Search

Nitric oxide (NO), also known as endothelium-derived relaxing factor, is produced by endothelial nitric oxide synthase (eNOS) in the intima and by neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels. It dilates the arteries in response to shear stress, metabolic demands, pterygopalatine ganglion stimulation, and chemoregulation. Subarachnoid haemorrhage (SAH) interrupts this regulation of cerebral blood flow. Hemoglobin, gradually released from erythrocytes in the subarachnoid space destroys nNOS-containing neurons in the conductive arteries. This deprives the arteries of NO, leading to the initiation of delayed vasospasm. But such vessel narrowing increases shear stress, which stimulates eNOS. This mechanism normally would lead to increased production of NO and dilation of arteries. However, a transient eNOS dysfunction evoked by an increase of the endogenous competitive nitric oxide synthase (NOS) inhibitor, asymmetric dimethyl-arginine (ADMA), prevents this vasodilation. eNOS dysfunction has been recently shown to be evoked by increased levels of ADMA in CSF in response to the presence of bilirubin-oxidized fragments (BOXes). A direct cause of the increased ADMA CSF level is most likely decreased ADMA elimination due to the disappearance of ADMA-hydrolyzing enzyme (DDAH II) immunoreactivity in the arteries in spasm. This eNOS dysfunction sustains vasospasm. CSF ADMA levels are closely associated with the degree and time-course of vasospasm; when CSF ADMA levels decrease, vasospasm resolves. Thus, the exogenous delivery of NO, inhibiting the L-arginine-methylating enzyme (IPRMT3) or stimulating DDAH II, may provide new therapeutic modalities to prevent and treat vasospasm. This paper will present results of preclinical studies supporting the NO-based hypothesis of delayed cerebral vasospasm development and its prevention by increased NO availability.

Unlabelled: This paper discusses the arguments for and against radical tumor resection as a strategy for treatment of cerebral gliomas., Method: Data from the Glioma Outcome Project were analyzed to determine whether survival could be related to extent of resection in 666 patients treated by biopsy or resection for malignant cerebral gliomas., Findings: Consistent survival advantages were noted for those patients treated with resection., Interpretation: This observational study, although undoubtedly reflecting selection bias, provides data that support resection as a major factor in survival after surgery for malignant gliomas.

Studies of error and adverse events in medicine have brought a growing awareness of the extent of harm to patients. The psychology of human error strongly suggests that individual liability to error is strongly influenced by the conditions and organisation of the working environment and the nature of the task, in particular the complex and inherently uncertain judgements frequently made in medicine. Research into accidents in medicine and other high risk areas has lead to a much broader concept of causation, with less focus on individuals and more on pre-existing organisational factors. These ideas have been adapted to practical use in healthcare in the analysis of adverse events and in working towards developing safer systems of care. The final section of the paper summarises the implications of this approach for healthcare in terms of an overall systems approach, the need for basic information about clinical incidents, the benefits of systematic investigation and analysis, the nature of safety interventions, the need to study success as well as failure and the need to develop an open, safety aware culture in healthcare.