Biomedical subjects

M Pascual

Publications and source records attributed to M Pascual.

At least 91 records · Page 5Linked to original sources

PubMed1998

Contribution of native kidney function to total glomerular filtration rate after combined kidney-pancreas transplantation.

BACKGROUND: Combined kidney-pancreas transplantation (CKPT) with its associated euglycemia has been shown to prevent or reduce recurrent diabetic nephropathy in the renal allograft. There has been no evaluation of residual native kidney function after CKPT. The purpose of this study was to determine whether native kidney function may be present in diabetic recipients years after CKPT. METHODS: Between 1986 and 1992, 37 patients with type 1 insulin-dependent diabetes mellitus with renal failure underwent CKPT. In each case, a single native nephrectomy was performed. We studied 16 patients who had continuing renal and pancreas function more than 4 years after CKPT. Fourteen diabetics with a functioning renal allograft but no pancreas function were used as a control group. Simultaneous renal scans (technetium-99m diethylenetriamine pentaacetic acid) of the native and transplanted kidneys were obtained with a dual-head scintillation camera. Total glomerular filtration rate (GFR) was determined from the rate of clearance of the tracer from the extracellular space measured for 2 hr with an ambulatory renal monitor. RESULTS: The study groups had similar pretransplant characteristics. At the time of the study, the mean serum creatinine level was not significantly different in the CKPT and control groups (1.7+/-0.7 vs. 1.5+/-0.3 mg/dl, respectively). In the CKPT and control groups, total GFRs were 70.1+/-33 vs. 72.1+/-16.5 ml/min (NS), allograft GFRs were 63+/-34.2 vs. 70.4+/-16 ml/min (NS), and native kidney GFRs were 7.1+/-7.2 vs. 1.7+/-1.9 ml/min (P < 0.05), respectively. In both groups, there was a significant correlation between total GFR and allograft GFR (P < 0.001), but not between total GFR and native kidney GFR. Significant single native kidney GFR (more than 8 ml/min) was found in 7/16 (44%) patients in the CKPT group, but in none of the controls. CONCLUSIONS: These results suggest that residual native kidney function can be present and contribute moderately to total GFR after CKPT. Euglycemia after CKPT may have a protective role in native kidneys.

Adult↗

PubMed1998

Chronic rejection and chronic cyclosporin toxicity in renal allografts.

Recent evidence indicates that growth factors are critically important in both chronic rejection and chronic cyclosporin A toxicity, suggesting that these two entities share a common pathophysiological pathway, leading to progressive allograft failure. Here, Manuel Pascual and colleagues discuss the relevance of growth factors to chronic allograft nephropathy, and the implications for therapy in view of the great choice of immunosuppressive drugs now available.

Animals↗

PubMed1998

Selection of lactobacilli for chicken probiotic adjuncts.

During inhibitory activity screening of 296 strains of lactic acid bacteria from the gastro-intestinal tract of chicks, 77 strains showed inhibition against enteric indicator strains (Salmonella enteritidis and Escherichia coli). Eight different strains identified as Lactobacillus salivarius were selected for the following attributes: their ability to inhibit all the indicator strains; a high adhesion efficiency to the epithelial cells of chickens and also their resistance to a number of antibiotics, monensin, bile salts and pH 3.0. The inhibitory action was not affected by the addition of catalase and no inhibition was detected after neutralizing the supernatant culture fluid. The competitiveness of the most promising strains, Lact. salivarius CTC2183 and CTC2197, was assessed in chicken feed mixture and in vivo. It was concluded that both strains were capable of becoming predominant over the indigenous flora in the incubated chicken feed mixture. In vivo tests showed that Lact. salivarius CTC2197 was able to colonize and overcome Lact. salivarius CTC2183 and the indigenous flora in the crop and caecum of the inoculated chicks.

Animal Feed↗

PubMed1998

In vivo glucose contribution to glutamate synthesis is maintained while its contribution to acetyl CoA is lowered in adult mice fed a diet with a high fat:carbohydrate ratio.

To investigate the contribution of dietary carbohydrate to glutamate and acetyl CoA synthesis, two groups of adult mice were fed a high- (HCD) or a low-carbohydrate diet (LCD) in which 5% of the carbohydrate was [U-13C]-glucose. Four animals from each dietary group were killed after 1, 2 and 5 d. The tracer:tracee ratios of [13C3] and [13C6]blood glucose and of the [13C2] and [13C3] isotopomers of blood, mucosal, hepatic and muscle alanine and glutamate were used to calculate the fractional contribution of glucose to the 3-carbon, acetyl CoA and oxaloacetate pools of each tissue. In the HCD mice, glucose contributed 66, 33 and 31% of the acetyl CoA pool of muscle, liver and mucosa, respectively. The contribution of glucose to acetyl CoA was lowered by 33% (P < 0.05) and 55% (P < 0.01) in the liver and muscle of the LCD group, respectively, but was unaltered in the mucosa. Glucose made a minor contribution to glutamate synthesis via oxaloacetate in the liver (23%) and muscle (10%) of the HCD group. The fraction of hepatic and muscle glutamate synthesis derived from glucose was not affected by the diet. We conclude that glucose oxidation in liver and muscle parallels the contribution of carbohydrate to dietary energy and that glucose is not a major carbon precursor for muscle glutamate synthesis. Net glutamate synthesis in extraintestinal tissues is preserved when dietary carbohydrate is restricted.

Acetyl Coenzyme A↗

PubMed1998

The prognostic significance of specific arterial lesions in acute renal allograft rejection.

Diagnosis of allograft dysfunction relies on the assessment of arterial lesions. This study was designed to evaluate the prognostic significance of common specific vascular lesions in acute allograft rejection. Renal allograft biopsies (n = 111) with acute cellular rejection were scored for endarteritis, mononuclear cell adherence to endothelial cells, endothelial activation, fibrinoid necrosis, foam cells, and intimal fibrosis. These vascular lesions and other classic histologic features were correlated with outcome. Rejection with endarteritis (found in 54% of biopsies) was less responsive to steroid treatment than rejection without endarteritis, as judged by recovery of creatinine in 3 wk (P = 0.03). Larger numbers of sampled arteries improved the predictive accuracy. Sticking of mononuclear cells to endothelial cells also correlated with steroid resistance (P < 0.05). Rejection with or without endarteritis responded to OKT3/antithymocyte globulin treatment equally well (61% versus 65%, respectively). Rejection with fibrinoid arterial necrosis (4% of biopsies) did not respond to either steroids or antibodies (0%). One-year graft failure was 21% without endarteritis, 28% with endarteritis, and 100% with fibrinoid necrosis. Activated endothelial cells and interstitial hemorrhage were associated with endarteritis and graft failure (all P < 0.05). None of the other scored features had any statistically significant correlation with outcome. Thus, specific arterial lesions (endarteritis, fibrinoid necrosis, activated endothelial cells, mononuclear cell margination) and interstitial hemorrhage, but not the extent of the interstitial infiltrate or tubulitis, are correlated with response to antirejection therapy and/or 1-yr clinical outcome. Grading systems for therapeutic trials and clinical management should emphasize scoring of specific vascular lesions.

Acute Disease↗

PubMed1998

WWW accessible system for national/regional registries of clinical results of cord blood transplants: a tool to facilitate cooperative clinical research.

A system, accessible via internet, has been developed to support the Spanish Registry of Cord Blood Transplants (RETSCU). The system includes a database of clinical results directly accessible by transplant centers (TCs) and cord blood banks (CBBs) (restricted to own cases regarding primary data and unrestricted regarding statistics derived from validated data) and gives open access to Web pages containing results approved for publication. It also includes internal mail for two-way and broadcast messages. Patients' data are essentially those included in Eurocord forms. Additional features of the system are: confidentiality; inalterability of validated primary data; identifiability of data sources. The Unix central computer is accessible via the WWW. For security, data transmission is encrypted and passwords are required for access. Copies are regularly updated. Data can be loaded from CBBs and TCs. The procedure for creating and updating records is user-friendly, with the possibility of errors being minimized by extensive automated checks. Validation of patients' records by a manager is required before making data available for general statistical analysis. TCs and CBBs may retrieve data on their own cases, regardless of validation, as individual records or in tables directly transferable to common statistical programs. Statistical analysis may be done on validated data from all the patients in the Registry or from groups selected according to HLA compatibility and disease, type of transplant (related/unrelated), or protocol. Several similarly designed and managed national/regional Registries might be networked and their data integrated into a multinational Registry. Our system would require some additional developments to be used in this way.

Hematopoietic Stem Cell Transplantation↗

PubMed1997

Anticardiolipin antibodies and hepatic artery thrombosis after liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) remains a devastating complication after liver transplantation. Various factors have been implicated in the pathogenesis of HAT, such as clotting abnormalities, increased hematocrit, and technical complications, but the role of anticardiolipin antibodies has not been evaluated. We investigated the possible association between HAT and anticardiolipin antibodies in adult patients who underwent liver transplantation. METHODS: Seven patients with HAT after orthotopic liver transplantation, 28 liver recipients without HAT, and 35 normal blood donors were evaluated. Determination of IgM and IgG anticardiolipin antibodies was performed by enzyme-linked immunosorbent assay using pretransplant serum from all allograft recipients. Clinical information was obtained from chart review. Fisher's exact test and Wilcoxon rank sum test were used for statistical analysis, and all P-values were two-tailed. RESULTS: Overall, 22 of 35 (63%) liver recipients had a positive anticardiolipin antibody test (either IgG or IgM titer >4 SD from the normal controls). The test was positive in 7 liver recipients (100%) with HAT compared with 15 out of 28 patients (54%) without HAT (P=0.031). As compared with liver recipients without HAT, patients with HAT also tended to have a higher mean anticardiolipin titer of IgG and IgM and a lower pretransplant platelet count; however, these differences were not significant. CONCLUSIONS: Our findings indicate that anticardiolipin antibodies are frequently elevated in patients with liver failure and may contribute to the pathogenesis of HAT after liver transplantation. Other potential consequences of anticardiolipin antibodies in end-stage liver disease remain to be determined.

Adult↗

PubMed1997

Nephrotic syndrome after liver transplantation in a patient with hepatitis C virus-associated glomerulonephritis.

In recent years, hepatitis C virus infection has been reported to be typically associated with membranoproliferative glomerulonephritis and less frequently with membranous nephropathy. Treatment of hepatitis C with interferon-alpha can reduce viremia and improve renal disease. After liver transplantation for hepatitis C virus-associated liver failure, standard immunosuppressive protocols result in a significant increase in hepatitis C viremia. In this report we describe a patient with end-stage liver disease and biopsy-proven hepatitis C-associated glomerulonephritis who underwent liver transplantation. Within 1 month after transplantation, he developed a severe nephrotic syndrome that paralleled a marked increase in viremia. We discuss the possible pathogenic relationship between hepatitis C virus infection and the nephrotic syndrome that followed liver transplantation.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Biological effects and fate of a soluble, dimeric, 80-kDa tumor necrosis factor receptor in renal transplant recipients who receive OKT3 therapy.

A preliminary clinical study of renal allograft recipients revealed that a dimeric form of the human 80 kDa soluble receptor (sTNFR:Fc) for tumor necrosis factor (TNF) is well tolerated and attenuates the OKT3-induced acute clinical syndrome. The current study determined the in vivo biological effects and fate of sTNFR:Fc in these patients. Serial assessment of both antigenic and biological activities of circulating TNF and sTNFR:Fc have led to the following observations. (1) Although control patients typically responded to the first OKT3 injection with a rapid increase of biologically active TNFalpha, patients on sTNFR:Fc therapy had markedly higher serum TNFalpha antigenic levels, but no detectable bioactivity. Thus, sTNFR:Fc functioned as a potent antagonist, despite its cytokine-carrier effect. (2) Peak sTNFR:Fc levels averaging 800 and 2500 ng/ml were routinely achieved in vivo, using the low-dose (0.05 mg/kg) and high-dose (0.15 mg/kg) protocols. (3) The half-life of circulating sTNFR:Fc was estimated to be approximately 4.4 days, and levels of p80 receptors in treated patients remained significantly above those in control patients for at least 20 days. (4) In vitro blocking studies demonstrated that circulating sTNFR:Fc remained biologically active for 2 weeks. These results demonstrate that under current protocols, significant serum levels of sTNFR:Fc, capable of effectively neutralizing TNF activity over prolonged periods, can be achieved. The persistent OKT3 side effects observed, despite sTNFR:Fc therapy, are therefore likely to be caused by factors other than TNF.

Dimerization↗

PubMed1997

Dialysis membrane adsorption during CRRT.

Experimental and clinical studies have suggested that dialysis membrane biocompatibility may influence the morbidity and mortality of patients with acute renal failure. Complement activation by dialysis membranes may also prolong the recovery from acute renal failure. In this article, we review the concept of dialysis membrane adsorption, with particular attention to adsorption/inhibition of factor D, a highly specific serine protease of the alternative pathway of complement. The adsorptive properties of some dialysis membranes may be useful during continuous renal replacement therapies (CRRT) in critically ill patients.

Acute Kidney Injury↗

PubMed1997

Diagnosis of sibling species of Drosophila involved in the colonization of North America by D. subobscura.

To determine the effects of the recent colonization of the west coast of North America by the Palaearctic species Drosophila subobscura on the dynamics of the Drosophila populations, the sibling species D. athabasca and D. azteca must be classified unambiguously. We have characterized these two species using three molecular techniques: allozymes, mtDNA and RAPDs. All three techniques allow the classification of any individual as belonging to either species. The study of five localities in northern California and southern Oregon show that the area of overlap is larger than previously described.

Animals↗

PubMed1997

Impaired intestinal sugar transport in cirrhotic rats: correction by low doses of insulin-like growth factor I.

BACKGROUND & AIMS: Malnutrition is a complication of liver cirrhosis accompanied by reduced insulin-like growth factor I (IGF-I) availability. The aim of this study was to analyze the effect of IGF-I on intestinal D-galactose absorption in cirrhotic rats. METHODS: IGF-I (2 micrograms.100 g body wt-1.day-1) or saline were given for 14 days to rats in whom cirrhosis was induced with CCl4. Galactose transport and sodium-glucose/galactose-ligand transporter 1 (SGLT-1) expression were assessed in jejunal rings and in brush border membrane vesicles (BBMVs). RESULTS: Compared with that in controls, galactose transport in everted jejunal rings was significantly reduced in cirrhotic rats but showed normal values after IGF-I treatment. The kinetic study of D-galactose uptake by BBMVs showed decreased maximal velocity (Vmax) and diminished transporter affinity in cirrhotic rats. These kinetic parameters reverted to normal after IGF-I treatment. Microvilli were significantly elongated in cirrhotic rats but of normal size in the IGF-I-treated group. The expression of SGLT-1 on BBMVs (Western blot) and on the luminal membrane of enterocytes (immunohistochemistry) was not reduced in cirrhotic animals compared with controls or IGF-treated cirrhotic rats. CONCLUSIONS: Intestinal sugar transport is disturbed in experimental cirrhosis, and this alteration is corrected by IGF-I.

Alanine Transaminase↗

PubMed1997

Dietary glucose is extensively recycled in the splanchnic bed of fed adult mice.

Quantification of the metabolism of dietary glucose by the splanchnic tissues is incomplete. Whether habitual carbohydrate intake affects splanchnic glucose metabolism is not known. Female mice were offered isoenergetic and isonitrogenous quantities of diets containing high (HCD) or low (LCD) amounts of carbohydrate, 5% of which was [U-13C]-glucose. Four mice from each dietary group were killed after 24, 48 and 120 h. The 13C-isotopomer distribution in blood glucose, lactate and alanine and in hepatic alanine and glycogen was measured by selected ion monitoring mass spectrometry. [U-13C]-Glucose and its products, [U-13C]-lactate and alanine, were in complete isotopic equilibrium in the blood. The tracer:tracee ratio of hepatic [U-13C]-alanine was significantly higher (P < 0.01) than that of circulating alanine. In both groups, the tracer:tracee ratio of circulating [U-13C]-glucose was significantly (P < 0.001) lower than that of the dietary carbohydrate, and the ratio of [13C3]-glucose:[U-13C]-glucose [0.57 (HCD) and 0.78 (LCD); diet effect P < 0.05], a measure of glucose metabolic cycling, was between two- and fivefold higher than published values obtained with intravenous tracer glucose. The tracer:tracee ratio of [U-13C]-glycogen glucose was significantly (P < 0.05) higher than that of arterial glucose. We conclude the following: 1) dietary glucose is extensively recycled, via pyruvate, within the liver; 2) this metabolic cycle is maintained in mice consuming low carbohydrate diets; and 3) dietary carbohydrate is channelled to hepatic glycogen. We speculate that the metabolic cycling of enteral glucose is related to the hepatic catabolism of dietary protein.

Alanine↗

PubMed1997

Acute renal failure: role of dialysis membrane biocompatibility.

Recent clinical studies of acute renal failure in adults have focused attention on the biocompatibility of the dialysis membrane as a possible factor influencing patient morbidity and mortality. In this article, we review the concept of dialysis membrane biocompatibility and highlight the difficulty of finding an ideal definition. We then expand on the possible roles of complement and neutrophil activation by dialysis membranes, which may prolong the recovery from acute renal failure. The results of several clinical studies analyzing the impact of dialysis membranes on the course and outcome of acute renal failure are discussed. Finally, the possible relevance of biocompatibility in continuous renal replacement therapies is emphasized.

Adult↗

PubMed1997

Paraproteins and complement depletion: pathogenesis and clinical syndromes.

Various clinical syndromes that associate paraproteinemia and complement depletion have been described in the last three decades. Among these, cryoglobulinemias, acquired Clq deficiency, and acquired deficiencies of the classical pathway of complement can be associated with B-cell lymphoproliferative disorders. Some specific symptoms should alert the clinician to suspect an underlying malignancy. In this report, we review the pathogenesis, symptomatology and therapeutic options of these clinical conditions.

Agammaglobulinemia↗

PubMed1997

Cytotoxicity and apoptosis in human renal allografts: identification, distribution, and quantitation of cells with a cytotoxic granule protein GMP-17 (TIA-1) and cells with fragmented nuclear DNA.

In the present study, we analyzed human renal allografts using immunohistochemical techniques to determine the site, identity, and frequency of (a) cytotoxic and apoptotic cells, as identified by staining for GMP-17 (TIA-1), a component of cytotoxic granules; and (b) DNA fragmentation in situ, as detected by the TUNEL method. In acute cellular rejection (n = 15), GMP-17+ mononuclear cells accounted for 29% +/- 12% of the infiltrating cells in the interstitium (341 +/- 164/mm2) and were significantly more concentrated in tubulitis lesions, where they amounted to 65% +/- 14% of the mononuclear cells (96 +/- 61/mm2) (p < 0.01 versus interstitium). GMP-17+ mononuclear cells were also found in sites of endothelialitis. An estimated 80% of the GMP-17+ lymphocytes expressed CD8, and 10% to 20% expressed either CD4 or the macrophage marker CD14. The latter finding led us to analyze normal peripheral blood monocytes by flow cytometry, all of which were found to contain GMP-17. NK cells and neutrophils, which are known to express GMP-17, were detected only rarely in allografts. Specimens with cyclosporine A toxicity (n = 7) or acute tubular necrosis (n = 13) showed fewer GMP-17+ cells in the interstitium (22 +/- 46/mm2 and 62 +/- 50/mm2, respectively) and tubules (2 +/- 6/mm2 and 10 +/- 10/mm2, respectively) (all p < 0.01 versus rejection). These differences were due largely to less intense mononuclear cell infiltration. In cyclosporine A toxicity, however, the percentages of GMP-17+ mononuclear cells within tubules and the interstitium were significantly lower than in rejection (p = 0.02), whereas in acute tubular necrosis significantly lower percentages were found in the tubules (p = 0.04) but not in the interstitium. Native kidneys with end-stage diabetic nephropathy (n = 5) had very low proportions of GMP-17+ cells in interstitial infiltrates (7% +/- 6%) and in tubules (11% +/- 15%), although the infiltrates were focally intense (517 +/- 355/mm2). TUNEL+ cells were found in acute cellular rejection, predominantly in areas with intense mononuclear infiltrates and also within lesions of tubulitis and endothelialitis. Although some TUNEL+ cells were intrinsic renal cells, most appeared to be infiltrating mononuclear cells, and we were able to detect CD3 in some. In areas of intense cellular infiltration, the percentages of TUNEL+ cells (range, 0.5% to 4.2%) were comparable to those seen in the rat thymus, indicating a high level of apoptosis. Overall, in the allograft samples, the numbers of GMP-17+ cells and TUNEL+ cells were significantly correlated (r = 0.79; p < 0.01). These data provide new evidence that T cell (and possibly macrophage)-mediated cytotoxicity plays an important role in acute renal allograft rejection, particularly in the case of tubular injury, and furthermore suggest that apoptosis may be a mechanism not only for graft cell destruction, but also for elimination of activated T cells in the infiltrate.

Apoptosis↗

PubMed1997

Ambulatory system to aid in decision making and risk stratification in postinfarction patients.

Knowledge of the clinical and electrophysiological features of certain cardiovascular risk groups, the adaptation and specialization of clinical protocols, the availability of tools to make determinations for use in patient follow-up and to assess the efficacy of the treatments applied, and the proper processing of different parameters can aid in decision making, leading to the application of a given therapeutic approach, and can facilitate the performance of group and multicenter studies. To address these needs, a simple, low-cost, portable ECG processing system has been designed that complements the current techniques for managing patients with ischemic heart disease and nonmalignant ventricular arrhythmias. This system, consisting of an electrocardiograph and a laptop PC, determines the following parameters on the basis of the ECG: incidence of arrhythmia, heart rate variability, QT dispersion, ECG criteria for ventricular hypertrophy and late potentials. Left ventricular ejection fraction and diastolic function (according to Doppler ultrasound) and other basic epidemiological parameters are typed in. Moreover, the system integrates these parameters, which have usually been considered separately, to arrive at second-level indicators with a greater predictive capacity during the long-term follow-up of patients with ischemic heart disease and ventricular arrhythmias, thus providing an idea of the risk of mortality and the onset of arrhythmic events and allowing risk stratification in this patient population. Finally, the system includes a database of all the patients analyzed, with tools that make it possible to follow the course of their disease and to assess the efficacy of the treatments applied.

Arrhythmias, Cardiac↗

PubMed1996

Upregulation of BDNF mRNA expression in the barrel cortex of adult mice after sensory stimulation.

Upregulation of brain-derived neurotrophic factor (BDNF) mRNA expression by neuronal activity has been reported in cultured hippocampal cells and in different in vivo excitotoxic paradigms. The aim of the present study was to determine whether sensory stimulation of the whisker-to-barrel pathway alters BDNF mRNA expression in the cortex and, if so, to evaluate the specificity of this effect. To this end, a set of mystacial whiskers was unilaterally stimulated by mechanical deflection, and the expression of BDNF mRNA was analyzed in the barrel cortex by in situ hybridization (ISH) using a 35S-labeled antisense BDNF riboprobe and emulsion autoradiography. A clear-cut and specific upregulation of the BDNF mRNA expression was found at the level of the somatosensory cortex after the increased peripheral stimulation. In the barrel cortex of control mice, BDNF mRNA was present in a few cells in layers II/III and VI, whereas it was almost undetectable in layer IV. After 6 hr of whisker stimulation, increased levels of BDNF mRNA were found in layers II to VI of the contralateral barrel cortex. In layer IV, BDNF upregulation was confined to the barrels corresponding to the stimulated follicles. ISH combined with immunocytochemistry against the three calcium-binding proteins parvalbumin, calretinin, and calbindin-D28K revealed that BDNF mRNA-expressing cells do not belong to the GABAergic cell population of the barrel cortex. The present results support a role for BDNF in activity-dependent modifications of the adult cerebral cortex.

Animals↗