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141.
142.
Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use Nα‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of Nα‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of Nα‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification. 相似文献
143.
The objective of this study is to determine whether a normal fetal morphology ultrasound scan in women older than 35 years reduces the risk of aneuploidy. We reviewed the results of amniocentesis and second trimester sonogram in all women older than 35 years from 1991 to 1995. None had prior screening. We excluded fetuses with structural anomalies. We determined the sensitivity and specificity of minor markers in detecting Down syndrome and also determined the reduction in risk of a normal sonogram. Among the 2060 women older than 35 years giving birth during the study period, 16 (0.78%) delivered an infant with Down syndrome. Of the 16 fetuses, two had no prenatal testing or ultrasound, two had invasive testing but no second trimester sonogram, five had a normal sonogram and seven had one or more sonographic markers of Down syndrome. At least 17% of women older than 35 years did not participate in prenatal testing or ultrasound. Ultrasound detected Down syndrome with a sensitivity of 59% (95% confidence interval: 45–72%), a false‐positive rate of 10.6% (9.4–11.8%) and a positive predictor value of 1 in 9. The likelihood of having normal karyotype if the sonogram was normal was 0.46 (0.31–0.61). In women older than 35 years, a normal second trimester sonogram reduces the risk of Down syndrome by more than 50%. At least 17% of women older than 35 years do not participate in prenatal testing or ultrasound. 相似文献
144.
Anthony M Dart Jan Erik Otterstad Bridget-Anne Kirwan John D Parker Sophie de Brouwer Philip A Poole-Wilson Jacobus Lubsen 《European journal of echocardiography》2007,8(4):275-283
AIMS: To evaluate the relationship between echocardiographic cardiac function and outcome in patients with stable symptomatic angina. METHODS: Baseline echo left ventricular ejection fraction and volume data measured in a central laboratory was available for 7016 patients (92% of the total) participating in the ACTION trial (A Coronary disease Trial Investigating Outcome with Nifedipine GITS). Ejection fraction was also measured by investigators. Evaluation of the different echocardiographic variables was based on adjusted hazard ratios comparing the unfavourable limit of the 90% range of the variable concerned to the favourable limit. RESULTS: The centrally measured ejection fraction was the most powerful predictor of all-cause death (adjusted hazard ratio=2.5), myocardial infarction, any stroke or transient ischaemic attack and overt heart failure (adjusted hazard ratio=4.5). The addition of either end systolic volume or end diastolic volume to ejection fraction did not materially affect the power of prediction. Compared to the central ejection fraction measurement, the investigator-measured ejection fraction was a less powerful predictor for all outcomes considered. CONCLUSION: Routine echocardiography carefully analysed by standardised methods provides useful prognostic information in patients with stable angina, including for total mortality. 相似文献
145.
146.
Laureano Fernández-Cruz Rebeca Cosa Laia Blanco Sammy Levi Miguel-Angel López-Boado Salvador Navarro 《Journal of gastrointestinal surgery》2007,11(12):1607-1622
Laparoscopic pancreatic surgery (LPS) has seen significant development but much of the knowledge refers to small and benign
pancreatic tumors. This study aims to evaluate the feasibility, safety, and long-term outcome of the laparoscopic approach
in patients with benign, premalignant, and overt malignant lesions of the pancreas. This study, currently, is the largest
single center experience worldwide. One hundred twenty-three consecutive patients underwent laparoscopic pancreatic surgery
from April 1998 to April 2007, 20 patients with cysts or pseudocysts for acute and chronic pancreatitis, laparoscopic pancreatic
drainage was performed, and were excluded from the analysis. The 103 patients were divided based on preoperative diagnosis:
group I, inflammatory tumors for chronic pancreatitis (eight patients); group II, cystic pancreatic neoplasms (29 patients);
group III, intraductal papillary mucinous neoplasms (10 patients); group IV, neuroendocrine pancreatic tumors (NETs) (43 patients);
and group V ductal adenocarcinoma (13 patients). The median tumor size was 5.3 cm. Pathologic data include R
0 or R
1 resection (transection margins on the specimen were inked). Perioperative data, postoperative complications, and resection
modalities were compared using statistical analysis. Long-term outcomes were analysed by tumor recurrence and patient survival.
The overall conversion rate was 7%. Laparoscopic distal pancreatic resection was performed in 82 patients (79.6%). Laparoscopic
spleen-preserving distal pancreatectomy (Lap SPDP) was performed in 52 patients (63.7%), but with splenic vessels preservation
in 22% and without splenic vessels preservation in 41.5%. Laparoscopic en-bloc splenopancreatectomy (Lap SxDP) was performed
in 30 patients (36.6%) and laparoscopic enucleation (Lap En) in 20 patients (19.4%). There was no mortality. The overall complication
rate was 25.2, 16.7, and 40% after Lap SPDP, Lap SxDP, and Lap En, respectively. The overall morbidity rate was significantly
higher (p > 0.05) in the group of Lap SPDP without splenic vessels preservation comparing with Lap SPDP with splenic vessels preservation
because of the occurrence of splenic complications (20.6%). The overall pancreatic fistulas was 7.7, 10, and 35% after Lap
SPDP, Lap SxDP, and Lap En, respectively; the severity of fistula was significantly higher in the Lap En group (p > 0.05). The mean hospital stay was within 1 week in all groups, except in the group of ductal adenocarcinoma, which is 8 days.
In this series, 27 patients (26.2%) had malignant disease. R
0 resection was achieved in 90% of ductal adenocarcinoma and 100% for other malignant tumors. The median survival for ductal
adenocarcinoma patients was 14 months. This series demonstrates that LPS is feasible and safe in benign-appearing and malignant
lesions of the pancreas. 相似文献
147.
多层螺旋CT(MSCT)使扫描速度,薄层,覆盖范围达到了很好的统一,是胰腺癌最佳的单项检查手段。本文介绍了MSCT运用于胰腺的技术优势以及具体检查方法,重点叙述其在胰腺癌的诊断,术前可切除性的评估等方面的应用。 相似文献
148.
Geir Håland Kai-Håkon Carlsen Chandra Sekhar Devulapalli Morten Pettersen Petter Mowinckel Karin C. Lødrup Carlsen 《Pediatric allergy and immunology》2007,18(6):528-534
The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p < 0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr. 相似文献
149.
Sung Hee Chung Olof Heimbürger Bengt Lindholm Hi Bahl Lee 《Nephrology, dialysis, transplantation》2005,20(6):1207-1213
BACKGROUND: Dialysis patient mortality remains high, and this high mortality may be due to many factors. In peritoneal dialysis (PD) patients, old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and a high peritoneal transport rate have been shown to influence survival, but the relative importance of these factors may differ between different patient populations. Besides, centre practice patterns may differ between centres and may influence patient survival. In addition, the literature suggests that dialysis patient survival may be better in Asian than in Caucasian patients. METHODS: The influence of centre and patient characteristics on patient survival was investigated in 132 Korean and 106 Swedish incident PD patients, who underwent initial biochemical measurements and assessment of adequacy of dialysis, nutritional status, RRF and peritoneal transport characteristics. RESULTS: At the start of PD, Korean patients had a higher prevalence of diabetes, peritoneal Kt/V(urea), peritoneal creatinine clearance and peritoneal fluid removal, and lower body mass index, RRF and dialysate to plasma creatinine concentration ratio (D/P Cr) compared with Swedish patients. Significantly more patients from Korea were placed on temporary haemodialysis before PD (100 out of 132) when compared with Swedish patients (21 out of 106). During the follow-up, there was a significantly higher rate of transfer to other units in Korea and a significantly higher rate of kidney transplantation in Sweden. On Kaplan-Meier analysis, overall patient survival did not differ and relative risk for death was also not different between the two centres even after adjustment for age, diabetes, cardiovascular disease, RRF and D/P Cr. On Cox proportional hazards multivariate analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. While age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, age and RRF independently predicted mortality in Swedish patients. CONCLUSION: Although there were significant differences in centre and patient characteristics, we were unable to confirm a survival advantage for Korean over Swedish PD patients. The results of this study suggest that the reported difference in survival between Asian and Caucasian dialysis patients may have been due, in part, to differences in centre and patient characteristics rather than to race as such. The genetic influence on patient characteristics remains, however, to be elucidated. 相似文献
150.
目的观察葛根素对血管性痴呆(VaD)患者认知功能和听觉事件相关电位P300的影响。方法将70例VaD患者随机分成两组各35例,葛根素治疗组和对照组。应用简易精神状态检查量表(MMSE)评定两组患者治疗前后认知功能状况,并进行治疗前后P300检查。同时记录药物不良反应。结果两组各35例进入结果分析。治疗前两组MMSE评分、P300的潜伏期及波幅差异无显著性(均P〉0.05)。治疗14d、30d时,两组MMSE评分显著提高(均P〈0.01),P300潜伏期均有缩短,波幅均有提高(葛根素组P〈0.01,对照组P〈0.05);治疗后14d时认知功能改善葛根素组明显优于对照组(总有效率分别为91.4%,71.4%)(P〈0.05)。两组治疗期间无严重不良反应。结论葛根素能够改善VaD患者的认知功能,这可能与葛根素的扩血管、脑保护作用有关。 相似文献