Evaluation of EC50 of factor VIII as predictor of prophylaxis efficacy in patients with severe haemophilia A.

Trough factor (F) VIII level is a not reliable bleeding risk indicator to predict prophylaxis efficacy in severe haemophilia A (SHA), therefore, accurate biomarkers are much needed. Thrombelastography (TEG) monitors both thrombin and clot formation addressing the global haemostatic status but its usefulness to tailor prophylaxis in haemophilia has been poorly evaluated. In this study, correspondence between individual pharmacodynamic/pharmacokinetic profile of FVIII and joint condition, physical activity and bleeding phenotype of SHA patients under prophylactic treatment was assessed. Nineteen SHA patients < 18 years old on long-term prophylaxis treatment with FVIII were studied in an observational cross-sectional study. Whole blood was withdrawn before FVIII administration and at five time-points after infusion for a TEG-based pharmacodynamic- and pharmacokinetic-study. Type of prophylaxis and joint condition at inclusion and physical activity as well as onset of treated spontaneous bleeding events in the previous two years were retrospectively assessed. Six patients had suffered at least one treated spontaneous bleeding event and were named as "bleeders". The rest were named as "non-bleeders". Only the half maximal effective concentration of FVIII (FVIII-EC50) for TEG parameters R-time, K-time and α-angle correlated with the bleeding phenotype being significantly higher in bleeders suggestive of a poorer response to FVIII. Poorer joint condition, trough FVIII levels or type of prophylaxis were not definitive predicting variables of bleeding phenotype. In conclusion, this study reveals FVIII-EC50 for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in SHA.

A meta-analysis of published studies of endothelial dysfunction does not support its routine clinical use.

BACKGROUND: Endothelial dysfunction is a marker of future cardiovascular disease (CVD) risk, yet epidemiological studies have yielded inconsistent results. We therefore studied the association between endothelial dysfunction and CVD under diverse circumstances. METHODS AND RESULTS: Literature-based meta-analysis of prospective observational studies with ≥ 12 months of follow-up published in Medline and having information on endothelial function and CVD outcomes. Tabular data on participant characteristics, endothelial function assessments and incident CVD outcomes were abstracted from individual studies. Random-effects meta-analysis was used to quantify pooled associations, and I(2) statistic to evaluate between-study heterogeneity. Potential sources of heterogeneity were explored by subgroup analyses and meta-regression. Thirty five studies involving 17,206 participants met the inclusion criteria. During more than 80,000 person-years of observation, up to 2755 CVD events were accrued, yielding a pooled relative risk (RR) of 1.25 (95% confidence interval 1.15-1.35) for CVD comparing top (i.e. more severe) vs. bottom (less severe) third of endothelial dysfunction. There was significant between-study heterogeneity and evidence of publication bias. RRs varied importantly according to the method used to ascertain endothelial function, and were higher among older individuals and among participants with risk factors for CVD or established CVD at baseline. CONCLUSIONS: Although endothelial dysfunction is an important determinant of cardiovascular outcomes in people with pre-existing CVD, current evidence base does not support its use as a potentially useful measurement for risk stratification in people at lower risk of CVD.

Body mass index and myocardium at risk in patients with acute coronary syndrome.

BACKGROUND AND OBJECTIVES: Whilst traditional studies have shown that obese individuals are at a higher risk of cardiovascular events compared to lean subjects, recent studies in patients with acute myocardial infarction (AMI) have suggested that obesity may exert protective effects (the "obesity paradox"). We sought to assess the relationship between body mass index (BMI) and the BARI score (BARIsc), a validated tool used to assess myocardium at risk, in patients with acute coronary syndrome. PATIENTS AND METHODS: Participants were 116 consecutive patients (mean age, 60.6 years; 97 men) with AMI (68 ST elevated myocardial infarction, STEMI; 48 non-ST elevated myocardial infarction, NSTEMI). Demographics, BMI, risk factors, biochemistry data, left ventricular function, angiographic data and the BARIsc were assessed in every patient. RESULTS: Multiple linear regression analyses showed that BMI significantly correlated with BARIsc; ß=.23, p<0.02. This was found only in the overweight/obese patients, ß=.27, p<0.01, but not in patients with normal BMIs, ß=0.08, p=0.71. CONCLUSIONS: An increased body weight is associated with an increased area of myocardium at risk in patients with ACS.

[Inadvertent epidural infusion of paracetamol]. / Infusión errónea de paracetamol por vía epidural.

A 45-year-old woman was accidentally administered an epidural infusion of paracetamol instead of levobupivacaine for postoperative pain therapy during the postoperative period of abdominal hysterectomy under general anesthesia combined with epidural analgesia. The patient had no neurological symptoms at any time, although a slight tendency to arterial hypotension that did not require treatment was observed. No rescue analgesia was necessary until 8h after the start of epidural infusion. The incidence of these types of errors is probably underestimated, although there are several cases reported with various drugs.

Urodynamic alterations after pelvic floor exercises for treatment of stress urinary incontinence in women.

The following study improves the effectiveness of pelvic floor exercise in women with stress urinary incontinence. A group of 27 women with stress urinary incontinence performed specific pelvic floor exercises twice a week for 45 minutes under a therapist's supervision for a period of 12 weeks. This group had urodynamic and urethral pressure profile studies and filled in a daily diary. The patients self-evaluated their symptoms. After the therapy, the urodynamic and urethreal pressure profile studies were repeated and the results were: 66.7% patients were self-evaluated as cured; 14.8% improved and 18.5% unchanged. The urodynamic results showed that 48.2 % of the patients did not have urinary loss, however, 51,8% of the patients that had a loss showed an increase in vesicle volume, and only 7.3% remained unchanged. The results show that pelvic floor exercises are an effective and low cost treatment for stress urinary incontinence rehabilitation.

[Zieve's syndrome. A case report]. / Síndrome de Zieve. Descripción de un caso clínico.

We report a case of Zieve's Syndrome that developed after an important alcohol consumption in a 32-yr-old female patient. She was admitted to the hospital with anorexia, asthenia and jaundice. Physical examination showed liver stigmata and hepatomegaly. Laboratory tests demonstrated increased aminotransferase levels, hyperbilirubinemia, hyperlipidemia and normocytic and normochromic anemia with dianocytes in peripheral blood smear. Ultrasonography showed a hyperechoic liver and a liver biopsy showed acute and chronic alcoholic liver disease. Clinical evolution was satisfactory and the therapy consisted of blood transfusion, parenteral fluids, B-complex vitamin and a fatty free diet. Jaundice, hyperlipidemia and haemolytic anemia define Zieve's Syndrome (Z.S.) There is a pathogenetic relationship among the clinical and biological phenomena in this syndrome, whose starter is an acute alcohol intake. Haemolysis is the distinctive feature with respect to the classical acute alcoholic hepatitis, and it is due to erythrocyte's metabolic and osmotic instability in relation to lipids abnormalities. Its clinical resolution precedes the normalization of serum lipids levels. Therapy is similar to that for acute alcoholic hepatitis although sometimes the anemia requires blood transfusion.

Structural characteristics of gap junctions. I. Channel number in coupled and uncoupled conditions.

Gap junctions between crayfish lateral axons were studied by combining anatomical and electrophysiological measurements to determine structural changes associated during uncoupling by axoplasmic acidification. In basal conditions, the junctional resistance, Rj, was approximately 60-80 k omega and the synapses appeared as two adhering membranes; 18-20-nm overall thickness, containing transverse densities (channels) spanning both membranes and the narrow extracellular gap (4-6 nm). In freeze-fracture replicas, the synapses contained greater than 3 X 10(3) gap junction plaques having a total of approximately 3.5 X 10(5) intramembrane particles. "Single" gap junction particles represented approximately 10% of the total number of gap junction particles present in the synapse. Therefore, in basal conditions, most of the gap junction particles were organized in plaques. Moreover, correlations of the total number of gap junction particles with Rj suggested that most of the junctional particles in plaques corresponded to conducting channels. Upon acidification of the axoplasm to pH 6.7-6.8, the junctional resistance increased to approximately 300 k omega and action potentials failed to propagate across the septum. Morphological measurements showed that the total number of gap junction particles in plaques decreased approximately 11-fold to 3.1 X 10(4) whereas the number of single particles dispersed in the axolemmae increased significantly. Thin sections of these synapses showed that the width of the extracellular gap increased from 4-6 nm in basal conditions to 10-20 nm under conditions where axoplasmic pH was 6.7-6.8. These observations suggest that single gap junction particles dispersed in the synapse most likely represent hemi-channels produced by the dissasembly of channels previously arranged in plaques.