotensive and hypertensive patients, without the need of dose titration.

In order to assess the incidence of chronic renal failure (CRF) and the demographic characteristics of affected patients, a prospective, multicenter epidemiologic study was conducted with the cooperation of all nephrology and dialysis units in the Ile-de-France district, the total population of which is 10660000 inhabitants (source: national census, march 1990). Included were patients with a plasma creatinine (Pcr) concentration > or = 200 mumol/l referred during the one-year period from July 1, 1991 until June 30, 1992. The overall response rate was 98.5%. A total of 2775 adult patients were recorded, including 1780 males (64%) with a mean (+/- SD) age of 58.1 +/- 16.3 years and a mean Pcr of 447 +/- 214 mumol/l, and 995 females (36%) with a mean age of 59.2 +/- 16.4 years and a mean Pcr of 425 +/- 185 mumol/l. Age of patients was < 40 in 16%, 40-59 in 31%, 60-74 in 34% and > or = 75 years in 19%. Pcr was 200-399 mumol/l in 54%, 400-599 mumol/l in 25%, 600-799 mumol/l in 12% and > or = 800 mumol/l in 9%. The overall incidence of CRF was 260/million population/year, twice higher in males than in females (348 vs 179/10(6)/year, p < 0.001). Incidence of CRF dramatically rose with age in both genders, with figures as high as 1124 and 356/10(6)/year respectively in male and female patients aged > or = 75 years, vs 288 and 151/10(6)/year in patients aged < 40 years. A sequential evaluation was performed in a representative sample of 251 patients with initial Pcr > or = 300 mumol/l. End-stage renal failure (ESRF) was reached within one year in 99% of patients with PCr > 600, 49% with Pcr 500-599, 24% with PCr 400-499 and 11% with PCr 300-399 mumol/l. Based on these figures, the predicted incidence of ESRF within one year of referral was 864 out of the 2775 patients, an estimated annual incidence of 81 patients per million population. In conclusion, this prospective study affords the first direct information on the incidence of chronic renal failure and the demographic characteristics of patients with CRF in the Ile-de-France district. Due to the design of the study conducted only in nephrology units, the estimated figure of 81 new patients per million population per year reaching ESRF is a minimal evaluation. In view of the relentless aging of population in France, an incidence of at least 100 ESRF patients per million population per year is to be expected in the next future.

In order to assess the incidence of chronic renal failure (CRF) and the demographic characteristics of affected patients, a prospective, multicenter epidemiologic study was conducted with the cooperation of all nephrology and dialysis units in the Ile-de-france district, the total population of which is 10 660 000 inhabitants (source: national census, march 1990). Included were patients with a plasma creatinine (Per) concentration greater than or equal to 200 mu mol/l referred during the one-year period from July 1, 1991 until June 30, 1992. The overall response rate was 98.5%. A total of 2775 adult patients were recorded, including 1780 males (64%) with a mean (+/- SD) age of 58.1 +/- 16.3 years and a mean Per of 447 +/- 214 mu mol/l, and 995 females (36%) with a mean age of 59.2 +/- 16.4 years and a mean Per of 425 +/- 185 mu mol/l. Age of patients was < 40 in 16%, 40-59 in 31%, 60-74 in 34% and greater than or equal to 75 years in 19%. Per was 200-399 mu mol/l in 54%, 400-599 mu mol/l in 25%, 600-799 mu mol/l in 12% and greater than or equal to 800 mu mol/l in 9%. The overall incidence of CRF was 260/million population/year, twice higher in males than in females (348 vs 179/10(6)/year, p < 0.001). Incidence of CRF dramatically rose with age in both genders, with figures as high as 1124 and 356/10(6)/year respectively in male and female patients aged greater than or equal to 75 years, vs 288 and 151/10(6)/year in patients aged < 40 years. A sequential evaluation was performed in a representative sample of 251 patients with initial Per greater than or equal to 300 mu mol/l. End-stage renal failure (ESRF) was reached within one year in 99% of patients with PCr > 600, 49% with Per 500-599, 24% with PCr 400-499 and 11% with PCr 300-399 mu mol/l. Based on these figures, the predicted incidence of ESRF within one year of referral was 864 out of the 2775 patients, an estimated annual incidence of 81 patients per million population. In conclusion, this prospective study affords the first direct information on the incidence of chronic renal failure and the demographic characteristics of patients with CRF in the Ile-de-France district. Due to the design of the study conducted only in nephrology units, the estimated figure of 81 new patients per million population per year reaching ESRF is a minimal evaluation. In view of the relentless aging of population in France, an incidence of at least 100 ESRF patients per million population per year is to be expected in the next future.

Clinical and histological data leading to precise diagnosis were retrospectively obtained in 98 patients with antineutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence (IIF). Specificity was determined by myeloperoxidase (MPO) and proteinase 3 (PR3) specific ELISA in all and a comparative study based on ANCA specificity was performed. Vasculitis was present in all cases. PR3-ANCA occurred predominantly in males (25/38) with WG (19/38). MPO-ANCA occurred predominantly in older women and were often associated with various autoimmune disorders. There was a high prevalence of lung hemorrhage (18/45) and mPA (26/45) in this group. Patients with negative MPO and PR3 specific ELISA despite positive IIF (n = 15) were almost exclusively WG (13/15) and were characterized by a high prevalence of hepatic and digestive manifestations. Renal and patient survival at the 75th percentile was 15 months with MPO-ANCA and 16 months with PR3, and was similar for patients with WG and mPA. With immunosuppressive treatment, ANCA disappeared in 66% of cases and this disappearance was always associated with absence of disease activity.

UNLABELLED:From 1987 to 1991, 2500 sera were tested for presence of anti-neutrophil cytoplasmic antibodies (ANCA) by standard indirect immunofluorescence (IIF) and specific proteinase 3 (PR3) and myeloperoxydase (MPO) ELISA. Clinical and histological data leading to precise diagnosis were retrospectively obtained in 98 patients with ANCA positivity by IIF and then a comparative study based on ANCA specificity was performed. Vasculitis was present in all cases. Among patients with anti-PR3 (n = 38), 19 had Wegener's granulomatosis (WG), 15 microscopic polyarteritis (mPA), 2 idiopathic necrotizing and crescentic glomerulonephritis (NCGN) and 2 relapsing polychondritis (RP). Among patients with anti-MPO (n = 45), 26 had mPA, 3 classical polyarteritis nodosa (PAN), 5 WG, 8 NCGN, 2 systemic lupus erythematosus (SLE) and one Churg-Strauss syndrome (CSS). Negative MPO and PR3 specific ELISA despite positive IIF were observed in 15 patients (13 WG, 1 mPA, 1 PAN). In the PR3 group, males predominated (66%) and the mean age was 49 years (range 13-85); in the MPO group, females predominated (62%) and the mean age was 57 years (range 13-85). These differences were statistically significant (p < 0.05). Renal involvement was present in 92% of patients and renal biopsy showed pauci-immune necrotizing and crescentic glomerulonephritis in nearly all cases. PR3 specificity was associated with frequent eye involvement (32%) and presence of granulomas (45%), but was not associated with other autoantibodies. MPO specificity was associated with a higher prevalence of pulmonary hemorrhage (40%) and various autoimmune disorders, especially antinuclear antibodies. Cholestasis was observed in 50% of WG with negative MPO and PR3 ELISA. Renal and patient survival at the 75th percentile was 15 months with MPO-ANCA and 16 months with PR3, and was similar for patients with WG and mPA. Relapses occurred in 20% of patients with anti-MPO and 36% of patients with anti-PR3. Serological follow-up was obtained in 44 patients. With immunosuppressive treatment, ANCA disappeared in 66% of cases and this disappearance was always associated with absence of disease activity.IN CONCLUSION:1. This study confirms that the presence of ANCA is a good marker of vasculitis. 2. Despite some clinical differences, MPO and PR3-associated vasculitis have a similar prognosis. 3. The titer of ANCA determined by ELISA is not correlated with the severity of vasculitis but disappearance of ANCA is always associated with absence of disease activity.