N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However, this deficit was not ameliorated by NAC, implying that the therapeutic effect of NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced excitotoxicity. Assessment of mitochondrial function in the striatum and cortex revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific to the striatum. This deficit was rescued by chronic treatment with NAC. There was a selective increase in markers of oxidative damage in mitochondria, which was rescued by NAC. In conclusion, NAC is able to delay the onset of motor deficits in the R6/1 model of Huntington's disease and it may do so by ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential therapeutic agent in HD. Furthermore, our data suggest that NAC may also have broader antidepressant efficacy.

An updated national survey on seclusion and restraint.

A survey of the use of seclusion and restraint during 1994 was conducted at 124 state psychiatric hospitals to update data from a survey of 108 such hospitals conducted for 1991. Rates of patients' placement in seclusion and restraint, hours spent in placement, and discrete incidents of seclusion and restraint were examined. The 1994 results were highly similar to those for 1991. Smaller hospitals providing acute care had higher rates of seclusion and restraint than their larger counterparts providing chronic care. Small positive correlations were found between seclusion and restraint and between the proportion of beds occupied by patients committed as criminally insane and the use of restrictive procedures.

A national survey on seclusion and restraint in state psychiatric hospitals.

OBJECTIVES: State psychiatric hospitals across the U.S. were surveyed to develop national normative data on the incidence of seclusion and restrain and of injuries to patients and staff resulting from aggression by patients. METHODS: A survey instrument was sent to 225 state hospitals requesting information for a one-year period on the number of patients placed in seclusion or restraint, the number of discrete incidents of seclusion and restraint, the number of hours patients spent in seclusion or restraint, and the number of injuries to patients and staff attributable to aggression by patients. Rates of seclusion, restraint, and injuries were calculated to control for variation in hospital censuses. Percentile ranks for the various rates were calculated to allow hospitals to compare their rates. RESULTS AND CONCLUSIONS: A total of 101 state hospitals in 44 states and the District of Columbia returned the survey. In general, smaller hospitals had higher rates of seclusion and restraint. However, large standard deviations in the mean rates suggested considerable variability between hospitals in the sample. Small positive correlations between rates of seclusion and rates of restraint suggested that the hospitals did not use of the two interventions exclusively.

Thin-walled cavities, cysts, and pneumothorax in Pneumocystis carinii pneumonia: further observations with histopathologic correlation.

Thin-walled pulmonary cystic lesions were found in five immunocompromised patients, four with acquired immunodeficiency syndrome (AIDS). Four patients had Pneumocystis carinii pneumonia (PCP), and one had pulmonary lesions and disseminated P carinii infection. Two patients demonstrated P carinii within necrotizing, thin-walled, smaller intraparenchymal cavities lined by organisms, exudate, and chronic inflammation. Larger, typically apical and subpleural cysts, lined by fibrosis and/or alveolar parenchyma with little inflammation, were also found during acute episodes. The larger subpleural cysts can arise via rupture of intraparenchymal necrotizing cavities into the subpleural area. Pneumothorax in the four patients with AIDS could not be cured by close thoracostomy drainage; all required pleurodesis. The cysts persisted in cases that were followed up. All cysts were more obvious and numerous with computed tomography (CT), especially with 1.5-mm collimation. CT may be indicated in immunocompromised patients with unexplained pneumothorax or when tube thoracostomy has failed and surgery is being considered, as it can positively influence the operative approach.

Selective coronary arteriography in infants and children.

The recent increase in incidence of Kawasaki disease with attendant coronary artery aneurysms spurred our interest in developing a technique for selective coronary arteriographic examination of infants and children. Right and left coronary artery catheters were shaped according to the aortic root diameters and ascending aorta lengths predicted from the patient's heights. Thirty-eight studies were done in 34 patients who were 7 months to 18 years of age (median 3.2 years) and no permanent sequelae resulted. Advantages of the use of selective coronary arteriography include the ability to visualize stenoses, important branches, and intercoronary anastomoses. The technique is also useful in evaluation of anomalous coronary arteries, myocardial ischemia, and coronary artery distribution before right ventricular outflow tract reconstruction.