Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism

The anti-CD20 monoclonal antibody rituximab induces remission in 40% to 60% of patients with indolent B-cell lymphoma, but virtually all patients have relapses. We evaluated the efficacy of concurrent administration of another biologic agent, N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo. Concurrent 4HPR and rituximab administration prevented tumor progression of lymphoma-bearing mice in a minimal disease model (rituximab + 4HPR, 100% progression free; rituximab alone, 37.5% progression free, P =.01; 4HPR alone, 12.5% progression free, P <.01; controls, 0% progression free, P <.01). Combinations of 4HPR + rituximab exceeded the predicted 50% additive rate of disease control from each agent alone (P =.038). Administering 4HPR and rituximab to mice with established tumors induced complete responses (CRs) in 80% of animals compared with 20% to 40% CRs using either agent alone (P =.07), resulting in significantly improved survival. Tumors harvested from 4HPR + rituximab-treated mice displayed elevated caspase activation compared with untreated controls (P =.02). Adding a broad-spectrum caspase inhibitor in vivo fully abrogated the antitumor effects of 4HPR + rituximab (P =.05). These results establish the efficacy of 4HPR/rituximab combinations, confirm their caspase-mediated mechanism of action, and offer the potential for disease control with minimal toxicity for patients with B-cell malignancies.     

Development and validation of algorithms for heart failure patient care: a Delphi study

INTRODUCTION

Although heart failure (HF) management is available at primary and secondary care facilities in Malaysia, the optimisation of drug therapy is still suboptimal. Although pharmacists can help bridge the gap in optimising HF therapy, pharmacists in Malaysia currently do not manage and titrate HF pharmacotherapy. The aim of this study was to develop treatment algorithms and monitoring protocols for angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers and spironolactone based on extensive literature review for validation and utilisation by pharmacists involved in HF management.

METHODS

A Delphi survey involving 32 panellists from private and government hospitals that provide cardiac services in Malaysia was conducted to obtain a consensus of opinion on the treatment protocols. The panellists completed two rounds of self-administered questionnaires to determine their level of agreement with all the components in the protocols.

RESULTS

Consensus was achieved for most of the sections of the protocols for the four classes of drugs. The panellists’ opinions were taken into consideration when amending the components of the protocols that did not achieve consensus of opinion. Full consensus was achieved with the second survey conducted, enabling the finalisation of the drug titration protocols.

CONCLUSION

The resulting validated HF titration protocols can be used as a guide for pharmacists when recommending the initiation and titration of HF drug therapy in daily clinical practice. Recommendations should be made in collaboration with the patient’s treating physician, with concomitant monitoring of the patient’s response to the drugs.     

Role of Fibrin Glue as a Sealant to Esophageal Anastomosis in Cases of Congenital Esophageal Atresia with Tracheoesophageal Fistula

Objective The aim of this study was to characterize a successful approach for the management of infants with long-gap esophageal atresia (EA) with tracheoesophageal fistula (TEF). The goal was to preserve the native esophagus and minimize the incidence of esophageal anastomotic leaks using fibrin glue as a sealant over the esophageal anastomosis. Method A total of 52 patients were evaluated in this study. Only patients in whom, gap between the two ends of the esophagus was ≥ 2 cm were selected during January 2005 to January 2007. Patients were divided in two groups on the basis of block randomization. Group A comprised the patients in whom fibrin sealant was used as reinforcement on a primary end-to-end esophageal anastomosis; in group B, fibrin glue was not used. The two groups were compared in terms of esophageal anastomotic leak (EL), postoperative esophageal stricture (ES), and mortality. The statistical analysis was done using Fisher’s exact test and the chi-squared test. Result The number of anastomotic leaks in group A (glue group) was about one-fifth that in group B (no glue group). The incidence of ES was almost twice as high in group B as in group A. The mortality rate was almost threefold higher in group B (no-glue group). The higher incidence of EL and ES in group B compared to group A was statistically significant. Conclusion Thus, fibrin glue when used as an adjunct to esophageal anastomosis for primary repair of long-gap EA with TEF appears safe in the clinical setting and may lower the chances of esophageal leak and anastomosis-site strictures. Hence, it can diminish the mortality and morbidity of these patients.     

Electromyographic investigation of unstable patella before and after its realignment operation

Background:

Patellar dislocations are either due to superolateral contracture of the soft tissue or imbalance of the power between the vastus medialis (VM) and the vastus lateralis (VL). The imbalance of muscle power as an etiology of patellar dislocation has not been studied. Hence, we studied the recurrent, habitual and permanent dislocations of the patella with an electromyogram (EMG) of the vastus medialis, vastus lateralis, and pes anserinus, before and after realignment operations, to document the muscle imbalance and effectiveness of the realignment operation.

Materials and Methods:

An electromyographic investigation was carried out on the vastus medialis and vastus lateralis in nine recurrent, 20 habitual, and 13 permanent dislocations of the patella, before and after their realignment operations. Pes anserinus transposition, which acted as a medial stabilizer of the patella, was also investigated with an EMG study, to understand its role on patellar stability at 0°, 30°, 60°, 90°, 120°, 150°, and full flexion of the knee. The age of the patients varied from nine to 30 (mean 15) years. There were 24 males and 18 females. Twenty-six patellar dislocations were on the right and 16 were on the left side.

Results:

Electromyographic pictures reveal subnormal activity of the vastus medialis in all types of dislocations and similar activities of the vastus lateralis in permanent and habitual dislocations recorded pre operatively, which recovered to almost normal values postoperatively, at the mean one-year follow-up. Pes anserinus, which was used for medial stabilization of the patella after its realignment, maintained normal EMG activity before and after the operation.

Conclusion:

This study is significant for understanding the imbalance of muscle activities in patients with an unstable patella, which can be rectified without recurrence after pes anserinus transposition.     

Pain after mastectomy and breast reconstruction

Breast cancer is a potentially deadly disease affecting one in eight women. With the trend toward minimally invasive therapies for breast cancer, such as breast conserving therapies, sentinel node biopsies, and early treatments of radiation and chemotherapy, life expectancy after breast cancer has increased. However, pain after breast cancer surgery is a major problem and women undergoing mastectomy and breast reconstruction experience postoperative pain syndromes in approximately one-half of all cases. Patients post mastectomy and breast reconstruction can suffer from acute nociceptive pain and chronic neuropathic pain syndromes. Several preventative measures to control acute post operative pain and chronic pain states such as post mastectomy pain and phantom pain have been tried. This review focuses on the recent research done to control acute and chronic pain in patients receiving minimally invasive therapies for breast cancer, such as breast conserving therapies of mastectomies and breast reconstruction, sentinel node biopsies, and early treatments of radiation and chemotherapy.     

Potential hazards of contrast study diagnosis of esophageal atresia

Delay in the diagnosis of esophageal atresia (EA) is rare. We present a child with EA and distal tracheoesophageal fistula who was diagnosed 9 days from birth after a contrast study performed at the referring hospital. This article aims to highlight the potential hazards of using contrast to diagnose EA.