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J Tyson L Tranebjaerg S Bellman C Wren JF Taylor J Bathen B Aslaksen SJ S?rland O Lund S Malcolm M Pembrey S Bhattacharya M Bitner-Glindzicz 《Canadian Metallurgical Quarterly》1997,6(12):2179-2185
The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules. 相似文献
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We have studied the function of partial orthotopic liver transplantation in the rat by evaluating prothrombin time (PT), liver blood flow, basal and glucose-stimulated insulin secretion and glucose tolerance, and the reticuloendothelial function (RES) in hepatectomized rats subjected to partial liver transplantation. A graft corresponding to 68% of a normal liver was transplanted to totally hepatectomized rats. Comparison was made between control rats and rats subjected to 32% liver resection. PT was not significantly different in the transplanted group compared with liver-resected and control rats. Laser Doppler flowmetry showed that at 28 days after surgery, blood flow had increased in the transplanted livers. Furthermore, on the third day after transplantation, basal plasma insulin was increased and the plasma insulin response to glucose was exaggerated, suggesting reduced insulin action and impaired insulin degradation. Finally, uptake of radioactive-labeled E. coli bacteria, as a measure of RES function, was not compromised in transplanted animals. Based on these results, we conclude that reduced-size liver transplant in out-bred rats results in fast normalization of liver function after surgery although, immediately after surgery, glucose intolerance is seen. 相似文献
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OBJECTIVE: To examine the association between sexual abuse in childhood and adult depression in women. DESIGN: Two stage, case detection and case identification design, using the 30-item general health questionnaire and the Beck depression inventory for screening and the affective items relating to current functioning on the schizophrenia and affective disorders schedule to identify depressed cases. Details of sexual abuse in childhood were elicited retrospectively by semistructured interview, and social problems by the social problems questionnaire. SETTING: Three general practices, in middle class suburban, deprived inner city, and rural areas. SUBJECTS: 1189 women were screened and 237 subsequently interviewed; 132 were depressed. RESULTS: 49 (37%) of the depressed interviews and 24 (23%) of the non-depressed interviews reported experience of sexual abuse when they were aged under 16 years. A positive association existed between the more severe abuse and depression--all those who had experienced penetration were depressed as adults. A relation was also found between sexual abuse in childhood and sexual problems, housing problems, and problems with their children at school. CONCLUSION: A positive association between child sexual abuse and depression was confirmed, but this was confined to more severe abuse (penetration or attempted penetration). 相似文献
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The implementation of Medicare's prospective payment system in acute care has coincided with a steady increase in medically unstable admissions to our freestanding rehabilitation facility. We investigated the consequences of these admissions by collecting medical information regarding transfers beginning in 1983. Patients requiring transfer back to the acute setting within 1 day of admission were considered medically unstable and their charts were reviewed. The number of patients requiring transfer back within 1 day increased from 1.5% of all first admissions to 3.1% in 1988 (Mantel - Haenszel chi 2 = 8.03, (df = 1), p < .01), but the increase among Medicare patients alone was not significant. This progressive increase was most pronounced in the cerebrovascular accident and spinal cord injury populations. Beginning in 1988, an intensified preadmission evaluation program was implemented, resulting in a significant decline in unstable patient transfers from hospitals where our consultants were on staff. Physiatric consultations at referral institutions decreased the number of unstable patients at admission. 相似文献
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The purpose of this study was to identify family physicians' firearm safety counseling beliefs and behaviors. A survey was mailed to a random sample of 600 members of the American Academy of Family Physicians. A three wave mailing technique was used to maximize the response rate and yielded 271 usable surveys (55% response rate). Outcome measures included training experience in firearm safety counseling, the prevalence of firearm safety counseling by family physicians, and their perceptions regarding such counseling. The majority (78%) of family physicians lacked formal training on how to counsel patients about firearm safety and 49% believed more time should be spent in residency programs on firearm safety counseling. The majority (84%) of respondents never or rarely counseled patients on firearm safety and 50% believed firearm safety counseling should be a low priority in their delivery of primary care. The majority of respondents did not regularly counsel patients about firearm safety, did not believe firearm safety counseling should be a priority, and did not believe firearm safety counseling would be effective in reducing firearm-related trauma. 相似文献
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OBJECTIVE: Highly sulfated glycosaminoglycans (GAG) have been demonstrated in every form of amyloid examined to date. Based on temporal studies in murine amyloidogenesis heparan sulfate is deposited coincidentally with the amyloid protein. Our purpose was to follow in vivo GAG synthesis by monitoring 35SO4 incorporation during amyloidogenesis. Several necessary previously unexamined nonamyloidogenic controls were also examined. METHODS: Murine splenic amyloid was induced with lipopolysaccharide (LPS) and amyloid enhancing factor (AEF). Splenic GAG synthesis was monitored by 35SO4 incorporation. Corrections were made for alterations in SO4 metabolism which occur during inflammation. RESULTS: All animals with an inflammatory reaction had a marked increase in GAG synthesis. Those animals receiving AEF, or AEF+LPS, had a significant increase in heparan sulfate synthesis. This was particularly profound in the group developing amyloid (i.e., AEF+LPS). CONCLUSION: Our results indicate that critical factors in amyloid deposition include quantitative as well as qualitative changes that take place in tissue GAG synthesis. A distinct metabolic effect of AEF is demonstrated for the first time. 相似文献
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The association of antiphospholipid antibodies with unexplained thrombo-occlusive vascular disease is well known but often remains unrecognized. The most well-studied clinical manifestation is venous thrombosis, but arterial occlusive disease involving multiple sites is also well documented. Twenty-six cases of thrombo-occlusive disease were observed in 22 patients over a 3-year period. Magnetic resonance imaging and angiography were used to make the diagnoses. None of the patients who underwent angiography or venography developed thrombolytic disease related to the puncture site. This group of patients with antiphospholipid antibody syndrome had a wide distribution of arterial and venous thrombotic disease. Radiologists should consider antiphospholipid antibody syndrome in the differential diagnosis when evaluating thrombo-occlusive vascular disease that is unexpected or occurs without risk factors. Knowledge of antiphospholipid antibody status has important implications for prognosis and therapy. 相似文献