Citations

Abstract Percutaneous cholecystostomy offers a potentially important therapeutic modality for critically ill patients with acute cholecystitis who represent a high risk for general anaesthesia. The aim of the study was to assess experience with percutaneous cholecystostomy in resolving the acute episode of cholecystitis without operative intervention. Twenty-two consecutive patients with a clinical diagnosis of acute cholecystitis underwent the procedure. All were at high risk for general anaesthesia, and all but one developed cholecystitis while hospitalized for another co-morbid condition; 14 were in an intensive care unit. Twenty-one of the 22 patients proved to have acute cholecystitis (11 acalculous, ten cholelithiasis). There were no acute technical complications. Toxaemia resolved in 17 of the 21 patients with acute cholecystitis. Acute cholecystitis failed to resolve in three patients; all died within 48 h from overwhelming generalized sepsis. One patient required emergency cholecystectomy for bile peritonitis when the cholecystostomy catheter became dislodged 24 h after placement. The 60-day mortality rate for the acalculous and calculous patient groups was 55 and 20 per cent, respectively. Only three interval cholecystectomies have been performed at a mean follow-up of 19 months. In conclusion, percutaneous cholecystostomy may be the procedure of choice for the management of acute cholecystitis in the very high-risk critically ill patient. If symptoms fail to resolve quickly, ongoing sepsis, cholangitis or gallbladder necrosis should be suspected.

Abstract Bcl family members Bcl-2, Bcl-xL, and Mcl-1, are frequently expressed and implicated in the survival of myeloma cells. Obatoclax (GX015-070) is a novel, small-molecule antagonist of the BH3-binding groove of the Bcl family of proteins. We show that GX015-070 inhibits the binding of Bak to Mcl-1, up-regulates Bim, induces cytochrome c release, and activates capase-3 in human myeloma cell lines (HMCLs), confirming the predicted mechanism of action. Consequently, GX015-070 potently inhibited the viability of 15 of 16 HMCLs (mean IC50 of 246 nM), including those resistant to melphalan and dexamethasone. In combination studies, GX015-070 enhanced the antimyeloma activity induced by melphalan, dexamethasone, or bortezomib. Sensitivity to GX015-070 correlated with the absence or near absence of Bcl-xL. Coculture with interleukin-6 or adherence to bone marrow stroma conferred modest resistance; however, it did not overcome GX015-070–induced cytotoxicity. Of importance, GX015-070 as a single agent induced potent cytotoxic responses against patient-derived tumor cells. GX015-070 inhibited normal bone marrow–derived colony formation; however, cytotoxicity to human blood lymphocytes was not observed. Taken together, these studies describe a novel BH3 mimic with selectivity for Mcl-1, and support the therapeutic application of GX015-070 for diverse neoplasias including multiple myeloma.

Objective: The five-factor model of personality was used to describe the correlates of smoking abstinence. Methods: Following treatment in the Mayo Clinic Nicotine Dependence Center, the six month abstinence status was determined by self-report. Sixteen months to 2.4 years following the initial treatment evaluation, and 10 months to 1.9 years after the abstinence status was determined, 475 patients were mailed a Neuroticism, Extraversion, Openness, Five-Factor Inventory questionnaire. Ninety-nine abstinent and 151 smoking patients returned a completed questionnaire. Results: Multivariate analysis showed that low scores on neuroticism and openness were associated with tobacco abstinence. In addition, high scores on neuroticism and low scores on agreeableness and conscientiousness were associated with predictors of poor outcome including greater number of cigarettes smoked per day, initiation of smoking prior to age 18, and a Fagerström Test for Nicotine Dependence score of ≥ 6. Conclusions: Personality characteristics as predictors of smoking abstinence following treatment warrant further investigation in prospective clinical trails. Treatment matching using personality profiling as a guide may be a valuable tool for improving abstinence rates following treatment for nicotine dependence.

To determine if dehydroepiandrosterone (DHEA) replacement improves insulin secretion, insulin action, and/or postprandial glucose metabolism, 112 elderly subjects with relative DHEA deficiency ingested a labeled mixed meal and underwent a frequently sampled intravenous glucose tolerance test before and after 2 years of either DHEA or placebo. Despite restoring DHEA sulphate concentrations to values observed in young men and women, the changes over time in fasting and postprandial glucose concentrations, meal appearance, glucose disposal, and endogenous glucose production were identical to those observed after 2 years of placebo. The change over time in postmeal and intravenous glucose tolerance test insulin and C-peptide concentrations did not differ in men treated with DHEA or placebo. In contrast, postmeal and intravenous glucose tolerance test change over time in insulin and C-peptide concentrations were greater (P < 0.05) in women after DHEA than after placebo. However, since DHEA tended to decrease insulin action, the change over time in disposition indexes did not differ between DHEA- and placebo-treated women, indicating that the slight increase in insulin secretion was a compensatory response to a slight decrease in insulin action. We conclude that 2 years of replacement of DHEA in elderly men and women does not improve insulin secretion, insulin action, or the pattern of postprandial glucose metabolism.

Background The Detect Supraventricular Tachycardia (Detect SVT) trial was a randomized single blind study in subjects receiving a dual chamber implantable cardioverter defibrillator (ICD). The primary goal was to evaluate whether dual chamber enhancements result in greater discrimination between supraventricular tachycardia (SVT) and ventricular episodes when compared to ventricular-only enhancements. Purpose The purpose of this report is to describe our experiences from an analytic perspective, including overall study design, the value of blinded episode review, and the statistical analysis plan. Methods The Detect SVT study was a parallel group study, with blinded central review of all arrhythmia episodes occurring over a six-month period. The primary response was the proportion of inappropriate detections (SVT episodes that are inappropriately classified as ventricular by the device). Results A parallel group design was essential as unplanned crossovers were very differential. The blinded review of episodes was a major use of resources, with over 2300 episodes observed. This review did not materially alter the findings, however, the avoidance of any perceived bias was a major strength. The value of collecting large numbers of episodes on a single subject was found to be minimal. A Kaplan–Meier analysis of the number of SVT episodes until first inappropriate detection was found to add additional information. Limitations The recommendations reported here relate to cardiac arrhythmia trials, or other studies with very similar endpoints. These observations are based on the results of a single trial and should be confirmed in other studies. Conclusions The parallel group design was essential, as was accounting for within-subject correlation in the analysis. The blinded review process was also important, but significant resources could be saved by closing-out episode collection after a fixed number of episodes. Lessons learned from the Detect SVT trial may prove useful to others designing trials in this active research area.

The Modern Technology of Radiation Oncology, Vol. 2, edited by Jacob Van Dyk, Medical Physics Publishing, 2005, ISBN‐10:1‐930524‐25‐0 (hard cover), list price $120 hard cover, $100 soft cover

The purpose of this study was to evaluate electronic portal imaging (EPI) as a means of identifying and correcting field displacement in patients with problematic external beam radiotherapy setups. Fourteen patients with problematic setups were identified for pretreatment daily EPI beam monitoring as part of a physician‐directed therapist intervention protocol. Pretreatment EPIs were used to realign fields as necessary to bring the setup within the physician‐prescribed tolerance level. For comparison, daily EPIs were available for 12 control patients who had no particular setup difficulties and for whom online beam realignment was not made. Anatomy‐matching software was used to measure setup variation along medial‐lateral, superior‐inferior, and anterior‐posterior axes. Online field realignment yielded a significant improvement when comparing initial and final setup variations. The mean standard deviation of setup displacement averaged over three axes was reduced from 6.4 mm to 3.1 mm after realignment. The final variation of protocol patients was comparable to that of control patients. In conclusion, EPI provided effective means to perform online beam realignment in a group of difficult‐to‐position patients. This procedure resulted in a reduction in setup displacement that was statistically significant, clinically relevant, and approached that of a more typical patient group.PACS number: 87.53.Oq

This manuscript presents a case of early stage squamous cell carcinoma of the left buccal mucosa treated with intensity‐modulated radiation therapy (IMRT) followed by a high‐dose rate (HDR) brachytherapy boost. With limited literature available on HDR mold (stent) radiotherapy for oral cancer, a discussion on the issues encountered during treatment planning and delivery may prove to be insightful for facilities faced with a similar challenge.PACS numbers: 87.53.Jw, 87.53.Tf, 87.59.Ci, 87.59.Fm