Anti-cancer activity of withaferin A in B-cell lymphoma

Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear translocation in diffuse large B cell lymphomas and found that WA treatment resulted in a significant decrease in protein levels involved in B cell receptor signaling and cell cycle regulation. WA inhibited the activity of heat shock protein (Hsp) 90 as reflected by a sharp increase in Hsp70 expression levels. Hence, we propose that the anti-cancer effects of WA in lymphomas are likely due to its ability to inhibit Hsp90 function and subsequent reduction of critical kinases and cell cycle regulators that are clients of Hsp90.     

Large-volume Paracentesis versus Dialytic Ultrafiltration in the Treatment of Cirrhotic Ascites

We compared the clinical efficacy and safety of large-volumeparacentesis and dialytic ultrafiltration in the treatment ofrefractory ascites in cirrhotic patients. A group of cirrhoticsubjects (age 49–80 years) were randomly allocated toeither continuous paracentesis (1–1.5 1/hour) or dialyticultrafiltration until disappearance of ascites. Each patientwas maintained on bed rest, fluid restriction (1 1/day) anda low (25 mmol/day) sodium diet for 14 days. Five patients (threein the paracentesis group and two in dialytic ultrafiltrationgroup) developed massive ascites 3–5 months later, andreceived the crossover treatment. The average volume of fluidremoved was similar in the two groups (4.70±1.47 1 fordialytic ultrafiltration versus 4.69±1.84 1 for paracentesis),but the treatment period was significantly shorter with dialyticultrafiltration. The plasma creatinine significantly increasedthree days after paracentesis but did not increase in patientstreated with dialytic ultrafiltration. There was an initialfall in mean arterial pressure during the first two hours ofeither treatment; a further fall in blood pressure was observedwith paracentesis but not with dialytic ultrafiltration. Pretreatmentplasma renin activity was elevated, but was not altered by eithertreatment. Plasma atrial natriuretic peptide levels were inthe high-normal range before treatment. Paracentesis was associatedwith a delayed fall in plasma atrial natriuretic peptide, whiledialytic ultrafiltration induced a modest but significant rise.No complication was experienced with dialytic ultrafiltrationin the two weeks following treatment, but four of the eightpatients who underwent paracentesis had developed severe complications.Dialytic ultrafiltration of ascitic fluid is a safe procedurein cirrhotic patients. Large-volume paracentesis without intravenouscolloid reinfusion causes complications and carries the potentialrisk of reducing the effective intravascular volume.     

Barriers to the effective management of bipolar disorder: a survey of psychiatrists based in the UK and USA

Objective:  To identify and prioritize barriers, challenges, and unmet needs in the management of patients with bipolar disorder, as perceived by their psychiatrists.
Methods:  A total of 500 US- or UK-based psychiatrists were surveyed by telephone using a validated, semi-structured questionnaire. Both preidentified and participant-elicited barriers, challenges and unmet needs were ranked on a 0–6 point scale in four phases of management: I, entry into care; II, the manic/hypomanic phase; III, the depressive phase; and IV, the long-term/maintenance phase.
Results:  Education and support for patients and families as well as earlier referral to specialist care were the highest ranked needs at entry into care. During treatment of acute episodes and long-term management the highest ranked needs were for treatments with improved effectiveness and patient adherence, in addition to improved long-term safety in the maintenance phase. Patients with comorbid alcohol and/or substance use disorders, followed by patients with a rapid-cycling disease course, were rated as having the highest level of unmet need. Similarities were predominantly seen between the overall pattern of responses from UK- and US-based psychiatrists.
Conclusions:  The highest priority items across the spectrum of treatment related to the need for clinically effective therapeutic agents with broad efficacy and favorable tolerability. At the time of initial diagnosis, patient education, family support, and earlier referral to specialist care were the highest priority needs.     

Upper urinary tract calculi: extrusion into perinephric and periureteric tissues during percutaneous management

While the goal of percutaneous management of renal and ureteral calculi is stone extraction or disintegration, perforation of the renal pelvis or ureter may allow stones or stone fragments to become extruded during endourologic manipulations. The authors have encountered six such patients: two with renal and four with ureteral calculi. Three stones were extruded into the perinephric or periureteric tissues during nephroscopy, two during attempted dislodgement with a balloon catheter, and one during antegrade passage of a ureteral catheter. All patients were managed conservatively by means of nephrostomy drainage and, in the four cases of ureteral laceration, ureteral stenting. Follow-up study, ranging from 12 to 24 months, has documented a benign clinical and radiological course. No ureteral strictures have ensued. In the absence of infected urine, urothelial laceration with calculus extrusion appears to be a benign occurrence and may be managed conservatively.