Westerly Hospital

Abstract: Background Idiopathic hypereosinophilic syndrome involves a prolonged state of eosinophilia associated with organ dysfunction. It is of unknown cause. Recent reports of responses to imatinib in patients with the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause. Methods We treated 11 patients with the hypereosinophilic syndrome with imatinib and identified the molecular basis for the response. Results Nine of the 11 patients treated with imatinib had responses lasting more than three months in which the eosinophil count returned to normal. One such patient had a complex chromosomal abnormality, leading to the identification of a fusion of the Fip1-like 1 (FIP1L1) gene to the PDGFRα (PDGFRA) gene generated by an interstitial deletion on chromosome 4q12. FIP1L1-PDGFRα is a constitutively activated tyrosine kinase that transforms hematopoietic cells and is inhibited by imatinib (50 perce...

Abstract: FIP1L1-PDGFRalpha causes hypereosinophilic syndrome (HES) and is inhibited by the tyrosine kinase inhibitor imatinib (Gleevec). Imatinib is a potent inhibitor of ABL, ARG, PDGFRalpha, PDGFRbeta, and KIT and induces durable hematologic responses in HES patients. However, we observed relapse with resistance to imatinib as consequence of a T674I mutation in FIP1L1-PDGFRalpha, analogous to the imatinib-resistant T315I mutation in BCR-ABL. We developed a murine bone marrow transplant model of FIP1L1-PDGFRalpha-induced myeloproliferative disease to evaluate the efficacy of PKC412, an alternative inhibitor of PDGFRalpha, for the treatment of HES. PKC412 is effective for treatment of FIP1L1-PDGFRalpha-induced disease and of imatinib-induced resistance due to the T674I mutation. Our data establish PKC412 as molecularly targeted therapy for HES and other diseases expressing activated PDGFRalpha and demonstrate the potential of alternative kinase inhibitors to overcome resistance in target tyrosine kinases.

Abstract: Alcohol use disorders are a major public health concern. Despite the demonstrated efficacy of a number of different treatments for alcohol dependence, relapse remains a major problem. Healthy lifestyle changes may contribute to long-term maintenance of recovery, and interventions targeting physical activity, in particular, may be especially valuable as an adjunct to alcohol treatment. In this article, the authors discuss the rationale and review potential mechanisms of action whereby exercise might benefit alcohol dependent patients in recovery. They then describe the development of a 12-week moderate-intensity aerobic exercise program as an adjunctive intervention for alcohol dependent patients in recovery. Preliminary data from a pilot study (N = 19) are presented, and the overall significance of this research effort is discussed.

Abstract: Intervention to increase exercise in drug dependent patients represents a potentially useful yet unexplored strategy for preventing relapse. However, there are currently no established exercise interventions for use with this population. The purpose of this pilot study was to examine the feasibility of aerobic exercise as an adjunct to substance abuse treatment among drug dependent patients. Participants included 16 (31% female, 38.3 years old) drug dependent patients who participated in a 12-week, moderate-intensity aerobic exercise intervention. Participants attended a mean of 8.6 sessions (out of 12). Participants demonstrated a significant increase in percent days abstinent for both alcohol and drugs at the end of treatment, and those who attended at least 75% of the exercise sessions had significantly better substance use outcomes than those who did not. In addition, participants showed a significant increase in their cardiorespiratory fitness by the end of treatment. While preliminary, this study is one of the first to demonstrate the feasibility of incorporating aerobic exercise during drug abuse treatment. Future randomized control trials are a necessary next step to test the efficacy of a moderate-intensity aerobic exercise intervention as an adjunct to drug abuse treatment in this patient population.

Abstract: Limited ureteroscopy can be carried out in adults, using a regular pediatric cystoscope. This equipment is now available in many hospitals. Three illustrative cases are repoted.