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J Vilardell

Publications and source records attributed to J Vilardell.

At least 19 recordsLinked to original sources
PubMed2005

Use of quality index in the evaluation of organ procurement and transplant programs in a University Hospital.

AIM: To evaluate organ procurement efficiency at Hospital Clinic of Barcelona (HCP), a University Hospital, in 2000 and 2003 compared with other Catalan, other Spanish, and American (US) results. METHODS: Efficacy rate of the donor procurement was calculated per million population per year (pmp/y). Efficacy rate in kidney, liver, and heart transplantation was calculated also in pmp/y. We evaluated 1-year graft survival. RESULTS: During this period, the average rate number of donors was 49.1 pmp/y in HCP, 38 in Catalonia, 33.4 in Spain, and 21.7 in the United States. The average rate of kidney transplantation was 74 pmp/y in HCP, 55 in Catalonia, 47 in Spain, and 24.6 in the United States. The average rate of liver transplantation was 44.5, 26.6, 23.2, and 18 pmp/y, respectively. The average rate of heart transplantation was 13.3, 8.5, 7.8, and 6.4 pmp/y, respectively. One-year graft survival in HCP was 90.6% for kidney, 89.5% for liver, and 88.2% for heart transplants. DISCUSSION: The results show that organ procurement and transplantation programs in HCP are efficient. The organizational model is based on a hospital transplant coordinator and efficient, well-trained transplant teams.

Graft Survival↗
PubMed2003

Functions, responsibilities, dedication, payment, organization, and profile of the hospital transplant coordination in Spain in 2002.

In Spain, the number of donors per million of population and the activity of transplantation is a direct consequence of the continued work of the hospital transplant coordinators. There are 146 procurement hospitals with approximately 534 transplant coordinators (13.6 coordinators per hospital and 12.7 per million of population). A voluntary survey of 74 Spanish transplant coordinators revealed 67.6% to be men and 32.4% women of average age 43 years with specialization of 75.7%, Intensive Care Medicine; 8.1%, Anesthesiology; 6.7%, Nephrologists; and the rest, General Surgery or without any specialization. Among the group who responded to the injury, 86.5% were doctors and 13.5%, nurses. The overall team is composed of 52% doctors, 27.7% nurses and others with 70.3% working part-time and 27%, full-time. Previous experience was noted to be less than 5 years among 51.4%, and more in the rest of the cases. The 85% work under medical direction by management. Their payment includes salary plus activity in 48.7% of the cases; 21.6%, only salary, and 18.9%, only activity. Each coordinator generates between 3 and 7 organ as well as 3 and 11 of tissue donors. In conclusion, comparing this data with the practice in the United States demonstrates the unique aspects of the Spanish system.

Adult↗
PubMed2003

Optimizing cadaveric organ procurement: the catalan and Spanish experience.

The need to face the increasing gap between the supply and the demand of transplants has led to the development of a permanent network of trained medical staff responsible for the organ donation and removal process in all centers accredited for that process. In Spain, this activity received a specific budget, like any other medical activity in hospitals, and the responsible staff became accountable for performance. This system dramatically increased the number of potential donors referred, not only young donors with trauma, but also elderly donors dying from stroke. The effect was that the donation rate increased by more than 100% in 10 years (from 14 to 34 donors per million population). Consequently, so did all the transplant figures. In some areas, such as Catalonia, it has been demonstrated that sustained kidney transplant activity of over 60 procedures per million population can maintain or slightly decrease the waiting list, despite increasing incidence and prevalence of end-stage renal failure. Quality monitoring of the donation and retrieval process shows that there are still opportunities for improvement if all potential donors are referred and all technical problems are overcome. Living donation and nonheart beating organ retrieval should also be promoted.

Adolescent↗
PubMed2001

Mycophenolic acid plasma concentrations: influence of comedication.

Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11-8.33) and 0.56 (0.11-14.3), respectively (p < 0.0001). According to the post transplant period (1-3, 4-6 and >6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations. These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction.

Adult↗
PubMed2000

Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Adolescent↗
PubMed2000

Multiple functions of an evolutionarily conserved RNA binding domain.

Ribosomal protein L30 of Saccharomyces cerevisiae binds to a distinct RNA structure to inhibit the splicing and the translation of its own transcript. Remarkably, the ortholog of L30 from the archaeon Sulfolobus acidocaldarius binds specifically to the same RNA fragment and inhibits splicing both in vitro and in vivo. Indeed, expression of Sulfolobus L30 in yeast severely reduces growth by limiting production of the endogenous L30. This conservation of binding specificity implies that the target of regulation in the RPL30 transcript mimics a site in the rRNA that has been conserved for more than a billion years. We identify this site, whose location suggests that L30, which has no apparent eubacterial ortholog, is responsible for establishing the orientation of a key bridge between the large and small ribosomal subunits.

Amino Acid Sequence↗
PubMed2000

The odyssey of a regulated transcript.

The transcript of the Saccharomyces cerevisiae gene, RPL30, is subject to regulated splicing and regulated translation, due to a structure that interacts with its own product, ribosomal protein L30. We have followed the fate of the regulated RPL30 transcripts in vivo. Initially, these transcripts abortively enter the splicing pathway, forming an unusually stable association with U1 snRNP. A large proportion of the unspliced molecules, however, are found in the cytoplasm. Most of these are still bound by L30, as only a small fraction are engaged in translation. Eventually, the unspliced RPL30 transcripts escape the grasp of L30, associate with ribosomes, and fall prey to nonsense mediated decay.

Biological Transport↗
PubMed2000

Assessment of mycophenolic acid-induced immunosuppression: a new approach.

BACKGROUND: Mycophenolic acid (MPA), a metabolite of mycophenolate mofetil (MMF), is an immunosuppressive agent that inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the ex novo synthesis of GTP. We measured IMPDH activity in peripheral blood mononuclear cells (PBMCs) from MMF-treated patients to evaluate the efficacy of MMF in individual patients. METHODS: IMPDH activity was measured by (3)H released from [2,8-(3)H]IMP that had been formed in the cells from added [2,8-(3)H]hypoxanthine in PBMCs of 35 renal transplant recipients treated with cyclosporin A and corticoids plus MMF: 2 g (n = 10), 1.5 g (n = 7), 1 g (n = 10), or 0 g (n = 8) per day. An alternative method, based on the capacity of the patients' sera to inhibit spontaneous proliferation of the CEM cell line, was also analyzed. RESULTS: The IMPDH activity of PBMCs in transplanted patients was highly variable. For the method based on CEM cell line proliferation: (a) cell proliferation was inhibited only in MMF-treated patients; (b) there was a clear postdose increase in inhibition; (c) inhibition was not affected by other immunosuppressants in vitro or in vivo; (d) inhibition from predose to predose sample was correlated; and (e) when the MMF dosage was <20 mg. kg(-1). day(-1), two groups of patients were identified, one that maintained a high inhibitory capacity in all dose intervals, and one with periods of low inhibitory capacity. CONCLUSIONS: Measurement of the inhibition of CEM cell line proliferation by sera from MMF-treated patients may be useful for evaluating the relative efficacy of MMF treatment in individual patients, especially those receiving low doses of MMF.

Adult↗
PubMed1997

Ribosomal protein L32 of Saccharomyces cerevisiae influences both the splicing of its own transcript and the processing of rRNA.

Ribosomal protein L32 of Saccharomyces cerevisiae binds to and regulates the splicing and the translation of the transcript of its own gene. Selecting for mutants deficient in the regulation of splicing, we have identified a mutant form of L32 that no longer binds to the transcript of RPL32 and therefore does not regulate its splicing. The mutation is the deletion of an isoleucine residue from a highly conserved hydrophobic domain near the middle of L32. The mutant protein supports growth, at a reduced rate, and is found at normal levels in mature ribosomes. However, in cells homozygous for the mutant gene, the rate of processing of the ribosomal RNA component of the 60S ribosomal subunit is severely reduced, leading to an insufficiency of 60S subunits. L32 must be considered a remarkable protein. Composed of only 104 amino acids, it appears to interact with three distinct RNA molecules to influence three different elements of RNA processing and function in three different locations of the cell: the processing of pre-rRNA in the nucleolus, the splicing of the RPL32 transcript in the nucleus, and the translation of the spliced RPL32 mRNA in the cytoplasm.

Amino Acid Sequence↗
PubMed1996

An RNA structure involved in feedback regulation of splicing and of translation is critical for biological fitness.

While studies of the regulation of gene expression have generally concerned qualitative changes in the selection or the level of expression of a gene, much of the regulation that occurs within a cell involves the continuous subtle optimization of the levels of proteins used in macromolecular complexes. An example is the biosynthesis of the ribosome, in which equimolar amounts of nearly 80 ribosomal proteins must be supplied by the cytoplasm to the nucleolus. We have found that the transcript of one of the ribosomal protein genes of Saccharomyces cerevisiae, RPL32, participates in such fine tuning. Sequences from exon I of the RPL32 transcript interact with nucleotides from the intron to form a structure that binds L32 to regulate splicing. In the spliced transcript, the same sequences interact with nucleotides from exon II to form a structure that binds L32 to regulate translation, thus providing two levels of autoregulation. We now show, by using a sensitive cocultivation assay, that these RNA structures and their interaction with L32 play a role in the fitness of the cell. The change of a single nucleotide within the 5' leader of the RPL32 transcript, which abolishes the site for L32 binding, leads to detectably slower growth and to eventual loss of the mutant strain from the culture. Experiments designed to assess independently the regulation of splicing and the regulation of translation are presented. These observations demonstrate that, in evolutionary terms, subtle regulatory compensations can be critical. The change in structure of an RNA, due to alteration of just one noncoding nucleotide, can spell the difference between biological success and failure.

Base Sequence↗
PubMed1996

Study of kidney rejection following simultaneous kidney-pancreas transplantation.

Simultaneous kidney-pancreas (SKP) transplantation is associated with increased risk of kidney rejection (KR) due to an unknown mechanism. The aim of this study is to analyze the characteristics of KR in 44 SKP transplantations under quadruple immunosuppressive therapy and to evaluate the response to treatment and its effect on renal allograft survival and renal function. The mean follow-up was 25 +/- 14 months. Seventy-seven percent of the patients (34 of 44) presented an acute renal allograft rejection. Sixty-six percent (29 of 44) had one rejection episode and 11% (5 of 4) 2 episodes. KR was early (85% in the first month after transplantation), intense (3.7-fold increase in creatinine) and had great clinical features. Twenty-eight percent of the patients had an early relapse during the first month after treatment. KR did not affect the survival of the renal allograft in the short-term (1 and 2 years). Overall, 62% were corticosensitive (CS) and the remaining 38% were corticoresistant (CR). The group with an isolated rejection without relapse was CS in 69% of the cases, achieved complete remission in 73% and renal function was not affected at 1 and 2 years [115 +/- 26 mumol/l (1.3 +/- 0.3 mg/dl) and 150 +/- 53 mumol/l (1.7 +/- 0.6 mg/dl)] in comparison with the group without rejection [97 +/- 18 mumol/l (1.1 +/- 0.2 mg/dl) and 115 +/- 35 mumol/l (1.3 +/- 0.4 mg/dl); p = NS]. On the other hand, the group with an early relapse of the first rejection and the group with two rejections were principally CR (62 and 60%, respectively), had partial remission with treatment (50 and 60%) and had worse renal function at 1 and 2 years [212 +/- 71 mumol/l (2.4 +/- 0.8 mg/dl) and 221 +/- 53 mumol/l (2.5 +/- 0.6 mg/dl)] than in the group with isolated KR (p < 0.05 and p < 0.001). In conclusion, despite intense immunosuppressive treatment, the frequency of rejection of a renal allograft in SKP is high. The response to treatment is satisfactory and does not affect the survival of the allograft in the short-term. However, multiple episodes or early relapse of rejection are associated with higher creatinine levels.

Adult↗