Up-regulation of PPARgamma in myocardial infarction

BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are key regulators for cardiac energy metabolism after myocardial injury. We hypothesized, that PPARs are regulated in myocardial infarction (MI) and their activity is modulated by angiotensin receptor blockers (ARBs). METHODS: Following induction of MI, male rats were treated with placebo or the ARB irbesartan for three weeks. PPARalpha, beta/delta and gamma protein expression and gene expression of PPAR target genes and glucose transporters were measured. PPARgamma-protein expression was analyzed by immunofluorescence. RESULTS: MI decreased LVP and dp/dtmax and increased LVEDP, this effect was counteracted by irbesartan. PPARalpha and PPARbeta/delta protein expression was not altered in MI and was not affected by irbesartan. PPARgamma protein content was increased in the infarcted area and localized to cardiac myocytes and fibroblasts. In parallel, expression of CTGF was increased 10-fold in the infarcted zone. PPAR target genes (CD36, MCAD, ACO and GLUT4) were significantly decreased in infarcted tissue, and this was unaffected by irbesartan. However, CD36 and ACO in the non-infarcted areas were up-regulated by irbesartan. CONCLUSION: Endogenous up-regulation of PPARgamma in MI is insufficient to counteract the decrease in metabolic genes, but parallels an increase in the profibrotic mediator CTGF. Irbesartan increases fatty acid oxidating enzymes after MI independent of PPARgamma regulation.     

Soft-tissue sarcomas of the chest wall: prognostic factors

OBJECTIVE: To evaluate factors that are predictive of outcome for patients with chest wall soft-tissue sarcomas. PATIENTS AND METHODS: A retrospective review of 55 surgically treated patients, from March 1964 to October 1996. RESULTS: The median age of the patients was 47.5 years (age range, 15 to 76.3 years), and 56.4% were men. The most common presenting symptom was chest wall mass in 29 patients (52.7%). The median symptom duration was 12 months. Tumor size ranged from 1 to 26 cm (median size, 9.7 cm). The most common histologic type of tumor was fibrosarcoma (52.7%). Twenty-three sarcomas (41.8%) were high-grade, and 32 sarcomas (52.8%) were low-grade. Of the 55 patients, 27 (49.1%) had previously been treated elsewhere (surgical resection, 23 patients; radiation therapy and surgery, 3 patients; chemoradiation therapy, 1 patient). Previously treated patients presented either with residual disease (10 cases) or recurrence of disease (17 cases). All 55 patients underwent surgical resection, 15 patients (27.3%) were treated by neoadjuvant chemoradiation therapy, and 2 patients were treated by adjuvant radiotherapy. Wide surgical resection was performed in 45 patients (81.8%), and marginal resection was performed in 10 patients (18.2%). The median follow-up time was 51.9 months. Local recurrence of disease developed in 6 patients, and metastases developed in 10 patients. The overall survival rates at 5 and 10 years were 87.3% and 79.3%, respectively. Tumor size < 5 cm and low histologic grade were determinants of better survival at univariate analyses. Multivariate analyses disclosed only histologic grade as an independent predictor for the risk of death. Disease-free survival rates at 5 and 10 years were 75.3% and 64.2%, respectively. Tumor size < 5 cm, performance of wide surgical resection, and low histologic grade were determinants of a better disease-free survival rate. Independent prognostic factors for disease-free survival were histologic grade and type of surgical resection. CONCLUSION: The clinical behavior of chest wall soft-tissue sarcomas is similar to that of extremity sarcomas. Thoracic wall soft-tissue sarcomas are best controlled by wide surgical resection.     

Successful embolization of hepatocelluar carcinoma with yttrium-90 glass microspheres prior to liver transplantation

We report a case of a patient with end-stage liver disease secondary to hepatitis C, complicated by a large hepatocellular carcinoma. Because of the size of the tumor exceeded the Milan criteria, he was not a can-didate for liver transplantation. However, after two treatments with yttrium-90 glass microsphere infu-sions, the tumor became smaller and the patient’s α-fetoprotein level dropped to normal range. He was listed for transplantation and subsequently received a deceased donor liver transplant. Two years after his transplantation, he remains tumor free and has normal α-fetoprotein levels. This is the first reported case in the literature of using yttrium-90 microspheres as a bridge to liver transplantation in a patient with a large hepatocellular carcinoma. This therapy should be considered in patients with cirrhosis and large hepatocellular carcinomas exceeding current size criterion, who would otherwise be good candidates for transplantation. Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Fort Lauderdale, Florida, April 14–17, 2005.     

The Use of Health Care Services by People With Diabetes in Rural Areas

Abstract: Current standards of health care support the view that diabetes can be managed in an outpatient setting, thereby preventing costly hospitalization. Yet, recent studies on access to care suggest that rural residents do not receive the same services for diabetes care as their urban counterparts. This study identifies differences in use for three types of services-hospital care, home health visits, and physician office visits—by geographical location. Using a sample of 6,698 Medicare beneficiaries, the authors performed multivariate analysis of variance to test the influence of geographical differences on each type of service use after controlling for the other types of service use and individual factors. Results showed significant differences among the geographical categories, with diabetic individuals in the most sparsely populated communities reporting fewer physician office visits and more home health visits than their urban counterparts. Because this pattern may have a negative impact on health outcomes, additional research is needed to determine the optimal array of services necessary to manage chronic diseases, such as diabetes, in rural areas.     

Nerve stimulator guided pudendal nerve blockversus general anesthesia for hemorrhoidectomy

PURPOSE: A randomized clinical trial was undertaken to test the hypothesis that patients receiving a nerve stimulator guided pudendal nerve block for hemorrhoidectomy would experience more effective and prolonged postoperative analgesia and shorter hospital stay compared to patients receiving general anesthesia. METHODS: This was a prospective randomized observer-blinded study. Following Ethics Committee approval and informed consent, 80 patients scheduled for hemorrhoidectomy were randomized to two groups of 40 patients each: general anesthesia alone, or nerve stimulator guided pudendal nerve block. Postoperative pain, the primary outcome variable of the study, was assessed by visual analogue scale scores at predetermined intervals during the postoperative period. Analgesic consumption, time to return to normal activities, patients' and surgeons' satisfaction, and duration of hospital stay were recorded. RESULTS: The guided pudendal nerve block group failed in three patients, requiring their conversion to general anesthesia. Otherwise, patients in the pudendal nerve block group experienced better postoperative pain relief at rest (P < 0.0001), on walking, sitting, and defecation (P < 0.001), reduced need for opioids (11/35 vs 32/37; P < 0.0001), a more rapid return to normal activities (7.2 vs 13.8 days; P < 0.0001) and also a shorter hospital stay (25/35 vs 3/37 outpatient cases; P < 0.0001) compared to the general anesthesia group. Pudendal nerve block was also associated with overall higher patient satisfaction compared to general anesthesia (30/35 vs 9/37; P < 0.0001). CONCLUSION: Nerve stimulator guided pudendal nerve block is associated with reduced postoperative pain, shortened hospital stay, and earlier return to normal activity compared to general anesthesia for hemorrhoidectomy.