Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

Clinical and epidemiologic features of group a streptococcal pneumonia in Ontario,Canada

BACKGROUND: Since the 1960s, group A streptococcus (GAS) has accounted for less than 1% of cases of community-acquired pneumonia. During the past 2 decades there has been a resurgence of invasive GAS infection, but no large study of GAS pneumonia has been performed. METHODS: To determine the clinical and epidemiologic features of GAS pneumonia, we conducted prospective, population-based surveillance of all invasive GAS infection in residents of Ontario from January 1, 1992, through December 31, 1999. RESULTS: Of 2079 cases of invasive GAS infection, 222 (11%) represented GAS pneumonia. The incidence of GAS pneumonia ranged from 0.16 per 100 000 in 1992 to 0.35 per 100 000 in 1999. Most cases were community acquired (81%). Forty-four percent of nursing home-acquired cases occurred during outbreaks. The case fatality rate was 38% for GAS pneumonia, compared with 12% for the entire cohort with invasive GAS infection and 26% for patients with necrotizing fasciitis. The presence of streptococcal toxic shock syndrome (odds ratio, 19; 95% confidence interval, 8.4-42; P =.001) and increasing age (odds ratio per decade, 1.45; 95% confidence interval, 1.2-1.7; P<.001) were associated with fatal outcome. Time to death was rapid, with a median of 2 days despite antimicrobial therapy and supportive measures. CONCLUSIONS: Group A streptococcal pneumonia is a common form of invasive GAS disease but remains an uncommon cause of community-acquired pneumonia. Progression is rapid despite appropriate therapy. The incidence is similar to, and the case fatality rate higher than, that of necrotizing fasciitis.     

CPR-only survivors of out-of-hospital cardiac arrest: implications for out-of-hospital care and cardiac arrest research methodology

STUDY OBJECTIVE: There is little evidence that cardiopulmonary resuscitation (CPR) alone may lead to the resuscitation of cardiac arrest victims with other than respiratory causes (eg, pediatric arrest, drowning, drug overdose). The objective of this study was to identify out-of-hospital cardiac arrest survivors resuscitated without defibrillation or advanced cardiac life support. METHODS: This observational cohort included all adult survivors of out-of-hospital cardiac arrest of a cardiac cause from phases I and II of the Ontario Prehospital Advanced Life Support Study. During the study period, the system provided a basic life support/defibrillation level of care but no advanced life support. CPR-only patients were patients determined to be without vital signs by EMS personnel who regained a palpable pulse in the field with precordial thump or CPR only and then were admitted alive to the hospital. Six members of a 7-member expert review panel had to rate the patient as either probably or definitely having an out-of-hospital cardiac arrest, and a rhythm strip consistent with a cardiac arrest rhythm had to be present to be considered a patient. Criteria considered were witness status, citizen or first responder CPR, CPR duration, arrest rhythm and rate, and performance of precordial thump. RESULTS: From January 1, 1991, to June 30, 1997, 9,667 patients with out-of-hospital cardiac arrest were treated. The overall survival rate to hospital discharge was 4.6%. There were 97 apparent CPR-only patients admitted to the hospital. Application of the inclusion criteria yielded 24 CPR-only patients who had true out-of-hospital cardiac arrest and 73 patients judged not to have cardiac arrest. Of the 24 true CPR-only patients admitted to the hospital, 15 patients were discharged alive, 10 patients were witnessed by bystanders, and 7 patients were witnessed by EMS personnel. The initial arrest rhythm was pulseless electrical activity in 9 patients, asystole in 12 patients, and ventricular tachycardia in 3 patients. One patient with ventricular tachycardia converted to sinus tachycardia with a single precordial thump. CONCLUSION: CPR-only survivors of true out-of-hospital cardiac arrest do exist; some victims of out-of-hospital cardiac arrest of primary cardiac cause can survive after provision of out-of-hospital basic life support care only. However, many patients found to be pulseless by means of out-of-hospital evaluation likely did not have a true cardiac arrest. This has implications for the survival rates of most, if not all, previous cardiac arrest reports. Survival rates from cardiac arrest may actually be lower if one excludes survivors who never had a true arrest. The absence of vital signs by out-of-hospital assessment alone is not adequate to include patients in research reports or quality evaluations for cardiac arrest.     

CASE STUDIES OF THE TREATMENT OF HYPOTHYROIDISM BY MERIDIAN THEORY OF CHINESE MEDICINE

Some patients with hypothyroidism still remain symptom after prolonged treatment with thyroxine. Alternative treatment needs to be explored. The treatment is described as overlapof acupunture, supplemented with electric acupuncture, magnetic acupuncture, ear acupuncture, herbaltreatment, and acupressure of thyroid. The result of two case studies will be discussed in the presentation.The theoretical basis for the approach will also be explored.In Chinese medicine, hypothyroidismis often defined as spleen deficiency in the early stage and can be treated with ISRQ recipes (Invigorating the Spleen and Replenishing the Qi). In the chronic stage, hypothyroidism can be seen as kidneydeficiency and can be treated with KRR (Kidney Reinforcing Regimen). Hypthyroidism symptoms aresometimes diffcult to treat. However, TCM (Traditional Chinese Medicine) diagnosis and treatmentare based on an overall analysis of the illness according to patients' condition. After successful treamentof TCM, patients can stop taking Thy     

Identifying individuals with a reduced GFR using ambulatory laboratory database surveillance

The use of outpatient laboratory databases to identify people with a low GFR may be part of an effective strategy to increase their use of treatments to prevent kidney failure. All renal function data from 17 independent outpatient laboratories in Eastern Ontario were combined to determine the proportion of adults with at least one serum creatinine measurement during a 1-yr period. The detection rates of low GFR were measured using different algorithms, and what proportion of identified low GFR was transient was considered. Canadian census data were used to calculate rates and proportions. Renal function testing was common. Of the 1,090,000 adult residents, 32% of the entire population and 63% of seniors had at least one serum creatinine measured during the study year. Sixteen percent of the population (49% of those with tests performed) had at least one GFR <80 ml/min per 1.73 m2, 5% (16%) had at least one GFR <60 ml/min per 1.73 m2, and 0.6% (1.7%) had at least one GFR <30 ml/min per 1.73 m2. Low GFR were usually not transient: 68% of individuals with subsequent testing at least 30 d later had a similar or worse GFR. Ambulatory laboratory database case finding, particularly in older patients, seems to be a promising method for easily identifying large segments of the population with persistent reductions in GFR. Whether such identification leads to improved health outcomes warrants further study.     

The Ontario Cardiac Rehabilitation Pilot Project: Recommendations for health planning and policy

BACKGROUND: Expansion of cardiac rehabilitation (CR) could save both lives and costs by reducing illness and use of health care services. In February 2001, the Ontario Ministry of Health and Long-Term Care (the Ministry) announced a pilot project (the Pilot) to implement and evaluate a comprehensive, multifactoral model of CR service delivery at 17 centres across Ontario. OBJECTIVES: To design, coordinate and evaluate a coordinated model of CR service delivery, and to collect and evaluate an extensive set of clinical and administrative data. METHODS AND RESULTS: The Pilot was a large, province-wide observational investigation of a health service delivery model for CR and secondary prevention care. The present paper is the third in a three-part, policy-related series. In the present paper, the results of the evaluation of the service delivery model and the final health policy recommendations that were made to the Ministry in September 2002 are presented. CONCLUSIONS: Within approximately one year, 4922 patients were enrolled in the Pilot at participating sites throughout Ontario; 88% of sites implemented all elements of the comprehensive services model, either on-site or through internal/external partnerships, and 94% of sites implemented the multidisciplinary Pilot staffing model. Based on this rapid and near-total implementation of the Pilot model, it was concluded that the Pilot model of care was generalizable. Furthermore, regional coordination was achieved through operationalization of the coordinating centres' roles in quality management, regional planning and program development, education and outreach.