Dieulafoy's Lesion of Jejunum: Presenting Small Bowel Mass and Stricture

Dieulafoy's lesion is an uncommon cause of gastrointestinal bleeding. Hemorrhage occurs through mucosal erosion from an abnormally dilated submucosal artery. Although Dieulafoy's lesion is usually located in the stomach, it may occur anywhere in the gastrointestinal tract. We report here on a case of jejunal Dieulafoy's lesion presenting as a mass and short segment stricture on CT and enteroclysis

Visceral Myopathy of Intestinal Pseudoobstruction

Intestinal pseudoobstruction is a syndrome complex caused by a variety of disorders of various etiology. It can be classified pathologically as visceral myopathy and visceral neuropathy. The sporadic form of visceral myopathy is characterized histologically by vacuolar degeneration and fibrosis of smooth muscle but differs from the familial form only by the absence of other affected family members. We studied 6 cases with intestinal pseudoobstruction classified as sporadic visceral myopathy. They were four boys and two girls, and were two neonates, two infants and two children. The duration of symptoms ranged from two days to two years. Two babies were dead from pneumonia and sepsis. Others were alleviated after surgical resection of the bowel. Both small and large intestines were found affected in autopsy cases. Histopathologic features were vacuolar degeneration of muscularis propria, disproportionate hypoplasia of outer muscle layer, abnormal muscle direction of muscularis propria, submucosal and/or interstitial fibrosis and extra muscle layering. It is presumed that a variety of histopathologic features accounts for visceral myopathy of intestinal pseudoobstruction

Prenatal selective serotonin reuptake inhibitor (SSRI) exposure induces working memory and social recognition deficits by disrupting inhibitory synaptic networks in male mice

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressant drugs in pregnant women. Infants born following prenatal exposure to SSRIs have a higher risk for behavioral abnormalities, however, the underlying mechanisms remains unknown. Therefore, we examined the effects of prenatal fluoxetine, the most commonly prescribed SSRI, in mice. Intriguingly, chronic in utero fluoxetine treatment impaired working memory and social novelty recognition in adult males. In the medial prefrontal cortex (mPFC), a key region regulating these behaviors, we found augmented spontaneous inhibitory synaptic transmission onto the layer 5 pyramidal neurons. Fast-spiking interneurons in mPFC exhibited enhanced intrinsic excitability and serotonin-induced excitability due to upregulated serotonin (5-HT) 2A receptor (5-HT2AR) signaling. More importantly, the behavioral deficits in prenatal fluoxetine treated mice were reversed by the application of a 5-HT2AR antagonist. Taken together, our findings suggest that alterations in inhibitory neuronal modulation are responsible for the behavioral alterations following prenatal exposure to SSRIs

Prognostic Factors and Clinical Outcomes of High-Dose Chemotherapy followed by Autologous Stem Cell Transplantation in Patients with Peripheral T Cell Lymphoma, Unspecified: Complete Remission at Transplantation and the Prognostic Index of Peripheral T Cell Lymphoma Are the Major Factors Predictive of Outcome

AbstractHigh-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) offers a rescue option for T cell lymphoma patients with poor prognosis. However, the effectiveness of HDT/ASCT in patients with various peripheral T cell subtypes, optimal transplant timing, and the prognostic factors that predict better outcomes, have not been identified. We retrospectively investigated the clinical outcomes and prognostic factors for HDT/ASCT in 64 Korean patients with peripheral T cell lymphoma, unspecified (PTCL-U) between March 1995 and February 2007. The median age at transplantation was 44 years (range: 15-63 years). According to the age-adjusted International Prognostic Index (a-IPI) and the prognostic index of PTCL (PIT), 8 patients (12.5%) were in the high-risk group and 16 (26.6%) had the 2-3 PIT factors, respectively. After a median follow-up of 29.7 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 53.0% ± 7.5% and 44.3% ± 7.0%, respectively. Univariate analysis showed that poor performance status, high lactate dehydrogenase (LDH) levels, high a-IPI score, high PIT classes, failure to achieve complete response (CR) at transplantation, and nonfrontline transplantation were associated with poor OS. Multivariate analysis showed that failure to achieve CR at transplantation (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.78-7.93) and 2-3 PIT factors (HR 3.76; 95% CI 1.02-5.42) were independent prognostic factors for OS. Failure to achieve CR at transplantation and high PIT are negative predictable factors for survival following HDT/ASCT in patients with PTCL-U

Clinical Outcomes and Prognostic Factors of Up-Front Autologous Stem Cell Transplantation in Patients with Extranodal Natural Killer/T Cell Lymphoma

AbstractLimited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy

TonEBP suppresses IL-10-mediated immunomodulation

TonEBP is a key transcriptional activator of M1 phenotype in macrophage, and its high expression is associated with many inflammatory diseases. During the progression of the inflammatory responses, the M1 to M2 phenotypic switch enables the dual role of macrophages in controlling the initiation and resolution of inflammation. Here we report that in human and mouse M1 macrophages TonEBP suppresses IL-10 expression and M2 phenotype. TonEBP knockdown promoted the transcription of the IL-10 gene by enhancing chromatin accessibility and Sp1 recruitment to its promoter. The enhanced expression of M2 genes by TonEBP knockdown was abrogated by antagonism of IL-10 by either neutralizing antibodies or siRNA-mediated silencing. In addition, pharmacological suppression of TonEBP leads to similar upregulation of IL-10 and M2 genes. Thus, TonEBP suppresses M2 phenotype via downregulation of the IL-10 in M1 macrophagesope