Hippocampal damage and cytoskeletal disruption resulting from impaired energy metabolism

To determine if impaired energy metabolism might contribute to some aspects of Alzheimer disease (AD), including the vulnerability of the CA1 region of the hippocampal formation and the altered cytoskeleton evident in neurofibrillary tangles, we examined the effects of metabolic poisons on neuronal damage and cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death, particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but sparing of axonal τ. MK-801 (a noncompetitive NMDA receptor antagonist) did not atenuate the lesions produced by intrahippocampal injection of malonate. MK-801, however, was effective against intrastriatal malonate. Acute systemic 3-NP resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but sparing of τ. The neuronal loss in CA1 was delayed as compared to striatum. Chronic intraventricular infusion of 3-NP produced a different pattern of neuronal damage. Loss of τ-1 immuno-reactivity was observed in CA3 and CA1 s. oriens, whereas MAP2 immunostaining was preserved. These results demonstrate that chronic and acute administration of metabolic inhibitors produce distinct patterns of neuronal damage and cytoskeletal disruption. The results further suggest a differential involvement of the NMDA receptor in malonate-induced neuronal damage in striatum as compared to the hippocampus. The pattern of neuronal damage and cytoskeletal disruption observed following acute metabolic impairment resembled some aspects of neurofibrillary pathology in AD, but did not result in τ hyperphosphorylation.     

Endoscopic laser vs open approach for cricopharyngeal myotomy.

OBJECTIVE: To illustrate the safety and efficacy of the endoscopic laser approach for cricopharyngeal myotomy (CPM) compared to the traditional transcervical approach. STUDY DESIGN AND SETTING: Retrospective chart review of 22 patients undergoing CPM from 1996 to 2003 at the Mayo Clinic, Jacksonville. RESULTS: The laser CPM technique was used in 14 patients, and an open approach in 8. The mean hospital stay and operative times were shorter for the laser group. Functional outcome analyses showed improvement in both groups. There were no major complications in the laser group, while 1 patient in the transcervical group had a pharyngocutaneous fistula. CONCLUSIONS: The laser technique is at least as effective as the transcervical approach for CPM to improve dysphagia symptoms in the properly selected patient, with a low risk of major complications. SIGNIFICANCE: In this report, we provide the reader with data to support the safety and efficacy of laser CPM. EBM rating: B-3b.     

维生素E有什么希望？

过去15年来，有关动脉粥样硬化的流行病学、基础生物学和实验研究均支持下述假设：抗氧化剂可通过抑制动脉壁低密度脂蛋白的氧化而抑制动脉粥样硬化的发生。这种作用机制可抑制胆固醇酯通过巨噬细胞清除受体在动脉斑块内发生病理性沉积。胆固醇酯病理沉积是一种可引起斑块破裂及心血管事件的过程。同样，生物机制亦已确定，癌基因可被抗氧化剂阻断。     

Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.

Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg x m(-2), primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.