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81.
Astuti D Hart-Holden N Latif F Lalloo F Black GC Lim C Moran A Grossman AB Hodgson SV Freemont A Ramsden R Eng C Evans DG Maher ER 《Clinical endocrinology》2003,59(6):728-733
BACKGROUND: Germline mutations in three subunits of mitochondrial complex II (SDHB, SDHC and SDHD) may be associated with susceptibility to phaeochromocytoma (PC) and/or head and neck paraganglioma (HNPGL). METHODS: To further define the role of SDH subunit mutations in these disorders, we analysed a series of 22 probands with PC and evidence of genetic susceptibility (seven with familial PC only, one with familial PC and HNPGL, 10 sporadic cases with multiple PC and four cases of isolated paediatric onset PC) for germline SDHB, SDHC and SDHD mutations. In addition, we analysed 34 cases of HNPGL (30 isolated cases with single tumours, three isolated cases with multiple tumours and one familial case with multiple tumours) for somatic and germline mutations in SDHB, SDHC and SDHD. RESULTS: We identified four germline mutations (three SDHB and one SDHD, three novel) in the 22 PC probands. Combining these results with our previous series, we have detected germline SDHB or SDHD mutations in 2/12 (17%) of familial PC only kindreds, 4/5 (80%) of familial PC and HNPGL cases, 1/10 of sporadic multiple PC cases and 2/4 (50%) of paediatric PCs. No somatic mutations were detected in the HNPGL tumours, but four cases with multiple HNPGL had the common P81L germline SDHD mutation. Intriguingly a silent SNP (c.204C > T) in SDHD was significantly more common in HNPGL cases (6/34) than in controls (1/100, P = 0.0011). Combining our results with those from two other large studies in which both SDHB and SDHD have been analysed, SDHB mutations were most commonly associated with phaeochromocytoma susceptibility and SDHD with the development of HNPGL (P = 0.025). However, germline SDHB and SDHD mutations demonstrate considerable phenotypic variability and genotype-phenotype correlations are complex. CONCLUSION: The significantly lower frequency (P = 0.028) of germline SDH subunit mutations in familial PC only cases compared to those with familial PC and HNPGL suggests that further PC susceptibility gene(s) remain to be identified. 相似文献
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Syed Adibul Hasan Rizvi Syed Ali Anwar Naqvi Mirza Naqi Zafar Farida Mazhar Rana Muzaffar Rubina Naqvi Fazal Akhtar Ejaz Ahmed 《Transplant international》2009,22(6):615-621
Donor shortage and absence of transplant law lead to unrelated commercial transplants in Pakistan. We report the socio‐economic and outcome parameters of 126 local recipients of unrelated kidney vendor transplants presenting to our institute between 1997 and 2007. Their outcome was compared with 180 recipients of living‐related donor transplants matched for age, gender and transplant duration as controls. Age of commercial recipients was 35.63 ± 11.57 years with an M:F ratio of 2.4:1. Majority (92%) were transplanted in northern Pakistan paying US$7271 ± 2198. All were educated with 50% being graduates or above and rich earning a monthly salary of US$517 ± 518 with 44% earning >US$500. Comparison of commercial recipients with controls showed high comorbidities 35 (28%) vs. 14 (8%) (P = 0.0001) with diabetes, hepatitis‐C and cardiovascular diseases. Donor age was 29.97 ± 6.16 vs. 32.63 ± 9.3 years (P = 0.035). Biologic agents induction in 101 (80%) vs. 14 (8%) (P = 0.0001), acute rejections in 42 (33%) vs. 31 (17%) (P = 0.005), 1‐year creatinine 1.84 ± 1.28 vs. 1.27 ± 0.4 mg/dl (P = 0.0001), surgical complications 28 (22%) vs. 14 (8%) (P = 0.001), tuberculosis 14 (11%) vs. 6 (6%) (P = 0.007), acute hepatitis 20 (16%) vs. 3 (2%) (P = 0.0001), cytomegalovirus 33 (26%) vs. 21 (11%) (P = 0.001) and recurrent urinary tract infection 35 (28%) vs. 30 (16%) (P = 0.034). Overall 1‐ and 5‐year graft survival was 86% and 45% vs. 94% and 80%, respectively (P = 0.00001). Total deaths were 34 (27%) vs. 12 (6.0%) (P = 0.001). In conclusion, recipients of the vended kidneys are poor candidates, educated, rich and often self‐selecting. Their outcome is poor, which will leave them poorer still and back to dialysis if not death. 相似文献
85.
White M Lepage S Lavoie J De Denus S Leblanc MH Gossard D Whittom L Racine N Ducharme A Dabouz F Rouleau JL Touyz R 《Journal of cardiac failure》2007,13(2):86-94
BackgroundWe assessed the effects of candesartan in addition to angiotensin-converting enzyme (ACE) inhibitors on N-terminal pro-type natriuretic peptide (Nt-proBNP), systemic markers of inflammation and oxidative stress as well as on glucose regulation in patients with heart failure (HF).Methods and ResultsEighty patients with HF ages 62.5 ± 8.4 years presenting mostly with New York Heart Association class II symptoms (class II = 57.5%, III = 41.3%), and mean left ventricular ejection fraction 27.1 ± 7.3% were recruited. The patients were randomized to receive candesartan titrated to 32 mg 1 per day versus placebo in double-blind fashion for 6 months. Nt-proBNP, markers of inflammation and oxidative stress, glucose, insulin, and fasting insulin resistance index were analyzed. Candesartan decreased Nt-proBNP (median value = 12.4% versus −20.4%; [candesartan] P = .05), and high-sensitivity C-reactive protein (hsCRP) (+5.32% versus −20.3% [candesartan]; P = 0.046), without significantly influencing serum interleukin-6, interleukin-18, adhesion molecules, or markers of oxidative stress. Blood glucose decreased in patients treated with candesartan with a significantly greater effect in patients with higher blood glucose levels (P < .01 for interaction).ConclusionsThe addition of candesartan to ACE inhibitor and β-blocker decreases Nt-proBNP and hsCRP, but does not change the other markers of inflammation or oxidative stress in patients with heart failure. Dual angiotensin-II suppression also decreased blood glucose with a greater impact in patients with higher blood glucose level. 相似文献
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PURPOSE OF REVIEW: A review of recent studies was conducted to determine if guidelines promulgated by the American Society of Hematology and the British Committee for Standards in Haematology need to be updated as these were based mainly on expert opinion rather than outcomes derived from clinical trials. RECENT FINDINGS: Recent studies suggest that most patients with immune thrombocytopenic purpura have a disease that is generally well tolerated, with little morbidity. Splenectomy remains the best 'curative' treatment for adults with chronic disease (at least 6 months of follow up). Other treatments such as anti-D, rituximab or dexamethasone may allow the decision of splenectomy to be postponed, possibly indefinitely, if hemostatic platelet count is attained. Mortality from bleeding may be relevant only in patients refractory to splenectomy. Cytotoxic agents should be reserved for patients with bleeding refractory to other treatments. SUMMARY: Patients with platelet counts less than 30 x 10(9)/l or bleeding have to be treated but management decisions should also be based on lifestyle, age, and other medical conditions that may contribute to the risk of serious bleeding. An aggressive therapeutic approach is justified only in patients with platelet counts below 20 x 10(9)/l and those refractory to splenectomy. Newer therapies may be more targeted in their action. 相似文献
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Breton G Yahiaoui Y Deforges L Lebrun A Michel M Godeau B 《European Journal of Internal Medicine》2007,18(1):66-68
Q fever may lead to serious complications in chronically infected patients. We report two cases of psoas abscess due to Coxiella burnetii associated with lumbar osteomyelitis secondary to an aortic aneurysmal infection. Diagnosis was based on serology, and PCR detected C. burnetii DNA in an abscess sample. 相似文献
90.
Emran F Rihel J Adolph AR Wong KY Kraves S Dowling JE 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(48):19126-19131
Whereas the zebrafish retina has long been an important model system for developmental and genetic studies, little is known about the responses of the inner retinal neurons. Here we report single-unit ganglion cell recordings from 5- to 6-day-old zebrafish larvae. In wild-type larvae we identify at least five subtypes of ganglion cell responses to full-field illumination, with ON-OFF and ON-type cells predominating. In the nrc mutant retina, in which the photoreceptor terminals develop abnormally, we observe normal OFF responses but abnormal ON-OFF responses and no ON responses. Previously characterized as blind, these mutants lack an optokinetic reflex (OKR), but in another behavioral assay nrc mutant fish have near-normal responses to the offset of light and slow and sluggish responses to the onset of light. Pharmacological block of the ON pathway mimics most of the nrc visual defects. We conclude that the abnormal photoreceptor terminals in nrc mutants predominantly perturb the ON pathway and that the ON pathway is necessary to drive the OKR in larval zebrafish. 相似文献