[Antecedents of the Catalan health model]. / Antecedentes del modelo sanitario catalán.

The Catalan healthcare model is a particular way of addressing public health contingencies of the population as a whole, based on an organizational tradition that brings together stakeholders, such as the civil society, local government, the church, mutual care societies, public and private foundations, which for centuries have worked in coordination and complemented each other to provide quality public healthcare, far and beyond merely catering to the poor or those passing through. This model is based on a selfless, public spirited concept of society, achieved through a vocation to form social agreements, preserved in Catalan civil law. During the 3 periods of self-government Catalonia has enjoyed throughout the twentieth century, it has adapted to the economic, social, and scientific conditions, which define modern society, without sacrificing its fundamental features, thereby achieving a remarkable level of efficiency together with significant social consensus.

Antecedentes del modelo sanitario catalán / Antecedents of the Catalan health model

El modelo sanitario catalán es una forma peculiar de atender a las contingencias sociosanitarias del conjunto de la población, sobre la base de una tradición organizativa que integra a diferentes actores como la sociedad civil, los municipios, la Iglesia, las mutualidades, las fundaciones públicas o privadas, que a lo largo de los siglos se han coordinado y complementado para ofrecer una asistencia sociosanitaria de calidad, más allá del pobre o del transeúnte. Este modelo se basa en un concepto solidario de la sociedad alcanzado a través del pactismo social, preservado en el Derecho Civil catalán. A lo largo del siglo XX, en los 3 períodos de autogobierno que ha tenido Cataluña, se ha adaptado, sin perder sus rasgos esenciales, a las nuevas condiciones económicas, sociales y científicas que conforman la contemporaneidad, consiguiendo un remarcable nivel de eficiencia y un apreciable consenso social (AU)

The Catalan healthcare model is a particular way of addressing public health contingencies of the population as a whole, based on an organizational tradition that brings together stakeholders, such as the civil society, local government, the church, mutual care societies, public and private foundations, which for centuries have worked in coordination and complemented each other to provide quality public healthcare, far and beyond merely catering to the poor or those passing through. This model is based on a selfless, public spirited concept of society, achieved through a vocation to form social agreements, preserved in Catalan civil law. During the 3 periods of self-government Catalonia has enjoyed throughout the twentieth century, it has adapted to the economic, social, and scientific conditions, which define modern society, without sacrificing its fundamental features, thereby achieving a remarkable level of efficiency together with significant social consensus (AU)

[Effect of cyclosporin and tacrolimus on lipoprotein oxidation after renal transplantation]. / Efecto de ciclosporina y tacrólimus sobre la oxidación de las lipoproteínas después del trasplante renal.

BACKGROUND: Cyclosporin A is a lipogenic immunosuppressor that can induce posttransplant hyperlipidaemia. Oxidation of low-density lipoprotein (LDL) has been recognized as a major atherogenic factor. Tacrolimus seems to be less lipogenic with an apparently better cardiovascular profile than CsA. METHODS: We have studied the lipidic profile and the oxidation of HDL and LDL in 20 renal transplant patients, 12 male and 8 female, mean age 45 +/- 10 year, who where switched from CsA to tacrolimus due to CsA adverse effects. LDL were determined by ultracentrifugation. Oxidation study before and 6 months after conversion to tacrolimus was performed by adding CuSO4. RESULTS: After conversion, systolic blood pressure (BP) decreased from 154 +/- 21 to 133 +/- 21 mm Hg (p = 0.008), diastolic BP from 97 +/- 13 to 77 +/- 15 mm Hg (p = 0.016), total cholesterol from 6.08 +/- 0.9 to 5.68 +/- 1.1 mmol/l (p = 0.02), LDL-chol from 3.29 +/- 1.01 to 2.96 +/- 0.3 mmol/l (p = 0.04) and apo-B lipoprotein from 1.42 +/- 0.28 to 1.15 +/- 0.34 mg/dl (p = 0.003). The oxidation of LDL improved after conversion: the initial dienic compounds decreased from 95 +/- 20 to 63 +/- 12 umol/g and the final DC from 207 +/- 56 to 107 +/- 35 umol/g. Lag-phase increased from 33 +/- 21 to 45 +/- 17 min (p < 0.05). CONCLUSION: Tacrolimus has improved hyperlipidaemia in our cyclosporin previously treated patients and increased the resistance to oxidation of high and low-density lipoproteins.

Efecto de ciclosporina y tacrólimus sobre la oxidación de las lipoproteínas después del trasplante renal / Effect of cyclosporin and tacrolimus on the oxidation of lipoproteins after kidney transplantation

La ciclosporina es un inmunosupresor capaz de inducir dislipemia después del trasplante renal. La oxidación de las lipoproteínas de baja densidad (LDL) constituye un factor aterogénico importante que puede estar presente en los trasplantados renales. Tacrólimus parece mostrar un perfil aparentemente menos aterogénico que la ciclosporina. Hemos estudiado el perfil lipídico y la oxidación de las LDL en 20 trasplantados renales, 12 hombres y 8 mujeres, con edad media de 45 ñ 10 años, que fueron convertidos de CsA a tacrolimus por diversos efectos adversos de CsA. Se estudió la oxidación de las LDL antes y seis meses después de la conversión, mediante adición de sulfato de cobre. Después de la conversión, la PA sistólica descendió de 154 ñ 21 a 133 ñ 21 mmHg (p = 0,008), la PA diastólica de 97 ñ 13 a 77 ñ 15 mmHg (p = 0,016), el colesterol total de 6,08 ñ 0,9 a 5,68 ñ 1,1 (p = 0,02), el col-LDL de 3,29 ñ 1,10 a 2,96 ñ 0,3 (p = 0,04) y las apolipoproteínas B de 1,42 ñ 0,28 a 1,15 ñ 0,34 (p = 0,003). La oxidación de las LDL mejoró, disminuyendo la generación de compuestos diénicos iniciales de 95 ñ 20 a 63 ñ 12 umol/g y los CD finales de 207 ñ 56 a 107 ñ 35 umol/g. La fase lag aumentó de 33 ñ 21 a 45 ñ 17 minutos (p < 0,05).En conclusión, Tacrólimus mejoró la dislipemia de nuestros pacientes trasplantados renales previamente inmunosuprimidos con ciclosporina, incrementando la resistencia a la oxidación de las lipoproteínas de baja densidad. (AU)

Evaluation of the AxSYM monoclonal cyclosporin assay and comparison with radioimmunoassay.

Recently, a semiautomated fluorescence polarization immunoassay (FPIA) for determination of parent cyclosporin (CsA) has been developed for the Abbott AxSYM system. The new CsA assay measures the drug from an extracted whole blood specimen. The authors report here the evaluation of this new assay and the comparison with a previously validated radioimmunoassay (RIA) method (CYCLO-Trac SP). To assess the imprecision, the authors used tri-level controls supplied by both Abbott and Bio-Rad manufacturers. The within-run CV ranged from 4.4% to 7.3% and the between-day CV ranged from 4.4% to 7.6%. Mean recovery of the drug from clinical specimens spiked with kit calibrators was 108.4%. Fluorescence polarization immunoassay AxSYM (y) was correlated to RIA (x) by using 132 trough blood specimens (44 renal, 44 liver, and 44 heart) from transplant recipients and resulted in the following Passing-Bablok linear regression equation: y = 6.7 + 0.97x, r = 0.989, S(x/y) = 12.9. The percentage of overestimation (mean, range) by FPIA AxSYM versus RIA was (3.8%, range -17.7% to 39.1%). The results observed with this new method from follow-up studies in patients during the early course after transplant were not consistently higher than those obtained by RIA. These findings contrast with previously reported results that compared FPIA TDx assay with RIA. The authors conclude that FPIA AxSYM is a precise method for measuring CsA and offers results similar to those obtained by RIA with a marked reduction in assay time.

[Analysis of 500 liver transplantations at Bellvitge Hospital, Spain]. / Análisis de 500 trasplantes hepáticos en el Hospital de Bellvitge.

BACKGROUND: We present the experience of the liver transplantation program at the Hospital of Bellvitge with 500 transplantations performed during 15 years, to describe changes in liver transplantation observed throughout the time and to analyze the long term results. PATIENTS AND METHOD: Five groups each one including 100 consecutive transplantations are studied. RESULTS: The main indications were hepatocellular carcinoma (23%), alcoholic cirrhosis (22.8%), and post-hepatitis C cirrhosis (18.8%). Sixty-five retransplantations were performed in 59 patients (13%), being the more frequent indications arterial thrombosis (13 patients) and primary nonfunction of graft (10 patients). In 10 patients a hepatorenal transplantation was performed. In group I, the most frequent donor cause of death was cranial traumatism (80%), while in group V it was the vascular pathology (52%). There were other significative differences between these groups of patients (I vs V): patients with stage 2 or 3 from UNOS status (45 vs 19%), blood use (29.6 [26] vs 4.6 [5.3] PRBC), ICU stay (13 [13] vs 7.4 [11] days), hospital stay (40 [52] vs 23.7 [17] days), rejection rate (46 vs 20%) and primary graft nonfunction (9 vs 3%). However, the infection rates (48 vs 54.5%) and biliary tract complications (26 vs 20%) have not shown statistically significant differences. Actuarial one and 5-year survival are 83 and 70% respectively. CONCLUSIONS: An important and progressive improvement of liver transplantation results has been observed. However, de novo tumours, hepatitis C virus recurrence and chronic rejection can limit long term results.

Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function.

BACKGROUND: Cyclosporine (CsA) nephrotoxicity can be identified by functional changes and chronic renal damage. CsA-associated renal fibrosis has been related to the overproduction of transforming growth factor (TGF)-beta1, a fibrogenic cytokine. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. METHODS: We studied the impact of CsA dose reduction in association with MMF on renal function and TGF-beta1, production in 16 long-term renal allograft recipients with suspected CsA nephrotoxicity. Two grams/day of MMF were introduced, and CsA dose was reduced to reach whole-blood levels between 40 and 60 ng/ml within 1 month. CsA dose and levels, renal function parameters, and platelet-poor plasma TGF-beta1 levels were evaluated before and 6 months thereafter. RESULTS: MMF allowed a decrease in both the mean dose of CsA (3.8+/-1.35 vs. 2.2+/-0.73 mg/kg/day; P<0.01) and CsA levels (148+/-36 vs. 53+/-19 ng/ml; P<0.001). The reduction of CsA was associated with a decrement of serum creatinine levels (210+/-46 vs. 172+/-41 micromol/L; P<0.001) and an increase in both the glomerular filtration rate (32.9+/-12 vs. 39.1+/-14 ml/min/1.73 m2; P<0.02) and renal plasma flow (195+/-79 to 218.6+/-74.02 ml/min/1.73 m2; P<0.02). There was a reduction in plasma TGF-beta1 levels (4.6+/-4.2 vs. 2.0+/-1.4 ng/ml; P=0.003) and CsA levels correlated with TGF-beta1 (r=0.536, P=0.002). No rejection episodes occurred, and an improvement in both systolic (149+/-13 vs. 137+/-12 mmHg; P<0.01) and diastolic blood pressure (89+/-14 vs. 83+/-10 mmHg; P<0.04) were observed. CONCLUSIONS: These short-term results show that MMF introduction allows a CsA dose reduction, which improves renal function, reduces TGF-beta1 production, and improves the control of hypertension, without increasing the incidence of acute rejection.

Effect of ciclosporin on serum lipids and modification with LSL 90202, a lysine salt of eicosapentaenoic acid.

Ciclosporin (CS-A) has recently been considered a separate risk factor for the development of hyperlipidemia in transplant patients. In the present work, the effect of chronic CS-A administration on serum lipids and its modification using dietary supplementation with LSL 90202, a lysine salt of eicosapentaenoic acid, was studied. Thirty-one male Wistar rats were divided into four groups, receiving (1) 20 mg/kg CS-A in olive oil (CS-A group; n = 8); (2) isovolumetric olive oil (olive oil groups; n = 8); (3) 20 mg/kg CS-A in olive oil plus 20 mg/kg LSL 90202 (CS-A + LSL 20 group;) and (4) 20 mg/kg CS-A in olive oil plus 40 mg/kg LSL 90202 (CS-A+LSL 40 group; n = 8). Both, CS-A and LSL 90202 were given by daily gavage. On day 28, CS-A whole-blood levels and serum levels of total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol fractions (HDL, HDL-2, HDL-3, non-HDL), and malondialdehyde were measured. On day 28, the rats given CS-A showed significantly higher cholesterol, triglyceride, and non-HDL cholesterol serum levels than rats given olive oil. Rats given CS-A and LSL 90202 (20 mg/kg) showed significantly lower triglyceride serum levels than rats given CS-A only. Rats given CS-A and LSL 90202 (40 mg/kg) showed significantly lower triglyceride, total cholesterol, and non-HDL cholesterol serum levels than rats given CS-A only. There were no differences in HDL, HDL-2, and HDL-3 cholesterol serum levels between the groups. The CS-A whole-blood levels were not different between groups of animals given CS-A.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of experimental cyclosporine nephrotoxicity by dietary supplementation with LSL 90202, a lysine salt of eicosapentaenoic acid. Role of thromboxane and prostacyclin in renal tissue.

Cyclosporine (CsA) nephrotoxicity is partially mediated by renal vasoconstriction due to an imbalance between vasodilator and vasoconstrictor eicosanoids. LSL 90202 is a purified lysine salt of eicosapentaenoic acid which is a known inhibitor of renal eicosanoid synthesis. The aim of the present work was to determine if chronic dietary supplementation with LSL 90202 prevented CsA nephrotoxicity and to establish the role of thromboxane and prostacyclin in renal tissue. Thirty-three male Sprague-Dawley rats were divided into 4 groups: group 1, CsA in olive oil (n = 10); group 2, isovolumetric olive oil (n = 7); group 3, CsA in olive oil plus LSL 90202 (n = 8); group 4, isovolumetric olive oil plus LSL 90202 (n = 8). CsA and LSL 90202 were given at 20 mg/kg/day. Weight and creatinine clearance (CrCl) were determined before and on days 14 and 30. On day 30 whole-blood CsA was determined and renal tissue processed for renal malondialdehyde, thromboxane B2 and 6-keto-PGF1 alpha measurement and for conventional histology. CrCl was severely reduced in the CsA in olive oil group compared to olive oil and LSL 90202 control groups. On day 30, CrCl in the CsA in olive oil plus LSL 90202 group showed a slight decrease, but the mean CrCl was significantly higher than in the CsA in olive oil group. Trough whole blood CsA levels were not significantly different in both groups given the drug. No morphological differences were found between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin A (CsA) and azathioprine (AZA) combination in renal allografts with CsA nephrotoxicity.

Cyclosporin A (CsA) is a potent immunosuppressive drug whose effect is well known in the organ transplantation field. Treatment with CsA reduces the incidence of rejection and improves graft survival after renal transplantation (RT). However, to set against the clear advantages of CsA, a most important problem is nephrotoxicity. Scientists are therefore seeking new non-nephrotoxic Cs derivatives, but the search has not yet borne fruit. Teams working in organ transplantation attempt to avoid nephrotoxicity by switching to conventional treatment with azathioprine (AZA), starting 1, 3 or 6 months after transplantation. Conversion from CsA to AZA has not always been successful due to the high incidence of rejection. AZA has also been started immediately after transplantation in combination with CsA at low doses, and in some instances no CsA is administered when oliguric acute tubular necrosis is present. In a previous report, we presented the short-term results of the treatment with a CsA-AZA combination, reducing the CsA dose and giving a moderate dose of AZA in 21 transplanted patients not achieving acceptable graft function. In the present study we analysed the long-term results in a group of patients whose kidney biopsy examination results were compatible with CsA nephrotoxicity.

Evaluation of vancomycin for therapy of adult pneumococcal meningitis.

The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive initial CSF Gram stain were given intravenous vancomycin (usual dosage, 7.5 mg/kg every 6 h for 10 days). The MBCs of vancomycin ranged from 0.25 to 0.5 micrograms/ml. Early adjunctive therapy with intravenous dexamethasone, mannitol, and sodium phenytoin was also instituted. After 48 h of therapy, all 11 patients showed a satisfactory clinical response, although the CSF culture remained positive in one case; median trough CSF and serum vancomycin levels were 2 and 5.1 micrograms/ml, respectively, and trough CSF bactericidal titers ranged from less than 1:2 to 1:16. On day 3, one patient died of acute heart failure. Four patients had clinical failure at on days 4 (two patients), 7 (one), and 8 (one) of therapy; they all immediately responded to a change in antibiotic therapy. The remaining six patients were cured after 10 days of vancomycin therapy. At this point, median peak CSF and serum vancomycin levels were 1.9 and 18.5 micrograms/ml, respectively. A transient alteration of renal function occurred in two patients, and persistent slight hypoacusia occurred in three patients. In summary, 11 adults with pneumococcal meningitis were treated with vancomycin and early adjunctive therapy including dexamethasone. All patients initially improved, and 10 were ultimately cured of the infection. However, four patients experienced a therapeutic failure, which led to a change in vancomycin therapy.