An Intriguing Case Report of Functional Mitral Regurgitation Treated With MitraClip

Functional mitral regurgitation (FMR) is frequent in patients with heart failure (HF). It develops as a consequence of left ventricle (LV) geometry alterations, causing imbalance between increased tethering forces and decreased closing forces exerted on the mitral valve apparatus during systole.FMR is known to change at rest and during effort, due to preload–afterload changes, myocardial ischemia, and/or LV dysfunction. Despite optimized medical therapy, an FMR can be responsible of shortness of breath limiting quality of life and decompensation. In this report, we present a case of dynamic FMR treated with MitraClip.MitraClip implantation is a successful and innovative opportunity for HF patients with FMR.     

Exploring Autoimmunity in a Cohort of Children with Genetically Confirmed Aicardi–Goutières Syndrome

Purpose

The purpose of this study was to explore the presence of autoimmune manifestations and characterize the autoantibody production in a cohort of patients with Aicardi–Goutières syndrome (AGS).

Methods

Seventeen patients with a genetically-confirmed diagnosis of AGS were recruited. At the time of enrollment, past medical and family history was reviewed, looking for possible signs or symptoms of autoimmune disorders. Blood samples were taken, for the detection of a panel of autoantibodies: anti-nuclear, anti-double-stranded-DNA, anti-nucleosome, anti-extractable nuclear antigens, anti-cardiolipin IgG/IgM, anti-β2glycoprotein I IgG/IgM, and anti-neutrophil cytoplasmic. We also measured complement levels determined as C3 and C4 quantification and total complement activity, measured as CH50.

Results

Nine of seventeen patients presented with at least one first- or second-degree relative with a history of autoimmune diseases (the childrens’ mother or grand-mother in the majority of cases). A specific autoimmune disease was present in only one AGS patient, namely an autoimmune thyroiditis. Autoantibodies were present in 9/17 patients, with different patterns of positivity. Complement levels were normal in all the patients. There was no correlation between auto-antibody production and personal or family history of autoimmune diseases.

Conclusions

Definite autoimmune diseases are not common in patients with AGS. Autoantibodies are mainly directed towards nucleic acids-containing elements but seem not to be pathogenic and, rather, may represent an epiphenomenon of the enhanced interferon production.

     

Red cell pyruvate kinase deficiency: molecular and clinical aspects

Red cell pyruvate kinase (PK) deficiency is the most frequent enzyme abnormality of the glycolytic pathway causing hereditary non-spherocytic haemolytic anaemia. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life-threatening neonatal anaemia and jaundice necessitating exchange transfusions. Erythrocyte PK is synthesized under the control of the PK-LR gene located on chromosome 1. To date, more than 150 different mutations in the PK-LR gene have been associated with PK deficiency. First attempts to delineate the biochemical and clinical consequences of the molecular defect were mainly based on the observation of the few homozygous patients and on the analysis of the three-dimensional structure of the enzyme. More recently, the comparison of the recombinant mutants of human red cell PK with the wild-type enzyme has enabled the effects of amino acid replacements on the enzyme molecular properties to be determined and help to correlate genotype to clinical phenotype.     

Efficacy of oxycodone/acetaminophen and codeine/acetaminophen vs. conventional therapy in elderly women with persistent, moderate to severe osteoarthritis-related pain

We aimed to evaluate the efficacy and safety of oxycodone/acetaminophen (O/A) and codeine/acetaminophen (C/A) vs. conventional therapy (CT) without opioids in older women suffering from osteoarthritis (OA)-related pain, sub-optimally responsive to prior conventional treatments. We performed a 6 week, randomized, single blind, controlled study in three nursing homes. We enrolled 154 women with painful OA. They were assigned to treatment with O/A (n = 52) and C/A (n = 52) vs. CT (n = 50). We evaluated at baseline and at week 6: average pain in the last week (mean pain, MeP), pain at rest (RP), pain in movement (MP) (numeric rating scale, NRS); depressive symptoms (Beck Depression Inventory-II, BDI-II); functional status (activities of daily living, ADL) and cognitive status (mini mental state evaluation, MMSE). We considered the adverse events (AEs) in the study period. At week 6, MeP, RP and MP were significantly reduced in all three groups (p < 0.001); compared to CT, O/A and C/A were associated with greater reductions in MeP (p < 0.001 and p = 0.004, respectively), in RP (p = 0.028 and p = 0.032, respectively) in MP (p < 0.001 and p = 0.002, respectively) and with significant improvement in BDI-II score (p = 0.05 and p = 0.04, respectively) and ADL value (p = 0.04 and p = 0.05, respectively). AE rates did not differ between groups.     

Electrical and magnetic repetitive transcranial stimulation of the primary motor cortex in healthy subjects

Repetitive transcranial magnetic stimulation (rTMS) delivered in short trains at 5 Hz frequency and suprathreshold intensity over the primary motor cortex (M1) in healthy subjects facilitates the motor-evoked potential (MEP) amplitude by increasing cortical excitability through mechanisms resembling short-term synaptic plasticity. In this study, to investigate whether rTES acts through similar mechanisms we compared the effects of rTMS and repetitive transcranial electrical stimulation (rTES) (10 stimuli-trains, 5 Hz frequency, suprathreshold intensity) delivered over the M1 on the MEP amplitude. Four healthy subjects were studied in two separate sessions in a relaxed condition. rTMS and anodal rTES were delivered in trains to the left M1 over the motor area for evoking a MEP in the right first dorsal interosseous muscle. Changes in MEP size and latency during the course of the rTMS and rTES trains were compared. The possible effects of muscle activation on MEP amplitude were evaluated, and the possible effects of cutaneous trigeminal fibre activation on corticospinal excitability were excluded in a control experiment testing the MEP amplitude before and after supraorbital nerve repetitive electrical stimulation. Repeated measures analysis of variance (ANOVA) showed that rTES and rTMS trains elicited similar amplitude first MEPs and a similar magnitude MEP amplitude facilitation during the trains. rTES elicited a first MEP with a shorter latency than rTMS, without significant changes during the course of the train of stimuli. The MEP elicited by single-pulse TES delivered during muscle contraction had a smaller amplitude than the last MEP in the rTES trains. Repetitive supraorbital nerve stimulation left the conditioned MEP unchanged. Our results suggest that 5 Hz-rTES delivered in short trains increases cortical excitability and does so by acting on the excitatory interneurones probably through mechanisms similar to those underlying the rTMS-induced MEP facilitation.     

Genetic variability in the Guahibo population from venezuela

Four communities from Guahibo of Venezuela were analyzed for the genetic variants of nine erythrocyte enzymes and five serum proteins. Of the 14 loci determined, four were monomorphic. Significant frequency differentiation among communities, was present for ESD and TF markers. In general, Guahibo allele frequencies are in the variation ranges described for South American groups. The analysis indicates a relatively higher affinity of Guahibos with other Venezuelan groups within an irregular pattern of genetic distances that are likely related to the complex demographic history of the South American groups. Genetic diversity estimates reveal a moderate degree of genetic structure between the four Guahibo communities. This intra‐tribal variability in Guahibo appears to be lower than in Venezuelan Piaroa but higher than in other Amerindians and could be attributed to a combined effect of low population size and relative isolation of communities. At a continental level, the distribution of genetic diversity is consistent with preferential population movements along the eastern and western coastal areas. Am. J. Hum. Biol. 14:21–28, 2002. © 2002 Wiley‐Liss, Inc.