Platelet count is a sensitive predictor of autologous peripheral blood progenitor cell collection yield in previously treated plasma cell disease patients

BACKGROUND: It is often a clinical dilemma to determine when to collect autologous peripheral blood progenitor cells (PBPCs) in patients who received prior chemotherapy. It is also challenging to predict if the collected cells will be enough for one or two transplants. STUDY DESIGN AND METHODS: A total of 103 PBPC donors were followed to evaluate factors that predict poor autologous PBPC collection. The donors were categorized into three groups: plasma cell disorders (PCDs), lymphomas, and normal allogeneic donors. RESULTS: Our evaluation showed that platelet (PLT) count before growth factor administration significantly correlated with total CD34+ cell yield (Spearman r = 0.38, p < 0.001). Further analysis showed this correlation was only significant in plasma cell disease patients who received prior chemotherapy (Spearman r = 0.5, p = 0.008). Baseline PLT counts did not correlate with PBPC collection yield in untreated PCD, lymphoma, and normal allogeneic donors. In addition, daily PLT count during PBPC harvest correlated with CD34+ cell yield for that day (Spearman r = 0.41, p < 0.001). With a multiple linear regression model (adjusted R(2) = 0.31, AIC = 63.1), it has been determined that the baseline PLT count significantly correlates with total CD34+ cell yield in treated PCD patients. CONCLUSION: Baseline PLT count is a sensitive indicator of autologous PBPC mobilization in PCD patients who received prior chemotherapy. This finding may be considered before growth factor administration to determine the optimal period to mobilize treated PCD patients and to predict if enough cells can be collected for one or two transplants.     

A comprehensive study of nondysplastic and dysplastic serrated polyps of the vermiform appendix

Serrated colorectal polyps often show DNA hypermethylation and/or BRAF mutations and have been implicated in the "serrated neoplastic pathway." Although similar lesions occur in the appendix, they have never been systematically investigated. We evaluated a study group of 56 serrated polyps, a control group of 17 mucinous cystadenomas, and 4 adenocarcinomas with adjacent serrated polyps of the appendix to better understand their pathogenesis. The study cases were classified as nondysplastic or dysplastic serrated polyps and evaluated for MLH-1, MSH-2, MGMT, beta-catenin, p53, and Ki-67 expression, BRAF and KRAS mutations, and microsatellite instability. Serrated polyps usually occurred in older adults with no sex predilection. Most (59%) lacked dysplasia, but all showed similar molecular features, regardless of the degree of dysplasia present. Decreased MLH-1 (50%, P<0.001) and/or MGMT (59%, P<0.001) expression and BRAF (29%, P=0.007) mutations were significantly more common in serrated polyps, but BRAF mutations were detected in a minority of the extracted DNA in 15/16 cases. Of the 28 cases with decreased MLH-1 expression, none showed high-frequency microsatellite instability. Loss of MLH-1 (25%) or MGMT (50%) expression and BRAF or KRAS mutations (50%) were inconsistently present in adenocarcinomas and were not identified in combination in any cases. We conclude that molecular features of the "serrated neoplastic pathway" are present with similar frequencies among dysplastic and nondysplastic serrated appendiceal polyps and are not highly prevalent in adjacent carcinomas. These features, including BRAF mutations, may be more closely related to a serrated morphology in appendiceal polyps rather than biologically important changes.     

Use of density functional calculations to predict the regioselectivity of drugs and molecules metabolized by aldehyde oxidase

Aldehyde oxidase is a molybdenum hydroxylase that catalyzes the oxidation of aldehydes and nitrogen-containing heterocycles. The enzyme plays a dual role in the metabolism of physiologically important endogenous compounds and the biotransformation of xenobiotics. Using density functional theory methods, geometry optimization of tetrahedral intermediates of drugs and druglike compounds was examined to predict the likely metabolites of aldehyde oxidase. The calculations suggest that the lowest energy tetrahedral intermediate resulting from the initial substrate corresponds to the observed metabolite >or=90% of the time. Additional calculations were performed on a series of heterocyclic compounds where the products resulting from metabolism by xanthine oxidase and aldehyde oxidase differ in many instances. Again, the lowest energy tetrahedral intermediate corresponded to the observed product of aldehyde oxidase metabolism >or=90% for the compounds examined, while the observed products of xanthine oxidase were not well predicted.     

The Native Telehealth Outreach and Technical Assistance Program: a community-based approach to the development of multimedia-focused health care information

The development and dissemination of culturally relevant health care information has traditionally taken a "top-down" approach. Governmental funding agencies and research institutions have too often dictated the importance and focus of health-related research and information dissemination. In addition, the digital divide has affected rural communities in such a way that their members often do not possess the knowledge or experience necessary to use technological resources. And, even when they do, their skills may be limited, adequate only for implementing applications and programs designed by others who live and work outside of these communities. This need became the driving force in the creation of the Native Telehealth Outreach and Technical Assistance Program. The goal of the program is to equip Native community members, at both the lay and professional levels, with the means to use technology to address tribal health care needs. The transfer of relevant technical knowledge and skills enables participants to develop projects which enhance the community-wide dissemination of health care information. Nine community health advocates and professionals participated in the initial cohort. Eight of the participants successfully developed multimedia-based projects including Web sites, interactive CD-ROMs, and video focusing on a variety of health concerns. At the conclusion of the 18-month program period, projects were disseminated throughout rural communities. The NTOTAP staff continues to evaluate the use of these projects and their benefits within the rural communities.     

Perceptions of the process of care among caregivers and care recipients in dementia care networks

The Dementia Care Networks Study investigated 4 community-based, not-for-profit dementia care networks in Ontario, Canada. Investigators examined whether sociodemographic and health characteristics, type of support network, and amount of service use among care recipients and caregivers (n = 267 dyads) were associated with experiences with care processes. The process-of-care constructs were: family physicians' awareness of services; experiences with health care workers, and assessment and placement activities. The findings highlighted that family physicians' understanding of dementia and their ability to work with the dyad to become aware of and accept services, was an important component in the dyad's satisfaction. If caregivers received home support and the care recipients received emotional support from their social support network, they were more likely to be satisfied with their experiences with health care workers. In summary, increased awareness and provision of services were associated with more positive perceptions of network effectiveness.     

The importance of family environment for young adults burned during childhood

This study examined the role of family environment for young adult burn survivors making the transition from adolescence to adulthood. Ninety-three young adults who sustained large burns as children were asked to describe their families using the Family Environment Scale (FES). When examining the difference between burn survivors and the normative sample of the FES, burn survivors did not perceive their current family environment different than the normative group. However, burn survivors endorsed more items in the areas of achievement orientation and moral-religious emphasis, and less involvement in intellectual-cultural activities. We also examined the relationship between family characteristics on the FES and psychological adjustment of burn survivors as measured by the Young Adult Self-Report (YASR). Increased conflict on the FES was positively associated with YASR total problem score, internalizing behaviors, and externalizing behaviors. In addition, participation in recreational and social activities and organization both inversely correlated with YASR total problem score. In conclusion, increased family conflict was associated with decreased psychological adjustment of burn survivors as measured by the YASR total problem score.     

A patient with phonologic alexia can learn to read "much" from "mud pies"

People with phonologic alexia often have difficulty reading functors and verbs, in addition to pseudowords. Friedman et al. [Friedman, R. B., Sample, D. M, & Lott, S. N. (2002). The role of level of representation in the use of paired associate learning for rehabilitation of alexia. Neuropsychologia, 40, 223-234] reported a successful treatment for phonologic alexia that paired problematic functors and verbs with easily read relays that were homophonous nouns (e.g. "be" paired with "bee"). The current study evaluates the efficacy of pairing problematic grammatical words with relays that share initial phonemes, but vary in the relationship of their final phonemes. Results showed that reading of target grammatical words improved to criterion level (90% accuracy over two consecutive probes) in all experimental conditions with shared phonology, but remained far below criterion level in control conditions. There was a significant correlation between degree of phonologic relatedness and error rate. Maintenance of the treatment effect was poor as assessed by traditional measurement, however a dramatic savings during relearning was demonstrated during a subsequent treatment phase. The finding that reading can be re-organized by pairing target words not only with homophones, but with other phonologically related relays, suggests that this approach could be applied to a wide corpus of words and, therefore, potentially be of great use clinically. We suggest, within a connectionist account, that the treatment effect results from relays priming the initial phonologic units of the targets.     

Early blood-brain barrier permeability in cerebella of PLSJL mice immunized with myelin basic protein

The blood-brain barrier (BBB) is dramatically but transiently compromised in the cerebella of myelin basic protein immunized mice at least 1 week prior to the development of the paralytic phase of experimental allergic encephalomyelitis (EAE). Treatment of mice with the peroxynitrite-dependent radical scavenger uric acid (UA) during the first week after immunization blocks the early increase in cerebellar BBB permeability and the subsequent development of clinical signs of EAE. These results indicate that the early loss of BBB integrity in the cerebellum is likely to be a necessary step in the development of paralytic EAE.