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Kok K Dijkhuizen T Swart YE Zorgdrager H van der Vlies P Fehrmann R te Meerman GJ Gerssen-Schoorl KB van Essen T Sikkema-Raddatz B Buys CH 《European journal of medical genetics》2005,48(3):250-CGH
In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere. 相似文献
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Cheloff Abraham Z. Song Andrew B. D’Silva Kristin M. Al-Samkari Hanny 《Journal of thrombosis and thrombolysis》2022,53(3):708-711
Journal of Thrombosis and Thrombolysis - Bleeding gastrointestinal angiodysplasia may occur in patients with vasculitis and can be challenging to treat. We describe the novel use of bevacizumab... 相似文献
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Virk Zain M. Song Andrew B. Badran Yousef R. Al-Samkari Hanny 《Journal of thrombosis and thrombolysis》2022,54(2):255-259
Journal of Thrombosis and Thrombolysis - Heyde syndrome is characterized by the co-occurrence of aortic stenosis and bleeding gastrointestinal angiodysplasias, often with acquired von Willebrand... 相似文献
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Hanny Al-Samkari Aric D. Parnes Katayoon Goodarzi James I. Weitzman Jean M. Connors David J. Kuter 《Haematologica》2021,106(4):1148
Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x109/L and ≥30x109/L above baseline). Secondary outcomes included time to platelet count ≥100x109/L and rates of the following: platelet count <100×109/L, platelet count <75x109/L, platelet count <50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30-6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients. 相似文献
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Paul F. Lebeau Hanny Wassef Jae Hyun Byun Khrystyna Platko Brandon Ason Simon Jackson Joshua Dobroff Susan Shetterly William G. Richards Ali A. Al-Hashimi Kevin Doyoon Won Majambu Mbikay Annik Prat An Tang Guillaume Par Renata Pasqualini Nabil G. Seidah Wadih Arap Michel Chrtien Richard C. Austin 《The Journal of clinical investigation》2021,131(2)
Individuals harboring the loss-of-function (LOF) proprotein convertase subtilisin/kexin type 9 Gln152His variation (PCSK9Q152H) have low circulating low-density lipoprotein cholesterol levels and are therefore protected against cardiovascular disease (CVD). This uncleavable form of proPCSK9, however, is retained in the endoplasmic reticulum (ER) of liver hepatocytes, where it would be expected to contribute to ER storage disease (ERSD), a heritable condition known to cause systemic ER stress and liver injury. Here, we examined liver function in members of several French-Canadian families known to carry the PCSK9Q152H variation. We report that PCSK9Q152H carriers exhibited marked hypocholesterolemia and normal liver function despite their lifelong state of ER PCSK9 retention. Mechanistically, hepatic overexpression of PCSK9Q152H using adeno-associated viruses in male mice greatly increased the stability of key ER stress-response chaperones in liver hepatocytes and unexpectedly protected against ER stress and liver injury rather than inducing them. Our findings show that ER retention of PCSK9 not only reduced CVD risk in patients but may also protect against ERSD and other ER stress–driven conditions of the liver. In summary, we have uncovered a cochaperone function for PCSK9Q152H that explains its hepatoprotective effects and generated a translational mouse model for further mechanistic insights into this clinically relevant LOF PCSK9 variant. 相似文献
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Dental therapists’ expanded scope of practice in Australia: a 12‐month follow‐up of an educational bridging program to facilitate the provision of oral health care to patients 26+ years 下载免费PDF全文
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Michael J. Elliott Ravinder N. Maini Marc Feldmann Alice Long-Fox Peter Charles Peter Katsikis Fionula M. Brennan Jean Walker Hanny Bijl John Ghrayeb James N. Woody 《Arthritis \u0026amp; Rheumatology》1993,36(12):1681-1690
Objective. To evaluate the safety and efficacy of a chimeric monoclonal antibody to tumor necrosis factor α (TNFα) in the treatment of patients with rheumatoid arthritis (RA). Methods. Twenty patients with active RA were treated with 20 mg/kg of anti-TNFα in an open phase I/II trial lasting 8 weeks. Results. The treatment was well tolerated, with no serious adverse events. Significant improvements were seen in the Ritchie Articular Index, which fell from a median of 28 at study entry to a median of 6 by week 6 (P < 0.001), the swollen joint count, which fell from 18 to 5 (P < 0.001) over the same period, and in the other major clinical assessments. Serum C-reactive protein levels fell from a median of 39.5 mg/liter at study entry to 8 mg/liter at week 6 (P < 0.001), and significant decreases were also seen in serum amyloid A and interleukin-6 levels. Conclusion. Treatment with anti-TNFα was safe and well tolerated and resulted in significant clinical and laboratory improvements. These preliminary results support the hypothesis that TNFα is an important regulator in RA, and suggest that it may be a useful new therapeutic target in this disease. 相似文献