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Biomedical subjects

A Rimola

Publications and source records attributed to A Rimola.

At least 19 recordsLinked to original sources
PubMed2006

How ischaemic preconditioning protects small liver grafts.

Interleukin-1 (IL-1) and transforming growth factor-beta (TGFbeta) are key inhibitors of hepatocyte proliferation after hepatectomy. IL-1 inhibition by heat shock proteins (HSPs) has been reported in inflammatory processes. A recent study indicated the benefits of ischaemic preconditioning in reduced-size orthotopic liver transplantation (ROLT). The present study examined: (a) the effect of ischaemic preconditioning on IL-1 and TGFbeta in ROLT; (b) whether preconditioning protects small liver grafts through HSP induction; and (c) whether the potential benefits of preconditioning on HSP is related to IL-1 inhibition. Our results, obtained with an IL-1 receptor antagonist, indicated the injurious effects of IL-1 in ischaemia-reperfusion (I/R) injury and established a relationship between IL-1 and growth factors. Thus, IL-1 reduced hepatocyte growth factor (HGF) and promoted TGFbeta release, thus contributing to the impaired liver regeneration associated with ROLT. Preconditioning inhibited IL-1 through nitric oxide (NO), thereby protecting against the injurious effects of IL-1. In addition, by another pathway independent of NO, preconditioning induced HSP70 and haem-oxygenase-1 (HO-1). HO-1 protected against I/R injury and liver regeneration, whereas the benefits resulting from HSP70 were mainly related to hepatocyte proliferation. These results suggest a mechanism that explains the effectiveness of preconditioning in ROLT. They suggest, too, that other strategies, in addition to preconditioning, that modulate IL-1 and/or HSPs could be considered in clinical situations requiring liver regeneration such as small liver grafts.

Animals↗
PubMed2006

[Ischemia-reperfusion syndrome associated with liver transplantation: an update].

Ischemia-reperfusion (I/R) injury is the main cause of both initial graft dysfunction and primary failure in liver transplantation. The search for therapeutic strategies to prevent I/R injury has led to research into promising drugs, although most have not been used clinically. Gene therapy requires better transfection techniques, avoiding vector toxicity, and ethical debate before being used clinically. Ischemic preconditioning is the first therapeutic strategy used in clinical practice to reduce I/R injury in hepatectomies for tumors. Future research will provide data on the effectiveness of ischemic preconditioning in reducing I/R injury associated with liver transplantation, and in reducing the vulnerability of steatotic grafts to I/R syndrome so that they can be used in transplantation, thus relieving the organ shortage.

Adenosine Triphosphate↗
PubMed2005

Five-year follow-up of a trial comparing Tacrolimus and cyclosporine microemulsion in liver transplantation.

We evaluate 5-year results of a prospective randomized trial that compared cyclosporine microemulsion (CsA-me) and Tacrolimus (Tac) for primary immunosuppression. One hundred one adult patients undergoing liver transplantation were randomized to receive Tac (n = 50) or CsA-me (n = 51). The most frequent indication for the procedure was cirrhosis due to virus C followed by alcoholism. Survival rates at 1, 3, and 5 years were 86%, 75%, and 72%, respectively; there was no significant difference between CsA-me versus Tac arms. Acute rejection occurred in 30 cases (30%), independent of the type of primary immunosuppression. Serious adverse events were reported significantly more among patients under CsA-me (48 episodes) than under Tac (32 episodes). Nineteen patients were switched to the other calcineurin inhibitor. The switch was much more frequent from CsA-me to Tac (n = 15; 29.4%), mainly because of lack of efficacy (n = 10; 19.6%). There were no cases of chronic rejections in the Tac arm. Four patients were switched from Tac to CsA-me for side effects; only 1 remains alive, after treatment was changed from CsA-me to an antimetabolite. There were no statistical differences in renal dysfunction, diabetes, hypertension, neurologic disorders, new-onset malignancies, or infections. There were no differences in survival or rejection among the intention-to-treat groups. Serious adverse events, total patients with switch of calcineurin inhibitor, as well as switches due to lack of efficacy, were statistically more frequent under CsA-me. Tacrolimus seems to be a more appropriate drug to be used for primary immunosuppression in liver transplantation.

Cyclosporine↗
PubMed2005

One thousand liver transplants: the hospital clinic experience.

OBJECTIVES: Our goal was to study a consecutive series of 1000 liver transplants performed in our institution to evaluate the changes over time in donors, recipients, and results. PATIENTS AND METHODS: With the aim to evaluate differences between transplantation in the first period and the present period, the first consecutive 100 liver transplants performed from June 1988 to June 1990 (first period) were compared with the last consecutive 200 liver transplants performed from January 2001 to June 2003 (second period). RESULTS: Increased donor age, change in donor cerebral death etiology, and increasing numbers of grafts from alternative methods using cadaveric donors were observed in the second period. Piggy-back technique and the biliary anastomosis without a t-tube was also started in the second period. One-year actuarial patient survival was higher in the second period (84% vs 91.3%). The need for retransplantation in the overall series was 95%. One-, 5-, and 10-year actuarial retransplant survival was 67.7%, 51.3%, and 39.4%, respectively. CONCLUSIONS: Technical innovations, better understanding of donor and recipient aspects, and global improvements were the reasons for time-related improved results of liver transplantation.

Adult↗
PubMed2005

Steroids and living liver donation increase tacrolimus blood levels in living donor liver transplantation.

The aim of this study was to determine the tacrolimus blood levels in recipients of living donor liver transplants (LDLT) compared with recipients who undergo whole cadaveric liver grafts and to correlate the tacrolimus trough levels with the 12-hour area under the concentration (AUC) curve. From June 2002 to June 2003, the 10 LDLT were prospectively compared with 11 cadaveric transplants. The main immunosuppression was tacrolimus plus steroids. Intraoperative methylprednisolone was administered to all cadaveric organ recipients and only 6 of the 10 LDLT. Median tacrolimus trough levels at day 10 were 14.1 ng/mL for the LDLT group and 9.1 ng/mL for the CLT group (P = NS). The median tacrolimus AUC at day 10 were 185.2 ngxh/mL and 148.1 ngxh/mL for the LDLT group and the cadaveric group, respectively (P = NS). Median tacrolimus trough levels at day 2 were 24.3 ng/mL versus 9.9 ng/mL in the LDLT recipients with and without steroids, respectively (P < .05). Also, median tacrolimus AUC at day 2 were 239 ngxh/mL and 179.7 ngxh/mL when we compared LDLT recipients with and without steroids (P = NS). A significant correlation was observed between tacrolimus trough levels and AUC in the LDLT group (C.C. = 0.936; P < .0001). In conclusion, LDLT recipients display higher tacrolimus blood levels in comparison with cadaveric liver recipients, with a good correlation between tacrolimus trough levels and AUC. Intraoperative steroid administration induces higher tacrolimus levels in LDLT recipients.

Adrenal Cortex Hormones↗
PubMed2003

Role of ischemic preconditioning and the portosystemic shunt in the prevention of liver and lung damage after rat liver transplantation.

BACKGROUND: This study evaluates whether surgical strategies such as the portosystemic shunt and ischemic preconditioning can protect against hepatic and pulmonary injury associated with liver transplantation. METHODS: The effect of the portosystemic shunt, ischemic preconditioning, and both surgical procedures together were evaluated in rat liver transplantation. Alanine aminotransferase, hyaluronic acid levels in plasma, adenosine triphosphate and nucleotide levels in liver and edema, malondialdehyde levels, and myeloperoxidase activity were measured 24 hr posttransplantation. Plasmatic tumor necrosis factor (TNF) levels were measured as a possible proinflammatory factor responsible for hepatic and pulmonary damage associated with liver transplantation. RESULTS: Hepatocyte and cell endothelial damage were observed in liver grafts subjected to 8 hr of cold ischemia. This was associated with increased plasma TNF levels and lung inflammatory response. Portosystemic shunt application in the recipient protected endothelial cells but did not confer an effective protection from hepatocyte damage or reduce the increased plasma TNF levels and lung damage after liver transplantation. However, preconditioning of the donor liver conferred protection against both the endothelial cell and hepatocyte damage observed after liver transplantation. Preconditioning also attenuated the increased plasma TNF release and pulmonary damage. The combination of both surgical strategies resulted in levels of liver injury, TNF, and lung damage similar to those seen after liver transplantation. CONCLUSIONS: These findings indicate that ischemic preconditioning could be a preferred treatment to reduce hepatic and pulmonary damage associated with liver transplantation. However, this strategy may not be effective in several clinical situations requiring a portosystemic shunt.

Animals↗
PubMed2003

The process of adult living liver donation.

OBJECTIVE: To evaluate both the opinion that living liver donors have of the process and the psychological, economic, and social consequences of donation. MATERIAL AND METHODS: Six months after the donation, an anonymous survey was sent to 22 donors of the right liver lobe between March 2000 and December 2002. RESULTS: 15 surveys were returned with all of the questions answered. Almost all the donors had no prior knowledge of living donation. When they were considered to be suitable donors, all of them felt happy, 21% were scared and 15% felt joy and insecurity. The information provided was well understood and accurately described the experiences of 93% of donors. All donors understood the vital risk, and 93% understood that transplantation is not always completely successful. All donors would repeat the experience. Mean hospital stay was 12.6 days. Mean convalescence was 50.6 days. Salaried donors were on sick leave for a mean of 96.4 days (21-150 days), causing financial problems in six cases (36%), due to no financial compensation and compulsory redundancy in one case. All donors had completely recovered at six months after donation. DISCUSSION: Adult living donation of the right liver lobe is an accepted therapeutic alternative. In order to regulate medical and economic protection to avoid additional disturbances after donation, the public, patients, and physicians require more complete information about living donation.

Adult↗
PubMed2003

[Adult living donor liver transplantation. Analysis of the first 30 cases].

INTRODUCTION: In the last 2-3 years, adult living donor liver transplantation (ALDLT) has been developed on an international scale, multiplying the number of procedures performed. Despite this, analysis of the results is still incomplete. The aim of the present study was to perform a descriptive analysis of the results after the first 3 years of the initiation of the program. MATERIAL AND METHODS: During this period, 30 ALDLT were performed. In all procedures, right lobe grafts were used. The mean age of donors and recipients was 31.8 and 52.7 years, respectively. The main indication for liver transplantation was liver cirrhosis due to hepatitis C virus (70%) and 38% of recipients were stage C in the Child-Pugh classification. A total of 46.7% of recipients had hepatocellular carcinoma. RESULTS: Donors: The mean volume of the remnant liver was 632 cc (40.5% of the previous hepatic mass). Ten donors (33%) presented complications. The most frequent complication was biliary fistula (20%) and three patients required reintervention. The mean length of hospital stay among donors was 11.7 days. Recipients: The mean weight of the graft was 775 g, with a mean difference between graft weight and that of the recipient of 1.11. Fifteen recipients (50%) presented biliary leaks and nine of these (30%) required reintervention. There were no graft losses for technical reasons. Four patients died. With a median follow-up of 14 months, actuarial survival at 18 months was 92.9%. CONCLUSION: ALDLT is an effective method for reducing the number of patients on the waiting list. The probability of survival is similar to that of cadaveric transplantation. Biliary complications in the recipient constitute a problem, the long-term repercussions of which remain to be resolved.

Adolescent↗
PubMed2001

Alternariosis after liver transplantation.

Alternaria is a saprophytic fungus that is increasingly recognized as a human pathogen, particularly in immunocompromised hosts, including solid-organ transplant recipients. Although combined surgical and medical treatment seem to be useful in the management of this infection, an optimal antifungal therapy remains to be defined. Only four cases of alternariosis after orthotopic liver transplantation have been reported. We describe an additional case and review the literature on infections due to Alternaria in organ transplant recipients, with special emphasis on treatment.

Alternaria↗
PubMed2001

Endogenous nitric oxide and exogenous nitric oxide supplementation in hepatic ischemia-reperfusion injury in the rat.

BACKGROUND: Although nitric oxide (NO) is thought to be beneficial in hepatic ischemia-reperfusion (I/R), the mechanisms for this effect are not well established. METHODS: To investigate the effects of endogenous NO and exogenous NO supplementation on hepatic I/R injury and their pathogenic mechanisms, serum ALT and hyaluronic acid (endothelial cell damage), and hepatic malondialdehyde and H2O2 (oxidative stress), myeloperoxidase activity (leukocyte accumulation), and endothelin (vasoconstrictor peptide opposite to NO) were determined at different reperfusion periods in untreated rats and rats receiving L-NAME, L-NAME+L-arginine, and spermine NONOate (exogenous NO donor). RESULTS: After reperfusion every parameter increased in untreated animals. Endogenous NO synthesis inhibition by L-NAME increased hepatocyte and endothelial damage as compared to untreated rats, which was reverted and even improved by the addition of L-arginine. Spermine NONOate also improved this damage. However, different mechanisms account for the beneficial effect of endogenous and exogenous NO. Oxidative stress decreased by both L-NAME and L-NAME+L-arginine, but remained unmodified by spermine NONOate. Myeloperoxidase increased by L-NAME and this effect was reverted by the addition of L-arginine, whereas no change was observed with spermine NONOate. Endothelin levels were not modified by L-NAME and L-NAME+L-arginine, but decreased with spermine NONOate. CONCLUSIONS: These results suggest that, although both endogenous and exogenous NO exert a protective role in experimental hepatic I/R injury, the mechanisms of the beneficial effect of the two sources of NO are different.

Alanine Transaminase↗
PubMed2001

Influence of the dynamics of the hypervariable region 1 of hepatitis C virus (HCV) on the histological severity of HCV recurrence after liver transplantation.

Recurrence of hepatitis C virus (HCV) infection after liver transplantation is almost universal and usually leads to chronic hepatitis with different degrees of severity. The pathogenic mechanisms underlying the variable outcome of HCV infection recurrence are not well defined, but recent data suggest that the dynamics of HCV quasispecies may be involved. HCV quasispecies evolution was traced by longitudinal single strand conformation polymorphism, direct sequencing, and cloning analyses of pre- and post-transplant HCV-1b isolates from patients with histologically severe (seven cases) or mild or moderate (nine cases) HCV infection recurrence. Differences between the two groups of patients that concerned the level of viremia or the degree of HCV quasispecies complexity and diversity were not observed at any of the three time points analyzed. However, emergence of nucleotide and amino acid changes during the 12 months follow-up was significantly more frequent in patients with mild or moderate than in those with severe HCV infection recurrence. The ratio of non-synonymous to synonymous nucleotide substitutions 12 months after transplantation was also greater in the former, suggesting that the HVR1 of HCV is under stronger selective pressure in these subjects. These findings suggest that the degree of amino acid diversification in the HVR1 of HCV, which probably reflects the strength of immune pressure on HCV, is inversely related to the histological severity of HCV infection recurrence.

Amino Acid Sequence↗
PubMed2001

Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A.

The purpose of this study was to compare the effects of Cyclosporine A (CyA) and FK506 on bone mass and mineral metabolism in liver transplantation (LT) patients. A prospective study was performed on 18 male patients who underwent LT treated with CyA, and 7 LT patients who received FK506. Bone mineral density (BMD) of the lumbar spine and proximal femur (DPX-L) was measured before and at 6, 12, and 24 months after transplantation. Moreover, intact parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) levels were determined at the same time. The cumulative dose of glucocorticoids was calculated in all patients. At 6 months, lumbar BMD decreased 5.2 +/- 1.2% (P = 0.0005) and 2.9 +/- 2.1% (p = ns) in CyA and FK506 groups, respectively. Lumbar BMD reached baseline values at 1 year in the FK506 group and 2 years after LT in the CyA group. Moreover, significant intergroup differences in femoral neck BMD changes after 2 years of transplant were observed (CyA: -5.2 +/- 1.97 versus FK506: +1.55 +/- 2.2%; P = 0.039). In the first year posttransplant both groups showed a marked increase in PTH and 25OHD levels. The mean cumulative dose of glucocorticoids was higher in the CyA group (CyA group 11.06 +/- 0.46 g versus FK 506 group 6.71 +/- 0.42 g; P < 0.001), and multiple linear regression analysis showed a negative correlation between BMD changes at the lumbar spine and mean cumulative dose of glucocorticoids (P = 0.022). In conclusion, our data suggest that after liver transplantation treatment with FK506 shows a more favorable long-term effect on bone mass evolution than CyA therapy. These differences seem to be associated with the lower dose of glucocorticoids used in the FK506 group.

Absorptiometry, Photon↗
PubMed2001

Intrahepatic biliary lesions after orthotopic liver transplantation.

Intrahepatic biliary lesions (IBL) are rare (2-9%) after orthotopic liver transplantation (OLT). The aim was to evaluate the incidence, etiology and outcome. In nine years, a total 532 OLTs were performed in 481 patients. Twenty-four patients developed IBL. Eight were due to HAT, seven to ABOI, three to CDR and six to PI. The time until diagnosis of HAT is longest in patients (14+/-6) with IBL. ABOI is another cause of IBL. CDR is a rare cause of IBL, however when it takes place, patients must undergo Rtx. Finally, PI is a relevant cause of IBL. In order to suppress the incidence of IBL we should consider 1) the systematic use of Doppler-Ultrasound; 2) emergency reoperation of patients with HAT, 3) avoid ABOI in OLT; 4) Rtx in cases of CDR, and 5) OLT should still be performed as an emergency procedure.

ABO Blood-Group System↗