Ibuprofen for neuroprotection after cerebral ischemia

ObjectiveIbuprofen has been shown to reduce cerebral ischemic injury, such as may occur after deep hypothermic circulatory arrest. We investigated whether ibuprofen has direct protective effects against excitotoxic neuronal injury, as may be seen after cerebral ischemia, by using a cell culture model.MethodsMixed cortical cultures containing neuronal and glial cells were prepared from fetal mice at 13 to 15 days gestation, plated on a layer of confluent astrocytes from 1- to 3-day-old postnatal pups. Near-pure neuronal cultures containing less than 5% astrocytes were obtained from mice of the same gestational stage. Slowly triggered excitotoxic injury was induced at 37°C by 24-hour exposure to 12.5 μmol/L N-methyl-D-aspartate or 50 μmol/L kainate. Neuronal death was quantified by release of lactate dehydrogenase from damaged cells. Data were analyzed using 1-way analysis of variance with Tukey post hoc multiple comparisons.ResultsIn mixed cultures, ibuprofen concentrations of 25 μg/mL, 50 μg/mL, and 100 μg/mL all significantly reduced N-methyl-D-aspartate–induced neuronal cell death from 74.5% to 56.1%, 38.7%, and 12.3%, respectively, revealing a strong dose response (P < .001). In near-pure cultures, ibuprofen at a concentration of 25 μg/mL failed to protect neurons, indicating that the neuroprotective effects of ibuprofen require interaction with glial cells. Furthermore, ibuprofen at 100 μg/mL was not protective against neuronal cell death induced by kainate exitotoxicity in near-pure culture but was effective in mixed cultures.ConclusionIbuprofen provides neuroprotection through glial cells against excitotoxic neuronal injury caused by glutamatergic excitotoxicity after cerebral ischemia as demonstrated by reduced neuronal cell death in mixed cell cultures. Further studies are needed to evaluate the potential of ibuprofen to reduce neurologic injury in patients experiencing an hypoxic/ischemic insult

Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation

AbstractObjective: Low-velocity and nonlaminar flow patterns in the Fontan circulation, as well as abnormal liver function in some patients, may partly account for the coagulation abnormalities seen. We examined (1) coagulation factor abnormalities before and after the Fontan procedure and (2) regional coagulation factor abnormalities in the Fontan circulation. Methods: Levels of factors V, VII, VIII, X, antithrombin III, prothrombin fragment F1+2, protein C, and protein S were measured in 2 groups of patients: In 14 patients undergoing the Fontan procedure, blood was analyzed before the operation and 5 days after the operation (group 1). The median age in this group was 3.2 years. In 10 patients who had undergone the Fontan procedure, cardiac catheterization was performed and samples were taken from the femoral vein, inferior vena cava, right atrium, and pulmonary artery (group 2). The median age in this group was 6.2 years and the median follow-up from the Fontan procedure was 4.1 years. Results: In group 1 a significant increase was noted postoperatively in the concentration of factor VIII (P < .001), factor X (P < .001), and prothrombin fraction F1+2 (P < .001). A significant decrease in the levels of antithrombin III (P < .001), protein C (P < .004), and protein S (P < .02) was also found. The increase in factors VIII and X persisted at 4 years' follow-up in group 2 patients. In group 2, no significant regional differences were observed between the coagulation factors measured at different sites. Conclusions: There is an increased tendency toward coagulation after the Fontan procedure. A prothrombotic state is supported by thrombin generation associated with reduced antithrombin III concentration. This increase in coagulation may contribute to the early and late risks of thromboembolism observed after the Fontan procedure. We did not find any regional differences in coagulation abnormalities in patients late after the Fontan procedure. Therefore, the mechanisms and causes of the coagulation abnormalities remain unclear. (J Thorac Cardiovasc Surg 2000;120:778-82

Psychosocial Factors Associated with Breast Cancer Patients

Breast Cancer is the most complex treatment in the present scenario. When the patient is diagnosed with breast cancer, it affects patients' psychosocial condition. During the treatment process, patients suffer from depression, loss of hope, stress and other associated psychological issues. This study suggests that psychosocial factors are highly significant for persons with breast cancer. This paper also discusses the methodology of the study, level of psychological factors and provide recommendations for the health care institution and health care professionals focusing on patients' mental health aspects

Internationalism as A Current in The Peace Movement: A Symposium

Internationalism as A Current in The Peace Movement: A Symposiu

Cavopulmonary assist: Long-term reversal of the Fontan paradox

Objective Fontan circulatory inefficiency can be addressed by replacing the missing subpulmonary power source to reverse the Fontan paradox. An implantable cavopulmonary assist device is described that will simultaneously reduce systemic venous pressure and increase pulmonary arterial pressure, improving preload and cardiac output, in a univentricular Fontan circulation on a long-term basis. Methods A rotary blood pump that was based on the von Karman viscous pump was designed for implantation into the total cavopulmonary connection (TCPC). It will impart modest pressure energy to augment Fontan flow without risk of obstruction. In the event of rotational failure, it is designed to default to a passive flow diverter. Pressure-flow performance was characterized in vitro in a Fontan mock circulatory loop with blood analog. Results The pump performed through the fully specified operating range, augmenting flow in all 4 directions of the TCPC. Pressure rise of 6 to 8 mm Hg was readily achieved, ranging to 14 mm Hg at highest speed (5600 rpm). Performance was consistent across a wide range of cardiac outputs. In stalled condition (0 rpm), there was no discernible pressure loss across the TCPC. Conclusions A blood pump technology is described that can reverse the Fontan paradox and may permit a surgical strategy of long-term biventricular maintenance of a univentricular Fontan circulation. The technology is intended for Fontan failure in which right-sided circulatory inefficiencies predominate and ventricular systolic function is preserved. It may also apply before clinical Fontan failure as health maintenance to preempt the progression of Fontan disease

Surgical management of subaortic obstruction in single left ventricle and tricuspid atresia

Subaortic obstruction caused by either a restrictive bulboventricular foramen in single left ventricle with an outflow chamber or by a restrictive ventricular septal defect in tricuspid atresia with transposition of the great arteries can lead to a hypertrophied, noncompliant ventricle and excessive pulmonary blood flow. This combination is disadvantageous to potential Fontan procedure candidates because they are dependent on good ventricular function and low pulmonary vascular resistance for survival.The results of surgical procedures to directly or indirectly relieve significant subaortic obstruction (gradient 30 mm Hg) in 24 patients, 16 with single left ventricle and 8 with tricuspid atresia, were reviewed. Four patients had a left ventricular apex to descending aorta valved conduit; none survived. Seven patients had resection of subaortic tissue; four survived and four developed heart block at surgery. Adequate gradient relief was evident in only one of the four survivors. Thirteen patients had a main pulmonary artery to ascending aorta anastomosis or conduit; six survived. AH survivors had adequate gradient relief. The overall survival was 42% (10 of 24). None of seven patients with a subaortic gradient >75 mm Hg survived.These data show that: 1) Surgical relief of established subaortic obstruction in patients with single left ventricle and tricuspid atresia carries a high mortality rate, especially if the subaortic gradient is >75 mm Hg. 2) The best procedure appears to be the pulmonary artery to ascending aorta anastomosis. 3) A clearer understanding of the factors leading to the development of significant subaortic obstruction is necessary to prevent it or to devise improved therapeutic strategies

732-1 An Institutional Experience with Second and Third Stage Palliative Procedures for Hypoplastic Left Heart Syndrome: The Impact of the Bidirectional Cavopulmonary Shunt

We reviewed 71 consecutive pts who underwent stage II and III operations following stage I palliation for hypoplastic left heart syndrome (HLHS) at our institution since 1983. 6 surgeons participated in the care of these pts. Follow-up is 97% complete. We examined 17 potential risk factors for mortality, including preoperative anatomic and physiologic factors, and procedural features of the stage II operation. Multivariate analysis revealed that the only significant risk factor for stage II mortality was the performance of a non-fenestrated completion Fontan procedure (p&lt;0.001). There were 9 hospital deaths (69%) in the 13 pts undergoing the Fontan procedure at stage II. In contrast, 49 pts underwent bidirectional cavopulmonary shunting (47) or hemi-Fontan procedure(2) as an intermediate step to the Fontan procedure with 4 (8%) early deaths. The first bidirectional cavopulmonary shunt was performed in this population in 1988. Median age at this stage II procedure was 8.4 months. Surgical augmentation of the pulmonary arteries was performed in 18 (37%) pts at the time of stage II surgery and was not associated with increased operative risk. Also, HLHS anatomic subtype was not a risk factor for stage II mortality or pre-stage III attrition. There have been 2 (4%) intermediate deaths prior to the performance of a stage III procedure, which at our institution is the fenestrated Fontan procedure. This has been performed in 25 pts at a median age of 30 months with 1 early death and no mortality at a median follow-up of 22 months. There are presently 34 HLHS pts who have modified Fontan anatomy following a course of surgical palliation performed entirely at this institution. Follow-up in this group ranges up to 92 months, with a median of 28 months. 33 of these patients are NYHA class 1 or 2.2 pts have required pacemaker implantation, but there have otherwise been no surgical reinterventions in pts who have completed palliation. We conclude that the incorporation of the bidirectional cavopulmonary shunt into a course of surgical palliation for HLHS has dramatically reduced mortality in this challenging group of pts, allowing them to undergo the modified fenestrated Fontan procedure with low operative mortality and good intermediate outcome

Interaction of temperature with hematocrit level and pH determines safe duration of hypothermic circulatory arrest

AbstractObjectivePrevious studies have demonstrated that both hematocrit level and pH influence the protection afforded by deep hypothermic circulatory arrest. The current study examines how temperature modulates the effect of hematocrit level and pH in determining a safe duration of circulatory arrest. The study also builds on previous work investigating the utility of near-infrared spectroscopy as a real-time monitor of cerebral protection during circulatory arrest.MethodsSeventy-six piglets (9.3 ± 1.2 kg) underwent circulatory arrest under varying conditions with continuous monitoring by means of near-infrared spectroscopy (hematocrit level of 20% or 30%; pH-stat or alpha-stat strategy; temperature of 15°C or 25°C; arrest time of 60, 80, or 100 minutes). Neurologic recovery was evaluated daily by a veterinarian, and the brain was fixed in situ on postoperative day 4 to be examined on the basis of histologic score in a blinded fashion.ResultsMultivariable analysis of total histologic score revealed that higher temperature, lower hematocrit level, more alkaline pH, and longer hypothermic circulatory arrest duration were predictive of more severe damage to the brain (P < .01). Regression modeling revealed that higher temperature exacerbated the disadvantage of a lower hematocrit level and longer arrest times but not pH strategy. Normalized oxyhemoglobin nadir time, derived from near-infrared spectroscopy, was positively correlated with neurologic recovery on the fourth postoperative day and with total histologic injury score (P < .0001).ConclusionHematocrit level and pH, as well as temperature, determine the safe duration of hypothermic circulatory arrest. Near-infrared spectroscopy is a useful real-time monitor of safe duration of circulatory arrest

Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis

Pharmacologic treatments for Alzheimer’s disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July) for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs’ modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively). Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine