P53 expression is associated with a high-degree of tumor DNA aneuploidy and incidence of p53 gene mutation, and is localized to the aneuploid component in colorectal carcinomas

p53 protein expression was studied by immunoblotting in 34 colorectal carcinomas and 28 of the corresponding normal mucosas, and correlated with tumor DNA ploidy as measured by flow cytometry. p53 protein was detected in 35% (12/34) of the tumors; the normal mucosas were negative. Fifty-five percent (12/22) of the tumors examined for mutations within the four hotspots (exons 5-8) of the p53 gene had point mutations. p53 expression correlated significantly with the presence of p53 gene mutations; 67% (8/12) of the tumors with mutations expressed p53, whereas only one of 10 tumors where no mutations were detected expressed the protein (p=0.01). Four tumors with p53 gene mutations did not express p53. Fifty-nine percent (20/34) of the tumors were aneuploid. p53 expression correlated significantly with aneuploidy; a total of 55% (11/20) of the aneuploid tumors were positive for p53 compared to 7% (1/14) of the diploid tumors (p=0.009). All of the 11 highly aneuploid tumors (1.31 less-than-or-equal-to DNA index (DI); less-than-or-equal-to 1.86) expressed p53, whereas all of the 9 moderately aneuploid tumors (1.11 less-than-or-equal-to DI less-than-or-equal-to 1.29) were p53-negative. Flow cytometry was also used to resolve cell cycle- and ploidy specific p53 expression in nuclei in 4 aneuploid tumors. p53 expression in these tumors was confined to the aneuploid component, whereas the diploid component was negative. p53 was seen in nuclei in all phases of the cell cycle of proliferating aneuploid cells. Neither p53 expression nor tumor DNA ploidy were correlated with Dukes' stage (p=1.00 and 0.72, respectively). The data suggest that high levels of mutant p53 may play a causative role in the generation of highly aneuploid tumors.     

Global transcriptome response to ionic liquid by a tropical rain forest soil bacterium, Enterobacter lignolyticus

To process plant-based renewable biofuels, pretreatment of plant feedstock with ionic liquids has significant advantages over current methods for deconstruction of lignocellulosic feedstocks. However, ionic liquids are often toxic to the microorganisms used subsequently for biomass saccharification and fermentation. We previously isolated Enterobacter lignolyticus strain SCF1, a lignocellulolytic bacterium from tropical rain forest soil, and report here that it can grow in the presence of 0.5 M 1-ethyl-3-methylimidazolium chloride, a commonly used ionic liquid. We investigated molecular mechanisms of SCF1 ionic liquid tolerance using a combination of phenotypic growth assays, phospholipid fatty acid analysis, and RNA sequencing technologies. Potential modes of resistance to 1-ethyl-3-methylimidazolium chloride include an increase in cyclopropane fatty acids in the cell membrane, scavenging of compatible solutes, up-regulation of osmoprotectant transporters and drug efflux pumps, and down-regulation of membrane porins. These findings represent an important first step in understanding mechanisms of ionic liquid resistance in bacteria and provide a basis for engineering microbial tolerance.     

Increased cerebral blood flow after brain arteriovenous malformation resection is substantially independent of changes in cardiac output

Brain arteriovenous malformation (BAVM) resection can result in an acute increase in cerebral blood flow (CBF) of unclear etiology. This observational study investigated the relationship between changes in CBF and cardiac output (CO) in patients undergoing microsurgical resection of BAVMs. In 20 patients undergoing a BAVM resection during an isoflurane-based anesthesia, we measured CBF and systemic cardiovascular parameters immediately before and after BAVM resection. CBF was measured on the hemisphere ipsilateral to the lesions and on the contralateral side, using intravenous cold 133Xe washout. Cardiac output was measured using thermodilution technique via a pulmonary artery catheter. There was an increase in global CBF after resection (25 +/- 8 versus 31 +/- 13 mL/100 g/min, preresection versus postresection, mean +/- SD, P =.002), ipsilateral CBF (25 +/- 8 versus 31 +/- 13 mL/100 g/min, P =.002), and contralateral CBF (24 +/- 7 versus 30 +/- 13 mL/100 g/min, P =.003). There was no change in CO, mean systemic arterial pressure, central venous pressure, or pulmonary artery diastolic pressure. The change in CBFGLOBAL was not correlated with changes in CO (r =.154, P =.517). BAVM resection resulted in global increases in CBF that was not substantially related to changes in CO or other systemic parameters.     

Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage

BACKGROUND: Aneurysm rebleeding has historically been an important cause of mortality after subarachnoid hemorrhage (SAH). OBJECTIVE: To describe the frequency and impact of rebleeding in the modern era of aneurysm care, which emphasizes early surgical or endovascular treatment. DESIGN: Inception cohort. SETTING: Tertiary care medical center. PATIENTS: A total of 574 patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. Early aneurysm repair was performed whenever feasible. MAIN OUTCOME MEASURES: Rebleeding was defined by prespecified clinical and radiographic criteria, excluding prehospital, intraprocedural, and postrepair events. Functional outcome was assessed at 3 months with the modified Rankin Scale. Multiple logistic regression was used to identify predictors of rebleeding, poor functional outcome, and mortality. RESULTS: Rebleeding occurred in 40 (6.9%) of the 574 patients; most cases (73%) occurred within 3 days of ictus. Hunt-Hess grade on admission (odds ratio [OR], 1.92 per grade; 95% confidence interval [CI], 1.33-2.75; P<.001) and maximal aneurysm diameter (OR, 1.07/mm; 95% CI, 1.01-1.13; P = .005) were independent predictors of rebleeding. After controlling for Hunt-Hess grade and aneurysm size, rebleeding was associated with a markedly reduced chance of survival with functional independence (modified Rankin Scale score, 相似文献   

Anatomy of the superficial peroneal nerve in relation to fixation of tibia fractures with the less invasive stabilization system

OBJECTIVE: To examine the danger to the superficial peroneal nerve during percutaneous screw placement in the distal holes of the 13-hole proximal tibia Less Invasive Stabilization System plate in a cadaver. DESIGN: Anatomic study. SETTING: Medical school anatomy laboratory. INTERVENTIONS: Fourteen adult cadaveric lower extremities were used. A 13-hole proximal tibia Less Invasive Stabilization System plate was placed as described by the manufacturer. Dissection of the superficial peroneal nerve was performed following localization of screw holes 7 through 13 using insertion sleeves, centering sleeves, and 2.0-mm Kirschner wires passed through the insertion guide. RESULTS: The average distance from the superficial peroneal nerve to the center of holes 11, 12, and 13 was 10.0 mm (range 0-21, standard deviation 5.6), 6.8 mm (range 0-16, standard deviation 4.3), and 2.7 mm (0-11, standard deviation 3.7), respectively. In 12 of 14 legs (86%), the superficial peroneal nerve was 5.0 mm or less from the center of hole 13. The nerve was touching the guide wire at hole 11 in 1 specimen (7%), at hole 12 in 2 specimens (14%), and at hole 13 in 6 specimens (43%). In 1 specimen (7%), the guide wire pierced the superficial peroneal nerve at hole 13. CONCLUSION: These findings suggest that the superficial peroneal nerve is at significant risk during percutaneous screw placement in holes 11 through 13 of the 13-hole proximal tibia Less Invasive Stabilization System plate. Use of a larger incision and careful dissection down to the plate in this region may minimize the risk of damage to the nerve.     

Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions

Background: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.

Methods: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micro gram [center dot] kg [center dot] sup -1 min sup -1) or remifentanil (n = 31; 1 micro [center dot] kg sup -1 [center dot] min sup -1). After tracheal intubation, infusion rates were reduced to 0.03 micro gram [center dot] kg sup -1 [center dot] min sup -1 (fentanyl) or 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil ([nearly equal] 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7.

Results: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar.     

Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction.

AIMS: Congestive heart failure (CHF) is associated with severe structural changes of atria, contributing to impaired atrial function and the risk of arrhythmia. This study investigated the effects of CHF treatments on atrial remodelling. METHODS AND RESULTS: Three months after myocardial infarction (MI), rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. Echocardiography-Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring were used to characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining. Left atrial diameter was increased (5.8+/-0.6 mm in MI vs. 3.6+/-0.3 mm in sham; P<0.0001), as was atrial fibrosis (26.7+/-3.8% in MI vs. 10.5+/-2.2% in sham; P<0.0001), which correlated with left ventricular (LV) dysfunction after 3 months of MI. P-wave duration was also increased and premature atrial beats were frequent on the 24-h electrocardiogram. Similar improvements in LV dysfunction were observed after 1 month of spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination. Atrial hyperexcitability was reduced by all the treatments, but only spironolactone attenuated atrial fibrosis and reduced P-wave duration. CONCLUSION: Atrial fibrosis caused by chronic CHF is reduced by spironolactone.     

Cerebral Blood Flow and CO2 Reactivity Is Similar during Remifentanil/N2 O and Fentanyl/N2 O Anesthesia

Background: Remifentanil, a rapidly metabolized [micro sign]-opioid agonist, may offer advantages for neurosurgical procedures in which prolonged anesthetic effects can delay assessment of the patient. This study compared the effects of remifentanil-nitrous oxide on cerebral blood flow (CBF) and carbon dioxide reactivity with those of fentanyl-nitrous oxide anesthesia during craniotomy.

Methods: After institutional approval and informed patient consent were obtained, 23 patients scheduled to undergo supratentorial tumor surgery were randomly assigned to remifentanil or fentanyl infusion groups in a double-blinded manner. Midazolam, thiopental, and pancuronium induction was followed by equipotent narcotic loading infusions of remifentanil (1 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or fentanyl (2 [micro sign]g [middle dot] kg-1 [middle dot] min-1) for 5-10 min. Patients were ventilated with 2:1 nitrous oxide-oxygen, and opioid rates were reduced and then titrated to a stable hemodynamic effect. After dural exposure, CBF was measured by the intravenous133 xenon technique at normocapnia and hypocapnia. Reactivity of CBF to carbon dioxide was calculated as the absolute increase in CBF per millimeters of mercury increase in the partial pressure of carbon dioxide (PaCO2). Data were analyzed by repeated-measures analysis of variance, unpaired Student's t tests, or contingency analysis.

Results: In the remifentanil group (n = 10), CBF decreased from 36 +/- 11 to 27 +/- 8 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 33 +/- 5 to 25 +/- 2 mmHg. In the fentanyl group (n = 8), CBF decreased from 37 +/- 11 to 25 +/- 6 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 34 +/- 3 to 25 +/- 3 mmHg. Absolute carbon dioxide reactivity was preserved with both agents: 1 +/- 1.2 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for remifentanil and 1.5 +/- 0.5 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for fentanyl (P = 0.318).