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 Whole blood was withdrawn before FVIII administration and at five time-points after infusion for a TEG-based pharmacodynamic- and pharmacokinetic-study.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.

Elevación de seno maxilar. Análisis clínico de nuestra experiencia en más de 100 casos / Clinical analysis of our experience in over 100 cases of maxillary sinus lift

Objetivos: La elevación de seno maxilar es uno de los procedimientosmás versátiles en cirugía oral, de modo que hay descritos diversos abordajes,tipos de injertos, posibilidad de asociar otras técnicas preprotésicas y colocarimplantes de manera simultánea o diferida, dependiendo de la altura ósea inicial.Nuestro propósito es comunicar nuestra experiencia después de intervenir131 casos. Materiales y métodos: Se analizó una serie de 131 procedimientosllevados a cabo en 91 pacientes consecutivos, entre 1996 y 2007. La edadmedia fue de 50,43 años (23-69). El control radiológico pre y postoperatoriose realizó mediante ortopantomografía y TC dental. Se analizó la tasa de éxitoimplantario (implantes osteointegrados y cargados) comparando los distintosinjertos, el hábito tabáquico, las patologías asociadas y la colocación simultáneao diferida de los implantes. Así mismo, el tiempo (meses) necesario paracargar la prótesis se ha comparado entre los diferentes tipos de injerto. Resultados:En las zonas aumentadas se colocaron un total de 228 implantes roscados.La altura preoperatoria media del suelo del seno fue de 6,59±2,11 mmy la postoperatoria de 14,57±2,33 mm. El seguimiento medio fue de 2,94 años(1-12). La tasa de éxito implantario global fue de 96,91%, no habiéndoseencontrado diferencias significativas entre los distintos injertos, patologías asociadaso el hábito tabáquico. Conclusiones: En base a este análisis retrospectivo,se concluye que la elevación de seno es una técnica versátil, eficaz, seguray predecible; con una tasa de éxito implantario muy alta independientedel tipo de injerto, comorbilidad, hábito tabáquico y colocación simultánea odiferida de los implantes. El empleo de injerto óseo autólogo requiere un tiempode espera para la carga protésica significativamente menor(AU)

Purpose: Maxillary sinus elevation surgery is one ofthe most versatile surgical procedures in maxillofacial surgery:there are various approaches to the sinus, different materials forsinus grafting, other preprosthetic procedures can be associatedand the implants placement can be simultaneous or delayed,depending on the initial bone height. The aim of this studywas to demonstrate this versatility by means of reporting theclinical outcome of sinus augmentation surgery in 131 cases.Materials and Methods: 131 sinus augmentation procedureswere undertaken on 91 consecutive patients (mean age 50,43years (26-69)). The preoperative and postoperative radiologicalstudy was developed by means of orthopantomography andDental-TC. The survival rate of implants, as measured by integrationand succesfull loading, was compared between differentgraft materials, smoking/non-smoking patients, differentgroups of associated pathologies and simultaneous/delayedimplants placement. The time (months) necessary for prosthesisloading was measured and compared between the differentgraft material groups. Results: 228 screw-type implantswere placed in sinus lifted regions. The mean residual ridge heightwas 6,59±2,11 mm. The mean postsurgical ridge height was14,57±2,33 mm. After a mean follow-up period of 2,94 years(range 1 to 12 years) the global implant survival rate was96,91%. There were not significant differences between differentbone grafts, associated comorbidity and smoking habits.Conclusions: On the basis of this retrospective study, it mightbe concluded that the sinus augmentation surgery is a very versatileprocedure. Its efficacy and predictability in terms of implantsurvival rate is extremely high and independent on the bonegraft material, surgical technique, associated morbility, smokinghabit and immediate/delayed implant placement. The useof autologous bone requires less time to load the prosthesis(AU)

Estadios precoces de cancer oral: pronóstico en relación con gradación histológica, linfagiogénesis intratumoral y expresión de factor de crecimiento endotelial vascular Tipo-C (VEGF-C) / Early stage oral cancer: prognosis with regard to histological grading, intratumoral lymphangiogenesis, and the expression of vascular endothelial growth factor-C (VEGF-C)

Los sistemas de gradación histológica se han usadoclásicamente como factor pronóstico y marcadores de comportamiento clínico en el carcinoma epidermoide intra-oral (CEI). Sin embargo, su utilidad pronóstica permanece controvertida. Nuestro objetivo ha sido evaluarla presencia de linfangiogénesis intratumoral (LI), un nuevo hallazgo morfológico, en un análisis retrospectivo de muestras de tejido en parafina dentro de un grupo de estadios precoces de CEI, relacionándolo con clásicos sistemas de gradación histológica y teniendo en cuenta su importancia pronóstica. Asimismo, pretendemos determinar si la expresión del factor de crecimiento endotelial vascular –C (VEGF-C) se correlaciona conla evolución de la enfermedad.Diseño. Realizamos un estudio retrospectivo basado en 96 casos de CEI. Todos los pacientes presentaban tumores intraorales T1-T2 y fueron tratados primariamente mediante resección local asociada con disección cervicalelectiva, la cual mostró ausencia de afectación ganglionar regional. En el grupo de 96 muestras analizamos la LI utilizando el marcador específicodel endotelio linfático PA2.26. Adicionalmente, estudiamos la expresión del VEGF-C. Todos los casos fueron clasificados de acuerdo con los sisintratutemasde gradación histológica descritos por Broders, Anneroth y Bryne. El estudio estadístico se fundamentó en el análisis univariante de supervivenciacausa-específica y supervivencia libre de recidiva según el método de Kaplan-Meier.Resultados. El grupo de pacientes con ausencia de LI mostró mejor pronóstico en cuanto a supervivencia y periodo libre de enfermedad, aunque la diferenciano mostró valores estadísticamente significativos. El estudio no mostró una relación entre la expresión de VEGF-C y la presencia de LI. Sin embargo, no observamos recidivas entre el grupo con ausencia de expresión deVEGF-C. El análisis comparativo de los sistemas de gradación histológica mostró una relación estadísticamente significativa entre los sistemas de Broders y Anneroth (p<0,01) y entre los sistemas de Broders y Bryne (p<0,001). Nuestro estudio demostró una relación inversa entre los valores de los sistemasde gradación Anneroth (p<0,01) – Bryne (p<0,001) y la presencia de LI.Conclusión. El valor clínico de los sistemas de gradación histológica puede incrementarse si se incluyen nuevos parámetros que consideren el comportamientobiológico del tumor. La expresión de VEGF-C y la presencia de linfáticos intratumorales pueden ser marcadores marcadores pronósticos de utilidad en el CEI

Objectives. Histological grading systems have been classically used as a prognostic factor and clinical behavior markers in oral squamous cell carcinoma (OSCC). However, their prognostic usefulness remains controversial. Our aim was to evaluate the presence of intratumoral lymphangiogenesis (IL), a new morphologicalfinding, in a retrospective analysis of paraffin embedded tissue samples that corresponded to a group of early stage oral squamous cell carcinoma cases, and to relate this with histological grading systems while keeping in mind their prognostic significance.We also wanted to determine if the expression of vascular endothelial growth factor-C (VEGF-C) is correlated with the evolution of the disease.Design. We performed a retrospective analysis of 96 patients with OSCC. All cases were T1-T2 neoplasms and were treated primarily by local resection and elective neck dissection that showed no neck involvement. In the group of 96 specimens, we analyzed IL using the specific marker PA2.26 for lymphatic endothelium. Also,we studied the expression of (VEGF-C). All cases were classified according to the histological grading systems described by Broders, Anneroth and Bryne. The statistical analysis was based on the univariateanalysis of cause-specific survival and disease recurrence free-survival according to the Kaplan-Meier method.Results. The group of patients without intratumoral lymphangiogenesis showed a better prognosis with regard to survival and disease-free period, but the difference was not statistically significant. The study showed no relationship between VEGF-C expression and the presence of intratumoral lymphangiogenesis. However, no recurrences were observed in the group without VEGF-C expression. The comparative analysis of the histological grading system showed a statistical relationship between the Broders and Anneroth systems (p<0.01) and between the Broders and Bryne systems (p<0.001). Our study demonstrated an inverse relationship between the valuesof the Anneroth system (p<0.01) - Bryne system (p<0.001) and the presence of intratumoral lymphangiogenesis.Conclusion. The clinical value of the histological grading systems can increase by including new parameters that take into account the biological behavior of the tumor. Expression of VEGF-C and intratumoral lymphatics may thus be useful prognostic markers for oralsquamous cell carcinoma

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.