Is diabetic nephropathy an inherited complication?

For yet unidentified reasons less than 50% of patients with insulin-dependent mellitus develop diabetic nephropathy. Genetic factors have been suggested as risk markers for development of nephropathy in diabetes. To further evaluate this hypothesis we studied the prevalence of nephropathy in diabetic siblings of diabetic patients with and without nephropathy. From a representative sample of 619 patients with insulin-dependent diabetes, we identified 20 patients with and 29 patients without nephropathy having diabetic siblings. Diabetic nephropathy (defined as urinary albumin excretion greater than 300 mg/24 hr) was found in 7 out of 21 siblings to patients with nephropathy and 3 out of 30 siblings to normoalbuminuric patients (P less than 0.04). No significant differences between the two groups of siblings with respect to age, diabetes duration, sex distribution, blood pressure or glycosylated hemoglobin A1c-levels were found. A significant correlation within sib-pair of glycosylated hemoglobin A1c was found (r = 0.47; P less than 0.001). We conclude that familial clustering of diabetic nephropathy does occur. This clustering may either be due to genetic inheritance or to sib-similarities due to shared environment, as indicated by the correlation of glycosylated hemoglobin A1c within sib-pairs.     

Insights from latent partition analysis into categories inherent in wellness-illness

How health–disease is perceived or conceptualized is important for nursing research There is increasing evidence that individual representations are important in constructing the experience of health–disease What is the personal saliency of health–disease for the individual? To explore the patterns of meaning inherent in health–disease, a card sort was undertaken among 15 healthy individuals and 15 individuals with chronic renal disease Both groups were given 28 cards to sort twice once for when they felt ‘well’ and again for when they felt ‘ill’ The theoretical basis underlying the items of the card sort was a model of wellness-illness being developed Latent partition analysis was used to cluster the concepts from each data set followed by multi-dimensional scaling to analyse the structure of the intercategory probability estimates A possible unidimensional pattern of meaning (harmony) emerged for the ‘well’ data and a two-dimensional pattern (disharmony and optimism) for the ‘ill’ data This represents a preliminary step in the development of a theoretical model that would permit assessment of the meaning of health–disease for the individual     

On the isolation of mast cells from human adenoids and tonsils

Human adenoids and tonsils were disintegrated mechanically and the cells dispersed by passage through a stainless-steel screen in EDTA-containing buffer. Collagenase digestion did not increase the yield of adenoidal cells. The mast cell content of the cell suspensions was in the range of 1–10 mast cells/10⁴ cells with an estimated mean of 1–2 mast cells/10⁴ cells, a value considerably below previous reports on adenoidal cell suspensions. The mast cell content was determined by staining with toluidine blue at low pH (to prevent interference by phagocytes). The mast cell count as assessed by alcian blue staining and by fluorescence microscopy after FITC-anti-human IgE binding was similar. Various attempts to enrich the cell suspension (i.e. by differential centrifugation, by gradient centrifugation on Ficoll or Ficoll-Hypaque and by velocity sedimentation at unit gravity) all gave negative results.     

Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.     

An efficient method for cloning human autoantigen-specific T cells

T-cell clones are valuable tools for investigating T-cell specificity in infectious, autoimmune and malignant diseases. T cells specific for clinically-relevant autoantigens are difficult to clone using traditional methods. Here we describe an efficient method for cloning human autoantigen-specific CD4+ T cells pre-labelled with CFSE. Proliferating, antigen-responsive CD4+ cells were identified flow cytometrically by their reduction in CFSE staining and single cells were sorted into separate wells. The conditions (cytokines, mitogens and tissue culture plates) for raising T-cell clones were optimised. Media supplemented with IL-2+IL-4 supported growth of the largest number of antigen-specific clones. Three mitogens, PHA, anti-CD3 and anti-CD3+anti-CD28, each stimulated the growth of similar numbers of antigen-specific clones. Cloning efficiency was similar in flat- and round-bottom plates. Based on these findings, IL-2+IL-4, anti-CD3 and round-bottom plates were used to clone FACS-sorted autoantigen-specific CFSE-labelled CD4+ T cells. Sixty proinsulin- and 47 glutamic acid decarboxylase-specific clones were obtained from six and two donors, respectively. In conclusion, the CFSE-based method is ideal for cloning rare, autoantigen-specific, human CD4+ T cells.     

Dibasic staining of large epoxy tissue sections and applications to surgical pathology

A variety of normal and pathologic aldehyde-fixed osmium postfixed human tissues were prepared as large sections embedded in Spurr epoxy. They were stained with a sequential basic fuchsin--methylene blue stain which gives "hematoxylin- and eosin-like" staining and additionally functions as several special stains. This technic also allows for electron microscopy directly on the embedded tissue. The histologic and cytologic preservation and overall staining was superior to tissue embedded in glycol methacrylate. The methods and technics presented in this article have important applications in diagnostic surgical pathology and histology in general.