Accuracy of systolic aortic regurgitation in the diagnosis of heart failure: a predictive approach.

BACKGROUND: Systolic aortic regurgitation (SAR) is a curious phenomenon that has been found to be associated with heart failure (HF). We aimed to determine de diagnostic value of SAR as a black box predictive tool in patients with suspected HF admitted to hospital with dyspnea as leading symptom. METHODS AND RESULTS: Cross-sectional study including 269 consecutive patients admitted to hospital with dyspnea as leading symptom without definite clinical diagnosis. SAR was defined by echocardiography as the presence of blood flow from the aorta to the left ventricular outflow tract during a complete systole. The reference standard was the presence of HF diagnosis at discharge. SAR was present in 9 (3.3%) patients. Prevalence of HF was 40.3%. Specificity of SAR in the diagnosis of HF was high at 99.4% (95% CI 96.5-99.9%). Sensitivity was 7.5% (95% CI 3.9-14.2%). Positive predictive value (PPV) was 88.9% (95% CI 56.5-98.0%). Positive likelihood ratio was 11.85. Estimated PPV of SAR was significantly higher than 50% for any hypothetical prevalence of HF. CONCLUSION: In patients admitted to hospital with dyspnea, the finding of systolic aortic regurgitation in echocardiography has a high PPV for HF diagnosis at discharge.

Uso de profilaxis local en la prevención de infecciones en amputaciones mayores en pacientes diabéticos / Use of local prophylaxis in the prevention of infections in greater amputatons in diabetic patients

INTRODUCCIÓN. A pesar de los avances en materia de información, prevención y alternativas terapéuticas médicoquirúrgicas,la tasa de amputación en el enfermo diabético sigue presentando una prevalencia elevada. Por este motivo, los objetivos de la misma deben ser el conseguir un muñón bien cicatrizado, estable, protetizable adecuadamente en un corto intervalo de tiempo y que permita al enfermo retornar con las máximas posibilidades a una vida normalizada. MÉTODO. Se realizó un estudio descriptivo para conocer si el hecho de realizar lavado antiséptico en sala como profilaxis de sepsis del muñón en pacientes diabéticos que se iban a realizar una amputación mayor sirvió de prevención a dicha sépsis. RESULTADOS. Se muestra un predominio del sexo femenino, en edades por encima de los 50 años haciéndose más evidente después de los 70 años, con menos de 20 años de evolución de la diabetes y predominando la diabetes tipo II, que el mayor número de pacientes ingresaron con un pie diabético isquémico. Se reportaron 22 casos complicados (19 con infección y 3 con isquemia del muñón), dividiéndose en 12 amputaciones supracondileas y 10 infracondileas. A su vez 7 fueron en el 2004, 9 en el 2005 y 6 en el2006; solo el 50% de los casos amputados evaluados se realizó la profilaxis local pero a pesar de esto los casos complicados fueron en su mayor porciento los que no se realizaron la profilaxis local (15-68.2%). CONCLUSIONES. A pesar de que se realizó el estudio en solo tres meses de cada año evaluado, realmente se demostró que las complicaciones de las amputaciones mayores mejoran con la profilaxis local en sala (AU)

INTRODUCTION. In spite of the advances in the matter of surgical information, prevention and therapeutic alternatives, the rate of amputation in the diabetic patient continues presenting/displaying a high prevalence. For this reason, the objectives of the same one must suitably be to obtain a healed, stable, prosthesis application stump, in a short time interval and that allows the patient to return with the maximum possibilities to a standardized life. METHOD. A descriptive study was made to know if the fact to make antiseptic washing in room like sepsis prophylaxis of the stump in diabetic patients who were going away to make a greater amputation served as prevention this sepsis. RESULTS. Is a predominance of feminine sex, in ages over the 50 years becoming more evident after the 70 years, with less than 20 years of evolution of the diabetes and predominating the diabetes type II that the greater number of patients entered with ischaemic diabetic foot. 22 complicated cases were reported(19 with infection and 3 with ischaemia of the stump), dividing in 12 above the knee amputations and 10 below the knee amputations. 7 were as well in the 2004, 9 in 2005 and 6 in the 2006; single 50% of the amputated cases evaluated were made the local prophylaxis but in spite of this the complicated cases were in their greater percent those than the local prophylaxis was not made (15-68,2%). CONCLUSIONS. Although the single study was made in three months of every evaluated year, it really demonstrated that the complications of the greater amputations improve with the local prophylaxis in room (AU)

Estabilometría y calidad de vida en las algias vertebrales. Un estudio transversal analítico / Stabilometry and quality of life in the spinal pain. An analytic transversal study

Objetivos. Las algias vertebrales son un problema de salud que ocasiona un alto coste socio-económico. Su fisiopatología aún no está muy clara y muchos pacientes son derivados a la Atención Especializada cuando no se obtiene una mejoría suficiente. La estabilometría permite la valoración de la insuficiencia postural. El objetivo de este estudio es comprobar la relación entre distintas variables estabilométricas y la Calidad de Vida de los pacientes afectados por raquialgias. Material y métodos. Para el estudio se seleccionaron 20 pacientes que presentaban dolor en más de un segmento raquídeo durante el último año. La variable dependiente fue la Calidad de Vida medida con la escala de Roland-Morris. Como variables independientes se tomaron las derivadas del análisis estabilométrico y de la huella plantar. Para hallar las relaciones se utilizaron el Coeficiente de Correlación de Pearson y de Spearman así como un modelo de Regresión Lineal Múltiple. Resultados. La Calidad de Vida presentó un Coeficiente de Correlación de Spearman de 0,496 (p = 0,026) con la Superficie con ojos cerrados y gomaespuma bajo los pies, un Coeficiente de Correlación de Pearson de 0,484 (p = 0,031) con la asimetría en la presión plantar y una correlación no significativa con el Cociente Total de 0,354 (p = 0,126). El modelo de regresión lineal múltiple construido explicó el 38,7 % de la varianza de la variable dependiente (p = 0,012). Conclusiones. Los datos de estudio apoyan la hipótesis de una relación positiva entre la afectación de la estabilidad y el empeoramiento de la Calidad de Vida en pacientes afectados por algias vertebrales

Objetives. The spinal pain is a problem of health that causes a high socio-economic cost. Their physiopathology is not still very clear and many patients are derived to the Secondary Care when it doesn't obtain an enough improvement. The stabilometry allows the valuation of the postural inadequacy. The objective of this study is to check the relationship among different stabilometryc variables and the Quality of the patients' Life affected by spinal pain. Methods. For the study 20 patients were selected that presented pain in more than one spinal segment during the last year. The dependent variable was the Quality of Life measured with the scale of Roland-Morris. As independent variables were taken those derived of the analysis estabilométric and of the footprint. To find the relationships were used the Pearson's Coefficient of Correlation and Spearman as well as a model of Multiple Lineal Regression. Results. The Quality of Life presented a Spearman's Coefficient of Correlation of 0,496 (p = 0,026) with the Surface with closed eyes and foam rubber under the feet, a Pearson's Coefficient of Correlation of 0,484 (p = 0,031) with the asymmetry in the sole pressure and a not significant correlation with the Total Quotient of 0,354 (p = 0,126). The model of multiple lineal regression explained 38,7 % of the variance of the dependent variable (p = 0,012). Conclusions. The study data support the hypothesis of a positive relationship between the affectation of the stability and the worsening of the Quality of Life in patients affected by spinal pain

Descripción de los procedimientos de valoración fisioterápica de las cervicalgias mecánicas / Description of the physical therapy assessment procedures of mechanical cervicalgia

Dada la elevada incidencia de las cervicalgias mecánicas entre los usuarios de nuestros servicios, hemos considerado que una correcta exploración va a garantizar la calidad de la atención fisioterápica, asegurando la posterior adecuación del tratamiento. Por ello vamos a ofrecer una descripción basada en los procedimientos de valoración fisioterápica más comúnmente aceptados y utilizados. Hemos encontrado la necesidad de estudiar las características e intensidad del dolor, realizar una exhaustiva palpación de la región cervical incluyendo la localización de las zonas álgicas y la exploración de los puntos gatillo de los principales músculos que puedan estar en relación con la existencia de una cervicalgia de origen mecánico. El estudio de la movilidad articular y la identificación de posibles disfunciones articulares serán un elemento clave de nuestra valoración. Asimismo presentamos los tests de provocación que nos van a posibilitar la inclusión o exclusión del paciente en el protocolo de tratamiento de las cervicalgias de origen mecánico (AU)

Modulation of guanosine triphosphatase activity of G proteins by arachidonic acid in rat Leydig cell membranes.

Previous results from our group have indicated that arachidonic acid decrease cAMP production through a modification of heterotrimeric G proteins. In the present study, we have characterized the high affinity GTPase activity present in Leydig cell membranes and its regulation by fatty acids. The high-affinity GTPase activity, measured as [gamma32P] GTP hydrolysis rate, was both time and protein concentration dependent. Arachidonic acid elicited a dose-dependent inhibition of enzyme activity with an IC50 = 26.7+/-1.1 microM. The existence of only two double bonds in linoleic acid is reflected by a decrease in its inhibitory activity (IC50 = 34+/-2.3 microM). Saturated fatty acids showed no effect at this level. The kinetic analysis as interpreted by Lineweaver-Burk plots, indicated that 50 microM arachidonic acid had no effect on the apparent affinity for GTP, but resulted in a 40% decreases in the maximal velocity of the reaction. Arachidonic acid modulation of GTPase activity was not attenuated by blocking eicosanoid metabolism with inhibitors of 5'-lipoxygenase, cyclooxygenase, or epoxygenase P-450. The addition of arachidonic acid to pertussis toxin-treated membranes had no effect on the enzyme activity, indicating that arachidonic acid does not modify the GTPase activity present in Galphas protein. However, ADP-ribosylation with cholera toxin followed by arachidonic acid treatment led to a further 40% inhibition when compared with cholera toxin treatment alone. These results allowed us to postulate that arachidonic acid inhibits the GTPase activity of Gi protein family. To further analyze the mechanism of arachidonic acid inhibition of GTPase activity, the effect of arachidonic acid on the [35S]GTPgammaS binding was studied. No effect of this fatty acid on GTP binding was found. Combining our previous results with those found here, we can conclude that arachidonic acid maintains Gi proteins in their active state, which in turn inhibit adenylate cyclase and results in decrease cAMP levels.

Tratamiento manipulativo articular de columna cervical / Manipulative join treatment in cervical spine

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Specific effect of arachidonic acid on 17beta-hydroxysteroid dehydrogenase in rat Leydig cells.

It is well known that arachidonic acid (AA) acts as an intratesticular factor regulating luteinizing hormone-mediated testicular steroidogenesis. The present studies were conducted to determine the effect of AA on steroidogenic enzymes in rat Leydig cells. Exogenously added AA significantly inhibited 22(R)-hydroxy-cholesterol-stimulated testosterone production, which is a clear indication that AA is acting at some point after cholesterol transport to the inner mitochondrial membrane. AA failed to block the conversion of 22(R)-hydroxycholesterol to pregnenolone, indicating that the cytochrome P-450 side-chain cleavage enzyme complex is not the site of inhibition. The present results demonstrate that only 17beta-hydroxysteroid dehydrogenase seems to be involved in the AA action, since nearly 60% inhibition of testosterone production was found when the cells were incubated with androstenedione. Furthermore, no effect of AA was found when androstenediol was used as substrate in the testosterone synthesis, which indicates that 3beta-hydroxysteroid dehydrogenase is not affected by AA. The conversion of AA to its metabolites is not required for its action on 17beta-hydroxysteroid dehydrogenase and the activation of protein kinase C is not involved in the inhibitory effect.

Different sites of action of arachidonic acid on steroidogenesis in rat Leydig cells.

The present study in purified rat Leydig cells shows that arachidonic acid may act as an intratesticular factor regulating LH-mediated testicular steroidogenesis. Arachidonic acid decreased, in a dose-dependent manner, the LH-stimulated cAMP and testosterone levels, over 2 h incubation. Incubation of Leydig cells with arachidonic acid did not modify 125I-hCG binding to the cells as compared to control, showing that the action of arachidonic acid is not related to a decrease of hCG binding to the cells. Forskolin-stimulated cAMP and testosterone production were inhibited by 51.65 and 70.9%, respectively, in the presence of arachidonic acid (100 microM), although the ED50 for the diterpene was not changed. When isobutyl-methyl-xanthine was added to the incubation medium, the same percentage of inhibition was found indicating that arachidonic acid inhibition of cAMP production is not due to stimulation of Leydig cell phosphodiesterase activity. Pretreatment of the cells with pertussis toxin, to inactivate Gi, was also without effect on arachidonic acid inhibition of LH-stimulated cAMP production, but pertussis toxin abolished the inhibitory effects of arachidonic acid when adenylate cyclase was stimulated with forskolin. However, arachidonic acid addition resulted in inhibition of LH- and forskolin-stimulated testosterone production, even if the cells were pretreated with pertussis toxin. It can be concluded that: (1) The inhibitory effect of arachidonic acid is neither due to a decrease of hCG binding to Leydig cells nor to a stimulation of cell phosphodiesterase activity; (2) arachidonic acid modulates cAMP production at two different levels, either by activation of Gi protein and by inhibition of Gs protein or adenylate cyclase; (3) the effect of arachidonic acid on steroidogenesis is also beyond cAMP formation.

Control of steroidogenesis in Leydig cells.

Luteinizing hormone (LH) interacts with its plasma membrane receptor to stimulate steroidogenesis not only via cyclic AMP but also other pathways which include arachidonic acid and leukotrienes and regulation of chloride and calcium channels. The same stimulatory pathways may lead to desensitization and down-regulation of the LH receptor and steroidogenesis. The LH receptor exists in a dynamic state, being truncated, or internalized, degraded or recycled. Desensitization is controlled by protein kinase C (PKC) in the rat and by cyclic AMP dependent protein kinase and PKC in the mouse Leydig cells. Using an adapted anti-sense oligonucleotide strategy we have shown that the cytoplasmic C-terminal sequence of the LH receptor is essential for desensitization to occur. In contrast, these sequences of the LH receptor are not required for the stimulation of cyclic AMP and steroid production. We have also shown that the extracellular domain of the LH receptor is secreted from the Leydig cell and may act as a LH-binding protein.

Somatostatin inhibits VIP- and forskolin-stimulated cyclic AMP accumulation in enterocytes from rat jejunum.

This study demonstrates the dual regulation by somatostatin of vasoactive intestinal peptide (VIP)-stimulated and forskolin-stimulated cyclic AMP accumulation by isolated rat intestinal epithelial cells. Somatostatin non-competitively inhibited (IC50 = 1 microM) the stimulatory effect of VIP on cyclic AMP accumulation, suggesting that the two neuropeptides act through separate receptors. The cyclic AMP accumulation produced by forskolin (a diterpene that stimulates directly the catalytic subunit of adenylate cyclase) was also inhibited by somatostatin in a dose-dependent manner. However, somatostatin did not modify the stimulatory effect of VIP on adenylate cyclase activity in a membrane preparation from the same cells, making it difficult to explain the mechanism of somatostatin action at this level. The data presented here suggest that somatostatin may play a physiological role in the regulation of nutrient absorption and the release of gut hormones or exocrine secretions by intestinal epithelial cells through the modulation of cyclic AMP production.

Direct effect of arachidonic acid on protein kinase C and LH-stimulated steroidogenesis in rat Leydig cells; evidence for tonic inhibitory control of steroidogenesis by protein kinase C.

The role of arachidonic acid in the regulation of steroidogenesis in rat Leydig cells was studied. A dose- and time-dependent biphasic effect on maximal and submaximal LH- and dibutyryl-cAMP-stimulated testosterone production was found. The locus of the inhibition, which occurred during 3 h incubation, was prior to the side chain cleavage of cholesterol and after cAMP production. The same inhibitory effect was found with the protein kinase C (PKC) activators, phorbol-12-myristate, 13-acetate (PMA) and oleic acid, also with no change in LH-stimulated cAMP production. Arachidonic acid, PMA, and diolein, all stimulated PKC activity in a dose-dependent fashion in partially purified Leydig cell homogenates. When the cells were incubated for 5 h, arachidonic acid potentiated LH- and dibutyryl-cAMP-stimulated testosterone production. Similarly, incubation with PMA for 5 h, potentiated subsequent basal and dibutyryl-cAMP-stimulated testosterone production. PKC was down-regulated over 5 h (but not during 3 h) by pretreating Leydig cells with PMA or arachidonic acid in the presence of LH. Lipoxygenase and cyclooxygenase inhibitors did not alter the stimulatory effects of arachidonic acid. We conclude that the short-term inhibitory effect of arachidonic acid (and PMA) is via activation of PKC, but when protein kinase C (PKC) is down-regulated by these ligands, steroidogenesis is enhanced. These results suggest that steroidogenesis is normally under tonic inhibitory control by PKC.

Differences in LH receptor down-regulation between rat and mouse Leydig cells: effects of 3',5'-cyclic AMP and phorbol esters.

The role of cyclic AMP and phorbol esters in luteinizing hormone (LH) receptor down-regulation in Leydig cells has been studied. Dibutyryl cyclic AMP (db-cAMP) (0.01, 0.1 and 1 mM), forskolin (80 microM) and cholera toxin (1.19 nM) caused a 30-50% loss of [125I]hCG binding sites and an inhibition of receptor-[125I]hCG complex internalization in mouse tumour Leydig (MA10, MLTC-1) cells during 2 h. In contrast, db-cAMP had no effect on the level of binding sites or internalization of the hormone receptor complex in rat testis Leydig cells or a rat tumour (R2C) Leydig cell. Phorbol 12-myristate 13-acetate (PMA) at concentrations from 10(-9) to 10(-5) M had no effect on hormone binding or hormone-receptor complex internalization in any of the Leydig cells. In contrast a 2 h preincubation of MLTC-1 cells with 10(-7) M PMA caused a loss of subsequent LH-stimulated cyclic AMP and pregnenolone production. These results indicate that LH receptor down-regulation is mediated by cyclic AMP dependent kinase, but not protein kinase C, in mouse Leydig cells. No down-regulation of rat Leydig cell LH receptor occurs with either kinase.

Somatostatin inhibition of VIP- and isoproterenol-stimulated cyclic AMP accumulation in dissociated cells from rat cerebral cortex.

Freshly dissociated cerebral cortex cells from adult rats have been used in the present study to determine if dual regulation of cyclic AMP levels by inhibitory and stimulatory agents can be expressed in the mature brain. Somatostatin, an inhibitory agent, barely affected the basal cyclic AMP metabolism while vasoactive intestinal peptide (VIP) and isoproterenol, two stimulatory agents enhanced cyclic AMP production. However, this increase was depressed by somatostatin, which decreased the efficiency, but not the potency, of the effects of the two stimulatory agents on cyclic AMP accumulation.

Effect of morphine and acetylcholine on contractile activity and cyclic AMP in guinea-pig ileum.

Neither acute nor prolonged exposure to morphine altered cAMP content or spontaneous movements of longitudinal muscle-myenteric plexus strips of the guinea-pig ileum. By contrast, exogenous acetylcholine or electrical stimulation of the strips elicited both a decrease of cAMP concentration and a twitch response. Atropine blocked the effects of stimulation on these parameters. Addition of morphine to electrically stimulated strips inhibited the twitch response but did not affect cAMP levels. Incubation with morphine led to the development of tolerance to the inhibitory effect on twitch activity and prevented the fall in cAMP normally elicited by electrical stimulation. These results suggest that muscarinic activation is associated with a reduction of cAMP content, an effect which would be impaired in opiate-tolerant tissues.

Effect of haloperidol withdrawal on somatostatin level and binding in rat brain.

The effects of withdrawal on the level and specific binding of somatostatin in the frontoparietal cortex and hippocampus of the rat after chronic haloperidol treatment were examined using 125I-Tyr11 somatostatin as tracer. One week after haloperiodol withdrawal the number of specific somatostatin receptors in both brain areas returned to control values, after having decreased as the result of chronic administration. Neither administration of haloperidol nor withdrawal of it affected the levels of somatostatin-like immunoreactivity (SLI) in the two brain areas studied. The return of the somatostatin receptor number to control values after haloperidol withdrawal may be related to the motor side-effects that are clinically observed when the haloperidol treatment is terminated.

Long-term haloperidol treatment decreases somatostatin binding in rat brain.

The effects of short and long-term haloperidol treatment on somatostatin concentration and specific binding in rat cerebral cortex and hippocampus were examined using the binding ligand 125I-Tyr1-somatostatin. Haloperidol treatment did not affect the concentration of somatostatin-like immunoreactivity in the two brain areas. Nevertheless, long-term, and not short-term, haloperidol treatment decreased the number of somatostatin receptors in the cerebral cortex and hippocampus. No significant differences in the apparent binding affinity values were seen after haloperidol treatment. When added at the time of the binding assay haloperidol 34.2 microM produced a 42% and 27% decrease in cerebrocortical and hippocampal membrane somatostatin receptors respectively.

Cysteamine normalizes cerebral somatostatin level and binding in pentylenetetrazol-kindled rats.

Rats were kindled by intraperitoneal injection of pentylenetetrazol (PTZ) (30 mg/Kg) every 48 h. Once kindled, some of the animals received a single injection of cysteamine (200 mg/Kg). Somatostatin-like immunoreactivity (SLI) and 125 I-Tyr11-somatostatin binding were measured in the frontoparietal cortex and hippocampus of the two experimental groups and the control rats. After PTZ kindling the following was observed: 1) SLI content was increased in the two areas; 2) Somatostatin receptor affinity decreased in the frontoparietal cortex and was unaltered in the hippocampus; 3) The number of somatostatin receptors decreased in the hippocampus and was unaltered in the frontoparietal cortex. Cysteamine, an agent which depletes brain somatostatin and suppresses kindled seizures in PTZ-treated rats, reversed the altered SLI levels and binding in these rats.

Effects of alloxan-induced diabetes on somatostatin binding to cytosolic components of rabbit gastric fundic mucosa.

Diabetes was induced by administration of alloxan (150 mg/Kg) to 24 h-fasted rabbits. Somatostatin-like immunoreactivity (SLI) and cytosolic binding sites for somatostatin in gastric fundic mucosa were studied using radiolabelled Tyr11-somatostatin. Three months after the onset of the disease, the specific binding of somatostatin to these sites was seen to be significantly lower, due to a reduction in the number (but not the affinity) of specific somatostatin binding sites of high-affinity and a disappearance of the specific somatostatin binding sites of low-affinity. These changes were associated with an increase in the SLI concentration in both gastric fundic mucosa and plasma.

Species variations of somatostatin concentrations and binding sites in jejunal mucosa.

1. Somatostatin-like immunoreactivity (SLI) and specific binding of 125I-Tyr11-somatostatin were measured in jejunal mucosa of the mouse, rat, hamster, rabbit and guinea-pig. 2. The SLI concentrations in guinea-pig and rabbit were much greater than those in other rodents considered. 3. Somatostatin binding varied greatly with the species examined, the highest values being observed in cytosolic fraction of guinea-pig and rabbit jejunal mucosa, but the lowest ones in mouse. 4. The observed differences in somatostatin binding were not related to varying extents of degradation by the diverse cytosolic preparations studied. 5. The binding sites were highly specific for somatostatin in all rodent species studied. 6. There appears to be a direct relationship between somatostatin levels and somatostatin binding sites in jejunal mucosa when considering a variety of rodent species usually employed as laboratory animals.