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Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing 总被引:1,自引:0,他引:1
Hutchin T Coy NN Conlon H Telford E Bromelow K Blaydon D Taylor G Coghill E Brown S Trembath R Liu XZ Bitner-Glindzicz M Mueller R 《Clinical genetics》2005,68(6):506-512
Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work. 相似文献
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Brain imaging of pain has made remarkable strides in the past year and a half. The basic regional activation pattern after acute nociceptive stimulation is now fairly well clarified. The extension of imaging studies from normal subjects to include cohorts of pathological pain patients is occurring. The techniques of positron emission tomography, functional magnetic resonance imaging and single photon emission computed tomography have all been applied to the study of human pain processing and the assessment of physiological interventions or psychological manipulations. Studies using labelled ligands to trace receptor alterations have also been conducted. Although more work could be done on the pharmacology and physiology of anesthesiology, the resulting set of observations provides a deeper understanding of the basic human neurophysiology of pain and a potential neural framework for better pain management. 相似文献
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DR Brewster MJ Manary IS Menzies EV O'Loughlin RL Henry 《Archives of disease in childhood》1997,76(3):236-241
Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation. 相似文献
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Interactive suppression of aberrant crypt foci induced by azoxymethane in rat colon by phytic acid and green tea 总被引:1,自引:2,他引:1
Several epidemiological studies point to a strong correlation between
nutrient composition of the diet and cancer of the colon. Phytic acid,
present in grains, has been credited with reducing the risk of cancer of
the colon. A number of reports are available indicating the benefits of
green tea consumption in reducing the risk of stomach, lung and skin
cancer, but little data are available on the effect of green tea in
reducing the risk of colon cancer. Also, there are no studies on the
combined effect of these compounds on colon tumorigenesis. Thus the primary
objective of this investigation was to elucidate the combined effects of
green tea and phytic acid on colonic preneoplastic lesions and the Phase II
enzyme glutathione S-transferase. Fisher 344 male weanling rats were
divided into nine groups of 15 rats each and fed the experimental diet for
13 weeks. Rats received two s.c. injections of azoxymethane in saline at 16
mg/kg body wt at 7 and 8 weeks of age. Rats received three levels (0, 1 and
2%) of phytic acid with three levels (0, 1 and 2%) of green tea within each
phytic acid level in a 3 x 3 factorial experiment. Results indicate that
while green tea had a marginal effect (P < 0.14), phytic acid
significantly reduced the incidence of aberrant crypt foci (P < 0.008).
The interaction between green tea and phytic acid was significant (P <
0.029 for distal and < 0.0168 for entire colon) and positive, pointing
to a synergistic effect of green tea and phytic acid.
相似文献
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Reza Saeidi Pour DR MED DENT Otto Zuhr DR MED DENT Markus Hürzeler PROF DR MED DENT Otto Prandtner MDT Caroline Freitas Rafael Daniel Edelhoff PROF DR MED DENT Anja Liebermann DR MED DENT 《Journal of esthetic and restorative dentistry : official publication of the American Academy of Esthetic Dentistry ... [et al.]》2017,29(2):93-101
30.
BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602) 相似文献