Registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.
BackgroundThe study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN).MethodsPatients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria.ResultsDuring 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission.ConclusionsThe results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.
The Kru¨ppel-like zinc-finger protein GLI1 functions as a downstream transcription factor of Hedgehog signaling and plays a pivotal role in the cellular proliferation of many types of tumors, including pancreatic ductal adenocarcinoma (PDA). PDA develops from dysplastic lesions called pancreatic intraepithelial neoplasia (PanIN) through a multistep carcinogenesis process that changes its cellular characteristics, including a mucin expression profile. Increased expression of a gel-forming mucin, MUC5AC, was previously revealed as a major biomarker for the poor prognosis of PDA patients, but the molecular mechanisms responsible for its expression and correlation with poor prognosis are not fully understood. Here we show that MUC5AC is a direct transcriptional target of GLI1 in PDA cells. Overexpression of GLI1 enhanced MUC5AC expression, and a double knockdown of GLI1 and GLI2 suppressed endogenous MUC5AC expression in PDA cells. Luciferase reporter assays revealed that GLI1 and GLI2 can activate the MUC5AC promoter through its conserved CACCC-box-like cis-regulatory elements. We also found that GLI1-upregulated MUC5AC was expressed in the intercellular junction between cultured PDA cells and interfered with the membrane localization of E-cadherin, leading to decreased E-cadherin-dependent cell-cell adhesion and promoting the migration and invasion of PDA cells. Consistently, GLI1 induced the nuclear accumulation and target gene expression of b-catenin in a MUC5AC-dependent manner. Finally, immunohistochemical analysis revealed that GLI1 expression statistically correlated with MUC5AC expression and also with altered subcellular localization of E-cadherin and b-catenin in PanIN lesions and PDA. This evidence revealed a new aspect of GLI1 function in modulating E-cadherin/ b-catenin-regulated cancer cell properties through the expression of a gel-forming mucin.
Primary cardiac lymphoma (PCL) is a rare and usually fatal neoplasma. A case of PCL in a 78-year-old man who complained of exertional dyspnea and peripheral edema is presented. Echocardiography revealed a mass in the right atrium and a diagnosis of low-grade B-cell lymphoma was obtained with the surgically resected tumor. The lesion appeared to have originated in the right atrium and involved the right ventricle. The patient died of bronchopneumonia 8 months after the initial consultation. The present case and 39 patients with PCL reported between 1995 and 2002 were reviewed. Forty patients showed various and non-specific symptoms such as dyspnea, edema, arrhythmia and pericardial effusion. Primary cardiac lymphoma occurred slightly more often in male patients (M : F = 23:17) and in the elderly in general (mean age, 67 years), with lesions found in the following locations, listed in order of frequency: right atrium, pericardium, right ventricle, left atrium, left ventricle, and other sites. Antemortem diagnosis was obtained in 37 of the 40 patients. Thirty-seven cases were of B-cell lineage and two cases were of T-cell lineage. Complete remission was obtained in only 15 of the 40 patients. Although PCL antemortem diagnoses have been made in the majority of recent cases, the prognosis still remains poor.
♦ Introduction: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD). Over the past decade in Japan, a multidisciplinary approach has been adopted to minimize the incidence and improve outcomes of EPS. This strategy includes planned PD discontinuation for high-risk patients and the introduction of biocompatible solutions. This study examined the current clinical status of EPS in representative PD centers in Japan. ♦ Design, setting, participants and measurements: Patients (n = 1,338) from 55 PD centers in Japan who were using neutral-pH solutions from the initiation of therapy (mean age, 62 years; median PD duration, 32 months; concomitant use of icodextrin, 35.2%; PD and hemodialysis combination therapy, 12.2%) were assessed every 6 months to ascertain the reasons for PD discontinuation and the development of EPS development. Outcomes were also recorded. The study period was from November 2008 to March 2012. ♦ Results: There were 727 patients who discontinued PD, including 163 deaths. Among all causes of PD withdrawal except for death, planned PD discontinuation to avoid EPS was utilized in 58 cases (7.1% in total). The strategy was increasingly utilized in proportion to the duration of PD: 0.5% for patients undergoing PD for < 3 years, 0.6% for patients undergoing PD for 5 years, 14.7% for patients undergoing PD for 8 years, and 35.5% for patients undergoing PD for > 8 years. Fourteen patients developed EPS (three cases after PD), which corresponded with an overall incidence of 1.0%. The incidence according to the duration of PD was 0.3% for PD < 3 years, 0.6% for PD = 5 years, 2.3% for PD = 8 years, and 1.2% for PD > 8 years. In terms of therapy, 11 patients were treated with prednisolone (PSL), and surgical enterolysis was utilized in two cases. Complete remission of abdominal symptoms was achieved in twelve patients (85.7%), and three died due to EPS (mortality rate of 21.4%). ♦ Conclusions: Use of the multidisciplinary approach described above reduces the risk of the development of EPS according to PD duration. In cases of de novo EPS cases in Japan, this strategy can also attenuate the clinical course of the condition.
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