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131.
J Tsiaoussis E Chrysos M Glynos JS Vassilakis E Xynos 《Canadian Metallurgical Quarterly》1998,85(12):1699-1702
BACKGROUND: The study was designed to investigate the clinical presentation and laboratory findings of anterior rectal mucosal prolapse (ARMP) and to assess the results of two therapeutic modalities. METHODS: Some 162 women with ARMP were assessed clinically and by defaecography and rectoanal manometry before and 1 year after one or two sessions of submucosal sclerotherapy or, in the case of recurrence, after transanal excision of the prolapsing mucosa. RESULTS: Almost all patients reported a combination of symptoms suggesting obstructive defaecation. At defaecography anterior rectocele and excessive perineal descent at straining were present in 78 and 72 per cent respectively. The size of coexisting anterior rectocele and the extent of perineal descent were significantly related to the duration of the disease (P< 0.001). One or, in the event of recurrence, two sessions of sclerotherapy led to an overall success rate of 51 per cent. Improvement after sclerotherapy was associated with partial recovery of anal tone and improvement of anal sampling and rectal sensation. Failure of sclerotherapy was related to rectocele of larger size (P< 0.001) and a longer perineal descent at straining (P< 0.001) than in patients with a successful outcome. Excision of the prolapsing mucosa resulted in symptomatic improvement in 42 of 47 patients and was associated with significant improvement of the defaecographic and manometric findings. CONCLUSION: ARMP is usually associated with anterior rectocele and excessive perineal descent. Submucosal sclerotherapy is successful in half of the cases, but only in the presence of a rather small anterior rectocele and short perineal descent. Failures after sclerotherapy can be treated by transanal excision of the prolapsing mucosa. 相似文献
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OBJECTIVE: To reveal the relationship between fasting and 2-h postload plasma glucose and to examine the appropriate fasting glucose cutoff as the primary screening test for diabetes. RESEARCH DESIGN AND METHODS: We recruited 5,303 subjects from preventive services of the National Cheng Kung University Hospital. Exclusion criteria were age <20 years, pregnancy, known diabetes, and a history of recent surgery, trauma, or illness. All subjects received the 75-g oral glucose tolerance test. The relationship between fasting and 2-h glucose was examined. Sensitivities, specificities, efficiency, and predictive values were assessed at different cutoffs of fasting glucose for prediction of diabetes. RESULTS: The best fit model for the relationship between fasting and 2-h glucose was fasting glucose = 4.914-0.060 x (2-h glucose) + 0.0144 x (2-h glucose)2. From this model, the fasting glucose was 6.0 mmol/l when 2-h glucose was 11.1 mmol/l. A fasting glucose with 6.25 mmol/l gave the same diabetes prevalence as the World Health Organization 2-h glucose criterion. When 7.8 mmol/l was the fasting glucose cutoff, the sensitivity was 28.5%. Lowering the cutoff from 7.8 to 7.0 mmol/l increased the sensitivity by 11.2% and slightly reduced the specificity and positive predictive value. If the cutoffs were 6.25 and 6.0 mmol/l, the sensitivity increased and the specificity and the positive predictive value decreased accordingly. CONCLUSIONS: Our results suggest that fasting glucose as a screening criterion for diabetes could be revised downward to 7.0 mmol/l, because the slight reduction of positive predictive value was more than balanced by an apparent increase of sensitivity and insignificant change of specificity. 相似文献
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Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. Unfortunately, viruses are limited in their ability to diffuse through tissue. This makes it virtually impossible to infect the majority of tumor cells in vivo and results in inadequate gene transfer. This problem can be addressed by allowing limited viral replication. Limited viral replication facilitates greater penetration of virions into tissue and can improve gene transfer. We have developed a strategy of limited viral replication using AdRSVlaclys, a chemically modified E1-deleted adenovirus, to codeliver an exogenous plasmid encoding the adenovirus E1 region. This system allows one round of viral replication. We examined the effect of this limited adenovirus replication in vitro and in vivo. In culture, codelivery of virus and pE1 resulted in a large increase in infected cells when compared with control cells exposed to virus and pUC19. In experiments on nude mice bearing HeLa ascites tumors, intraperitoneal injection of AdRSVlaclys/pE1 resulted in a significantly higher percentage of infected HeLa cells as compared with the PBS controls (p < 0.05) or the AdRSVlaclys/pUC19 controls (p < 0.01). These data demonstrate that the transcomplementation of replication-deficient adenovirus with exogenous E1 DNA leads to limited replication, and this controlled replication enhances gene transfer efficiency of adenovirus in vivo. 相似文献
136.
Ginseng root, a traditional oriental medicine, contains more than a dozen biologically active saponins called ginsenosides, including one present in only trace amounts called ginsenoside-Rf (Rf). Previously, we showed that Rf inhibits Ca2+ channels in mammalian sensory neurons through a mechanism requiring G-proteins, whereas a variety of other ginsenosides were relatively ineffective. Since inhibition of Ca2+ channels in sensory neurons contributes to antinociception by opioids, we tested for analgesic actions of Rf. We find dose-dependent antinociception by systemic administration of Rf in mice using two separate assays of tonic pain: in the acetic acid abdominal constriction test, the ED50 was 56+/-9 mg/kg, a concentration similar to those reported for aspirin and acetaminophen in the same assay; in the tonic phase of the biphasic formalin test, the ED50 was 129+/-32 mg/kg. Rf failed to affect nociception measured in three assays of acute pain: the acute phase of the formalin test, and the thermal (49 degrees C) tail-flick and increasing-temperature (3 degrees C/min) hot-plate tests. The simplest explanation is that Rf inhibits tonic pain without affecting acute pain, but other possibilities exist. Seeking a cellular explanation for the effect, we tested whether Rf suppresses Ca2+ channels on identified nociceptors. Inhibition was seen on large, but not small, nociceptors. This is inconsistent with a selective effect on tonic pain, so it seems unlikely that Ca2+ channel inhibition on primary sensory neurons can fully explain the behavioral antinociception we have demonstrated for Rf. 相似文献
137.
OBJECTIVE: To determine the quantitative utility of transesophageal echocardiographic assessments of left ventricular function in pediatric patients with congenital heart disease by evaluating the variability between observers and between echocardiographic windows. DESIGN: Retrospective, blinded analysis. SETTING: University-associated pediatric hospital. PARTICIPANTS: Transthoracic and transesophageal echocardiographic images of 25 pediatric patients with congenital heart disease were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: End-diastolic area, end-systolic area, and fractional area change were measured from short-axis images of the left ventricle at the midpapillary level by two separate investigators. These measurements were compared by the method of Bland and Altman and Sheiner and Beal. Significant differences in measurements of end-diastolic and end-systolic area by different observers were noted, but they were systematic. A similar situation was noted for the comparison of transthoracic and transesophageal measurements of end-diastolic and end-systolic area. In the comparison of fractional area change between observers or windows, bias and absolute prediction error were lower, with 95% confidence limits of bias or absolute prediction error of 10% or less. CONCLUSIONS: The potential error in the measurement of fractional area change in 10% under optimal conditions. This would suggest that the assessment of ventricular function in the operating room or intensive care unit, under less than optimal conditions, should be viewed as a qualitative, rather quantitative, measurement. There may be significant interobserver and interwindow variability. 相似文献
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OBJECTIVE: The institutional review board (IRB) is a critical element in the protection of patients' and subjects' rights with regard to their participation in research protocols. The purpose of this study was to describe the structure and current practices of IRBs in the United States. METHODS: A self-administered questionnaire was mailed to the IRB chair of each U.S. hospital with a capacity of at least 400 beds (n = 907). The survey contained 21 questions outlining committee size and structure, review of research proposals, and policies concerning scientific misconduct. Chairs also were asked what advice they would offer a young investigator preparing a proposal for submission. RESULTS: A total of 488 surveys (54%) were returned; 447 of the responding institutions had an IRB committee. Committees had an average of 14 members, representing 27 medical specialties. Orthopedics had the least IRB representation (10% of committees), followed by emergency medicine (12%) and ophthalmology (15%). The majority of research proposals go through 5 specific steps once submitted for review. Common reasons for proposal rejection were improperly designed consent form (54%), poor study design (44%), unacceptable risk to subjects (34%), ethical or legal reasons (24%), and scientific merit (14%). When a research proposal is rejected, 86% of the responding IRBs assist the investigator in making appropriate revisions. Although a number of IRBs (17%) have dealt with scientific misconduct allegations, only 58% have a written policy regarding research integrity. CONCLUSION: Despite variations in committee structure and representation, IRBs have similar procedures for governing research. Investigators should be familiar with these procedures and are encouraged to discuss their proposal with an IRB representative prior to formal review. 相似文献
140.
Diaminopimelate dehydrogenase catalyzes the NADPH-dependent reduction of ammonia and L-2-amino-6-ketopimelate to form meso-diaminopimelate, the direct precursor of L-lysine in the bacterial lysine biosynthetic pathway. Since mammals lack this metabolic pathway inhibitors of enzymes in this pathway may be useful as antibiotics or herbicides. Diaminopimelate dehydrogenase catalyzes the only oxidative deamination of an amino acid of D configuration and must additionally distinguish between two chiral amino acid centers on the same symmetric substrate. The Corynebacterium glutamicum enzyme has been cloned, expressed in Escherichia coli, and purified to homogeneity using standard biochemical procedures [Reddy, S. G., Scapin, G., & Blanchard, J. S. (1996) Proteins: Structure, Funct. Genet. 25, 514-516]. The three-dimensional structure of the binary complex of diaminopimelate dehydrogenase with NADP+ has been solved using multiple isomorphous replacement procedures and noncrystallographic symmetry averaging. The resulting model has been refined against 2.2 A diffraction data to a conventional crystallographic R-factor of 17.0%. Diaminopimelate dehydrogenase is a homodimer of structurally not identical subunits. Each subunit is composed of three domains. The N-terminal domain contains a modified dinucleotide binding domain, or Rossman fold (six central beta-strands in a 213456 topology surrounded by five alpha-helices). The second domain contains two alpha-helices and three beta-strands. This domain is referred to as the dimerization domain, since it is involved in forming the monomer--monomer interface of the dimer. The third or C-terminal domain is composed of six beta-strands and five alpha-helices. The relative position of the N- and C-terminal domain in the two monomers is different, defining an open and a closed conformation that may represent the enzyme's binding and active state, respectively. In both monomers the nucleotide is bound in an extended conformation across the C-terminal portion of the beta-sheet of the Rossman fold, with its C4 facing the C-terminal domain. In the closed conformer two molecules of acetate have been refined in this region, and we postulate that they define the DAP binding site. The structure of diaminopimelate dehydrogenase shows interesting similarities to the structure of glutamate dehydrogenase [Baker, P. J., Britton, K. L., Rice, D. W., Rob, A., & Stillmann, T.J. (1992a) J. Mol. Biol. 228, 662-671] and leucine dehydrogenase [Baker, P.J., Turnbull, A.P., Sedelnikova, S.E., Stillman, T. J., & Rice, D. W. (1995) Structure 3, 693-705] and also resembles the structure of dihydrodipicolinate reductase [Scapin, G., Blanchard, J. S., & Sacchettini, J. C. (1995) Biochemistry 34, 3502-3512], the enzyme immediately preceding it in the diaminopimelic acid/lysine biosynthetic pathway. 相似文献