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.     

Baroreflex sensitivity in the elderly with silent myocardial ischemia

In order to assess high-pressure barocepture sensitivity and parasympathetic function in elderly patients with silent myocardial ischemia, we selected 45 inpatients in our geriatric unit for a prospective cohort study of patients with coronary heart disease. All patients were over 65 years of age (37 men and 8 women) and had coronary heart disease, documented by an angiographic study and electrocardiographic evidence of myocardial ischemia during exercise stress testing, performed according to the Bruce protocol. The subjects were divided in three subgroups: group 1 (22 patients) with electrocardiographic and echocardiographic history of myocardial infarction but no angina chest pain during exercise testing; group 2 (13 patients) with no exercise induced chest pain; and group 3 (10 patients) with exercise-induced chest pain. Baroceptor sensitivity was assessed in all subjects, by evaluating heart rate changes expressed in RR interval on the basis of changes in the mean arterial pressure during intravenous infusion of stepwise doses (50-100 and 150 mug) of phenylephrine hydrochloride. Heart rate changes were also evaluated during overshoot of the Valsalva maneuver (Valsalva max.), providing an index of parasympathetic activity. Our results showed that group two patients (only silent ischemia) had significantly (P>0.001) greater baroceptor sensitivity than the other two groups (group 2; 15.2+/-1.9 ms/mmHg; group 1: 10.0+/-1.7 ms/mmHg; and group 3: 9.8+/-1.7 ms/mmHg). Group two also showed a significant positive correlation (r=0.58; P<0.05) between baroceptor sensitivity and end-diastolic pressure and a significant inverse correlation (r=-0.672; P<0.05) between baroceptor sensitivity and the ejection fraction. Group 2 patients had a significantly longer RR interval than group 1 (P<0.05) and group 3 (P<0.05); a significant positive correlation (r=0.620; P<0.05) between Valsalva max. and end-diastolic pressure; and a significant inverse correlation (r=0.694; P<0.05) between Valsalva max. and the ejection fraction. Valsalva max. and baroceptor sensitivity correlated significantly in all three groups (group 1, r=0.707; P<0.001; group 2, r=0.94; P<0.001; and group 3; r=0.833; P<0.05). In conclusion our data suggest that elderly patients with silent ischemia appear to have an increased capacity for evoking parasympathetic reflexes that could inhibit pain perception.     

Vitamin D: drug of the future. A new therapeutic approach

Besides increasing calcium absorption in the bowel and promoting the normal formation and mineralization of bone, vitamin D exerts relevant pleiotropic effects in different tissues. Serum levels of vitamin D show correlation with the risk of infections, cardiovascular diseases, cancer and autoimmune disorders. The possible therapeutic role of vitamin D in different kind of diseases: inflammatory, immunologic, infectious and neoplastic ones, explains the growing interest in this vitamin due to its pleiotropic effects, and makes it a candidate to become a potential drug in the next future.     

Screening cognition in the elderly with metabolic syndrome

Abstract Background: Metabolic syndrome reaches its highest prevalence in the elderly, and evidence suggests that metabolic syndrome could be an independent risk factor for cognitive impairment. The aims of this study were to detect whether patients with metabolic syndrome have lower cognition and to investigate whether there is a relationship with cognition and single metabolic syndrome components. Methods: We assessed fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides, high-sensitivity C-reactive protein (hsCRP), and anthropometric measurements. Metabolic syndrome was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The population sample was divided into two groups according to the presence of metabolic syndrome. Cognitive function was investigated through the Mini-Mental State Examination (MMSE). Results: We enrolled 159 elderly subjects (mean age, 69.8±4.8 years). Seventy had metabolic syndrome. Metabolic syndrome subjects had higher hsCRP values (P<0.0001) and lower MMSE scores (P<0.0001) than those without metabolic syndrome. MMSE scores were significantly correlated with body mass index (BMI), hsCRP, metabolic syndrome, the number of metabolic syndrome components, and each of them. However, at multivariate regression analysis, only fasting blood glucose [FBG; B=-0.046; 95% confidence interval (CI) -0.066 to -0.028; P<0.0001] and the number of metabolic syndrome components (B=-0.317; 95% CI -0.572 to -0.010; P=0.042) were found to be independent predictors of lower MMSE scores. Conclusion: We found that subjects with metabolic syndrome have lower MMSE scores than those without, even without symptomatic cognitive impairment, and that the number of metabolic abnormalities is independently associated to lower MMSE scores. We suggest that these patients should always undergo cognitive screening to prevent more severe outcomes.     

Is blood pressure the major determinant of left ventricular mass in subjects over 50 years of age?

The weak relation of systolic blood pressure to left ventricular (LV) mass in hypertension has frequently been regarded as evidence of non-hemodynamic stimuli to muscle growth. Anyway, left ventricular hypertrophy (LVH) is associated with a significantly increased risk for cardiovascular events. Data were obtained from M-mode echocardiograms in 10 normotensives and 58 hypertensives over 50 years (range 50-85 years); 18 hypertensives; were without (LVH -) and 40 were with LVH (LVH +) - when LV mass, normalized for body surface area, was calculated according to the Penn's Convention. Cardiac output was derived by Teicholz formula for LV volumes. End-systolic stress/end-systolic dimension ratio (ESS/ ESD r), an index of myocardial contractility, was calculated as previously validated in the literature. We found that, in subjects ranging from 50 to 85 years of age, the presence of LV hypertrophy is not necessarily associated with raised blood pressure levels. Systolic function was substantially preserved among the study groups, irrespective of their age, hypertensive condition and/or presence of LVH. The increased wall thickness in subjects with LVH was associated with a significant reduction in wall stress (thus suggesting an adequateness of the compensatory role of LVH - at least at the observed stage of the hypertrophy process) and with a significant decrease of the contractile performance. On the multivariate analysis, the observed relation of LV mass to blood pressure and myocardial contractility (r = 0.621, P < 0.001) may explain some apparently conflicting findings, such as the lack of LV hypertrophy in a number of hypertensive patients.     

Hypovitaminosis D: Which oral supplement therapy?

Objectives

the possible therapeutic role of vitamin D in different kind of diseases explains the growing interest in this vitamin due to its pleiotropic effects. This short report shows preliminary results of prevalence of hypovitaminosis D in a group of patients and proposes a oral supplement therapy effective in correcting hypovitaminosis in a short time, without side effects.

Methods

243 patients (aged 26–93; 67 males) were enrolled at this study. We evaluated plasma levels of 25-hydroxyvitamin D [25(OH)D] with the following cut-off values: < 10ng/ml or <0–25 nmol/L (deficient), 10–30 ng/ml or 25–75nmol/L 30–50 (insufficient) and > 30 ng/ml or > 50 nmol/L (normal). The first 73 patients with hypovitaminosis D received at baseline 25,000 IU (Cholecalciferol) per os twice a month (Tp.A). The next patients (Tp.B) at baseline received a loading dose of 50,000 IU once a week for 8 weeks, followed by a maintenance dose of 25,000 IU twice a month.

Results

hypovitaminosis D is a widespread condition (i.e. 82.3%) not only in elderly (75.6% of 75 patients aged <65 yrs and 86.5% of 168 subjects aged >65 yrs). Preliminary results at 6 months show that Tp.B is more effective in correcting hypovitaminosis D (baseline 14.4 ± 5.3 ng/ml; 24 wk 43.3 ± 14.7 ng/ml; p<0.0001).

Conclusion

hypovitaminosis D is an important public health problem. We believe it is important to quickly achieve normal Vit. D plasma values in order to produce pleiotropic effects.