278 research outputs found

    Post Conviction Relief: Tribulation After Trial

    Get PDF

    Differential Expression of TRAF1 Aids in the Distinction of Cutaneous CD30-Positive Lymphoproliferations

    Get PDF
    Lymphomatoid papulosis (LyP), primary cutaneous anaplastic large T-cell lymphoma (cALCL), and cutaneous infiltrates of systemic anaplastic large cell lymphoma (sALCL) are CD30-positive lymphoproliferative disorders of the skin that overlap clinically, histopathologically, immunophenotypically, and genetically but differ considerably in their prognosis. In particular, lesions of LyP regress spontaneously, whereas those of cALCL and sALCL persist and may progress and spread to extracutaneous sites. In contrast to patients with cALCL, LyP patients do not benefit from an aggressive radio- and/or chemotherapeutic approach. We generated a novel tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) antibody that recognizes a formalin-resistant epitope (Ber-TRAF1A) and investigated the expression of TRAF1, an intracellular component of TNFR signaling, in LyP and ALCL. We could show a strong TRAF1 expression in the tumor cells of most LyP cases (42/49, 84%). In contrast, tumor cells of primary and secondary cALCL revealed TRAF1 expression in only a few cases (3/41, 7%) as shown for sALCL without skin manifestation. The data indicate that TRAF1 expression reliably distinguishes LyP from primary or secondary cALCL. This might be of crucial diagnostic importance and has a strong impact on the treatment decision for patients with cALCL and LyP

    Impact of Race on Hyperparathyroidism, Mineral Disarrays, Administered Vitamin D Mimetic, and Survival in Hemodialysis Patients

    Get PDF
    Blacks have high rates of chronic kidney disease, are overrepresented among the US dialysis patients, have higher parathyroid hormone levels, but greater survival compared to nonblacks. We hypothesized that mineral and bone disorders (MBDs) have a bearing on survival advantages of black hemodialysis patients. In 139,328 thrice-weekly treated hemodialysis patients, including 32% blacks, in a large dialysis organization, where most laboratory values were measured monthly for up to 60 months (July 2001 to June 2006), we examined differences across races in measures of MBDs and survival predictabilities of these markers and administered the active vitamin D medication paricalcitol. Across each age increment, blacks had higher serum calcium and parathyroid hormone (PTH) levels and almost the same serum phosphorus and alkaline phosphatase levels and were more likely to receive injectable active vitamin D in the dialysis clinic, mostly paricalcitol, at higher doses than nonblacks. Racial differences existed in mortality predictabilities of different ranges of serum calcium, phosphorus, and PTH but not alkaline phosphatase. Blacks who received the highest dose of paricalcitol (>10 µg/week) had a demonstrable survival advantage over nonblacks (case-mix-adjusted death hazard ratio = 0.87, 95% confidence level 0.83–0.91) compared with those who received lower doses (<10 µg/week) or no active vitamin D. Hence, in black hemodialysis patients, hyperparathyroidism and hypercalcemia are more prevalent than in nonblacks, whereas hyperphosphatemia or hyperphosphatasemia are not. Survival advantages of blacks appear restricted to those receiving higher doses of active vitamin D. Examining the effect of MBD modulation on racial survival disparities of hemodialysis patients is warranted. © 2010 American Society for Bone and Mineral Research

    Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the <it>CDK4 </it>gene reported to date. Beside those high penetrance genes, certain allelic variants of the <it>MC1R </it>gene modify the risk of developing the disease.</p> <p>The aims of our study were: to determine the prevalence of germline <it>CDKN2A </it>mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible <it>CDK4 </it>mutations, and to determine the frequency of variations in the <it>MC1R </it>gene.</p> <p>Methods</p> <p>From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing.</p> <p>Results</p> <p>Seven families with CDKN2A mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54). One p14ARF variant was discovered in the control group and no mutations of the <it>CDK4 </it>gene were found.</p> <p>Most frequently found variants of the <it>MC1R </it>gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant.</p> <p>Conclusion</p> <p>The present study has shown high prevalence of p16INK4A mutations in Slovenian population of familial melanoma patients (37%) and an absence of p14ARF or <it>CDK4 </it>mutations.</p

    Mortality of combined serum phosphorus and parathyroid hormone concentrations and their changes over time in hemodialysis patients

    Get PDF
    BACKGROUND: Mineral and bone disorder (MBD) is common and associated with mortality in patients with chronic kidney disease (CKD). Given that disarrays in serum phosphorus (P) and parathyroid hormone (PTH) levels and their changes over time are closely interrelated, modeling mortality-predictability of their combinations may help improve CKD patient management. METHODS: A historical cohort study was undertaken to evaluate the joint effect of serum P and PTH levels on mortality in 107,299 chronic hemodialysis (HD) patients. Changes in serum P and PTH levels over 6 months, in particular discordant changes, were also modeled with mortality. RESULTS: HD patients were 64±15 (mean±SD) years old and included 45% women, 33% African–American, and 59% diabetic. Compared with serum P level ≥7.0 mg/dL and PTH level ≥600 pg/mL, adjusted hazard ratio (HR) tended to be lowest in patients with serum P level of 3.5–<5.5 mg/dL combined with PTH level of 150–<300 pg/mL (HR 0.64, 95% confidence interval 0.61–0.67). A change over time in serum P level towards the 3.5–<5.5 mg/dL range from higher or lower ranges was associated with a decreased mortality, whereas only change in PTH level from <150 pg/mL to 150–<300 pg/mL range was associated with a lower risk of mortality. Upon discordant changes of PTH and P, i.e., decrease in one of the two measures while the other increased, no change in mortality risk was observed. CONCLUSION: In CKD–MBD management, patent survival is the greatest with controlling both serum P and PTH levels in balance. Tailoring an individualized treatment strategy in CKD-MBD may benefit patients. Further studies are needed
    • …
    corecore