Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria.

Chronic graft-versus-host disease (cGVHD), a common complication after stem cell transplant (SCT), has an impact on morbidity and survival. Previous classification of cGVHD has not been reproducible or prognostic for nonrelapse mortality (NRM). Recently the National Institutes of Health (NIH) consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown. Patients (N = 110) undergoing an SCT for a hematologic malignancy and surviving until day 100 posttransplant from 2001 to 2003 were studied. The overall survival (OS) using a landmark analysis at day 100 was 44% versus 66% (no GVHD vs. GVHD, P = .026). The OS of patients with various types of GVHD as proposed by the NIH criteria were significantly different (P < .0001). In a univariate analyses, this was more apparent when patients with any acute features of GVHD were compared to classic cGVHD (3-year OS 46% vs. 68%, P = .033). The 3-year NRM for the entire cohort was 21%, and was not affected by presence or absence of GVHD or subtypes of GVHD. In a multivariable analysis, extensive cGVHD (hazard ratio [HR] 0.35, P = .015) and having any acute feature of GVHD after day 100 (HR 3.36, P = .0144) were significant independent predictors of survival. The OS with different NIH subtypes of GVHD after day 100 from SCT varies, and is superior for patients with classic cGVHD.     

Preferential incorporation of 3'-azido-2',3'-dideoxythymidine (azt) in telomeric sequences of cho cells

3'-Azido-2',3'-dideoxythymidine (AZT), the thymidine analogue used against human immunodeficiency virus 1 (HIV-1), exhibits bone marrow and blood toxicity in humans, presumably as the result of genotoxic mechanisms induced by incorporation of AZT into eukaryotic DNA. Preferential incorporation of AZT into telomeric regions of DNA of Chinese hamster ovary (CHO) cells has been previously demonstrated by immunofluorescence using anti-AZT antibodies. We quantitatively compared the amount of [H-3]-AZT bound to telomeric and non-telomeric sequences of CHO cell DNA. DNA from cells exposed to [H-3]-AZT was digested by a mixture of restriction enzymes, frequent cutters in the overall genome, without restriction sites in the telomeric repeat. As a result, the telomeric fraction (TF): isolated by separation columns, comprised longer sequences (> 2 kb) than the non-telomeric fraction (NTF). Radioactivity associated with each fraction revealed a three fold increase in [H-3]-AZT incorporated in the TF compared with the NTF. No preferential telomeric binding was detected for [H-3]-thymidine (Tdr) or [H-3]-5'bromodeoxyuridine (BrdU) in similar experiments or in DNA of AZT-treated mouse primary fibroblasts, cells with large telomeric repeats that lack telomerase. When the chromosomal ends of high molecular weight [H-3]-AZT-DNA were digested with Pal 31, the radioactivity was double in the TF compared with the NTF. Therefore incorporation of AZT in CHO immortalized cells but not in primary fibroblasts (that lack telomerase) indirectly shows that AZT incorporation could be telomerase-mediated.     

Megalophallus as a sequela of priapism in sickle cell anemia: use of blood oxygen level-dependent magnetic resonance imaging

Priapism is a common complication of sickle cell anemia. We report a little known sequela of priapism: painless megalophallus, with significant penile enlargement. The patient had had an intense episode of priapism 9 years previously and his penis remained enlarged. Blood oxygen level-dependent magnetic resonance imaging revealed enlarged, hypoxic corpora cavernosa. Megalophallus probably resulted from permanent loss of elasticity of the tunica albuginea due to severe engorgement during the episode of priapism. This sequela needs to be recognized by physicians because no intervention is necessary and sexual function seems to remain intact.     

Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis.

PURPOSE: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue. RESULTS: The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity. CONCLUSION: This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.     

Context-specific food-based approach for ensuring nutrition security in developing countries: a review

Sustainable food strategies for meeting nutrient needs in developing countries are not well established. The available evidence shows that more than one-third of the world’s population is facing under-nutrition, of which the most affected individuals are children and mothers from poor countries. In most developing countries, losses resulting from malnutrition are between 3 and 16% of the gross domestic product. This burden is far larger than the donor-driven and government programmes can tackle alone. As such, an innovative approach, which is independent and not donor-based, is needed to reduce the burden of malnutrition in low-income countries. In this review, we describe a context specific food-based approach for addressing malnutrition in developing countries. The approach deploys the hybrid public–private delivery model that enables cost sharing and efficiency gains in resource-poor countries. The model influences players to consider consumers’ perspectives, which often are neglected and truly engage them as key stakeholders.     

Advanced Psychometric Methods for Developing and Evaluating Cut-Point-Based Indicators

In this study, we offer some advice on the use of empirical techniques to create categorical indicators from responses to multiple survey questions that ostensibly compose scales. We discuss the use of advanced psychometric methods, including confirmatory factor analysis for ordered categorical measures (CFA-OCM) and item response theory (IRT), to expand 12 previously published criteria for cut-point development and evaluation offered by Moore et al. (Indicators of Child Well-Being: The Promise for Positive Youth Development. Annals of the American Academy of Political and Social Science. Special Issue: Positive Development: Realizing the Potential of Youth. 591:125–145, 2004). We present an application of this advice by developing categorical cut-points for the social skills and behavior problems subscales of the U.S. National Survey of Children’s Health (NSCH) Social Competence Scale. We used data from the 2007 NSCH, a large cross-sectional, random-digit-dial telephone survey of a representative sample of the noninstitutionalized population of U.S. children 0–17 years of age. Parents of children aged 6 to 17 years (n = 63,364) responded to 4 questions about their children’s behavior problems and 4 questions about their children’s positive social skills. IRT analyses indicated that IRT model-based scores of +1.8 and −0.7 provided suitable high and low cut-points, respectively, for the behavior problems subscale. These cut-points had marginal reliabilities of 0.70 and 0.67 respectively, and corresponded to raw subscale scores of 13 and 8 IRT analyses indicated that an IRT model-based score of −1.8 provided a suitable cut-point for identifying children with low levels of positive social skills. This cut-point had a marginal reliability of 0.63 and corresponded to a raw subscale score of 13. For both subscales and cut-point sets, frequency distributions demonstrated that the cut-points identified sufficient proportions of children generally as well as within demographic subgroups. Our findings indicate that analysts can use raw subscale scores and cut-points of 13 and 8 to identify children with high, moderate, and low levels of behavior problems. Our results demonstrate that, for the positive social skills subscale, the subscale’s psychometric properties only support a single cut-point of 13 that identifies children with low levels of positive social skills. Our study highlights the iterative, empirically-based process that cut-point development should follow and shows the value of modern test theory-based psychometric methods to inform this process.     

Non-imaging-guided fine-needle aspiration of liver lesions: a retrospective study of 279 patients

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