Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Dementia: Weight Loss and Mealtime Challenges

Weight loss and problems with mealtime are challenges for people with Alzheimer’s disease and related dementias. These challenges are also difficult for caregivers who struggle to ensure that their family members have adequate nutritional intake. Although feeding tubes were once considered an effective solution, there is no evidence that they are effective, they may cause harm, and many authorities suggest that they not be used in people with advanced dementia. This article presents evidence-based recommendations for the assessment and management of weight loss in those with dementia and suggests supportive strategies for families striving to create meaningful mealtimes.     

Clopidogrel versus low‐dose aspirin as risk factors for epistaxis

Objectives: To quantify the relative risk of epistaxis for patients taking low‐dose aspirin or clopidogrel compared to patients taking neither drug. Design: Case‐control study. Setting: Primary care. Participants: 10,241 patients from three GP practices in the West Midlands. Main outcome measures: Epistaxis resulting in presentation to the GP, attendance at Accident & Emergency, or referral to ENT outpatients. Results: There was a significant difference in the proportion of patients with epistaxis across the three groups (χ² = 84.1; 2 degrees of freedom; P < 0.000001). Relative risk of epistaxis was increased in both the aspirin (RR = 9.04; 95% CI = 5.13–15.96) and clopidogrel (RR = 6.40; 95% CI = 2.33–17.56) groups compared to the no drug group. There was no increased risk of epistaxis with aspirin compared to clopidogrel (RR = 1.4; 95% CI = 0.6–3.4). Conclusion: There is an increased risk of troublesome epistaxis in patients taking aspirin or clopidogrel. There is no significant difference in risk of epistaxis between the two drug groups.     

Standards for total body fat and fat-free mass in infants

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altman's method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.