[Effect of priming solution and ultrafiltration on post-operative bleeding and blood transfusion in cardiac surgery. Randomized controlled trial]. / Repercusión del cebado con coloides y la ultrafiltración sobre el sangrado posoperatorio y la transfusión sanguínea en cirugía cardiaca. Ensayo clínico aleatorizado.

OBJECTIVE: Assess the effectiveness of priming the extracorporeal circulation system with albumin-mannitol combined with ultrafiltration during extracorporeal circulation to reduce post-operative bleeding and transfusion requirements in heart surgery, as well as its impact on the fluid balance, coagulation and hematocrit parameters, re-operation for bleeding, ICU, and hospital length of stay. MATERIAL AND METHODS: A total of 134 patients scheduled for heart surgery were randomized to receive Ringer's lactate 1,500mL in the priming reservoir (group C), or mannitol 20% 250mL, albumin 20% 150mL and Ringer's lactate 1,100mL combined with ultrafiltration (group T). Bleeding volume, transfusions, fluid balance, coagulation, and hematology parameters were determined until 48h in the post-operative period. RESULTS: There was a reduction of postoperative bleeding in group T, 1,165±789mL vs 992±662mL (P=.17), and red blood cell concentrate transfusions, 694±843mL vs 413±605mL (P=.03). Intra-operative and post-operative fluid balance was significantly less positive in group T, with an overall balance of 2,292±2,152mL vs 5,388±2,834mL (P<.001). There were higher values of hemoglobin and hematocrit, intraoperative (P<.001), on admission to ICU (P=.001), and at 6h (P=.05) in group T, and lower INR at 6h (P=.01) and 24h (P=.02). Re-operation rate and length of stay in ICU were higher in group C, but not statiscally significant. CONCLUSIONS: The priming of extracorporeal reservoir with mannitol, albumin, and Ringer's lactate, combined with ultrafiltration, significantly improves intra- and post-operative fluid balance, resulting in a reduction in blood transfusions, with no significant decrease in post-operative bleeding, re-operation bleeding rate, and length of stay in the ICU.

Principios activos autorizados en España en 2006 (2ª parte) / Active Principles authorized in Spain in 2006 (2ª part)

Como continuación de nuestro trabajo publicado con anterioridad de igual título como parte 1ª [Sanidad Militar 2007;64(2):118-127], presentamos el resto de fármacos que han sido comercializados en nuestro país durante el pasado año 2006, con atención a sus diversas características, algunas de ellas reflejadas en su ficha técnica, y otras comentadas para complementar su conocimiento (AU)

As a continuation of our previous article published with the same title as first part [Sanidad Militar 2007;64(2):118-127], we present the other drugs that have been commercialized in our country during 2006. They are presented in accordance with their different characteristics, some of them described in the technical data sheet and other commented in order to complement their knowledge. The active principles that we present in this second part represent, as has already been stated previously, a reduced contribution from the innovation point of view. However for certain patients or group of patients, and in concrete circumstances, they may represent a specific solution for a case that might have a worse outlook without this contribution. The drugs that we present in order to complete those commercialized during 2006 are the following (AU)

Principios activos autorizados en España en 2006 (I. ª parte) / No disponible

Cada año la Agencia Española de Medicamentos evalúa la documentación correspondiente a los fármacos que le son presentados con propuesta para su registro y aprobación. Otros fármacos lo hacen a través de la Agencia Europea. En nuestro país se han autorizado veinticuatro principios activos durante el pasado año 2006. Se presentan y comentan los datos correspondientes a aquellos considerados por los autores de mayor interés. Tres principios son considerados como «Innovación excepcional», y uno más es considerado «Innovación importante ». El resto presentan mejoras menores aunque en determinadas circunstancias o en pacientes específicos pueden llegar a ser la alternativa de mayor interés (AU)

No disponible

Effect of high extracellular Ca(2+) levels in spontaneously hypertensive rat aorta.

The release of endothelial relaxing factors has been suggested to be important in modulating the inhibition of the contractile activity caused by the increase in extracellular Ca(2+) concentration in arterial tissue. Since the hypertensive process in spontaneously hypertensive rats (SHR) could be associated with the release of endothelial vasoconstrictor factors (mainly cyclooxygenase-dependent endoperoxides and endothelin-1), we studied the contractile responses to KCl, methoxamine and phenylephrine in different aorta ring preparations (intact, de-endothelized, 10(-5) M indomethacin-treated, 10(-6) M CGS-27830 [meso-1,4-dihydro-5-methoxycarbonyl-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridine carboxylic acid anhydride]-treated, and treated simultaneously with 10(-5) M indomethacin and 10(-6) M CGS-27830) from SHR and normotensive Wistar Kyoto rats (WKY), at various Ca(2+) concentrations (1.25, 2.5, 5 and 10 mM) in the organ bath. In endothelium-intact preparations from WKY rats we observed a decrease in KCl, methoxamine and phenylephrine contractions with high Ca(2+) concentrations (5 and 10 mM), but in the endothelium-intact preparations from SHR, the increase in extracellular Ca(2+) concentration potentiated methoxamine contractions and caused no change in KCl and phenylephrine contractions. When the endothelium was disrupted in preparations from both WKY rats and SHR, we observed a decrease in KCl and methoxamine contractions with high Ca(2+) concentrations. The decrease in phenylephrine contractions caused by high Ca(2+) concentrations was clear in de-endothelized preparations from WKY rats but slight in de-endothelized preparations from SHR. In all indomethacin- and CGS-27830-treated preparations, and also in the preparations from WKY rats and SHR treated with both drugs, we observed a decrease in all the contractile responses with increased Ca(2+) concentration. Besides, there was a clear reduction in the responses of the alpha(1)-adrenoceptor agonists in the WKY and SHR preparations treated with both drugs. The results indicate that, in the hypertensive arteries, endothelium-derived contractile factors can counteract the relaxing effect of high extracellular Ca(2+) concentrations.

Alpha-adrenoceptor-mediated pressor responses in pithed rats fed diets with different calcium contents.

Results of many clinical and experimental studies indicate an inverse relationship between dietary calcium and the prevalence of hypertension. Our study was designed to evaluate the alterations in arterial blood pressure and the changes in alpha-adrenoceptor-mediated vascular reactivity in normotensive Sprague-Dawley and spontaneously hypertensive rats (SHR) fed from weaning (3 weeks of life) three diets: normal calcium (Ca 1%), low calcium (Ca 0.1%), and high calcium (Ca 2.5%). The systolic and the diastolic arterial blood pressures were measured weekly by the tail cuff method. The plasma calcium levels in the animals were also measured regularly by colourimetric methods, and the alpha-adrenoceptor-mediated vascular reactivity was evaluated by measuring the pressor responses to alpha-adrenoceptor agonists in pithed rats. These determinations were carried out at the end of the feeding periods (9 weeks of life in Sprague-Dawley rats and 20 weeks of life in SHR) and also at the moments when maximal differences in arterial blood pressure were observed between the conscious animals fed the normal calcium diet and those fed the other two diets. Dietary calcium deficiency increased arterial blood pressure in both strains but calcium supplements were effective to lower this only in hypertensive animals. The plasma calcium levels were altered in both strains when calcium administration was not normal. The low-calcium diet did not modify the pressor responses to either the alpha(1)-adrenoceptor agonist, methoxamine, or the alpha(2)-adrenoceptor agonist, B-HT 920 (5-allyl-2-amino-5,6,7, 8-tetrahydro-4H-thiazolo-(4,5-D)-acepin-dihydrochloride, talixepole), in the normotensive and the hypertensive rats. On the contrary, the high-calcium diet caused a definite decrease in alpha(1)- and alpha(2)-adrenoceptor-mediated vascular reactivity in both strains. The changes in the alpha-adrenoceptor-mediated vasoconstrictor responses were observed in pithed 9-week old Sprague-Dawley rats and in pithed 20-week old SHR, but none were observed in pithed 15-week old SHR, although at this age maximal differences in arterial blood pressure between the animals fed the high- and the normal calcium diet were observed. The results of this study suggest that the mechanisms implicated in the effects of dietary calcium supplements on arterial blood pressure are clearly different from the mechanisms, which bring about changes in arterial blood pressure when the diet is deficient in calcium. The results of this study also show that calcium administration causes variations in alpha-adrenoceptor-mediated vascular reactivity, but this is probably not the only mechanism implicated in the calcium effect on arterial blood pressure.

Parathyroid hormone and calcitriol in hypertension caused by dietary calcium deficiency in rats.

Hypertension caused by calcium deficiency in the diet has been linked with an increase in parathyroid hormone (PTH) and calcitriol levels. We evaluated arterial blood pressure (ABP), PTH, and calcitriol in normotensive Sprague-Dawley rats (SDR) and in spontaneously hypertensive rats (SHR) fed from weaning on a control diet with a normal calcium content (1%) or a low-calcium diet (0.1%). The calcemia was also measured in the rats by colorimetric methods. The low-calcium diet decreased the calcemia in both strains and brought about an increase in the ABP which was significant in adult SDR and particularly noticeable during the early hypertensive phase in SHR. The rats fed on this diet had higher hormonal plasma levels when compared with the corresponding values in rats fed on the control diet. In particular, the SDR fed on the low-calcium diet showed much higher PTH (122.6 +/- 31.0 pg/ml, p

Demonstration of the alpha-vasoconstriction-lowering effect of calcium in the pithed rat.

The mechanism by which calcium administration causes hypotension still remains to be explained. In this paper we have studied the alteration of the pressor effect caused by alpha 1- and alpha 2-adrenoceptor stimulation in the pithed rat after increasing the calcium plasma levels of the rats with an intraperitoneal administration of CaCl2. We compared the vasoconstrictor effect of the selective alpha 1-adrenoceptor agonist methoxamine (10-3,000 micrograms/kg) and the pressor effect of the selective alpha 2-adrenoceptor agonist B-HT 920 (1-1,000 micrograms/kg) in control rats (1.24 +/- 0.01 mmol/l ionic plasma calcium) and rats treated intraperitoneally with CaCl2 that had 1.89 +/- 0.04 or 3.03 +/- 0.11 mmol/l ionic plasma calcium. The pressor effect of methoxamine was noticeably less after both of the increases in ionic plasma calcium, and the pressor effect of B-HT 920 was also significantly reduced when the increase in calcium levels was more marked. We have also shown that administration of CaCl2 (8.8 mg Ca/100 g b.w. i.p.) did not alter the basal arterial blood pressure in the pitched rat; however, it caused an important decrease in blood pressure when administered 20 min after beginning an infusion of methoxamine (50 micrograms/min i.v.). The results indicated that the blood-pressure-lowering effect of acute calcium administration is at least in part due to peripheral mechanisms which include a reduction in the pressor responses caused by the alpha 1 and alpha 2 vascular receptor stimulation.

Comparative study of different methods of inducing acute and chronic hypercalcemia in rats.

Experimental studies are frequently carried out using calcium salt treatment in rats. Modifications in plasma calcium levels could suggest important changes in cellular functions, transmitters and drug responses. Changes during continuous maintenance of hypercalcemia could, on the other hand, be different from those produced by an acute increase in calcemia. Nevertheless, to date no specific studies exist which evaluate and compare the modifications in calcemia and other alterations when different methods of administering acute and chronic calcium are used in rats. This paper presents a method for inducing acute hypercalcemia in Sprague-Dawley rats after intraperitoneal administration of different quantities of CaCl2. Different oral calcium treatments to induce chronic hypercalcemia were also evaluated. Hypercalcemia was more consistent when calcium was administered in both the solid and liquid diets. On day 14 of treatment the highest total and ionic plasma calcium levels appeared in rats fed with CaCO3 in the solid diet (4% Ca) and with CaCl2 in the liquid diet (1.5% Ca). With this treatment hypercalcemia was maintained for 2 months.

Progression of minimal-change glomerulopathy to focal glomerulosclerosis in a patient with fenoprofen nephropathy.

We report a patient who presented with the classical features of fenoprofen-induced nephropathy. Initial response to a cessation of the drug and prednisone therapy was recovery of renal function, but proteinuria persisted. One year later, he experienced recurrence of the nephrotic syndrome with sustained renal failure. A clear progression from minimal-change lesions to focal glomerulosclerosis was shown in sequential renal biopsies. Not previously reported, this evolution is suggestive of the possibility that fenoprofen nephropathy may lead to chronic renal failure.