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101.
D Eccles P Lunt Y Wallis M Griffiths B Sandhu S McKay D Morton J Shea-Simonds F MacDonald 《Archives of disease in childhood》1997,77(5):431-435
Familial adenomatous polyposis (FAP) is a dominantly inherited predisposition to the development of many hundreds to thousands of adenomatous polyps of the colon. The mean age of onset is around 15 years, symptoms may arise in the third decade, and the median age for the development of colonic cancer is 35-40 years. Prophylactic colectomy reduces the risk of death from colorectal cancer to such an extent that late sequelae such as upper gastrointestinal tumours have become the main cause of mortality in appropriately managed patients. The age at which colonic surveillance begins reflects the natural history of the disease. Onset of polyp formation and cancer in childhood is very unusual, but has recently been associated with a specific mutation at codon 1309 in exon 15 where a more severe phenotype is sometimes observed. The case histories of two families are reported in which there is childhood onset of polyps in the youngest generation and in one case a carcinoma, in whom mutations have been identified in exon 11 of the APC gene. Several other affected relatives were diagnosed at ages ranging from 5-48 years, some already with a cancer at the time of first screening. Since the aim of screening for colonic polyps is prevention of colonic cancer, family members at risk should be offered genetic assessment and direct mutation testing where this is possible, usually in the early teens. In the absence of a genetic test (the situation in about one third of families) or in a known gene carrier, annual colonoscopy examination is advised from the same age. Clinicians should take note of the family history and be prepared to consider much earlier intervention if symptoms occur in a child with a family history of FAP. Where childhood onset of polyps has occurred, other children at risk in the family must be offered earlier genetic testing and endoscopic surveillance.
相似文献
102.
This study analysed a sample of food advertisements shown during 63 hours of children's programming to investigate compliance and non‐compliance with one of the Australian Children's Television Standards (CTS): CTS 20.2a. This standard regulates the way premium offers may, and may not, be used to sell products to children. Of the 1721 advertisements contained in the sample, 544 (32%) were for food. A significantly higher number of food advertisements (41%) were shown during ‘C’ programs (which are specifically regulated and produced for children six to 13 years of age and suitable for viewing without adult supervision), compared with 30% during the less regulated ‘G’ programs (P= < 0.001) (suitable for children to view without adult supervision but not produced specifically for a child audience). Over one‐third of food advertisements (36%) in ‘C’ time contained a premium offer compared with 17% in ‘G’ time (P= < 0.0001). Using a precisely defined interpretation of CTS 20.2a, this study found 30 (31%) of food advertisements breached the standard during ‘C’ programs. This was a significantly higher proportion than the 54 (12%) of breaches in ‘G’ time (P= < 0.0001). From this study, the current regulatory system has not resulted in more responsible food advertising during ‘C’ programs, and the widespread breaches of CTS 20.2a indicate this standard is ineffective as a means of regulating food advertising. The Australian Broadcasting Authority has recognised that children need protection from unfair marketing practices and the improper use of premium offers to promote a food product, therefore CTS 20.2a needs urgent review to make it more effective. 相似文献
103.
Collison M Glazier AM Graham D Morton JJ Dominiczak MH Aitman TJ Connell JM Gould GW Dominiczak AF 《Diabetes》2000,49(12):2222-2226
Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridemia, and hypertension map to a single region on rat chromosome 4. Genetic analysis of an SHR derived from a National Institutes of Health colony led to the identification of a causative mutation in the SHR Cd36. We have investigated glucose and fatty acid metabolism in the stroke-prone SHR (SHRSP). We demonstrate defects in insulin action on 2-deoxy-D-glucose transport (SHRSP 3.3 +/- 1.5 vs. 21.0 +/- 7.4 pmol x min(-1) x [20 microl packed cells](-1), SHRSP vs. WKY, respectively, P = 0.01) and inhibition of catecholamine-stimulated lipolysis (P < 0.05 at all concentrations of insulin) in adipocytes isolated from SHRSP. In contrast, basal levels of catecholamine-stimulated nonesterified free fatty acid (NEFA) release and plasma levels of NEFA are similar in SHRSP and WKY. These results are in agreement with the data on the SHR.4 congenic strain, which suggested that the QTL containing Cd36 mutations accounted for the entire defect in basal catecholamine action but only for approximately 40% of the SHR defect in insulin action. In the SHR, both abnormalities appear consequent of defective Cd36 expression. Because Cd36 sequence and expression are apparently normal in SHRSP, it is likely that the molecular mechanism for defective insulin action in this strain is caused by a gene(s) different than Cd36. 相似文献
104.
Collier GR McMillan JS Windmill K Walder K Tenne-Brown J de Silva A Trevaskis J Jones S Morton GJ Lee S Augert G Civitarese A Zimmet PZ 《Diabetes》2000,49(11):1766-1771
The hypothalamus plays a major role in the control of energy balance via the coordination of several neuropeptides and their receptors. We used a unique polygenic animal model of obesity, Psammomys obesus, and performed differential display polymerase chain reaction on hypothalamic mRNA samples to identify novel genes involved in obesity. In this study, we describe a novel gene that encodes a small protein we have termed "beacon." Beacon mRNA gene expression in the hypothalamus was positively correlated with percentage of body fat. Intracerebroventricular infusion of beacon resulted in a dose-dependent increase in food intake and body weight and an increase in hypothalamic expression of neuropeptide Y (NPY). Simultaneous infusion of beacon and NPY significantly potentiated the orexigenic response and resulted in rapid body weight gain. These data suggest a role for beacon in the regulation of energy balance and body weight homeostasis that may be mediated, at least in part, through the NPY pathway. 相似文献
105.
Botulinum toxin for cerebral palsy; where are we now? 总被引:1,自引:0,他引:1
In this article, the evidence base for botulinum-A treatment acquired in recent years is outlined, and the practicalities involved in providing this service are described. Botulinum-A is relatively new, and possible improvements for the future are considered. 相似文献
106.
Objectives: To determine 10-year quality-of-life (QOL) in head and neck cancer patients and to examine the potential predictors of late QOL. Design: Prospective 10-year (QOL) assessment in a cohort of head and neck cancer patients. Setting: Tertiary referral head and neck cancer centre in Auckland, New Zealand. Participants: Two hundred patients diagnosed and were treated for head and neck cancer. Exclusion criteria were blindness, learning difficulties or inability to understand or read English. Main outcome measures: Quality-of-life at 10 years measured by Auckland QOL questionnaire, and analysed for associations with the following co-variates: age, gender; co-morbidities (alcohol intake and smoking), type and stage of disease; treatment modality; and QOL measures. Results: At 10 years following diagnosis, overall QOL (life satisfaction), decreased significantly by an average of 11% (95% CI: −5, −17) compared with before treatment, and by 15% when compared with years 1 and 2. Pre-treatment QOL significantly predicted late QOL, whilst QOL 1 year after treatment did not. None of the socio-demographic, disease- or treatment-related factors predicted long-term QOL on univariate analysis, but this may be due to the small sample size. Conclusions: This observed, late drop in the QOL of head and neck cancer patients requires further corroboration and investigation. Due to small sample sizes associated with long-term studies in head and neck cancer cohorts, studies of predictors of long-term QOL will only be likely to succeed if done as multi-centre studies. As there is some evidence to suggest that psychosocial interventions improve the QOL of head and neck cancer patients, it may be appropriate to consider screening for risk of a late deterioration in QOL in order to plan appropriate psycho-social intervention. 相似文献
107.
Kuenzi FM Fitzjohn SM Morton RA Collingridge GL Seabrook GR 《Journal of neuroscience methods》2000,100(1-2):117-122
Sucrose-based artificial cerebrospinal fluid (aCSF) is sometimes used to prepare brain slices for in vitro electrophysiological experiments. This study compared the effect of preparing brain slices using chilled sucrose-based aCSF versus the conventional method using chilled aCSF on hippocampal synaptic plasticity. Brain slices from each treatment group were transferred to normal aCSF before electrophysiological recordings were made. The stimulus–response relationship of field excitatory postsynaptic potentials (fEPSPs) in the CA1 region was indistinguishable between the two treatment groups. However, the amount of LTP induced by either a θ-burst (four stimuli at 100 Hz repeated ten times at 200 ms intervals) or tetanic stimulation (100 Hz for 1 s) was significantly reduced in slices that had been prepared using sucrose-based aCSF. This was associated with reduced facilitation of the fEPSPs during the high frequency stimulus, reduced post-tetanic potentiation and short-term potentiation. In sucrose-cut slices the fEPSPs were slightly shorter in duration (29%, P<0.01), and during paired-pulse stimulation the broadening of the second fEPSP was enhanced. The LTP deficit in sucrose-cut slices was reversed by blocking GABAA receptor function with picrotoxin. These data suggest that the use of sucrose based aCSF better preserves GABA-mediated synaptic transmission, which limits the induction of LTP in hippocampal brain slices. 相似文献
108.
109.
Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph). 总被引:5,自引:0,他引:5
Lindsay M Morton Patricia Hartge Theodore R Holford Elizabeth A Holly Brian C H Chiu Paolo Vineis Emanuele Stagnaro Eleanor V Willett Silvia Franceschi Carlo La Vecchia Ann Maree Hughes Wendy Cozen Scott Davis Richard K Severson Leslie Bernstein Susan T Mayne Fred R Dee James R Cerhan Tongzhang Zheng 《Cancer epidemiology, biomarkers & prevention》2005,14(4):925-933
BACKGROUND: The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. METHODS: Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. RESULTS: In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1452). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking (> or = 36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. CONCLUSIONS: Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results. 相似文献
110.
Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma. 总被引:5,自引:0,他引:5
John P Leonard Morton Coleman Jamie Ketas Michelle Ashe Jennifer M Fiore Richard R Furman Ruben Niesvizky Tsiporah Shore Amy Chadburn Heather Horne Jacqueline Kovacs Cliff L Ding William A Wegener Ivan D Horak David M Goldenberg 《Journal of clinical oncology》2005,23(22):5044-5051
PURPOSE: To explore the safety and therapeutic activity of combination anti-B-cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m(2) and anti-CD20 rituximab 375 mg/m(2) monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate-risk or high-risk International Prognostic Index scores. All patients were rituximab na?ve. RESULTS: Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months. CONCLUSION: The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment. 相似文献