Involvement of Pca1 in ROS-mediated apoptotic cell death induced by alpha-thujone in the fission yeast (Schizosaccharomyces pombe).

Alpha-thujone, widely used in beverages (1-5 mg/kg), is known to have cytotoxic effects, but the mode of action and the role of potential apoptotic proteins in yeast cell death should be unraveled. In this study, we used Schizosaccharomyces pombe, which is a promising unicellular model organism in mechanistic toxicology and cell biology, to investigate the involvement of pro-apoptotic factors in alpha-thujone-induced cell death. We showed alpha-thujone-induced ROS accumulation-dependent cytotoxicity and apoptosis. In addition, we used superoxide dismutase-deficient cells (sod1 and sod2 mutants) to understand the effect of oxidative stress. Alpha-thujone caused significant cytotoxicity and apoptotic cell death, particularly in sod mutants. Moreover, two potential apoptotic factors, pca1 and pnu1 (pombe caspase-1 and pombe nuc1) were investigated to understand which factor mediates alpha-thujone-induced cell death. Pca1-deficient cells showed increased survival rates and reduced apoptosis in comparison to parental cells after chemical treatment while pnu1 mutation did not cause any significant change and the response was found identical as of parental cells. Yeast responded to alpha-thujone in caspase-dependent manner which was very similar to that for acetic acid. In conclusion, alfa-thujone-induced apoptosis and accounting mechanisms, which were mediated by ROS and driven by Pca1, were clarified in the unicellular model, S. pombe.

Blunt cardiac rupture: a 5-year NTDB analysis.

OBJECTIVE: Because of its rarity and high rate of mortality, traumatic blunt cardiac rupture (BCR) has been poorly studied. The objective of this study was to use the National Trauma Data Bank to review the epidemiology and outcomes associated with traumatic BCR. METHODS: After approved by the institutional review board, the National Trauma Data Bank (version 5.0) was queried for all BCR occurring between 2000 and 2005. Demographics, clinical injury data, interventions, and outcomes were abstracted for each patient. Statistical analysis was performed using an unpaired Student's t test or Mann-Whitney U test to compare means and chi analysis to compare proportions. Stepwise logistic regression analysis was performed to identify independent predictors of inhospital mortality. RESULTS: Of 811,531 blunt trauma patients, 366 (0.045%) had a BCR of which 334 were available for analysis, with the mean age of 45 years, 65% were men, and their mean Injury Severity Score was 58 +/- 19. The most common mechanism of injury was motor vehicle collision (73%), followed by pedestrian struck by auto (16%), and falls from height (8%). Twenty-one patients (6%) died on arrival and 140 (42%) died in the emergency room. The overall mortality for patients arriving alive to hospital was 89%. Of the patients surviving to operation, 42% survived >24 hours of which 87% were discharged. Survivors were significantly younger (39 vs. 46 years, p = 0.04), had a lower Injury Severity Score (47 vs. 56, p = 0.02), higher Glasgow Coma Scale (10 vs. 6, p < 0.001), and were more likely to present with an systolic blood pressure >or=90 mm Hg (p = 0.01). Nevertheless, none of these factors was found to be an independent risk factor for mortality. CONCLUSION: BCR is an exceedingly rare injury, occurring in 1 of 2400 blunt trauma patients. In patients arriving alive to hospital, traumatic BCR is associated with a high mortality rate, however, is not uniformly fatal.

Blood transfusions in trauma: six-year analysis of the transfusion practices at a Level I trauma center.

The objective of this study was to analyze the transfusion practices in trauma patients in one institution. A retrospective analysis of the Trauma Registry linked with the Blood Bank Database of a Level 1 trauma center was conducted. Over 6 years, 17 per cent of the 25,599 trauma patients received blood transfusions. The overall mortality in transfused patients was 20 per cent and remained the same during the study period. There was no change in the proportion of patients receiving transfusions throughout the years, however there was a significant 23.5 per cent reduction in the mean number of packed red blood cells (PRBC) units transfused (P < 0.001 for trend). This reduction in PRBC used remained true and even more evident in the group of more severely injured patients (Injury Severity Score > or = 16), with a 27.9 per cent decrease in mean units of PRBC (P < 0.001 for trend). The highest reduction in PRBC transfusion was seen in blunt trauma patients (34.6%, P < 0.001). During the study period there was a concurrent increase in mean units of fresh frozen plasma used (60.7%, P < 0.001) and no change in the use of platelets and cryoprecipitate. In conclusion, transfusions of PRBC were significantly reduced over time in trauma patients without any evident negative impact on mortality.

Brain lobectomy for severe head injuries is not a hopeless procedure.

INTRODUCTION: Posttraumatic transtentorial herniation or intractable intracranial hypertension are ominous signs, and are associated with very poor outcomes. Aggressive procedures, such as brain lobectomies, may benefit some of these patients. The published experience with brain lobectomies is very limited. PATIENTS: Retrospective study of head injury patients with focal brain lesions and intractable intracranial hypertension or herniation who underwent partial or anatomic brain lobectomies. The following parameters were included in the analysis: age, gender, mechanism of injury, hypotension at admission, initial Glasgow Coma Scale (GCS) score, Abbreviated Injury Scale for head, chest, and abdomen, Injury Severity Score, time from admission to operation, type of brain lobectomy, intensive care unit and hospital stays, survival, and Glasgow Outcome Score. Stepwise logistic regression analysis was used to identify independent risk factors for mortality and functional outcomes. RESULTS: During the 13-year study period, there were 183 patients who underwent brain lobectomy for traumatic injuries. Eighty-eight patients (48.1%) underwent frontal lobectomy, 67 (36.6%) temporal lobectomy, and the remaining 28 (15.3%) other or combination lobectomies. The mean follow-up was 22 days. There were 50 deaths (mortality 27.3%). Excluding patients with major extracranial injuries, there were 47 deaths (26.9%). Patients with blunt trauma had a significantly higher mortality than those with penetrating trauma had (33.1% vs. 12.0%, p = 0.005). Among the risk factors studied, blunt injury mechanism was identified as the only risk factor for mortality. Overall, 48% of the 133 survivors had good functional outcomes, and 51.9% had poor functional outcomes (including 15.0% with persistent vegetative state). Multiple-response logistic regression identified blunt trauma, low initial GCS score, and frontal lobectomy as independent risk factors for poor outcomes. CONCLUSION: Selected severe head injury patients with focal brain lesions and intractable intracranial hypertension or herniation may benefit from brain lobectomies. The survival and functional outcomes after this procedure are acceptable. Blunt trauma, low initial GCS score, and frontal lobectomies are significant risk factors for poor outcomes.

Blunt gastric injuries.

Gastric rupture after blunt abdominal trauma is a rare injury with few reports in the literature. The purpose of this study was to review our experience with blunt gastric injuries and compare outcomes with small bowel or colon injuries. All patients with hollow viscus perforations after blunt abdominal trauma from 1992 to 2005 at our level I trauma center were reviewed. Of 35,033 blunt trauma admissions, there were 268 (0.7%) patients with a total of 319 perforating hollow viscus injuries, 25 (0.07%) of which were blunt gastric injuries. When compared with the small bowel or colon injuries, the blunt gastric injury group had a higher Injury Severity Score (22 versus 17, P = 0.04), more patients with a chest Abbreviated Injury Score greater than 2 (36% versus 12%, P < 0.01), and a shorter interval from injury to laparotomy (221 versus 366 minutes, P = 0.017). Multivariate analysis identified five independent risk factors for mortality: age older than 55 years, head Abbreviated Injury Score greater than 2, chest Abbreviated Injury Score greater than 2, the presence of hypotension on admission, and Glasgow Coma Scale 8 or less. The results of this study suggest that mortality in patients with blunt hollow viscus injuries can be attributed to concurrent head and chest injuries, but not the specific hollow viscus organ that is injured.

Impact of the 80-hour workweek on patient care at a level I trauma center.

HYPOTHESIS: The 80-hour workweek limitation for surgical residents is associated with an increase in mortality and complication rates among adult trauma surgical patients. DESIGN: Retrospective cohort study. SETTING: Academic level I trauma center. PATIENTS: Trauma patients admitted before and after the 80-hour workweek limitation. METHODS: We compared death and complication rates for adult trauma patients admitted during a 24-month period before (2001-2003) and a 24-month period after (2004-2006) implementation of the 80-hour workweek at our institution. Relative risk and its 95% confidence intervals were examined. MAIN OUTCOME MEASURES: Patient care outcomes included preventable and nonpreventable complications and deaths. RESULTS: The patient populations from the 2 time periods were clinically similar. No significant differences were found in the total and the preventable death rates. The time period after the 80-hour workweek mandate had a significantly higher total complication rate (5.64% vs 7.28%; relative risk, 1.29; 95% confidence interval, 1.15-1.45; P < .001), preventable complication rate (0.89% vs 1.28%; relative risk, 1.43; 95% confidence interval, 1.06-1.91; P = .02), and nonpreventable complication rate (4.75% vs 5.81%; relative risk, 1.22; 95% confidence interval, 1.08-1.39; P = .002). CONCLUSION: Although there was no difference in deaths between the 2 time periods, there was a significant increase in total, preventable, and nonpreventable complications. This increase in complication rate may be due, in part, to the new 80-hour workweek policy.

Bile duct injury during cholecystectomy requiring delayed liver transplantation: a case report and literature review.

Major bile duct injury during cholecystectomy represents potentially severe complications with unpredictable long-term results. If these lesions are not treated adequately, they can lead to hepatic failure or secondary biliary cirrhosis therefore requiring liver transplantation. We report a patient who required liver transplantation 15 years after open cholecystectomy. A l0-year old girl underwent open cholecystectomy and duodenal repair for cholelithiasis and cholecystoduodenal fistula. She required two surgical interventions, hepaticojejunostomy which was performed in another center and portoenterostomy for biliary stricture at our institution seven years after the cholecystectomy. Eight years after the third operation, she required recurrent hospitalization for treatment of hepatic abscesses. The extremely short intervals between the three life threatening episodes and the rapid progression to severe sepsis were taken into consideration and liver transplantation was performed at the age of 25. She is leading a healthy life at 4 years post transplantation. Although iatrogenic biliary injury can usually be treated successfully by a combination of surgery, radiological and endoscopic techniques, patients with severe injuries develop irreversible liver disease. This case report and review of the literature suggest that liver transplantation is a treatment modality for a selected group of patients with end-stage liver disease secondary to bile duct injury.

Subphrenic abscess resulting in resection of the lower basal segment of the right lung: a severe complication following laparoscopic appendectomy.

We report the case of an 18-year-old boy who developed an intrathoracic abscess with rupture of the diaphragm following a laparoscopic appendectomy (LA) for a perforated appendicitis. LA is an established procedure in the treatment of appendicitis. It is a safe and efficacious technique, but several complications can occur with this procedure, and surgeons should be aware of the potential dangers. Herein, we present a previously unreported thoracic complication following an LA.