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991.
R. Kuefer M. Autenrieth K. Herkommer P. Blum A. Merseburger M. Hofer L. Rinnab J. Gschwend Dr. M. Ringhoffer 《Der Urologe. Ausg. A》2006,45(3):328-335
For patients with metastatic renal cell cancer (RCC), therapeutic options after cytokine failure are rather limited. There is a considerable need to identify new substances for systemic therapy. Due to upregulation after the loss of a functional von Hippel Lindau gene product, the vascular endothelial growth factor (VEGF) pathway is a promising target for a molecular based therapy. Over the last few years, therapeutic agents have been developed which inhibit this pathway at various levels. Here, we provide an overview of the molecular background and currently used drugs which have entered clinical trials in the setting of metastatic RCC disease. Until now, the results from early clinical trials are very promising, however, the best schedule, dosage, potential combination regimens, as well as long time efficacy, are still to be determined. 相似文献
992.
Robin R Blum Afshin Rahimizadeh Nataline Kardon Mark Lebwohl Huachen Wei 《Journal of cutaneous medicine and surgery》2001,5(3):228-230
BACKGROUND: In 1997, it was reported that a PTEN gene deletion, a common genetic mutation in Cowden's disease (CD), was identified in a patient with Bannayan-Riley-Ruvacalba (BRR), suggesting that the two diseases were allelic. However, the clinical overlap between the two diseases has largely remained unclear. OBJECTIVE: To confirm the genetic and clinical association in a family segregating both CD and BRR. METHODS: Clinical evaluation and genetic analysis using a denaturing gradient gel electrophoresis (DGGE), temporal temperature gradient electrophoresis (TTGE), and DNA sequencing techniques. RESULTS: Our patient presents with typical BRR clinical manifestations, including multiple lentigines on his penis, while his mother presents with typical manifestations of CD, including multiple malignancies. Genetic analyses of leukocytes from the patient and his mother showed mutations in exon 8 that was identified as the presumably truncating mutation R335X. CONCLUSION: This report provides clinical evidence that both BRR and CD are closely related and confirms the PTEN gene mutation in BRR and CD patients segregating in the same family, thus confirming the genetic linkage between the two genodermatoses. 相似文献
993.
Elevated liver enzymes are a frequent clinical finding with variable significance. The indication for further diagnostic work-up depends on the clinical presentation as well as on the extent and duration of liver enzyme elevation. It is important to recognize that liver enzymes within the normal range do not exclude liver disease, while healthy individuals can present with elevated liver enzymes. Blood chemistry analyses are very valuable as screening tests for liver diseases. They allow a differentiation between liver cell damage (ALT and AST elevated), cholestasis (alkaline phosphatase, bilirubin and y-GT elevated) and liver dysfunction (prolonged INR, albumin and cholinesterase reduced). If the laboratory values indicate any signs of liver disease, further diagnostic procedures are required. These should determine the etiology of the liver disease to allow a specific treatment and in addition provide information about progress and prognosis of the disease. 相似文献
994.
The effects of carbidopa on uptake of 6-18F-Fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma. 总被引:1,自引:0,他引:1
Henri J L M Timmers Mohiuddin Hadi Jorge A Carrasquillo Clara C Chen Lucia Martiniova Millie Whatley Alexander Ling Graeme Eisenhofer Karen T Adams Karel Pacak 《Journal of nuclear medicine》2007,48(10):1599-1606
6-(18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET is a useful tool for the detection of certain neuroendocrine tumors, especially with the preadministration of carbidopa, an inhibitor of DOPA decarboxylase. Whether carbidopa also improves (18)F-DOPA PET of adrenal pheochromocytomas and extraadrenal paragangliomas is unknown. The aim of this study was to investigate the sensitivity of (18)F-DOPA PET in the detection of paraganglioma and its metastatic lesions and to evaluate whether tracer uptake by the tumors is enhanced by carbidopa. METHODS: Two patients with nonmetastatic adrenal pheochromocytoma, and 9 patients with extraadrenal abdominal paraganglioma (1 nonmetastatic, 8 metastatic), underwent whole-body CT, MRI, baseline (18)F-DOPA PET, and (18)F-DOPA PET with oral preadministration of 200 mg of carbidopa. The dynamics of tracer uptake by these lesions and the physiologic distribution of (18)F-DOPA in normal tissues were recorded. RESULTS: Seventy-eight lesions were detected by CT or MRI, 54 by baseline (18)F-DOPA PET (P = 0.0022 vs. CT/MRI), and 57 by (18)F-DOPA PET plus carbidopa (P = 0.0075 vs. CT/MRI, not statistically significant vs. baseline). In reference to findings on CT and MRI, the sensitivities of baseline (18)F-DOPA PET were 47.4% for lesions and 55.6% for positive body regions, versus 50.0% (lesions) and 66.7% (regions) for (18)F-DOPA PET plus carbidopa (neither is statistically significant vs. baseline). Compared with baseline, carbidopa detected additional lesions in 3 (27%) of 11 patients. Carbidopa increased the mean (+/-SD) peak standardized uptake value in index tumor lesions from 6.4 +/- 3.9 to 9.1 +/- 5.6 (P = 0.037). Pancreatic physiologic (18)F-DOPA uptake, which may mask adrenal pheochromocytoma, is blocked by carbidopa. CONCLUSION: Carbidopa enhances the sensitivity of (18)F-DOPA PET for adrenal pheochromocytomas and extraadrenal abdominal paragangliomas by increasing the tumor-to-background ratio of tracer uptake. The sensitivity of (18)F-DOPA PET for metastases of paraganglioma appears to be limited. 相似文献
995.
Lawrence D. Kaplan Matthew J. Maurer Wendy Stock Nancy L. Bartlett Noreen Fulton Adam Pettinger John C. Byrd Kristie A. Blum Ann S. LaCasce Eric D. Hsi Yi Tian Liu David W. Scott David Hurd Amy S. Ruppert Francisco Hernandez-Ilizaliturri John P. Leonard Bruce D. Cheson 《American journal of hematology》2020,95(6):583-593
Immunochemotherapy followed by autologous transplant (ASCT) in CALGB/Alliance 59909 achieved a median progression-free survival (PFS) in mantle cell lymphoma (MCL) of 5 years, but late recurrences occurred. We evaluated tolerability and efficacy of adding post-transplant bortezomib consolidation (BC) or maintenance (BM) to this regimen in CALGB/Alliance 50403, a randomized phase II trial. Following augmented-dose R-CHOP/ methotrexate, high-dose cytarabine-based stem cell mobilization, cyclophosphamide/carmustine/etoposide (CBV) autotransplant, and rituximab, patients were randomized to BC (1.3 mg/m2 IV days 1, 4, 8, 11 of a 3-week cycle for four cycles) or BM (1.6 mg/m2 IV once weekly × 4 every 8 weeks for 18 months) beginning day 90. The primary endpoint was PFS, measured from randomization for each arm. Proliferation signature, Ki67, and postinduction minimal residual disease (MRD) in bone marrow were assessed. Of 151 patients enrolled; 118 (80%) underwent ASCT, and 102 (68%) were randomized. Both arms met the primary endpoint, with median PFS significantly greater than 4 years (P < .001). The 8-year PFS estimates in the BC and BM arms were 54.1% (95% CI 40.9%-71.5%) and 64.4% (95% 51.8%-79.0%), respectively. Progression-free survival was significantly longer for transplanted patients on 50403 compared with those on 59909. Both the PFS and OS were significantly better for those who were MRD-negative post-induction. The high risk proliferation signature was associated with adverse outcome. Both BM and BC were efficacious and tolerable, although toxicity was significant. The comparison between studies 50403 and 59909 with long-term follow up suggests a PFS benefit from the addition of BC or BM post- transplant. 相似文献
996.
997.
Ridhima Goel MD Davide Cao MD Rishi Chandiramani MD Anastasios Roumeliotis MD Moritz Blum BS Deepak L. Bhatt MD MPH Dominick J. Angiolillo MD PhD Junbo Ge MD Ashok Seth MD FRCP DSc Shigeru Saito MD Mitchell Krucoff MD Ken Kozuma MD PhD Rajendra M. Makkar MD Sripal Bangalore MD MHA Lijuan Wang PhD Kai Koo PhD Franz-Josef Neumann MD James Hermiller MD Giulio Stefanini MD PhD Marco Valgimigli MD PhD Roxana Mehran MD 《Catheterization and cardiovascular interventions》2021,98(6):1111-1119
998.
Ten polymorphic microsatellite loci were isolated for the Awaous guamensis, an amphidromous gobiid common to the Hawai’ian islands. The loci show a moderate to high degree of allelic diversity and observed levels of heterozygosity ranged from 0.13 to 0.87. Most loci conformed to Hardy–Weinberg equilibrium (HWE) and showed little evidence of linkage disequilibrium (LD). Our results indicate that all of the markers will be useful for assessing gene flow and population structure among evolutionary lineages of A. guamensis, and many could be useful for similar studies of congeners and other species native to Hawai’i. 相似文献
999.
1000.
Refractory chronic epilepsy associated with neuronal auto‐antibodies: could perisylvian semiology be a clue?
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Lisa Gillinder Linda Tjoa Basil Mantzioris Stefan Blum Sasha Dionisio 《Epileptic Disord》2017,19(4):439-449
Aims. We report a case series of 10 patients with chronic medically refractory antibody‐positive autoimmune epilepsy and assess their common clinical features. Immune‐mediated seizures are most commonly reported in the context of encephalitis or encephalopathy, with few reports focusing on lone, chronic epilepsy in the outpatient setting. Our aim was to define the potential diagnostic clues that might be present in these cases, leading to consideration of an autoimmune cause of the epilepsy. Methods. We performed a retrospective review of all patients presenting to the outpatient department of our unit who underwent autoimmune screening. All patients with chronic epilepsy and a positive result for an antibody known to be associated with epilepsy were included. Results. Sixty‐three patients underwent testing. Thirteen returned a positive result, however, only 10 of these were patients which chronic epilepsy who did not present with an acute illness. Common features in these cases included: perisylvian semiology, EEG abnormalities in the mid temporal region, normal or non‐specific MRI findings, depression, and head injury. Conclusion. In cases of medically refractory, lesion‐negative epilepsy, with predominantly perisylvian semiology, clinicians should have a high level of suspicion for the diagnosis of autoimmune aetiologies and a low threshold to perform autoantibody screening. This is especially true if there are atypical electrographic findings, a previous history of head injury, or co‐morbid depression. 相似文献