Epidemiologic data of primary glomerular diseases in western France.

Between January 1, 1976, and December 31, 2002, histologic diagnosis of primary glomerular diseases (PGD) was made in 898 patients born and living at the time of diagnosis in a region of France, comprising 412,735 inhabitants, of whom 391,265 were aged from 10 to 85 years. The prevalence of PGD during a 75-year exposure to risk (10 to 85 years of age) was evaluated to 6.9 in 1000 (8.2 in 1000 males and 5.1 in 1000 females) during the 27-year period. The most common PGD was IgA nephropathy (IgAN) with a prevalence of 2.4 in 1000 (3.6 in 1000 males and 1.3 in 1000 females). The annual incidence of PGD was evaluated separately for two consecutive 10-years periods: period A (1976 to 1985), period B (1986 to 1995) and for one 7-year period: period C (1996 to 2002). Within each of these three periods, annual incidence of PGD was 89, 76, and 65 per million inhabitants. During this 27-year period, the annual incidences of membranoproliferative glomerulonephritis (GN) and membranous nephropathy were declining and the incidence of crescentic proliferative GN was strongly progressing, whereas annual incidence of nephrosis remained stable. The incidence of IgAN remained the same throughout the three periods: 28, 28, and 26 per million inhabitants. Whereas the incidence of IgAN was three- to fourfold higher in the adult aged from 20 to 59 years than in the elderly during the periods A (38 vs. 11 per million inhabitants) and B (37 vs. 12 per million inhabitants), the incidence became similar whatever age groups during the last period C (20 to 59 years, 25 per million inhabitants; 60 to 79 years, 27 per million inhabitants; and 80 years and over, 28 per million inhabitants. The stability of annual incidence according to period and age, which is demonstrated for the first time during the last period, provides a new evidence of a role for genetic factors in the pathogenesis of IgAN.

Prospective evaluation of a new rapid urease test (Pronto Dry) for the diagnosis of Helicobacter pylori infection.

AIM: Rapid urease tests are commonly used to establish the diagnosis of Helicobacter pylori infection during upper endoscopy. The aim of this study was to evaluate the performance of a new rapid urease test (Pronto Dry) compared with histology as the gold standard. METHODS: Six gastric biopsies (three in the antrum and three in the fundus) were performed in 113 consecutive patients. Eighteen patients were later excluded from analysis because they did not fulfil the inclusion criteria. Four biopsies were examined by two experienced pathologists blinded to the rapid urease tests. Two biopsies (one from antrum and one from the fundus) were pooled for the rapid urease test which was read by the endoscopist 5 and 30 minutes later using the color scale (yellow, pink, orange, dark pink, fuchsia) provided by the manufacturer. RESULTS: According to the histology findings 32 of the 95 patients retained for analysis (33.7%) were positive for Helicobacter pylori. Considering that a positive test was indicated by the dark pink or fuchsia colors, sensitivity and specificity of Pronto Dry were 62.5% and 98.4% at 5 minutes and 84.4% and 98.4% at 30 minutes respectively. Twenty-one of the 28 positive rapid urease tests (75%) were already positive at 5 minutes. CONCLUSION: Considering positive tests are indicated solely by the two darkest colors on the color scale, the performance of Pronto Dry is similar to that of other rapid urease tests. The rapid results provided by Pronto Dry in routine practice would seem to provide obvious advantages.

Cytotoxic effector cells with antitumor activity can be amplified ex vivo from biopsies or blood of patients with renal cell carcinoma for cell therapy use.

Adoptive immunotherapy with antitumor effector cells is an attractive therapeutic approach in metastatic renal cell carcinoma (RCC). The aim of the work was to enhance in vitro activation of lymphocytes with optimal cytotoxic activity against tumor cells. We evaluated a procedure based on the use of dendritic cells (DCs) loaded with irradiated tumor cells (DC-Tu) to stimulate lymphocytes. Experimental conditions were established with cells from healthy donors and melanoma cell lines. Procedures were then applied to cells from RCC patients. A total of 30 tumor biopsies, 14 proximal lymph nodes, and 17 peripheral blood samples from 30 patients were used. When lymphocytes were stimulated in vitro with DC-Tu, they responded to tumor cells with an increased cytolytic activity for all the assays with donor cells (n=18). For RCC patients, DC-Tu stimulation improved the final cytotoxic activity in only half of the assays (16/31). When significantly enhanced (>10%, n=8), responder cells resulted in a final 43% cytotoxicity against autologous RCC cells. Mechanism of lysis was at least in part class I mediated. Effector cells have no lytic activity against normal renal cells. Percentage of cells with regulatory T-cell phenotype was not found to be enhanced in the DC-Tu stimulated lymphocytes. Individual differences were observed in the characteristics of DCs generated from RCC patients in contrast to that observed in donors and could explain why lymphocyte stimulation was not improved by DC-Tu in half of the RCC assays. T-cell spreading was suitable for a therapeutic use (>10(9) cells) irrespective of the procedure (with or without DC-Tu stimulation) or the tissular origin of lymphocytes from patients. Data show that precursors of selective antitumor effector cells are present in patients with RCC and can be amplified in vitro either with or without DC-Tu stimulation. One of these populations could be chosen for an adoptive transfer immunotherapy.

Combined effects of enalapril and spironolactone in hamsters with dilated cardiomyopathy.

Chronic angiotensin I-converting enzyme inhibition can be associated with aldosterone escape. We investigated the effects of enalapril, spironolactone, and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters to determine whether these drugs could exert additive effects. Cardiomyopathic hamsters, Bio TO-2 dilated strain, were orally treated with enalapril (20 mg. kg. day ) and/or spironolactone (20 mg. kg. day ) according to a 2 x 2 factorial design from 120 days of age. Animals were investigated at 180 (10 animals per group) and 240 (16 animals per group) days of age. Compared with corresponding untreated groups, enalapril significantly decreased mean blood pressure (-18%); enalapril and spironolactone significantly increased cardiac output (+28%, +11%) and femoral blood flow (+10%, +12%) and significantly decreased systemic (-38%, -17%) and femoral (-26%, -13%) vascular resistances. Enalapril and spironolactone significantly decreased left ventricle cavity area (-21%, -26%) and left (-34%, -47%) and right (-37%, -48%) ventricle collagen density. Spironolactone significantly increased left ventricle wall thickness (+4%). There were significant enalapril x spironolactone interactions for most variables (compared with control group, +52%, +36%, +45% for cardiac output; +26%, +28%, +26% for femoral blood flow; -50%, -30%, -45% for systemic vascular resistance; -33%, -20%, -35% for femoral vascular resistance; -27%, -31%, -40% for left ventricle cavity area; and -46%, -58%, -60% for left and -39%, -50%, -66% for right ventricle collagen density in enalapril, spironolactone, and enalapril + spironolactone groups, respectively). In cardiomyopathic hamsters, enalapril and spironolactone in combination did not improve hemodynamics more than enalapril alone but induced stronger effects than each drug alone on cardiac remodeling.

Squamous cell carcinoma arising in a hepatic forgut cyst.

We report the second case of squamous cell carcinoma arising in a hepatic foregut cyst (CHFC) in a 40-year-old woman. Microscopically, the lining of the cyst was composed of ciliated columnar epithelium, gastric and squamous epithelium. The squamous epithelium showed areas with dysplastic changes and other areas with carcinomatous transformation. In this congenital lesion, it was not surprising to find squamous and gastric mucosa because oesophagus, stomach, and tracheobronchic tree derive from the embryologic foregut. Squamous carcinoma might develop in a context of inflammation as in biliary cyst. In agreement with the first case described in the literature, this report also suggests that a large-sized symptomatic hepatic cyst should be excised.

Combined effects of metoprolol and spironolactone in dilated cardiomyopathic hamsters.

The use of beta-blockers reduces angiotensin II levels, but could not adequately suppress aldosterone production. Thus, the combination of a beta-blocker with an aldosterone receptor antagonist could exert additive effects. The effects of metoprolol and spironolactone and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters (CMH) were investigated. The Bio TO-2 dilated strain of CMH was treated orally with metoprolol (10 mg/kg/day), spironolactone (20 mg/kg/day), or both according to a 2 x 2 factorial design (24 animals per group) from 120 days of age and during 120 days. As compared to corresponding untreated groups, metoprolol significantly decreased mean blood pressure (-7%), and metoprolol and spironolactone significantly increased cardiac output (18% and 19%, respectively), mesenteric blood flow (11% and 14%), and femoral blood flow (13% and 17%), and significantly decreased systemic (-24% and -15%), mesenteric (-14% and -13%) and femoral (-19% and -10%) vascular resistances. Metoprolol significantly increased renal blood flow (22%) and significantly decreased renal vascular resistance (-23%). Metoprolol and spironolactone significantly decreased the cavity area of the left ventricle (-21% and -32%, respectively) and the collagen density of the left (-36% and -39%) and right (-38% and -43%) ventricles. Although the combination did not induce stronger effects than each drug alone on the systemic and most regional hemodynamic variables, it did have a stronger effect on the cardiac remodeling (compared to control group: -24%, -34%, and -46% for the left ventricle cavity area, -33%, -35%, and -62% for collagen density in the left ventricle, and -52%, -57%, and -59% for collagen density in the right ventricle, respectively, in the metoprolol, spironolactone, and metoprolol + spironolactone groups). In CMH, metoprolol and spironolactone combined did not improve hemodynamics more than each drug alone, but did exert additive effects on cardiac remodeling.

Systemic and regional hemodynamic and cardiac remodeling effects of candesartan in dilated cardiomyopathic hamsters with advanced congestive heart failure.

The effects of the selective angiotensin II type 1 receptor antagonist candesartan on cardiac, systemic, and regional hemodynamics and on cardiac, pulmonary, and hepatic histomorphometry were investigated in cardiomyopathic hamsters (CMHs), Bio TO-2 dilated strain, with advanced congestive heart failure (CHF). Two groups were treated orally with candesartan cilexetil at 22 or 50 mg/kg/d from 190 days of age and compared with a control group (38 animals/group). Investigations were performed at 225, 255, and 285 days of age. Left ventricle (LV) and systemic blood pressures and cardiac output and mesenteric and femoral blood flows were measured in anesthetized animals. LV cavity area, LV and right ventricle (RV) wall thickness and collagen density, and pulmonary and hepatic congestion were assessed. Compared with the control group, candesartan did not modify cardiac hemodynamics but significantly and dose-dependently decreased systemic vascular resistances (on average: -23 and -32% after 22 and 50 mg/kg, respectively) and increased stroke volume (+32 and +42%) and cardiac output (+27 and +34%). Candesartan did not modify mesenteric vascular resistances and blood flow but significantly and dose-dependently decreased femoral vascular resistances (-19 and -33%) and increased femoral blood flow (+33 and +43%). Candesartan significantly decreased LV cavity area (-14 and -8%) and LV (-15 and -31%) and RV (-16 and -24%) collagen density but did not modify LV and RV wall thickness. Candesartan decreased pulmonary congestion at 255 and 285 days of age but did not modify hepatic congestion. In CMHs with advanced CHF, candesartan cilexetil improves systemic and femoral hemodynamics, partly reverses cardiac remodeling, and decreases pulmonary congestion.

Early anti-remodeling effect of labetalol in the congestive heart failure model induced by aortic constriction in the guinea pig.

We investigated the effects of the beta1-beta2-alpha1-blocker, labetalol, in the congestive heart failure (CHF) model induced by aortic constriction in the guinea pig. One hundred days after aortic constriction, 52 animals were given either placebo, labetalol 2 mg/kg/d, or labetalol 20 mg/kg/d for 60 days. Eighteen sham-operated animals were used as controls. Investigations were performed at the end of the treatment period. Compared with sham-operated animals, banded animals receiving placebo showed signs of overt CHF with cardiac, systemic and regional (mesenteric and femoral) hemodynamic dysfunction, and pulmonary and hepatic congestion. An increase in whole heart, atria, and left and right ventricle weights associated with left ventricular cavity enlargement and left and right ventricular wall thickening indicated a remodeling process. Compared with placebo, labetalol did not significantly modify cardiac, systemic, or regional hemodynamic variables but significantly decreased pulmonary and hepatic congestion. Labetalol significantly reduced left ventricular cavity area (-10 and -20% after 2 and 20 mg/kg, respectively) and left ventricular (-4 and -16%) and right ventricular (-4 and -19%) wall thickness. In conclusion, labetalol induced partial regression of cardiac remodeling before hemodynamic improvement. This early anti-remodeling effect could play a role in the favorable effects observed with beta1-beta2-alpha1-blockers in humans.