De novo tumors after orthotopic liver transplantation.
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Biomedical subjects
Publications and source records attributed to I García.
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In order to know distribution patterns of polychlorinated biphenyl congeners in the marine environment from Galida, PCBs n degrees 31, 28, 52, 101, 118, 153, 105, 138, 156 and 180 were isolated by Soxhlet extraction from three fractions of different particle size (<0.063 mm, 0.063-0.2 mm and >0.2 mm) in surface marine sediments; the quantification was performed using GC-MS and GC-ECD. Distribution of PCB congeners was shifted in favour of higher chlorinated compounds (CBs 138,153 and 180) and highly correlated to TOC content. In general, the finest fractions (<0.063 mm) of sediment presented the highest loadings of PCBs, only the sediment from As Pías zone exhibited the highest concentration of chlorinated congeners in the coarsest fraction. CB 52 concentration, slightly volatile compound, was related to water temperature. By means of multivariate techniques of data exploration as hierarchical duster analysis and principal components analysis, sediment samples from un-contaminated and slightly contaminated areas were clearly separated; groupings between samples from nearby zones appeared.
On the 25th April 1998, toxic water and tailings from a pyrite mine of Aznalcóllar (southern Spain) spilled into the Agrio and Guadiamar River Basin affecting some 40 km2. In five sectors throughout the basin, we monitored the physical and chemical properties of the tailings as well as the degree of pollution in the soils on four different sampling dates: 5 May, 20 May, 4 June and 22 July 1998. The characteristics of the tailings deposited on the soils are shown to be related to distance from the spill. The oxidation rate of the tailings and the solubilization of the pollutant elements were more pronounced in the middle and lower sectors of the basin, where the particle size was finer, the sulfur content higher and the bulk density less. The increases in water-soluble sulfates, Zn. Cd and Cu were very rapid (the highest values being reached 25 days after the spill) and intense (reaching 45% of the total Cu, 65% of the total Zn and Cd). Meanwhile, the increases in water-soluble As, Bi, Sb, Pb and Tl were far lower (ranging between 0.002% of the total Tl and 2.5% of the total As) and less rapid in the case of As, Bi and Pb (the highest values for these elements being reached 40 days after the spill). These soluble elements infiltrated the soils with the rainwater, swiftly augmenting the soil pollution. Twenty-five days after the spill, when the rainfall ranged between 45 and 63 mm, the first 10-cm of the soils in the middle and lower sectors of the basin exceeded the maximum concentration permitted for agricultural soils in Zn, Cu and Tl. At 40 days after the spill, when the rainfall ranged between 60 and 89 mm, all the soils reached or exceeded the maximum permitted concentrations for As and Tl. Nevertheless, the pollutants tended to concentrate in the first 10 cm of the soils without seriously contaminating either the subsoil or the groundwaters. Consequently, a rapid removal of the tailings and the ploughing of the first 25-30 cm of the soils would be urgent measures to diminish pollutant concentration in the soils affected by the spill.
The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.
Molecular epidemiological studies suggest that particular Mycobacterium tuberculosis strains have an enhanced capacity to spread within a community. One strain, the Beijing genotype, has been associated with outbreaks in a number of communities throughout the world. IS6110 restriction fragment length polymorphism (RFLP) analysis was performed on M. tuberculosis isolates from 566 of the 721 patients (78.5%) diagnosed with tuberculosis (TB) on Gran Canaria Island from 1993 to 1996, as well as 35% of isolates from 1991-1992 (85 strains). RFLP identification of the family of strains of the Beijing genotype was confirmed by spoligotyping. Medical records of all patients were reviewed and epidemiological links were identified. Of 566 M. tuberculosis isolates from 1993 to 1996 with RFLP available, 72% belonged to clusters. The largest contained 75 cases and was caused by a strain of the Beijing genotype that was introduced to the island in 1993. It was found in 10 patients in 1993 (5.5%), 12 in 1994 (8.1%), 18 in 1995 (16.4%), and 35 in 1996 (27.1%). Epidemiological linkage was confirmed for 68% of cases. This study has demonstrated rapid dissemination of this strain of the Beijing genotype. This genotype might play an important role in the future of the worldwide tuberculosis epidemic.
Chronic biliary obstruction with repeated bouts of cholangitis adversely affects quality of life and may lead to secondary biliary cirrhosis with liver failure. We reviewed our experience with chronic biliary complications after surgical treatment of various diseases that at the end needed a liver transplantation. Twelve patients with previous biliary surgery developed secondary biliary cholangitis, secondary biliary cirrhosis, or both. Seven had surgery for liver hydatid disease by Echinococcus granulosus, another four had complicated biliary surgery unrelated to hydatid disease, and one had a history of a traffic accident with liver trauma and hepatectomy with chronic biliary fistula. The repeated cholangitis attacks and in two cases of hydatid disease the development of biliary-bronchial fistulas made these patients' lives miserable. All had had previous surgical procedures that made the transplantation procedure more difficult. Nevertheless, patient survival and graft actuarial survival after liver replacement were 75.0% and 69.2%, respectively, at 5 years.
Choledochocholedochostomy with tutor (CC-T) or without (CC) is the technique of choice for biliary reconstruction in orthotopic liver transplantation (OLT), however, its rate of complications is high and does not decrease significantly over the years. Biliary obstruction is the most frequent complication and surgical treatment frequently involves conversion to hepaticojejunostomy (H-J). Out of 412 patients (448 OLTs) analyzed retrospectively, 74 (18%) presented biliary complications and 25 (6%) required conversion to H-J because of biliary obstruction, generally due to anastomotic stenosis (17 patients, 68%). Sixteen out of the 25 presented after the first 3 months, and in two patients, stenosis was secondary to arterial thrombosis. Anastomotic stenosis was more frequent in the CC group than in the CC-T group (9.9% versus 2.6%, p < 0.05). Sixteen patients (64%) underwent percutaneous dilatations, but the response was only transitory. There were no postoperative deaths. At the follow-up, three (12%) of the 17 surviving patients presented episodes of cholangitis which required percutaneous dilatations (1), revision of the H-J (1), or conversion to hepaticojejunoduodenostomy (1). Mean survival of patients with H-J was 70.9%, and the actuarial survival rate was 68% at 5 years. This does not differ from the actuarial survival in our series of transplanted patients (65%). CC or CC-T (in selected cases) is an adequate biliary reconstruction for OLT, in spite of the fact that a small number of patients will require conversion to H-J. H-J is an excellent technique of rescue in cases of biliary obstruction that are not possible to resolve by percutaneous dilatations.
BASIS: To know the therapeutic efficiency in the genital herpes of two drugs: acyclovir and valaciclovir. METHODS: There were included in the study 142 patients with diagnostic of clinic first episode by genital herpes in two equal groups of 71 patients each one. The distribution in both groups was random to receive one of the following treatment standards: acyclovir 200 mg by verbal each 5 hours, during 7 days; valaciclovir: 500 mg by verbal each 12 hours during 7 days being valued objective and subjective response to the treatment. RESULTS: The prevailing symptom was the pain (45% and 46.4%), followed by the warmth or burning sensation. The most frequent lesions in both groups were blisters (39.4% and 46.4%). The analysis response to the treatment in relationship to the symptoms as well as in the lesions it could be appreciated that there are not significant differences in the patients treated in both groups (p = 0.3). The adverse effect communicated by the discussed patients were scarce and similar in both groups. CONCLUSIONS: Both drugs are suitable for the treatment of the genital herpes. The advantage observed with the valaciclovir is the dosing comfort and the facility of completing the treatment.
OBJECTIVE: To determine and analyze the degree of agreement and disagreement in the diagnosis of bronchial asthma (BA) by respiratory disease specialists and generalists in regional hospital and primary care settings. MATERIAL AND METHODS: Ninety-six outpatients (16 to 70 years of age) were studied; all had been assigned a diagnosis of BA by the referring physician or by the respiratory disease specialist. We recorded 1) clinical symptoms, determining the initial probability of a diagnosis (IPD)of BA to be high, medium or low; 2) results of spirometry and bronchodilator testing (BDT), peak flow variability and methacholine challenge testing; 3) prick test results, eosinophil levels and total serum IgE levels. Three diagnoses were recorded: the initial diagnosis (ID) by the referring physician to whom follow-up data were unavailable; diagnosis by the respiratory disease specialist based only on clinical symptoms (RSS); and the final diagnosis(FD). To arrive at a FD of BA, it was necessary to have a high or medium IPD and a positive BDT. A Kappa test was used to analyze the degree of agreement among the three diagnoses. Group features associated with greater or lesser agreement were analyzed by chi-square tests and analysis of variance. RESULTS: Agreement was acceptable between RSS and FD (K = 0.63) but very low between ID and RSS and between ID and FD. In the latter two cases, agreement was greatest for patients diagnosed in hospital and for those with high IgE levels (p < 0.05), with high IPD, longer course of disease and a history of asthma (p < 0.01) (odds ratio =59.8). Diagnostic disagreement occurred mainly for patients for whom a BA diagnosis was gained later, the of under-diagnosis being 39%. The patients involved visited the physician only because they had observed an isolated symptom related to asthma (odds ratio = 119) and to arrive at a diagnosis bronchomotor tests other than BDT were required (p < 0.01). CONCLUSIONS: a) The degree of agreement for a diagnosis of BA is low. b)The functional profile of patients for whom diagnostic agreement exists differs from that of patients for whom diagnosis is gained through testing. c) In the context of this study, a high rate of under-diagnosis is evident.
Veno-occlusive disease of the liver (VOD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). To determine the incidence of, and the risk factors for the development of VOD, we performed a retrospective analysis of a series of 178 patients, who underwent allogeneic HSCT at our institution between 1990 and 1999. Busulfan and cyclophosphamide constituted the conditioning regimen most frequently administered. Bone marrow was the source of stem cells in 129 patients (73%), and peripheral blood (PBSC) in 49 patients (27%). Thirty-one patients of the PBSC group received CD34(+) positively selected grafts. Most patients were given cyclosporin A and methotrexate (MTX) as graft-versus-host disease (GVHD) prophylaxis. Overall, 30 patients (17%) developed VOD. In univariate analyses, the incidence of VOD was significantly higher in recipients of unmanipulated grafts (20% vs 0%; P = 0.01), in patients with active malignant disease at transplantation (24% vs 9%; P = 0.03), in recipients of marrow from unrelated donors (33% vs 15%; P = 0.03), in patients grafted with bone marrow (21% vs 6%; P = 0.03), and in those receiving MTX as GVHD prophylaxis (21% vs 6%; P = 0.05). Under multivariate analysis, only CD34(+) positive selection (P = 0.0004) and the status of the disease at transplant (P = 0.03) were statistically significant variables for the development of VOD. We conclude that CD34(+) positively selected PBSC transplantation could result in a marked reduction in the incidence of VOD after allogeneic HSCT.
OBJECTIVE: To evaluate the uptake of HMR 3647 into human neutrophils (PMNs), human peritoneal macrophages (PMOs) and tissue-cultured cells (epithelial cells and fibroblasts), and to assess the intracellular activity of this drug. METHOD: Cell uptake of HMR 3647 was measured by radiometric assay, as described by Klemper and Styrt. Intracellular activity was determined by incubation for 3 h of PMNs containing bacteria in the presence of HMR 3647. RESULTS: The intracellular concentrations were 130 and 71 times higher than extracellular concentrations in PMNs and PMOs, respectively (extracellular concentrations: 2-25 mg/L). The cellular-to-extracellular concentration ratios (C/E) for tissue-cultured cells were lower than those obtained in phagocytic cells but still greater than 5. The uptake of HMR 3647 was rapid and non-saturable in all cells. HMR 3647 was released slowly from phagocytic cells. HMR 3647 (extracellular concentration: 0.5-10 mg/L) did not significantly reduce the intracellular survival rate of Staphylococcus aureus ATCC 25923 in PMNs. CONCLUSIONS: HMR 3647 reaches intracellular concentrations several times higher than extracellular concentrations within phagocytic and non-phagocytic cells. The slow efflux of this drug from phagocytic cells suggests that these cells may be a vehicle for it, delivering it to sites of infection.
BACKGROUND: Ciprofloxacin resistance influences the in vitro effect of new quinolones on Streptococcus pneumoniae. METHODS: The early (over 3 h) in vitro bactericidal activity of gemifloxacin, trovafloxacin and ciprofloxacin was explored by time-kill tests against two ciprofloxacin-susceptible (MIC = 0.5 and 1 microg/ml) and two ciprofloxacin-resistant (MIC = 16 microg/ml) S. pneumoniae strains. RESULTS: At subinhibitory concentrations (0.5 x MIC) and inhibitory concentrations (1 x MIC), only gemifloxacin exhibited significant bactericidal activity with, respectively, approximately 85 and approximately 95% decrease in the initial inoculum of the two ciprofloxacin-resistant strains. At concentrations similar to peak serum concentrations (1.5, 3 and 2.5 microg/ml for gemifloxacin, trovafloxacin and ciprofloxacin, respectively) after standard doses, only gemifloxacin exhibited an approximately 99.9% (3 log(10)) reduction in the initial inoculum for the four strains tested, regardless of their susceptibility to ciprofloxacin. No bactericidal activity was exhibited for the other two quinolones against the ciprofloxacin-resistant strains. CONCLUSIONS: Gemifloxacin offers high early bactericidal activity at concentrations similar to peak and trough levels, theoretically preventing regrowth over the dosing interval, and thus dealing with the problem of ciprofloxacin resistance in S. pneumoniae.
AIMS/HYPOTHESIS: To determine the association between exposure to enteroviruses and Type 1 diabetes. METHODS: We measured neutralizing antibodies to the following enteroviruses: Coxsackievirus CA9, CB1, CB2, CB3, CB4, CB5, CB6, and Echovirus E4, E6, E9, E11 in the sera of (1) Type 1 diabetic patients at diagnosis (n = 33), (2) healthy offspring of parents with Type 1 diabetes without islet cell antibodies (ICA) (n = 43) and (3) normal controls (n = 57). All subjects were less than 20 years old. We performed the neutralization test determining the cytopathogenic effect on Vero cells. HLA DR serotyping was also performed in Group 2. RESULTS: Type 1 diabetic patients showed a higher frequency (21.2%, p < 0.01) of neutralizing antibodies to E4 in relation to controls (1.8%), although there were no differences comparing with offspring of Type 1 diabetic patients (20.9%). Healthy offspring carrying Type 1 diabetes HLA DR susceptibility genes were also exposed to E4 (15.0%). High frequencies of neutralizing antibodies to most enteroviruses were found in the control group. CONCLUSION: This study shows the association between Type 1 diabetes and the presence of neutralizing antibodies to Echovirus 4, suggesting the possible participation of this virus as an environmental trigger of this autoimmune disease. Interestingly, our population displays high frequencies of exposure to enterovirus (including CB4) although the incidence for Type 1 diabetes is low (2.9 per 100,000 inhabitants).
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The mechanism of tumor necrosis factor alpha (TNFalpha)-induced cytotoxicity in metabolically inhibited cells is unclear, although some studies have suggested that mitochondrial dysfunction and generation of reactive oxygen species may be involved. Here we studied the effect of TNFalpha on the redox state of mitochondrial cytochromes and its involvement in the generation of reactive oxygen species in metabolically inhibited L929 cells. Treatment with TNFalpha and cycloheximide (TNFalpha/CHX) induced mitochondrial cytochrome c release, increased the steady-state reduction of cytochrome b, and decreased the steady-state reduction of cytochromes cc(1) and aa(3). TNFalpha/CHX treatment also induced lipid peroxidation, intracellular generation of reactive oxygen species, and cell death. Furthermore, as the cells died mitochondrial morphology changed from an orthodox to a hyperdense and condensed and finally to a swollen conformation. Antimycin A, a mitochondrial respiratory chain complex III inhibitor that binds to cytochrome b, blocked the formation of reactive oxygen species, suggesting that the free radicals are generated at the level of cytochrome b. Moreover, antimycin A, when added after 3 h of TNFalpha/CHX treatment, arrested the further release of cytochrome c and the cytotoxic response. We propose that the reduced cytochrome b promotes the formation of reactive oxygen species, lipid peroxidation of the cell membrane, and cell death.
Thermal trauma has a direct effect on mast cells, triggering the secretion of histamine. This secretion leads to an enhanced xanthine oxidase activity and an increased production of reactive oxygen species (ROS), the latter being produced after burns through differing mechanisms. As ROS have been shown to have deleterious effects on cellular membranes, a lesion of the mast cell membrane could close the circle of autoinjury due to the vasoactive actions of mast cell mediators. Our studies were designed to assess the potentiality of ROS as stimulators of mast cell degranulation after burns by comparing two groups of rats treated, respectively, with SOD and saline solution after a scald injury. Plasma levels of tryptase and histamine were analyzed as markers of mast cell activity. A comparison of the mean increases of tryptase between baseline and 3-h postburn levels in the two groups shows significant differences (p < 0.001) (control: 0.13+/-0.04, SOD: 0.03+/-0.01). When comparing the mean increases between the baseline and 3 h postburn levels of histamine in the two groups, significant differences were also found (p < 0.001) (control group: 2.70+/-0.57. SOD group: 1.22+/-0.32). The lower levels of histamine and tryptase induced by SOD provides indirect evidence that ROS are involved in the process, causing the release of such mediators by mast cells, which may in turn suggest that ROS can act as stimulators of mast cell degranulation in burns.