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F Pardo

Publications and source records attributed to F Pardo.

At least 37 records · Page 2Linked to original sources

Prognostic model for early acute rejection after liver transplantation.

Hepatic graft rejection is a common complication after liver transplantation (LT), with a maximum incidence within the first weeks. The identification of high-risk patients for early acute rejection (EAR) might be useful for clinicians. A series of 133 liver graft recipients treated with calcineurin inhibitors was retrospectively assessed to identify predisposing factors for EAR and develop a mathematical model to predict the individual risk of each patient. The incidence of EAR (< or =45 days after LT) was 35.3%. Multivariate analysis showed that recipient age, underlying liver disease, and Child's class before LT were independently associated with the development of EAR. Combining these 3 variables, the following risk score for the development of EAR was obtained: EAR score [F(x)] = 2.44 + (1.14 x hepatitis C virus cirrhosis) + (2.78 x immunologic cirrhosis) + (2.51 x metabolic cirrhosis)--(0.08 x recipient age in years) + (1.65 x Child's class A) [corrected]. Risk for rejection = e(F(x))/1 + e(F(x)). The combination of age, cause of liver disease, and Child's class may allow us to predict the risk for EAR.

Calcineurin Inhibitors↗

Influence of tumor characteristics on the outcome of liver transplantation among patients with liver cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) may recur after liver transplantation (LT), mainly in patients with multinodular and large tumors. However, factors predictive of outcome after LT in patients with small tumors remain ill defined. We investigated which factors were related to mortality or tumor recurrence among 47 liver transplant recipients with liver cirrhosis and HCC and compared them with 107 patients with liver cirrhosis without tumor who underwent LT in the same period. Patients with HCC were older (P <.001), more frequently had cirrhosis of a viral origin (P <.001), and had lower Child-Pugh scores (P <.001) than patients without tumor. Survival of patients with and without tumor was not significantly different (P =.20). Among patients with HCC, those with lower recurrence-free survival rates had liver cirrhosis of a viral origin, vascular invasion, bilobar disease, and tumor-node-metastasis (TNM) stage IV. At multivariate analysis, the only factor associated with mortality or recurrence was TNM stage IV (P =.02). Our results suggest that in patients with HCC and TNM stage IV, LT might be contraindicated.

Adult↗

Selection criteria for liver transplantation in early-stage hepatocellular carcinoma with cirrhosis: results of a multicenter study.

Orthotopic liver transplantation (OLT) offers the only chance to eliminate both tumor and liver disease in patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumor progression while on the waiting list and recurrence after OLT are frequent. We undertook a large multicenter study to assess survival and related factors of recurrence after OLT. This retrospective study analyses data from 307 consecutive patients with HCC and cirrhosis treated with OLT between 1990 and 1997 in eight centers in Spain. OLT was indicated only for small (<5 cm) localized tumors. Five-year rates after OLT were 63% for survival, 58% for disease-free survival, and 21% for recurrence. Tumor diameter larger than 5 cm was associated with other tumor characteristics that were significant indicators of poor outcome (absence of capsule, three or more nodules, bilobularity, satellite nodules, and vascular invasion). However, in multivariate analysis, alpha fetoprotein (AFP) levels greater than 300 ng/mL (P = .04; P = .02) and macroscopic vascular invasion (P = .01; P = .0001) were the only factors independently associated with mortality and recurrence, respectively. OLT is indicated in patients with small HCCs who have low AFP levels and no macroscopic vascular invasion or extrahepatic disease. By increasing our ability for preoperative tumor imaging, we will achieve better selection of patients with HCC before OLT.

Adult↗

Neonatal screening for cystic fibrosis: long-term clinical balance.

BACKGROUND/AIMS: Very few studies have been performed on the long-term clinical advantages of neonatal screening programs for cystic fibrosis (CF) and these have been inconclusive. This is a preliminary report of two observational cohort studies on this subject. METHODS: In the first study, CF patients born between 1973 and 1981 in northeastern Italy were split into 4 groups according to the modality of diagnosis: screening by meconium test (58 patients); meconium ileus (45 patients); symptoms and pancreatic insufficiency (PI; 75 patients), or symptoms and pancreatic sufficiency (PS; 19 patients). The patients were followed for up to 26 years by three CF centers sharing common treatment protocols. In the second study, two cohorts of CF patients born between 1983 and 1992 were compared. Patients from one cohort (126 patients) were born in the Veneto region, where a neonatal screening program had been established based on immunoreactive trypsinogen. Patients from the other cohort (152 patients) were born in Sicily, where an intensive program of early diagnosis by symptoms was implemented. The cohorts were comparable for CF incidence, CFTR genotypes, gender proportion and common treatment protocols. Statistical analyses were performed by Kaplan-Meier survival curves, a Cox proportional hazard model for survival and cross-sectional comparisons by 2-year periods for weight z score, height z score and body mass index. RESULTS: In the first study, the patients detected by newborn screening (PI) showed better survival and nutritional status compared to patients diagnosed through meconium ileus or symptom presentation with PI. PS patients diagnosed by symptoms showed the best outcome, but most of them had a mild genotype. In the second study, the Veneto cohort showed better outcome with regard to survival and nutritional status over 16 years of follow-up. CONCLUSIONS: Observational cohort studies cannot give definitive evidence of the clinical benefit of neonatal CF screening; however, data have been accumulated which strongly suggest a better clinical outcome for CF patients born in an area where a screening program is performed.

Adolescent↗

Endothelial perturbation in cystic fibrosis.

Cystic fibrosis (CF) is characterized by a persistent inflammatory state, which can be secondary to chronic pulmonary infection and may affect vascular endothelium. We measured circulating levels of von Willebrand factor (vWF), tissue-plasminogen activator (t-PA), and P-selectin in 20 CF patients and 20 healthy subjects. vWF, t-PA and P-selectin levels were significantly higher in CF patients. Endothelial perturbation (>2 SD increase in both vWF and t-PA) was present in 65% of CF patients. These patients displayed lower FEV1 values compared to individuals without endothelial perturbation and an inverse correlation between FEV1 and P-selectin levels was observed. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels were also increased in CF patients and significant direct correlations were found between TNF-alpha and vWF, t-PA or P-selectin levels. These results indicate that CF patients exhibit signs of endothelial dysfunction/perturbation, which are likely to be related to a persistent inflammatory state due to chronic pulmonary infection, and may play a role in the progression of this disease.

Adolescent↗

Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors.

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.

Creatinine↗

In vivo lipid peroxidation and platelet activation in cystic fibrosis.

F(2)-isoprostanes are bioactive peroxidation products of arachidonic acid whose urinary excretion provides an index of lipid peroxidation in vivo. We tested the hypothesis that formation of F(2)-isoprostanes is altered in patients with cystic fibrosis and contributes to platelet activation and pulmonary dysfunction in this setting. The urinary excretion of immunoreactive 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) was significantly (p = 0.0001) higher in 36 patients with cystic fibrosis than in 36 age-matched healthy subjects: 618 +/- 406 versus 168 +/- 48 pg/mg creatinine. The urinary excretion of immunoreactive 11-dehydro-thromboxane B(2) (TXB(2)), an index of in vivo platelet activation, was also significantly (p = 0.0001) higher in patients than in control subjects: 2,440 +/- 1,453 versus 325 +/- 184 pg/mg creatinine. The excretion rate of 8-iso-PGF(2alpha) was correlated with that of 11-dehydro-TXB(2) (rho = 0.51; p = 0.0026) and inversely related to FEV(1) (rho = -0.40; p = 0.0195). Urinary 8-iso-PGF(2alpha) excretion was largely unaffected during cyclooxygenase inhibition with low-dose aspirin, nimesulide, or ibuprofen, consistent with a noncyclooxygenase mechanism of F(2)-isoprostane formation in cystic fibrosis. Increased vitamin E supplementation (from 200 to 600 mg/d) was associated with statistically significant (p = 0.005) reductions in urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) excretion, by 42% and 29%, respectively. We conclude that enhanced lipid peroxidation is an important feature of cystic fibrosis and may contribute to persistent platelet activation and pulmonary dysfunction via generation of bioactive isoeicosanoids. Our results provide a rationale for reassessing the adequacy of vitamin E supplementation in this setting.

Adolescent↗

Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil.

The management of liver transplant recipients with renal function impairment remains controversial because cyclosporine withdrawal from triple immunosuppression regimens may be followed by graft rejection. A nonnephrotoxic and powerful immunosuppressant such as mycophenolate mofetil (MMF) could allow a reduction of cyclosporine dosage or its withdrawal and an improvement in renal function in these patients. Eleven patients with serum creatinine levels greater than 1.5 mg/dL, normal graft function, and a rejection-free period of at least 1 year started MMF at a dose of 2000 mg/d (reduced in case of adverse events) while cyclosporine dosage was slowly reduced. At last follow-up (63 +/- 5 weeks), 7 patients remained free of cyclosporine (6 of those patients are also free of steroids), 2 patients reduced their cyclosporine dose, and 2 patients developed mild acute rejection that responded to a switch to tacrolimus therapy. Serum creatinine and urea levels in the 7 patients free of cyclosporine decreased from 2.22 +/- 0.13 to 1.90 +/- 0.19 mg/dL (P =.05) and 0.95 +/- 0.10 to 0.60 +/- 0.10 g/L (P <.001), respectively. Creatinine clearance increased from 38.16 +/- 5.60 to 47.01 +/- 6. 76 mL/min (P =.005). Control of arterial hypertension also improved. Tolerance to MMF was good, but 6 patients required dose reductions, mainly because of asymptomatic anemia. In conclusion, in liver transplant recipients with stable graft function, MMF may allow cyclosporine dose reduction or discontinuation, thus improving renal function and the control of arterial hypertension. This change of treatment must be carefully monitored because of the frequent need for MMF dose reduction and the risk for rejection.

Aged↗

Evolution of residual levels of six pesticides during elaboration of red wines. Effect of wine-making procedures in their dissappearance.

The effect of wine-making procedures on the concentrations of six pesticides (chlorpyrifos, penconazole, fenarimol, vinclozolin, metalaxyl, and mancozeb) in red wines has been studied. During maceration stage (4 days), the percentage remaining of chlorpyrifos, penconazole, and metalaxyl was approximately 90%, whereas that of fenarimol, vinclozolin, and mancozeb is somewhat smaller (74-67%). The residual levels found in pressed must were </=20%, except for metalaxyl (69%). From the whole concentration of chlorpyrifos in must, 85% is eliminated from the racking step; clarification (bentonite plus gelatin) eliminates 43% of the product found in the decanted wine, and with filtration, all of the residue is eliminated. Penconazole and mancozeb are retained on the lees in proportions of 43 and 31%, respectively. The eliminated percentage of vinclozolin after racking is 29%, whereas clarification and filtration reduce its proportion in the wine to 33 and 28%, respectively. Finally, fenarimol and metalaxyl are eliminated in smaller proportion with the realization of these processes.

Pesticide Residues↗

Human immunoglobulin isotype profiles produced in response to antigens recognized by monoclonal antibodies specific to Anisakis simplex.

BACKGROUND: Anisakis simplex is a medically important pathogen which not only causes anisakiasis but may provoke allergy reactions, ranging from mild urticaria to anaphylactic shock. OBJECTIVE: To investigate anti-Anisakis isotype profiles in anisakiasis and Anisakis allergy patients. METHODS: Capture ELISA techniques were used to investigate the isotype profiles of antibodies specific for two defined Anisakis simplex antigens, in serum from Japanese patients with confirmed anisakiasis and from Spanish patients with allergy to Anisakis. The antigens were 'UA2R antigens' (two proteins with MW of 48 and 67 kDa, recognized by our monoclonal antibody UA2) and 'UA3R antigens' (two proteins with MW of 139 and 154 kDa, recognized by our monoclonal antibody UA3). RESULTS: Considering IgG, the two most frequent isotypes in the response to the UA2R antigens were IgG1 and IgG2, with IgG4 detected in only one case; in response to the UA3R antigens, by contrast, the two most frequent isotypes were IgG1 and IgG4 (though IgG2 remained reasonably frequent). As regards potential utility for serodiagnosis, 95% of the Japanese anisakiasis patients and 84% of the allergy patients showed detectable IgG1 antibodies to the UA3R antigens. Furthermore, all allergy patients showed IgE antibodies to these antigens. CONCLUSION: Anisakis simplex contains antigens that induce responses which are differentially regulated. Because of their immunogenicity, immunodominance and allergenic nature, we consider that the 139/154-kDa antigens recognized by our MoAb UA3 are good candidates for use in tests for the diagnosis of anisakiasis and of the allergy caused by this parasite.

Anaphylaxis↗

Splanchnic and leg substrate exchange after ingestion of a natural mixed meal in humans.

The disposal of a mixed meal was examined in 11 male subjects by multiple (splanchnic and femoral) catheterization combined with double-isotope technique (intravenous [2-3H]glucose plus oral U-[14C]starch). Glucose kinetics and organ substrate balance were measured basally and for 5 h after eating pizza (600 kcal) containing carbohydrates 75 g as starch, proteins 37 g, and lipids 17 g. The portal appearance of ingested carbohydrate was maximal (1.0 mmol/min) between 30 and 60 min after the meal and gradually declined thereafter, but was still incomplete at 300 min (0.46+/-0.08 mmol/min). The total amount of glucose absorbed by the gut over the 5 h of the study was 247+/-26 mmol (45+/-6 g), corresponding to 60+/-6% of the ingested starch. Net splanchnic glucose balance (-6.7+/-0.5 micromol x kg(-1) x min(-1), basal) rose by 250-300% between 30 and 60 min and then returned to baseline. Hepatic glucose production (HGP) was suppressed slightly and only tardily in response to meal ingestion (approximately 30% between 120 and 300 min). Splanchnic glucose uptake (3.7+/-0.6 micromol x kg(-1) x min(-1), basal) peaked to 9.8+/-2.0 micromol x kg(-1) x min(-1) (P<0.001) at 120 min and then returned slowly to baseline. Leg glucose uptake (34+/-5 micromol x leg(-1) x min(-1), basal) rose to 151+/-29 micromol x leg(-1) x min(-1) at 30 min (P<0.001) and remained above baseline until the end of the study, despite no increase in leg blood flow. The total amount of glucose taken up by the splanchnic area and total muscle mass was 161+/-16 mmol (29+/-3 g) and 128 mmol (23 g), respectively, which represent 39 and 30% of the ingested starch. Arterial blood lactate increased by 30% after meal ingestion. Net splanchnic lactate balance switched from a basal net uptake (3.2+/-0.6 micromol kg(-1) x min(-1) to a net output between 60 and 120 min and tended to zero thereafter. Leg lactate release (25+/-11 micromol x leg(-1) x min(-1), basal) drastically decreased postprandially. Arterial concentration of both branched-chain amino acids (BCAA) and non-branched-chain amino acids (N-BCAA) increased significantly after meal ingestion (P<0.001). The splanchnic area switched from a basal net amino acid uptake (31+/-16 and 92+/-48 micromol/min for BCAA and N-BCAA, respectively) to a net amino acid release postprandially. The net splanchnic amino acid release over 5 h was 11.3+/-4.2 mmol for BCAA and 37.8+/-9.7 mmol for N-BCAA. Basally, the net leg balance of BCAA was neutral (-3+/-5 micromol x leg(-1) x min(-1)), whereas that of N-BCAA indicated a net release (54+/-14 micromol x leg(-1) x min(-1)). After meal ingestion, there was a net leg uptake of BCAA (20+/-6 micromol x leg(-1) x min(-1)), whereas leg release of N-BCAA decreased by 50%. It is concluded that in human subjects, 1) the absorption of a natural mixed meal is still incomplete at 5 h after ingestion; 2) HGP is only marginally and tardily inhibited; 3) splanchnic and peripheral tissues contribute to the disposal of meal carbohydrate to approximately the same extent; 4) the splanchnic area transfers >30% of the ingested proteins to the systemic circulation; and 5) after meal ingestion, skeletal muscle takes up BCAA to replenish muscle protein stores.

Adult↗

[Usefulness of polymerase chain reaction (PCR) in the diagnosis of meningococcal meningitis].

BACKGROUND: The aim of this work was to evaluate the applicability of polymerase chain reaction (PCR) in the microbiological diagnostic of meningococcal meningitis as compared with the conventional methods (Gram stain and culture). METHODS: One hundred and fifteen cerebrospinalis fluid samples from 115 patients with suspicious symptoms of meningitis were studied. 47 of them belonged to patients suspicious for meningococcal disease; 28 to patients with bacterial meningitis of other infectious etiologies; 10 to patients with meningitis showing lymphocytic pleocytosis and 30 to patients with an unconfirmed meningitis. The cerebrospinalis fluid samples were processed for culture by standard procedures and by PCR according to the method described by Newcombe et al for peripheral blood samples. RESULTS: Thirty five out of 39 patients suspicious of meningococcal meningitis were microbiologically confirmed, being 22 culture and PCR positive, 3 microscopically and PCR positive, 1 only microscopically positive, and 9 positive only by PCR. By using PCR methodology, the number of confirmed diagnostics of meningococcal meningitis increased in a 23% as compared to those obtained by microscopic observation and culture. Sensitivity, specificity, predictive positive value and predictive negative value were 87.1, 98.7, 97.1 and 94.1 respectively for the PCR method. CONCLUSIONS: Our results indicate that PCR can be used on routine basis as a complementary technique to the standard laboratory procedures for diagnosis of meningococcal meningitis.

Humans↗

[Evaluation of an automatic system (MB/BacT) for the isolation of Mycobacterium spp].

BACKGROUND: The study purpose was to evaluate the MB/BacT automated system against Löwenstein-Jensen solid media for the isolation of Mycobacterium species. METHODS: 1,511 specimens were processed from 15/10/96 to 28/4/97. For digestion and decontamination NALC-NaOH was used. Auramine smear was performed and both culture media were inoculated after digestion-decontamination. Inoculation on MB/BacT bottles was performed according to the manufacturer's instructions, apart from a modification in MAS antibiotic supplement with the addition of vancomycin at 1 microgram/ml as final concentraction. Both media were incubated for 40 days at 37 degrees C. RESULTS: In total 101 (6.6%) mycobacteria species were isolated. 78 M. tuberculosis, 14 M. avium, 6 M. gordonae, 2 M. chelonae and 1 M. fortuitum. 98 (6.4%) Mycobacterium spp. were isolated in MB/BacT and 79 (5.2%) were isolated in Löwenstein-Jensen. 22 (1.4%) out of 101 grew only in MB/BacT and 3 (0.2%) out of 101 grew only in Löwenstein-Jensen. Sensitivity in MB/BacT was 97% compared to 78% in Löwenstein-Jensen, this difference was estatically significant (p < 0.001). Contamination rate was 1.8% in MB/BacT and 13.3% in Löwentein-Jensen. The average time to detection of Mycobacterium spp. was 15.9 days in MB/BacT and 22.4 in Löwenstein-Jensen. CONCLUSIONS: We believe that MB/BacT is a good system for rapid and reliable detection of Mycobacterium spp.

Automation↗