纪念黎磊石院士

<正>China and the world of nephrology lost one of their most distinguished clinicians and physician-scientists on 16 March 2010.     

Future Directions for Dissemination and Implementation Science: Aligning Ecological Theory and Public Health to Close the Research to Practice Gap

Dissemination and implementation science (DI) has evolved as a major research model for children's mental health in response to a long-standing call to integrate science and practice and bridge the elusive research to practice gap. However, to address the complex and urgent needs of the most vulnerable children and families, future directions for DI require a new alignment of ecological theory and public health to provide effective, sustainable, and accessible mental health services. We present core principles of ecological theory to emphasize how contextual factors impact behavior and allow for the reciprocal impact individuals have on the settings they occupy, and an alignment of these principles with a public health model to ensure that services span the prevention to intervention continuum. We provide exemplars from our ongoing work in urban schools and a new direction for research to address the mental health needs of immigrant Latino families. Through these examples we illustrate how DI can expand its reach by embedding within natural settings to build on local capacity and indigenous resources, incorporating the local knowledge necessary to more substantively address long-standing mental health disparities. This paradigm shift for DI, away from an overemphasis on promoting program adoption, calls for fitting interventions within settings that matter most to children's healthy development and for utilizing and strengthening available community resources. In this way, we can meet the challenge of addressing our nation's mental health burden by supporting the needs and values of families and communities within their own unique social ecologies.     

Association Between Sleep Problems and Perceived Cognitive Dysfunction Over 12 Months in Individuals with Multiple Sclerosis

Sleep problems are highly prevalent among individuals with multiple sclerosis (MS); however, the relationship between sleep problems and cognitive dysfunction is poorly understood in this population. In the present study, 163 individuals with MS and depression, fatigue, or pain completed self-report measures of sleep, cognitive dysfunction, and relevant demographic and clinical characteristics (e.g., disability severity, depressive symptomatology, pain intensity, fatigue impact) at four time points over 12 months. Mixed-effects regression demonstrated that poorer sleep was independently associated with worse perceived cognitive dysfunction (β = –0.05, p = .001), beyond the influence of depressive symptomatology. Fatigue impact was found to partially mediate this relationship. Results suggest that for individuals with MS and depression, fatigue, or pain, self-reported sleep problems are related to perceived cognitive dysfunction, and that fatigue impact accounts for part of this relationship.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Predictors of psychological distress in carers of people with amyotrophic lateral sclerosis: a longitudinal study

BACKGROUND: The majority of people providing informal care for people with amyotrophic lateral sclerosis (ALS) are spouses. This prospective study set out to examine changes in and predictors of psychological distress in spouse carers of people with ALS. METHOD: Fifty spouse carers of people with ALS underwent an initial interview and at least 21 underwent two further interviews, at median intervals of approximately 5-6 months. They rated the functional impact of their partner's ALS on everyday activities and everyday cognitive, emotional and behavioural changes that might have occurred in the person with ALS. They also rated their own social support and marital relationship, and completed measures of mood, burden and strain. The ALS Severity Scale was also completed for their partner with ALS. RESULTS: Over time, carers' psychological distress (a global measure combining mood, burden and strain) increased significantly. Initially carers' psychological distress was best predicted by the psychosocial impact of their spouse/partners' ALS, the extent to which their partner demonstrated emotional lability and how many other people were considered as dependents of the carer. Subsequently, carer distress was best predicted by an initial measure of negative social support and by their initial satisfaction with their social relationships. CONCLUSIONS: Despite the significant physical impairment associated with ALS, psychosocial factors appear important in determining short- and longer-term psychological well-being in carers of people with ALS and may help clinicians to predict which carers are likely to experience psychological difficulties as part of their caring role.     

Fine needle aspiration cytology of clear cell "sugar" tumor (PEComa) of the lung: report of a case

PEComa (clear cell "sugar" tumor) of the lung is a rare benign tumor of the lung probably arising from the perivascular epithelioid cells (PECs). We report a case of pulmonary PEComa arising from the periphery of the right lobe of a 64-year-old male. To our knowledge, this is the second case in the English literature diagnosed by fine needle aspiration biopsy. In this case report, the clinical, cytologic and immunohistochemical features clear cell "sugar" tumor of the lung are discussed and compared with the previously published literature. The differential diagnosis and methods for distinguishing the various clear cells lesions in the lung are discussed.     

Measuring maternal mortality: An overview of opportunities and options for developing countries

Background  

There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015.     

Phase I trial of BAY 50-4798, an interleukin-2-specific agonist in advanced melanoma and renal cancer.

PURPOSE: BAY 50-4798 is an analogue of interleukin-2 that selectively activates T cells over natural killer cells. This phase I study was designed to determine the maximum tolerated dose (MTD) and safety of BAY 50-4798, screen for tumor response, and assess pharmacokinetics. EXPERIMENTAL DESIGN: Forty-five patients with metastatic melanoma or renal cancer were enrolled, 31 on escalating doses to determine the MTD, with 20 renal cell carcinoma patients treated at MTD to detect antitumor activity. BAY 50-4798 was delivered i.v. every 8 h, days 1 to 5 and 15 to 19, and could be repeated after 9 weeks if tumor was stable or responding. RESULTS: The MTD was defined by and reported in terms of doses received. The doses tested ranged from 1.3 to 26.1 microg/kg, and the MTD was defined as 10.4 microg/kg based on toxicities similar to those of aldesleukin. Two patients achieved partial responses, one with melanoma and one with renal cell carcinoma. Among all 45 patients, 53% and 9% experienced a grade 3 and 4 toxicity, respectively. Among the patients treated at the MTD of 10.4 microg/kg, 71% and 10% experienced a grade 3 and 4 toxicity, respectively. Pharmacokinetics showed dose-dependent peak concentrations (C(max)) and area under the curve with a half-life of approximately 2 h and no evidence of accumulation. Lymphocyte subset analysis confirmed the preferential expansion of T-cell subsets over natural killer cells. CONCLUSIONS: The antitumor activity of BAY 50-4798 in malignancies that respond to high-dose interleukin-2 was low. BAY 50-4798 might provide advantages over aldesleukin in antigen-specific immunotherapies.     

Effects of the administration of high-dose interleukin-2 on immunoregulatory cell subsets in patients with advanced melanoma and renal cell cancer.

PURPOSE: High-dose recombinant human interleukin-2 (IL-2) therapy is of clinical benefit in a subset of patients with advanced melanoma and renal cell cancer. Although IL-2 is well known as a T-cell growth factor, its potential in vivo effects on human immunoregulatory cell subsets are largely unexplored. EXPERIMENTAL DESIGN: Here, we studied the effects of high-dose IL-2 therapy on circulating dendritic cell subsets (DC), CD1d-reactive invariant natural killer T cells (iNKT), and CD4(+)CD25(+) regulatory-type T cells. RESULTS: The frequency of both circulating myeloid DC1 and plasmacytoid DC decreased during high-dose IL-2 treatment. Of these, only a significant fraction of myeloid DC expressed CD1d. Although the proportion of Th1-type CD4(-) iNKT increased, similarly to DC subsets, the total frequency of iNKT decreased during high-dose IL-2 treatment. In contrast, the frequency of CD4(+)CD25(+) T cells, including CD4(+)Foxp3(+) T cells, which have been reported to suppress antitumor immune responses, increased during high-dose IL-2 therapy. However, there was little, if any, change of expression of GITR, CD30, or CTLA-4 on CD4(+)CD25(+) T cells in response to IL-2. Functionally, patient CD25(+) T cells at their peak level (immediately after the first cycle of high-dose IL-2) were less suppressive than healthy donor CD25(+) T cells and mostly failed to Th2 polarize iNKT. CONCLUSIONS: Our data show that there are reciprocal quantitative and qualitative alterations of immunoregulatory cell subsets with opposing functions during treatment with high-dose IL-2, some of which may compromise the establishment of effective antitumor immune responses.