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21.
Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer. 总被引:3,自引:0,他引:3
Amit Shah William A Swain Donna Richardson John Edwards Duncan J Stewart Catherine M Richardson Daniel E B Swinson Dipika Patel J Louise Jones Kenneth J O'Byrne 《Clinical cancer research》2005,11(8):2930-2936
Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC. 相似文献
22.
S. A. Baxendale W. van Paesschen P. J. Thompson A. Connelly J. S. Duncan W. F. Harkness S. D. Shorvon 《Epilepsia》1998,39(2):158-166
Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit. 相似文献
23.
Physical status score and trends in anesthetic complications 总被引:4,自引:0,他引:4
Since deaths due to anesthesia have now become rare, emphasis in quality assurance of anesthetic care must focus on morbidity rather than only on mortality. To facilitate comparisons of outcomes, data from a large anesthesia follow-up program (N = 112,000 anesthetics) were used to evaluate the usefulness of the American Society of Anesthesiologists' Physical Status score (PS) as an independent predictor of nonfatal adverse anesthetic complications. For each patient, the anesthesiologist filled out a form containing information about the patient, the anesthetic, the operative procedure, and outcomes in the operating and recovery rooms. Postoperative complications were assessed by a designated anesthesia follow-up nurse. We calculated the PS-specific complication rate by dividing the number of complications to patients in each PS category by the number of anesthetics given to patients in the same category. We found that PS-specific complication rates increased with increasing PS scores for most complications sought. For intraoperative and recovery room complications, the PS-specific rates increased from 1978-80 and 1981-83 as compared to 1975-77. However, there was no increase over time in the rate of postoperative major complications. After adjusting for patient, anesthesia, and surgery-related variables by multiple logistic regression, the relative odds of having an intraoperative or postoperative major complication were increased for patients classified PS2, PS3 and PS4 & 5 as compared to PS1. However, those in higher PS categories were less likely to have a recovery room complication than PS1 patients.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
24.
Duncan W. Blake Roger G. Evans John Ludbrook Oscar U. Petring 《Clinical and experimental pharmacology & physiology》1994,21(5):383-396
1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval-cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min. 2. Caval-cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O2, with and without the addition of 3–4% CO2, in randomized order. 3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased. 4. During Phase I, there were independent linear relationships between Pao2 (but not Pao2) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of Pao2, the greater was the rate of fall of SVCI and the less the rate of fall of MAP. 5. There was an inverted U-shaped effect of Pao2, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O2), Phase II occurred later than during normoxia (21% O2); and (b) across the normoxic and hypoxic gas mixtures (21–8% O2, with and without added CO2), there was an independent linear relationship between Pao2 (but not Pao2 or Pao2×Pao2) and the level of CI at which Phase II occurred. That is, the lower the level of Pao2, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia. 相似文献
25.
Calcium, cell signalling and cataract 总被引:5,自引:0,他引:5
26.
Liverpool, a seaport in NW England, suffered severely from lethal infectious diseases in the second half of the 19th century: the population was densely crowded and malnourished and life expectancy was low. Time-series analysis shows that the epidemics of whooping cough (i) had an interepidemic interval of 2.9 years, 1863-85, which lengthened to 3.4 years, 1885-1900 (ii) were strongly coherent with wheat prices (P < 0.001) and (iii) also correlated with cycles of seasonal weather conditions. It is suggested from mathematical modelling that the epidemics in this compromised population were maintained (i.e. the system was driven) by an oscillation of malnutrition and by seasonal weather conditions. A model that incorporates both the dynamics of whooping cough and the demographic characteristics of the population is presented. It has been shown to replicate the dynamics of the epidemics and has been used to predict the changes with time of (i) the force of the infection and (ii) the proportion of those infected with whooping cough who died. 相似文献
27.
David Langton Diana Way Lisbeth Trigg Duncan Blake Barry McGrath 《Clinical and experimental pharmacology & physiology》1990,17(3):219-223
1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process. 相似文献
28.
Data concerning rural youth drinking and driving practices werecollected from 622 junior and senior high school students innorthwest Ohio, utilizing an ex post facto cross-sectional survey-researchdesign. The results suggested that 69% of the sample had usedalcohol at least once. With regard to quantity of alcohol use,about 27% reported drinking four or more drinks at a sitting.Approximately 19% of the sample had driven under the influenceof alcohol and 35% had ridden in a car with an intoxicated school-agedriver; 35% had refused a ride from a friend who was intoxicated,while 43% had tried to stop a drunk friend from driving. Nosignificant differences were found between males and femalesregarding drinking and driving but grade level was a significantmoderating factor. As grade level increased, the frequency ofeach alcohol-related behavior increased substantially (P <0.01). This paper presents prevalence data concerning drinkingand driving among rural youth as well as recommendations forcommunity health education program development. 相似文献
29.
30.
Narendra Nathoo Sameer S Nadvi Duncan Royston Mahesh Rana Premjith Gathiram Pratistadevi K Ramdial James R van Dellen 《Journal of clinical neuroscience》2004,11(1):61-65
Patients with acute brain pathology requiring ferromagnetic bio-medical implants for on-going invasive monitoring are largely excluded from the benefits of MRI scanning. We evaluated the behaviour of a thermal diffusion cortical blood flow (TD-CBF) sensor both in vitro (phantom gelatin model) and in vivo environments in a high field strength MRI system.Two baboons underwent cranial subdural implantation of 2 TD-CBF sensors/hemisphere and a single left parietal sensor was implanted subcortically to determine any deleterious effects. Using standard MRI sequences, artefact size, thermal effects, current generation, movement and reliability of recordings were assessed during scanning.The deflection forces were negligible, no observable thermal effects were demonstrated, while wide fluctuations in cerebral blood flow recordings were recorded. Mean image artefact size for implanted sensors was 6 times larger than in vitro. Patients with an implanted TD-CBF sensor may be safely imaged provided the device is disconnected. The MRI images obtained are of an acceptable quality. 相似文献