The aim of this study was to elucidate the effects of long-term intake of leucine in dietary protein malnutrition on muscle protein synthesis and degradation. A reduction in muscle mass was suppressed by leucine-supplementation (1.5% leucine) in rats fed protein-free diet for 7 days. Furthermore, the rate of muscle protein degradation was decreased without an increase in muscle protein synthesis. In addition, to elucidate the mechanism involved in the suppressive effect of leucine, we measured the activities of degradation systems in muscle. Proteinase activity (calpain and proteasome) and ubiquitin ligase mRNA (Atrogin-1 and MuRF1) expression were not suppressed in animals fed a leucine-supplemented diet, whereas the autophagy marker, protein light chain 3 active form (LC3-II), expression was significantly decreased. These results suggest that the protein-free diet supplemented with leucine suppresses muscle protein degradation through inhibition of autophagy rather than protein synthesis.
We evaluated the treatment outcome of stereotactic radiosurgery (SRS) alone, allowing for salvage with repeat SRS or fractionated radiotherapy, for managing patients with brain metastases from non-small cell lung cancer (NSCLC). From October 1998 through November 2008, 84 patients with NSCLC metastatic to the brain were treated with linac SRS. The marginal dose of SRS ranged from 12 to 20 Gy. Twenty-one patients underwent salvage radiotherapy and repeat SRS was used for 12. The 1- and 5-year overall survival rates were 38% and 11%, respectively, and the median survival time was 9 months. The 1- and 2-year local control rates were 77% and 52%, respectively, and the median time of local control was 9 months. The most common cause of death was active extracranial disease, and central nervous system (CNS) failure was determined in 16%. Chronic CNS toxicity of grade 4 was observed in 2 patients. Uni- and multivariate analyses revealed that factors significantly affecting overall survival were the presence of active extracranial disease (P < 0.0001 and P = 0.003, respectively), performance status (P = 0.001 and P = 0.009, respectively), and number of brain metastases (P = 0.0003 and P = 0.019, respectively). There were 15 long-term survivors, surviving more than 2 years. A large proportion (87%) had a single brain metastasis initially and few intracranial distant metastases afterwards (20%). SRS alone allowing for salvage radiotherapy was effective for managing brain metastases and avoiding CNS failure from NSCLC. In consideration of appropriate prognostic factors and the so-called oligometastases situation for patient selection, the use of upfront whole brain radiotherapy might improve outcome.
A 75-year-old woman underwent Gamma Knife surgery (GKS) for a vestibular schwannoma. Eight years after GKS, she suffered sudden onset of headache. Computed tomography revealed diffuse subarachnoid hemorrhage around the cisterns of the posterior fossa. Right vertebral artery angiography showed an aneurysm arising from the lateral pontomedullary segment of the left anterior inferior cerebellar artery. The aneurysm was not located at a branching site. Trapping of the distal anterior inferior cerebellar artery aneurysm was performed, and the aneurysm was removed. The pathological features of this aneurysm are discussed. This aneurysm was diagnosed as a pseudoaneurysm pathologically. This is the first report of aneurysm formation with pathological findings following GKS for a vestibular schwannoma.
The authors have evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in patients with a diffuse thick subarachnoid hemorrhage (SAH). The present study examined 105 patients who underwent direct surgery within 48 hours of SAH and whose computerized tomography (CT) findings were classified as Fisher CT Group 3. Patients showing diffuse thick subarachnoid blood clots on CT with greater than 75 Hounsfield units (HU) were included in the tPA therapy group and those with below 75 HU comprised the control group. The surgical method was the same in both groups, and both groups had cisternal drainage instituted. On the day following the operation, the tPA group was given an intrathecal injection of tPA (2 mg), and this was continued for several days until all of the cisterns exhibited low density on CT scans. Follow-up angiography showed that 26 cases (87%) in the tPA group had no vasospasm, three (10%) had moderate vasospasm, and one (3%) had severe vasospasm. All four patients showing spasm on angiography were asymptomatic, and there were no cases of delayed ischemic neurological deficits (DIND). In contrast, there were 11 cases (15%) with DIND in the control group. In the tPA group, there was one case of SAH caused by drainage catheter removal, one with a small epidural hematoma, and one with subgaleal fluid accumulation; all of these were treated conservatively with favorable results. Overall, there were no infectious complications related to cisternal drainage and intrathecal injection of tPA. These results indicate that multiple intrathecal injections of small doses of tPA are effective and safe in preventing vasospasm. On the basis of this experience, the authors conclude that injection of 2 mg of tPA daily for 5 days (a total of 10 mg) is effective in preventing the development of vasospasm.
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