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991.
992.
Gluckman PD Lillycrop KA Vickers MH Pleasants AB Phillips ES Beedle AS Burdge GC Hanson MA 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(31):12796-12800
Developmental plasticity in response to environmental cues can take the form of polyphenism, as for the discrete morphs of some insects, or of an apparently continuous spectrum of phenotype, as for most mammalian traits. The metabolic phenotype of adult rats, including the propensity to obesity, hyperinsulinemia, and hyperphagia, shows plasticity in response to prenatal nutrition and to neonatal administration of the adipokine leptin. Here, we report that the effects of neonatal leptin on hepatic gene expression and epigenetic status in adulthood are directionally dependent on the animal's nutritional status in utero. These results demonstrate that, during mammalian development, the direction of the response to one cue can be determined by previous exposure to another, suggesting the potential for a discontinuous distribution of environmentally induced phenotypes, analogous to the phenomenon of polyphenism. 相似文献
993.
Osland EJ Powell EE Banks M Jonsson JR Hickman IJ 《Journal of gastroenterology and hepatology》2007,22(4):504-509
BACKGROUND AND AIMS: Despite the benefits of modest weight reduction for overweight patients with chronic liver disease, long-term maintenance of weight loss is difficult to achieve in clinical practice. The aims of this study were to determine if a nutrition research protocol could be translated into clinical practice and meet the demand for dietetic service, to evaluate the effectiveness and resource implications of intensive lifestyle intervention for weight loss, and to assess the effectiveness of standard dietetic therapy as a treatment option for patients unable to attend the program. METHOD: Using a modified research protocol, an intensive weight reduction program was introduced into standard clinical care for overweight patients attending a tertiary hospital liver outpatient clinic. An audit of weight loss and cost outcomes was conducted. RESULTS: Ninety-three patients were referred to the dietetic service for weight management. Of these, 50 enrolled in an intensive lifestyle intervention, 18 received standard dietetic therapy and 25 refused any intervention. After 6 months, 83% of patients in the intensive intervention achieved weight loss with a significant decrease in weight (P < 0.001) and waist circumference (P < 0.001). In contrast, only 24% of patients receiving standard dietetic therapy achieved weight loss with no significant change in mean weight or waist circumference. Cost per kilogram weight loss after intensive intervention was $AU31 and continuation of lifestyle intervention was calculated to be less than $AU100 per patient per year. CONCLUSIONS: A clinically based, intensive lifestyle intervention is a feasible treatment option for outpatient weight management in overweight patients with chronic liver disease. Providing patients who are unable to participate in intensive programs with standard dietetic therapy is not cost-effective. 相似文献
994.
Chow E Lipton L Carvajal-Carmona LG Arthur G Bhathal P Kaur G Jaeger E Woodford-Richens K Howarth K Tomlinson I Macrae F 《Journal of gastroenterology and hepatology》2007,22(12):2292-2297
BACKGROUND AND AIM: Familial juvenile polyposis syndrome (JPS) is a rare autosomal dominant condition in which patients develop hamartomatous gastrointestinal polyps with malignant potential. Pathogenic germline mutations in both the SMAD4 and BMPR1A genes involved in the transforming growth factor beta pathway account for 40% of cases of JPS. Genetic heterogeneity remains evident, as the balance of cases is not accounted for by mutations in these genes. The aim of this study was to determine the mutation responsible in a family with juvenile polyposis. METHODS: An Australian Caucasian family with juvenile polyposis have attended and followed surveillance plans through the Familial Bowel Cancer Clinic, The Royal Melbourne Hospital. A pedigree of the family was constructed with attention to the mixed phenotypic expression of polyps in affected members. Genetic testing for SMAD4 and BMPR1A mutations in germline DNA and linkage analysis to SMAD4, BMPR1A and 15q14 (CRAC1 locus) were performed. RESULTS: There were no pathogenic mutations in SMAD4 and BMPR1A. There was no linkage to SMAD4 or 15q14 (CRAC1 locus). Linkage analysis suggested a cryptic BMPR1A mutation or the presence of another gene in close proximity to the BMPR1A locus. Two additional candidate genes in the region of linkage (PTEN and MINPP1) were excluded. CONCLUSION: Most affected members of this Australian Caucasian family demonstrate a phenotype of mixed polyps: juvenile polyps, adenomas and/or hyperplastic polyps. Cloning of a potentially responsible gene closely linked to the BMPR1A locus or a cryptic mutation in BMPR1A may offer valuable insights into the pathogenesis of JPS. 相似文献
995.
Quantitative magnetization transfer imaging in Alzheimer disease 总被引:1,自引:0,他引:1
Ridha BH Tozer DJ Symms MR Stockton KC Lewis EB Siddique MM MacManus DG Rossor MN Fox NC Tofts PS 《Radiology》2007,244(3):832-837
PURPOSE: To prospectively measure magnetization transfer (MT) parameters, along with established atrophy parameters, in patients with Alzheimer disease (AD) and in age- and sex-matched control subjects. MATERIALS AND METHODS: Participants provided informed consent, and additional assent was obtained from next of kin of all patients with AD. The study was approved by the local ethics committee. Fourteen patients with AD (seven men; mean age, 67.2 years+/-6.5 [standard deviation]) and 14 control subjects (nine men; mean age, 65.5 years+/-9.4) underwent volumetric T1-weighted magnetic resonance and MT imaging. Whole-brain and total hippocampal volumes were adjusted for total intracranial volume. MT images were processed to derive four fundamental parameters in the hippocampal region by using the two-pool model of the MT phenomenon. Pearson correlation coefficients were used to assess the association between volumetric and MT parameters and Mini-Mental State Examination (MMSE) results. Logistic regression models were used to investigate whether combinations of parameters associated with MMSE could help provide better group discrimination. RESULTS: Patients with AD had significantly reduced whole-brain (P=.001) and total hippocampal (P<.001) volumes compared with those of control subjects. Two MT parameters were significantly reduced in the hippocampal region of patients: 1/(RAT2A)--that is, ratio of relaxation times of free proton pool, where RA equals 1/T1A and is the inverse of the longitudinal relaxation time of the free proton pool (P=.01)--and f*b, which equals fb/[RA(1-fb)], where fb is the restricted proton fraction (P<.001). Among patients with AD, whole-brain volume and hippocampal were correlated with MMSE results. When both parameters were included in a logistic regression model, only hippocampal was significantly associated with case-control status (P=.03). CONCLUSION: Certain MT parameters may serve as useful biomarkers of AD. 相似文献
996.
Definitive radiotherapy for medically inoperable early-stage serous and clear cell uterine carcinoma
High-risk, early-stage endometrial cancer is optimally treated by hysterectomy followed by adjuvant radiotherapy. In 1%–9%
of cases, the patient is medically unfit or personally unwilling to undergo primary surgery, and definitive radiotherapy may
be offered as an alternative definitive therapy. Although several series have reported excellent intrauterine control and
disease-specific survival for endometrioid histology, few outcome data are available for patients with serous or clear cell
histology treated with radiotherapy alone. We herein describe one case each of early-stage, medically inoperable serous/clear
cell histology endometrial cancer treated with definitive radiotherapy. Treatment was well tolerated by both patients, and
neither patient required a treatment break. Acute toxicity consisted of self-limited cystitis in one patient. One patient
was without evidence of disease progression at 54 months after radiotherapy. 相似文献
997.
998.
George RS Birks EJ Radley-Smith RC Khaghani A Yacoub M 《The Annals of thoracic surgery》2007,83(1):306-308
In recent years the conservative techniques to treat degenerative mitral valve insufficiency have developed to such an extent mainly due to a better understanding of the physiology and pathology of the mitral valve and to the possibility to get predictable and satisfactory results. Still a challenge persists for the cardiac surgeon when he has to deal with complex reconstructions. The technique described seems to offer an even better surgical option for patients with complex lesions involving the posterior mitral leaflet, especially as far as the hemodynamic performance is concerned. 相似文献
999.
Flanagan SE Patch AM Mackay DJ Edghill EL Gloyn AL Robinson D Shield JP Temple K Ellard S Hattersley AT 《Diabetes》2007,56(7):1930-1937
Transient neonatal diabetes mellitus (TNDM) is diagnosed in the first 6 months of life, with remission in infancy or early childhood. For approximately 50% of patients, their diabetes will relapse in later life. The majority of cases result from anomalies of the imprinted region on chromosome 6q24, and 14 patients with ATP-sensitive K+ channel (K(ATP) channel) gene mutations have been reported. We determined the 6q24 status in 97 patients with TNDM. In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced. K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities. The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001). K(ATP) channel mutations were identified in 26 additional family members, 17 of whom had diabetes. Of 42 diabetic patients, 91% diagnosed before 6 months remitted, but those diagnosed after 6 months had permanent diabetes (P < 0.0001). K(ATP) channel mutations account for 89% of patients with non-6q24 TNDM and result in a discrete clinical subtype that includes biphasic diabetes that can be treated with sulfonylureas. Remitting neonatal diabetes was observed in two of three mutation carriers, and permanent diabetes occurred after 6 months of age in subjects without an initial diagnosis of neonatal diabetes. 相似文献
1000.