Clinical factors predictive of spontaneous remission or relapse in cases of autoimmune pancreatitis

BACKGROUND: The rates of spontaneous remission and relapse of autoimmune pancreatitis (AIP) are not known. OBJECTIVE: To study the clinicopathologic factors predictive of remission and relapse in cases of AIP. DESIGN: Retrospective study. PATIENTS: Of the 20 patients with AIP, complete response to steroid therapy was recognized in 12 patients, and the remaining 8 patients improved without steroid therapy. Seven patients experienced a relapse. RESULTS: Patients who were seronegative for immunoglobulin (Ig) G4, had no obstructive jaundice, no diabetes mellitus, no swelling of the duodenal papilla, negative staining of the duodenal papilla for IgG4, and focal pancreatic swelling showed a greater tendency toward spontaneous remission (P < .05). The results of multivariate analysis revealed that negative staining of the duodenal papilla for IgG4 was the only independent predictor of spontaneous remission of AIP (odds ratio [OR] 1.395, P = .0304). Seropositivity for IgG4, diffuse swelling of the pancreas, and the presence of stricture in the lower part of the bile duct were significantly associated with a relapse of AIP (P < .05) according to the results of univariate analysis, whereas the results of multivariate analysis revealed only diffuse pancreatic swelling as an independent predictor of a relapse of AIP (OR 26.197, P = .0331). CONCLUSIONS: Endoscopic findings are of useful prognostic value, because patients with AIP and with negative staining of the duodenal papilla for IgG4 appeared to have a higher frequency of remission without steroid therapy. Patients with AIP and with diffuse pancreatic swelling were found to be at an increased risk of relapse after the initial steroid administration.     

Clinical significance of the duodenal papilla in patients with separate orifices for the bile and pancreatic ducts

BACKGROUND: There have been few reports of separate orifices (SPO) for the bile and pancreatic ducts. The aim of this study was to elucidate the clinical significance of SPO. METHODS: Clinical data of patients with SPO (n = 21) were compared with those of 324 patients without SPO. The duodenal papillae in the patients with SPO were classified endoscopically into three types. Furthermore, we compared three subgroups (n = 221) among 345 patients (group A, 10 patients with bile duct stones with SPO; group B, 66 patients with bile duct stones without SPO; and group C, 145 patients without bile duct dysfunction) to evaluate the bile stasis of SPO. Various factors were retrospectively analyzed to identify any relationship in patients with SPO. RESULTS: Univariate analysis revealed that the diameter of the common bile duct, cholangiographic angulation, and the presence of common bile duct stones (CBDS) were significantly associated with the presence of SPO. Multivariate analysis of the different risk factors for SPO in all patients revealed that the presence of CBDS (relative risk, 3.000; 95% confidence interval, 1.083-8.313; P = 0.0346) and cholangiographic angulation (relative risk, 1.041; 95% confidence interval, 1.010-1.072; P = 0.0085) were independent risk factors. Moreover, univariate analysis among the three subgroups revealed that age, the presence of periampullary diverticula, the diameter of the common bile duct, and the length of the short narrow distal segment were significantly associated with the presence of SPO. CONCLUSIONS: CBDS and cholangiographic angulation are independent risk factors for SPO. This result suggests that SPO may be associated with an elevated risk of CBDS owing to bile stasis.     

Successful cyclosporine treatment for thrombocytopenia after salvage therapy with arsenic trioxide therapy followed by autologous hematopoietic stem cell transplantation in acute promyelocytic leukemia

A 55-year-old man with acute promyelocytic leukemia in the first relapse was treated with arsenic trioxide as salvage therapy. After obtaining molecular remission, he underwent autologous peripheral blood stem cell transplantation (PBSCT) with busulfan and melphalan conditioning. The transplant dose of CD 34-positive cells was sufficient, and engraftment was prompt. Platelet count increased to 320 x 10(9)/1 on day 21; however, it rapidly decreased to 27 x 10(9)/l on day 37. Despite treatment with corticosteroid, the platelet count decreased to 6 x 10(9)/l on day 55. About one month after cyclosporine administration, thrombocytopenia gradually improved. This clinical course suggests immune-mediated thrombocytopenia following autologous PBSCT.     

Diabetic retinopathy and coronary implantation of sirolimus-eluting stents

INTRODUCTION: The prognostic value of identifying the retinal status of diabetic patients undergoing coronary implantation of drug-eluting stents is unknown. METHODS: We evaluated the outcomes of 318 consecutive patients undergoing implantation of sirolimus-eluting stents for coronary artery disease. Patients were divided into 5 groups according to the diabetic and retinal status: diabetic patients without retinopathy (43 patients); diabetic patients with nonproliferative retinopathy (34); diabetic patients with proliferative retinopathy (37); diabetic patients with unknown retinal status (30); and nondiabetic patients (174). RESULTS: During a mean follow-up of 385 days, 64 patients had target-vessel failure (defined as a composite of death from cardiac causes, myocardial infarction, and target-vessel revascularization). At 1 year, Kaplan-Meier estimates of the rate of target-vessel failure were 15.3% for diabetic patients without retinopathy, 56.6% for those with nonproliferative retinopathy, 17.3% for those with proliferative retinopathy, 19.0% for those with unknown retinal status, and 16.0% for nondiabetic patients. After adjustment for the potential confounders and differences between groups, the relation of nonproliferative retinopathy to target-vessel failure remained significant. In an analysis in which diabetic patients without retinopathy were used as the reference group, the hazard ratios for target-vessel failure were 3.9 for those with nonproliferative retinopathy, 1.3 for those with proliferative retinopathy, 1.1 for those with unknown retinal status, and 1.4 for nondiabetic patients (P for trend = 0.015). CONCLUSIONS: As compared with diabetic patients without retinopathy, those with nonproliferative retinopathy have an increased risk for target-vessel failure after coronary implantation of sirolimus-eluting stents.     

Recognition memory for unfamiliar faces in Parkinson's disease: behavioral and electrophysiologic measures

We analyzed event-related potentials (ERPs) and behavioral measurements during a recognition memory task in 15 normal elderly subjects and 15 patients with Parkinson's disease (PD). To elicit ERPs unfamiliar faces were repeated immediately after initial presentation (at lag 0), after one intervening face (at lag 1) or at lag 3. Compared to normal controls, PD patients showed decreased accuracy in recognizing new unfamiliar faces. P170 latency and amplitude were similar between both groups. ERP amplitude between 300 and 500 ms after the stimulus in control subjects showed a positive shift (ERP repetition effect) for lag 0 at all sites and for lag 1 and 3 repetitions at the Fz site, while effects in the PD group were not noted at any site, even for the lag 0 repetition. ERP waveforms for the first presentation of faces in PD patients showed a significant positive shift compared to normal controls. These data suggest intact perception but impaired recognition memory for unfamiliar faces in PD. In addition, recognition memory deficits in PD may result from impairment of comparison of structural representations of presented faces with stored representations of faces known to the observer.     

Impact of hepatitis B virus X protein on the DNA damage response during hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. The main HCC-associated diseases are chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), and HBV-associated HCC is still prevalent in Asia. Many studies have suggested that HBV X protein (HBX), which is the most common ORF integrated into the host genome, plays a crucial role in hepatocarcinogenesis. However, the accumulated evidence regarding HBX-mediated signaling pathways is not concordant, and it is difficult to understand the mechanistic nature of HBX-associated hepatocarcinogenesis. For example, HBX was reported to inactivate the early responses to DNA damage via p53-dependent and -independent pathways by interacting with several DNA damage-binding proteins and was also reported to sensitize cells to p53-mediated apoptosis via ataxia-telangiectasia and Rad3-related (ATR)-dependent signaling. HBX also interferes with the centrosome replication process, resulting in rearrangement of chromosomes with micronuclei. Moreover, HBX was found to sensitize protein kinases such as Ras/Raf/mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), stress-activated protein kinase/NH2-terminal-Jun kinase (SAPK/JNK), protein kinase B (PKB/Akt), and Janus kinase/STAT (JAK/STAT), indicating that a variety of signaling pathways may be activated by HBX. In this review, we focus on the roles of HBX in DNA damage repair during HCC development, with a view to achieving a better understanding of the significance of HBX in the early steps of hepatocarcinogenesis.     

IL‐15 is critical for the maintenance and innate functions of self‐specific CD8+ T cells

IL‐15 is a pleiotropic cytokine involved in host defense as well as autoimmunity. IL‐15‐deficient mice show a decrease of memory phenotype (MP) CD8⁺ T cells, which develop naturally in naïve mice and whose origin is unclear. It has been shown that self‐specific CD8⁺ T cells developed in male H‐Y antigen‐specific TCR transgenic mice share many similarities with naturally occurring MP CD8⁺ T cells in normal mice. In this study, we found that H‐Y antigen‐specific CD8⁺ T cells in male but not female mice decreased when they were crossed with IL‐15‐deficient mice, mainly due to impaired peripheral maintenance. The self‐specific TCR transgenic CD8⁺ T cells developed in IL‐15‐deficient mice showed altered surface phenotypes and reduced effector functions ex vivo. Bystander activation of the self‐specific CD8⁺ T cells was induced in vivo during infection with Listeria monocytogenes, in which proliferation but not IFN‐γ production was IL‐15‐dependent. These results indicated important roles for IL‐15 in the maintenance and functions of self‐specific CD8⁺ T cells, which may be included in the naturally occurring MP CD8⁺ T‐cell population in naïve normal mice and participate in innate host defense responses.     

Embolization of ruptured aneurysms in the acute stage: experience at a single institute

BACKGROUND: Recently, several reports have shown embolization to be more beneficial than surgical clipping for the treatment of ANs, because the former is less invasive. In our department, GDCE has been the first choice of treatment for ANs since 1977. In this work, we present our clinical results with GDCE and suggest this approach as an alternative treatment of ruptured ANs in the acute stage. METHODS: We treated 247 consecutive patients with acute-stage AN ruptures using GDC. To prevent symptomatic vasospasm, continuous lumbar drainage was performed before GDCE. If blood clots in the basal cisterns were dense on computerized tomography, TPA was administered through a lumbar spinal drainage tube. RESULTS: Of the 247 patients, 196 (79%) had excellent or good outcomes at 3 months after treatment. Symptomatic vasospasm occurred in 27 patients (13.9%), and 25 required chemical or mechanical angioplasty. Permanent morbidity due to vasospasm occurred in 8 patients (4.1%), and 3 patients died (1.5%). CONCLUSION: Subjects, perioperative treatment methods, and outcomes were assessed consecutively and prospectively in a single institution, making the results of this study particularly valuable. Although very long-term results of treating ANs with GDCE have yet to be obtained, our results suggest that embolization of ruptured ANs in the acute stage with GDC is a safe, feasible method of treatment.     

Two cases of ampulla (takotsubo-shaped) cardiomyopathy associated with hemophagocytic lymphohistiocytosis

There have been many reports of patients with ampulla cardiomyopathy described as takotsubo-shaped cardiomyopathy in the cardiovascular field. This unique cardiomyopathy is characterized by transient apical ballooning and hypokinesis of the left ventricle. We describe 2 cases of ampulla cardiomyopathy associated with hemophagocytic lymphohistiocytosis (HLH). In both of the patients, ventricular dysfunction suddenly occurred during the active phase of HLH. In each case, the findings on ECG, echocardiogram and left ventriculogram were compatible with ampulla cardiomyopathy. To our knowledge, this communication is the first to report cases of ampulla cardiomyopathy associated with HLH. Our cases suggest that HLH hypercytokinemia may have a role in causing ampulla cardiomyopathy.