SPDEF： a molecular switch for E-cadherin expression that promotes prostate cancer metastasis

In order to design effective therapies for prostate cancer, a clear understanding of mechanisms that contribute to various components of prostate cancer progression is necessary. Study of metastasis suppressor genes, i.e., genes that can inhibit metastasis, is an important field of study that can lead to identification of therapeutic targets to diminish metastasis.     

ERCP via gastrostomy vs. double balloon enteroscopy in patients with prior bariatric Roux-en-Y gastric bypass surgery

Background

Roux-en-Y gastric bypass (RYGB) is the most common bariatric surgery. The performance of ERCP in bariatric RYGB is challenging due to the long Roux limb. We herein compared the indications and technical outcomes of ERCP via percutaneous gastrostomy (GERCP) and double balloon enteroscopy (DBERCP) for patients with prior bariatric RYGB anatomy.

Methods

Between December 2005 and November 2011, consecutive ERCP patients who had undergone RYGB were identified using a prospectively maintained electronic ERCP database. Medical records were abstracted for ERCP indications and outcomes. In most cases, the gastrostomy was done by either laparoscopic or open surgery and allowed to mature at least 1 month before performing ERCP. The choice of route for ERCP was at discretion of managing physician.

Results

Forty-four patients (F = 42) with GERCP and 28 patients (F = 26) with DBERCP were identified. The mean age was younger in GERCP than DBERCP (44.8 vs. 56.1, p < 0.001). GERCP patients were more likely to have suspected sphincter of Oddi dysfunction (77 %) as the primary indication whereas DBERCP was suspected CBD stone (57 %). The mean total number of sessions/patient in GERCP and DBERCP was 1.7 ± 1.0 and 1.1 ± 0.4, respectively (p = 0.004). GERCP access to the major papilla was successful in all but two (97 %), whereas duct cannulation and interventions were successful in all. In DBERCP, the success rate of accessing major papilla, cannulation and therapeutic intervention was 78, 63, 56 %, respectively. There was one (3.1 %) post-ERCP pancreatitis in DBERCP. Complications occurred in 11 GERCP procedures (14.5 %) and 10 were related to the gastrostomy. This was significantly higher than that of DBERCP (p = 0.022).

Conclusions

GERCP is more effective than DBERCP in gaining access to the pancreatobiliary tree in patients with RYGB, but it is hindered by the gastrostomy maturation delay and a higher morbidity. Technical improvements in each method are needed.     

Management of Primary Gastrointestinal Non-Hodgkin Lymphomas: a Population-Based Survival Analysis

Introduction

Primary gastrointestinal non-Hodgkin lymphomas (PGINHL) are a heterogeneous group of rare GI malignancies with limited data to guide management. This study describes management of PGINHL in a population-based registry and aims to determine the association between receipt of surgery and long-term survival.

Methods

All adults diagnosed with PGINHL over 27 years in the Surveillance, Epidemiology, and End Results were identified (excluding mucosa-associated lymphoid tissue lymphomas). Demographic and clinical characteristics were assessed. Survival was compared using the log-rank method. Cox hazard modeling was used to determine independent prognostic factors.

Results

We identified 16,129 patients. The majority were of gastric origin and had diffuse large B cell histology. Surgery was performed in 46.9 % of patients, not recommended in 41.8 % and recommended but not performed in 10.1 %. Overall 1-year and 5-year survival rates were 65.6 and 35.6 %, respectively. Patients undergoing surgery had a 5-year survival of 43.6 % compared to 34.8 % for whom surgery was recommended but not performed (p?<?.0001), (receipt of chemotherapy not available). Female gender, gastric location, follicular or mantle cell histology, and radiation therapy were associated with improved survival.

Conclusions

Nearly 50 % of PGINHL patients underwent surgery. Surgery was not associated with improved survival. More prospective, case-matched studies are needed to guide management.

     

Fibrillary glomerulopathy secondary to light chain deposition disease in a patient with monoclonal gammopathy

The pathologic manifestations of renal diseases related to monoclonal plasma cell dyscrasia include light chain deposition disease, the AL type of amyloidosis, and myeloma cast nephropathy. Light chain deposit disease (LCDD) is an uncommon condition in which monoclonal light chains are deposited in the glomeruli, tubules, and vessels causing varying degree of damage. We report a case of LCDD coincident with fibrillary glomerulonephropathy (FGN) in a 73-yr-old man with a diagnosis of monoclonal gammopathy of undetermined significance who presented with progressive renal insufficiency and mild proteinuria. The serum kappa light chain level was markedly raised. Immunofluorescent stains showed IgG along with C3 and kappa staining in glomeruli, but lambda staining was negative. Electron microscopic studies revealed diffuse punctuate-type deposits along the subendothelial areas. There were also scattered randomly oriented fibrils with a mean fibril thickness of 15-25 nm seen mainly in the glomerular mesangium, consistent with FGN. The congo red stain was negative on the histologic section. The present case illustrates that LCDD can progress to develop FGN in a patient with monoclonal gammopathy.     

A review of suicide prevention programs and training policies for pharmacists

Objectives

The availability of suicide prevention training programs for pharmacists is unknown and may depend on state training requirements. This study’s objectives were to: 1) report state training requirements for pharmacist suicide education; and 2) describe educational resources that are available to prepare pharmacists for interactions with patients at risk of suicide.

A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy

Evidence suggests that inertial cavitation plays an important role in the renal injury incurred during shock-wave lithotripsy. However, it is unclear how tissue damage is initiated, and significant injury typically occurs only after a sufficient dose of shock waves. Although it has been suggested that shock-induced shearing might initiate injury, estimates indicate that individual shocks do not produce sufficient shear to do so. In this paper, we hypothesize that the cumulative shear of the many shocks is damaging. This mechanism depends on whether there is sufficient time between shocks for tissue to relax to its unstrained state. We investigate the mechanism with a physics-based simulation model, wherein the basement membranes that define the tubules and vessels in the inner medulla are represented as elastic shells surrounded by viscous fluid. Material properties are estimated from in-vitro tests of renal basement membranes and documented mechanical properties of cells and extracellular gels. Estimates for the net shear deformation from a typical lithotripter shock (approximately 0.1%) are found from a separate dynamic shock simulation. The results suggest that the larger interstitial volume (approximately 40%) near the papilla tip gives the tissue there a relaxation time comparable to clinical shock delivery rates (approximately 1 Hz), thus allowing shear to accumulate. Away from the papilla tip, where the interstitial volume is smaller (approximately 20%), the model tissue relaxes completely before the next shock would be delivered. Implications of the model are that slower delivery rates and broader focal zones should both decrease injury, consistent with some recent observations.     

Methylphenidate administration alters vesicular monoamine transporter-2 function in cytoplasmic and membrane-associated vesicles

In vivo methylphenidate (MPD) administration increases vesicular monoamine transporter-2 (VMAT-2) immunoreactivity, VMAT-2-mediated dopamine (DA) transport, and DA content in a nonmembrane-associated (referred to herein as cytoplasmic) vesicular subcellular fraction purified from rat striatum: a phenomenon attributed to a redistribution of VMAT-2-associated vesicles within nerve terminals. In contrast, the present study elucidated the nature of, and the impact of MPD on, VMAT-2-associated vesicles that cofractionate with synaptosomal membranes after osmotic lysis (referred to herein as membrane-associated vesicles). Results revealed that, in striking contrast to the cytoplasmic vesicles, DA transport velocity versus substrate concentration curves in the membrane-associated vesicles were sigmoidal, suggesting positive cooperativity with respect to DA transport. Additionally, DA transport into membrane-associated vesicles was greater in total capacity in the presence of high DA concentrations than transport into cytoplasmic vesicles. Of potential therapeutic relevance, MPD increased DA transport into the membrane-associated vesicles despite rapidly decreasing (presumably by redistributing) VMAT-2 immunoreactivity in this fraction. Functional relevance was suggested by findings that MPD treatment increased both the DA content of the membrane-associated vesicle fraction and K(+)-stimulated DA release from striatal suspensions. In summary, the present data demonstrate the existence of a previously uncharacterized pool of membrane-associated VMAT-2-containing vesicles that displays novel transport kinetics, has a large sequestration capacity, and responds to in vivo pharmacological manipulation. These findings provide insight into both the regulation of vesicular DA sequestration and the mechanism of action of MPD, and they may have implications regarding treatment of disorders involving abnormal DA disposition, including Parkinson's disease and substance abuse.