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991.
O Gimm DJ Marsh SD Andrew A Frilling PL Dahia LM Mulligan JD Zajac BG Robinson C Eng 《Canadian Metallurgical Quarterly》1997,82(11):3902-3904
The autosomal dominant multiple endocrine neoplasia type 2 syndromes (MEN 2) comprise three clinically distinct entities, MEN 2A, familial medullary thyroid carcinoma and MEN 2B, which share a common clinical feature: medullary thyroid carcinoma (MTC). MEN 2B is considered to have the most aggressive form of MTC. Therefore, early detection of MEN 2B in order to prevent potentially lethal MTC is important. More than 95% of all MEN 2B cases are caused by germline mutation at codon 918 (M918T) in exon 16 of the RET proto-oncogene. In this study, we demonstrate the presence of germline codon 883 mutation (A883F) in 2 of 3 unrelated MEN 2B cases without codon 918 mutation. Our data demonstrate a novel etiologic event which may have roles in predisposition to MEN 2B when present in the germline and in the pathogenesis of sporadic MTC when somatic. 相似文献
992.
BJ Giantonio RK Alpaugh J Schultz C McAleer DW Newton B Shannon Y Guedez M Kotb L Vitek R Persson PO Gunnarsson T Kalland M Dohlsten B Persson LM Weiner 《Canadian Metallurgical Quarterly》1997,15(5):1994-2007
PURPOSE: To establish the maximum-tolerated dose (MTD) and define the toxicities of a single-dose infusion of PNU-214565, a recombinant Escherichia coli-derived fusion protein of Staphylococcal enterotoxin A (SEA) and the Fab-fragment of the C242 monoclonal antibody in patients with advanced colorectal and pancreatic carcinomas. To investigate the capability of PNU-214565 to induce a superantigen (SAg) response resulting in cytokine production and tumor regression. PATIENTS AND METHODS: Twenty-one patients (age range, 39 to 76 years; median, 64; 12 men, nine women; 18 colorectal, three pancreatic cancers) were treated with a single 3-hour infusion of PNU-214565, with doses ranging from 0.01 to 1.5 ng/kg. All patients had prior chemotherapy and a good performance status Eastern Cooperative Oncology Group [ECOG] performance status [PS] = 0 [n = 10]; PS = 1 [n = 11]), 10 had prior radiation, and 18 had prior surgery. RESULTS: Fever and hypotension were the most common toxicities. Fever of any grade occurred in 16 of 21 patients (76%): four of 21 (19%) with grade 2 and two of 21 (9.5%) with grade 3. Hypotension of any grade occurred in 13 of 21 (62%): four of 21 with grade 2 and one of 21 (5%) with grade 3. Interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF alpha) induction correlated with toxicity. In the two patients with grade 3 fever, peak IL-2 and TNF alpha levels were 2.9 IU/mL and 165 pg/mL, and 8.3 IU/mL and 245 pg/mL, respectively. Transient, > or = 50% decreases in circulating monocytes were observed in 17 of 21 patients as early as 0.5 hours (median time, 2 hours) from the start of infusion. Decreases (mean 33%) in circulating lymphocytes were observed in seven of 21 patients. All three patients with grade 3 toxicity were treated at the 0.5-ng/kg dose. The significance of baseline anti-SEA, human antimouse antibody (HAMA), CA242-soluble antigen levels, and T-cell receptor variable beta region (TCR V beta) subsets and histocompatibility leukocyte antigen-DR (HLA-DR) genotypes was assessed as possible predictors of toxicity. All toxicities were transient and easily managed. No grade 3 toxicity occurred at the higher dose levels. CONCLUSION: PNU-214565, a SAg-based tumor targeted therapy, is safe when given as a single 3-hour infusion at doses up to 1.5 ng/kg. The MTD for a single dose was not determined. The safety of a repeated dose schedule is currently under investigation, beginning with doses determined to be safe in this trial. 相似文献
993.
JA Maassen JJ Jansen JM van den Ouweland LM Hart EH van Essen HH Lemkes 《Canadian Metallurgical Quarterly》1998,142(5):229-233
Diabetes mellitus comprises many subtypes, the pathogenesis of each of which involves a combination of inherited and environmental factors. Recently a new subtype of diabetes mellitus was recognized in a Dutch pedigree, designated as 'maternally inherited diabetes and deafness' (MIDD). Impaired hearing is an associated phenomenon of the disease. Approximately 1.3% of all diabetic cases in the Netherlands exhibit the MIDD subtype. MIDD shows a strictly maternal heredity. In MIDD there is a guanine-for-adenine substitution at position 3243 in mitochondrial DNA. Mitochondria carrying this mutation exhibit a decreased functionality. In carriers of the MIDD mutation the insulin secretion by the pancreas in response to stimulation by glucose is impaired. 相似文献
994.
OBJECTIVE: To evaluate prognostic factors and survival of adult patients with brainstem gliomas. BACKGROUND: Brainstem glioma is a disease found primarily in children, with a median survival of only 9 to 12 months. However, the prognosis and survival of adults with this disease has not been determined with precision. METHODS: We conducted a retrospective analysis of patients older than 16 years at Memorial Sloan-Kettering Cancer Center with histologically proved or presumed brainstem glioma diagnosed between 1989 and 1997. We assessed the effect of gender, age at diagnosis, cranial nerve involvement, duration of symptoms, exophytic component, MRI enhancement, site of disease, treatment, and Karnofsky performance status on survival. RESULTS: Twenty-three patients were identified, but complete information was available in only 19 (12 males and 7 females). Patients ranged in age from 17 to 70 years (median, 40 years). Twelve patients were treated with radiotherapy at diagnosis and seven were observed, three of whom received subsequent radiotherapy. Median survival is 54 months (range, 3 to 98 months) and the 5-year survival is 45%. There was a trend for patients with a higher performance status at diagnosis to have longer survival, but this did not reach statistical significance. Other factors did not affect survival. CONCLUSION: Adults with brainstem gliomas may survive significantly longer than children, suggesting the disease may be less aggressive in adults. Furthermore, some patients with a long duration of symptoms or tectal or cervicomedullary tumors may be managed initially with observation alone. 相似文献
995.
996.
CA Tulleken A van der Zwan WJ van Rooij LM Ramos 《Canadian Metallurgical Quarterly》1998,88(5):925-927
In a patient with a giant aneurysm of the basilar artery trunk, a vein graft was interposed between the external carotid artery in the neck and the P1 segment of the posterior cerebral artery. Balloon occlusion of both vertebral arteries was performed 3 days later. The sylvian route was used for the grafting procedure and the connection to the posterior cerebral artery was made by using the excimer laser-assisted nonocclusive anastomosis technique. 相似文献
997.
The perceptual and cognitive processes that allow a person to see and interpret color are described. Color is a distraction only when these processes and the documents upon which they operate are construed very narrowly. Functions for the use of color in documents that rely on the perceptual and cognitive processes are presented 相似文献
998.
The strength of the radius depends on the mechanical properties of cancellous and cortical bone. By assessing both compartments quantitatively with bone densitometry, we tried to identify the specificity of each in predicting the load at which the distal radius will fracture. Twenty human cadaver forearms were scanned for bone mineral and geometric properties with quantitative computed tomography and dual x-ray absorptiometry. In both a neutral loading situation and one in which the wrist was extended 45 degrees, the load distribution was determined with pressure-sensitive films, and a fracture simulating a fall on the hand was produced with a material testing machine. Fractures that occur with the wrist in extension were produced by a central impact of the scaphoid onto the radiocarpal joint, and those that occur under neutral loading conditions were produced by a more commonly distributed loading pattern. The load at fracture was most specifically predicted (r2=0.74) by bone mineral and geometric measures of the cortex at the shaft of the radius. Bone mineral density measures of trabecular (r2=0.64) and total (r2=0.66) bone were less successful in predicting the fracture load. After adjustment for bone size, the geometric and density measures revealed similar specificity. Cortical bone, therefore, contributes significantly to the strength of the distal radius and may play an important role in the prediction of osteoporotic wrist fractures. 相似文献
999.
1000.