L. Gerard Toussaint

Survival of Cardiac Arrest after Aneurysmal Subarachnoid Hemorrhage

OBJECTIVE:Survival of cardiac arrest (CA) after aneurysmal subarachnoid hemorrhage (SAH) is poorly characterized. We analyzed the clinical course and outcome of patients who survived resuscitation for CA after aneurysmal SAH. METHODS:Medical records of all patients with acute SAH treated at Mayo Clinic between 1990 and 1997 were reviewed. Three hundred five consecutive patients with angiographically proven aneurysmal SAH presenting within 7 days of ictus were analyzed. CA was defined as a pulseless state, documented by medical personnel, for which resuscitation was performed. Outcome was measured with the Glasgow Outcome Scale score at longest follow-up (mean, 16 mo). RESULTS:Data from 11 patients (3.6%) who had 14 episodes of CA were analyzed. Six patients had CA before reaching the hospital and were successfully resuscitated. Nine of 14 CA episodes occurred at hemorrhage or rehemorrhage. No patient with in-hospital CA failed to be resuscitated. Overall mortality in patients who had CA (46%) was higher than that of patients without CA (15%; P = 0.019). Outcome for all patients who had CA (mean Glasgow Outcome Scale score, 2.5) was worse than for patients without CA (mean Glasgow Outcome Scale score, 3.9; P = 0.005). However, half of the survivors of CA after SAH were living independently with limited deficit at longest follow-up. CONCLUSION:Most cases of CA occur at the time of initial or recurrent SAH. Resuscitation for in-hospital CA is likely to be successful. Although CA after aneurysmal SAH is associated with significantly higher mortality, the outcome of survivors of CA is not worse than that for other patients after aneurysmal SAH.

Functional proteomics analysis of GTPase signaling networks.

Publisher Summary This chapter discusses the functional proteomics analysis of GTPase signalling networks. Posttranslational modifications of GTPase have been found to be an essential component in GTPase action. Protein kinases are critical upstream and downstream regulators of GTPase signals. Thus, sensitive methods to assess targets of lipid modification, kinase levels, activation, and phosphorylation sites are required. Most importantly, multiprotein complexes, not individual proteins, are the most physiologically relevant mediators of signal transduction. Therefore, methods are needed to isolate native complexes from biologically appropriate cells and to identify the individual components. The chapter also describes the technique of farnesyltransferase inhibitors (FTIs) and prometic analysis. Potential applications of proteomics technology in Ras family biology include (1) determining the proteins that are activated in a given cell type after Ras transformation, including both immediate downstream effectors and elements further downstream not detectable by yeast two-hybrid, coimmunoprecipitation, or other analyses), (2) ascertaining the particular set of GEF (GTP/GDP exchange factor)/GTPase pairs or GTPase/effector pairs interacts in a given cell, (3) identifying individual components in a multiprotein signaling complex, including both signaling and scaffolding proteins, and (4) determining the consequences of inhibiting the function of Ras family or other signaling molecules to identify their mechanism of action. The chapter concludes with a a discussion on analysis of proteins from two-dimensional polyacrylamide.

Disseminated enterogenous cells at the cervicomedullary junction causing communicating hydrocephalus

The authors present a unique case of a patient with communicating hydrocephalus and repeated ventriculoperitoneal shunt obstructions resulting from mucin-secreting enterogenous cell deposits at the cervicomedullary junction. Pathological examinations revealed that these cellular deposits lacked characteristic cystic architecture and the patient had no history of previous cyst with dissemination. Because of the repeated shunt obstructions and inability to surgically resect the lesion in its entirety, the authors elected radiation therapy to the cervicomedullary junction, encompassing the radiological abnormality. As of this writing, the patient has remained at neurological baseline and has not required further shunt revisions for obstruction.

Farnesyltransferase and Geranylgeranyltransferase Inhibitors

Since 1982, when mutated and oncogenic forms of ras genes were first identified in human tumor cells, their protein products have attracted considerable interest as a target for anticancer drug development. Researchers were inspired to delineate the functions of Ras proteins in normal cells and to determine how mutated Ras proteins were altered in these functions. The impressive accumulation of information about the genetics, biochemistry, biology, and structure of Ras proteins over the last 17 years has provided important clues to how anti-Ras drugs may be developed.