A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland

The purpose of this investigation was to characterize a new mutation in the LDL-receptor (LDLR) gene in three families with clinically diagnosed familial hypercholesterolemia (FH) from the South-Eastern part of Poland. Mutational screening with exon by exon sequencing analysis was performed in all probands. The novel mutation c986G>T (Cys308Phe) in the exon 7 of LDLR gene was found in three apparently unrelated probands with FH. Analysis of the receptor activity of peripheral blood lymphocytes by binding and uptake of DiL-LDL showed a significant reduction (by 24% versus healthy control) of the fluorescent label in the lymphocytes of patients heterozygous for this mutation. Concentrations of serum LDL-C in probands before treatment were between 9.5 and 10.5 mmol/l. All patients had corneal arcus and tendon xanthoma. Clinically, families were characterized by premature coronary artery disease. This mutation occurred relatively frequently in our group of patients with FH, but this could be explained by a founder effect since we demonstrated their common ancestors

Ultrasonography and color Doppler in juvenile idiopathic arthritis: diagnosis and follow-up of ultrasound-guided steroid injection in the ankle region. A descriptive interventional study

BACKGROUND: The ankle region is frequently involved in juvenile idiopathic arthritis (JIA) but difficult to examine clinically due to its anatomical complexity. The aim of the study was to evaluate the role of ultrasonography (US) of the ankle and midfoot (ankle region) in JIA. Doppler-US detected synovial hypertrophy, effusion and hyperemia and US was used for guidance of steroid injection and to assess treatment efficacy. METHODS: Forty swollen ankles regions were studied in 30 patients (median age 6.5 years, range 1-16 years) with JIA. All patients were assessed clinically, by US (synovial hypertrophy, effusion) and by color Doppler (synovial hyperemia) before and 4 weeks after US-guided steroid injection. RESULTS: US detected 121 compartments with active disease (joints, tendon sheaths and 1 ganglion cyst). Multiple compartments were involved in 80% of the ankle regions. The talo-crural joint, posterior subtalar joint, midfoot joints and tendon sheaths were affected in 78%, 65%, 30% and 55% respectively. Fifty active tendon sheaths were detected, and multiple tendons were involved in 12 of the ankles. US-guidance allowed accurate placement of the corticosteroid in all 85 injected compartments, with a low rate of subcutaneous atrophy (4,7%). Normalization or regression of synovial hypertrophy was obtained in 89%, and normalization of synovial hyperemia in 89%. Clinical resolution of active arthritis was noted in 72% of the ankles. CONCLUSIONS: US enabled exact anatomical location of synovial inflammation in the ankle region of JIA patients. The talo-crural joint was not always involved. Disease was frequently found in compartments difficult to evaluate clinically. US enabled exact guidance of steroid injections, gave a low rate of subcutaneous atrophy and was proved valuable for follow-up examinations. Normalization or regression of synovial hypertrophy and hyperemia was achieved in most cases, which supports the notion that US is an important tool in the management of ankle involvement in JIA

A systematic review of different models of home and community care services for older persons

<p>Abstract</p> <p>Background</p> <p>Costs and consumer preference have led to a shift from the long-term institutional care of aged older people to home and community based care. The aim of this review is to evaluate the outcomes of case managed, integrated or consumer directed home and community care services for older persons, including those with dementia.</p> <p>Methods</p> <p>A systematic review was conducted of non-medical home and community care services for frail older persons. MEDLINE, PsycINFO, CINAHL, AgeLine, Scopus and PubMed were searched from 1994 to May 2009. Two researchers independently reviewed search results.</p> <p>Results</p> <p>Thirty five papers were included in this review. Evidence from randomized controlled trials showed that case management improves function and appropriate use of medications, increases use of community services and reduces nursing home admission. Evidence, mostly from non-randomized trials, showed that integrated care increases service use; randomized trials reported that integrated care does not improve clinical outcomes. The lowest quality evidence was for consumer directed care which appears to increase satisfaction with care and community service use but has little effect on clinical outcomes. Studies were heterogeneous in methodology and results were not consistent.</p> <p>Conclusions</p> <p>The outcomes of each model of care differ and correspond to the model's focus. Combining key elements of all three models may maximize outcomes.</p

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p &gt; 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine

Modeling “psychosis” in vitro by inducing disordered neuronal network activity in cortical brain slices

# The Author(s) 2009. This article is published with open access at Springerlink.com Introduction Dysregulation of neuronal networks has been suggested to underlie the cognitive and perceptual abnor-malities observed schizophrenia. Discussions An in vitro model of psychosis is proposed based on the two different approaches to cause aberrant networ

Dipoid-Specific Genome Stability Genes of S. cerevisiae: Genomic Screen Reveals Haploidization as an Escape from Persisting DNA Rearrangement Stress

Maintaining a stable genome is one of the most important tasks of every living cell and the mechanisms ensuring it are similar in all of them. The events leading to changes in DNA sequence (mutations) in diploid cells occur one to two orders of magnitude more frequently than in haploid cells. The majority of those events lead to loss of heterozygosity at the mutagenesis marker, thus diploid-specific genome stability mechanisms can be anticipated. In a new global screen for spontaneous loss of function at heterozygous forward mutagenesis marker locus, employing three different mutagenesis markers, we selected genes whose deletion causes genetic instability in diploid Saccharomyces cerevisiae cells. We have found numerous genes connected with DNA replication and repair, remodeling of chromatin, cell cycle control, stress response, and in particular the structural maintenance of chromosome complexes. We have also identified 59 uncharacterized or dubious ORFs, which show the genome instability phenotype when deleted. For one of the strongest mutators revealed in our screen, ctf18Δ/ctf18Δ the genome instability manifests as a tendency to lose the whole set of chromosomes. We postulate that this phenomenon might diminish the devastating effects of DNA rearrangements, thereby increasing the cell's chances of surviving stressful conditions. We believe that numerous new genes implicated in genome maintenance, together with newly discovered phenomenon of ploidy reduction, will help revealing novel molecular processes involved in the genome stability of diploid cells. They also provide the clues in the quest for new therapeutic targets to cure human genome instability-related diseases