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Biomedical subjects

E Moreno

Publications and source records attributed to E Moreno.

At least 37 records · Page 2Linked to original sources

Tissue concentrations of MDMA and its metabolite MDA in three fatal cases of overdose.

The recreational use of amphetamine derivatives has become increasingly popular in our country in past recent years. Their use is especially common among young people participating in dance parties known as "raves." As a direct consequence of their increased use, the number of fatal cases in which these compounds have been involved have increased dramatically since the second half of the last decade. In our laboratory, we have registered 25 cases related to amphetamine derivatives use since 1996. Three of them were deeply studied and the results obtained are presented in this paper. This information may be useful for the interpretation of the results obtained in toxicological analysis in the cases in which death may be attributed to MDMA use.

3,4-Methylenedioxyamphetamine↗

Results in split liver transplantation.

INTRODUCTION: The shortage in cadaveric grafts has prompted the development of alternative surgical techniques to expand the donor pool. OBJECTIVE: To evaluate the feasibility of split liver transplantation using an observational, retrospective, and longitudinal study. MATERIALS AND METHODS: Between April 1986 and October 2002 we performed 875 liver transplants. From April 1991 to date, we performed 18 split liver transplantations in patients of mean age 42.27+/-25.65 years; five children and 13 adults; and 83.3% women. Urgent transplants accounted for 38.9%. Mean patient weight was 52.29+/-20.87 kg. Ex situ splitting was performed in 33%. The mean cold ischemia time was 460+/-265.69 minutes with a mean warm time of 64.33+/-11.78 minutes. Mean consumption of packed blood was 5.59+/-4.87 units; of frozen fresh plasma, 11.56+/-7.42 units; and of platelets 4.89+/-4.99 units. RESULTS: After a mean follow-up of 10.83+/-12.51 months, 55.56% of the recipients are alive. Actuarial patient and graft survival rates at 1 year are 55.6% and 44.12%, respectively. Actuarial patient and graft survival rates at 1 year, excluding operative mortality were 77% and 68%, respectively. Actuarial patient and graft survival rates at 1 year, comparing urgent and elective transplantations are: 14.29 and 14%, respectively, for urgent cases and 90.91 and 90% for elective ones. Operative mortality was 16.6% while mortality during follow-up was 26.6%. The late complications included arterial thrombosis (n=2): of whom the first needed liver retransplantation 4 months after split liver transplantation; chronic rejection (n=2), recurrence of hepatitis (n=1). CONCLUSIONS: Split liver transplantation is a useful way to expand the graft pool and shows better results in elective liver transplantation.

Adult↗

Upper aerodigestive tract and lung tumors after liver transplantation.

BACKGROUND: The purpose of this study was to analyze the incidence, clinical characteristics, treatment, and outcome of upper aerodigestive (UAD) and lung de novo tumors after ortothopic liver transplantation (OLT). PATIENTS AND METHODS: Between April 1986 and June 2002, we performed 851 OLT in 753 patients. We excluded pediatric, partial, and hepatorenal transplants and recipients who died within 2 months after OLT. Thus, we analyzed the incidence and outcome of these tumors in 605 patients after OLT. RESULTS: We found 21 (3.5%) tumors in 20 (3.3%) recipients: 14 were UAD tumors (three in floor of the mouth, two in tonsil, one in tongue, one in pharynx, three in larynx, and four in esophagus) and seven were lung tumors. Nineteen patients were men and one was a woman, with a mean age at transplantation of 47.7+/-8.6 years. Mean time from OLT to tumor diagnosis was 61.7+/-35.1 years. As risk factors, 70% were heavy smokers, 75% were heavy drinkers, and 70% developed acute rejection. The incidence of these tumors was significantly higher in transplanted patients for alcoholic cirrhosis compared to the nonalcoholic cirrhosis (8.1% vs 0.8%; P<.0001). After surgical excision in 65% of patients, 1-, 2-, and 3-year patient survival were 47.6%, 37.0%, and 19.7%, respectively. CONCLUSION: There is a significantly higher incidence of these tumors in male heavy drinkers and/or smokers who underwent OLT for alcoholic cirrhosis; in spite of aggressive surgical treatment, the prognosis is poor.

Adult↗

Preliminary experience with living donor liver transplantation in adults and children.

INTRODUCTION: Living donor liver transplantation (LDLT) is becoming a widespread technique with good results. Its use may sharply decrease waiting list mortality. However, donor safety is of primary concern. The aim of this work was the preliminary evaluation of the LDLT program initiated in our institution in 1995. PATIENTS AND METHODS: Among 875 liver transplants (LT) performed from 1986 12 are LDLT in nine adults (50.0+/-10.0 years) and three children (1.9+/-1.1 years). All donors were relatives: son/daughter (six), brother (three), and father/mother (three). RESULTS: Donor right lobe graft weight was 758.3+/-137.4 g; left liver 525.3+/-97.1 g; and left lobe 293.3+/-30.5 g, with a graft weight/recipient weight ratio of 0.91+/-0.21 (0.64-1.36) in adults. Complications in five donors (42%) included biliary fistula in the first three cases, two pleural effusions and one intra-abdominal collection. Mean hospital stay was 16.9+/-15.2 days (median 12). Recipient indications for adults were: four HCV cirrhosis (+ alcoholic in one), one HBV cirrhosis, one cryptogenic, one alcoholic, one PBC, and one retransplant due to cholangiopathy. In children, the etiologies were two biliary atresia and one liver fibrosis. The first case was the only mortality (8.3%). Two patients were retransplanted (16.6%) due to arterial thrombosis (AT) and graft dysfunction. Actuarial survival at 1 year was 91.7%+/-8.0% for patients and 83.3%+/-10.8% for grafts. Complications in the recipients included AT (two), Acinetobacter sepsis, jaundice and upper digestive hemorrhage (due to a "small-for-size" graft), biliary fistula after T-tube removal, volvulus around the T tube, and intra-abdominal collection. CONCLUSIONS: Our experience suggests that good results can be achieved with LDLT. Standardization of the technique will allow refinement of the operation and decrease waiting list mortality. However, donor safety remains a fearful threat.

Adult↗

Liver transplantation and transjugular intrahepatic portosystemic shunt.

OBJECTIVE: Describe the results of liver transplantation after installing Transjugular Intrahepatic Portosystemic Shunt (TIPS) and compare them with those of a control group in a comparative, longitudinal, retrospective study. MATERIALS AND METHODS: Between April 1986 and October 2002, we performed 875 liver transplantations. Between January 1996 and October 2002, 26 transplantations were performed on TIPS carriers. This group was compared with a control cohort of 50 randomly selected patients who underwent transplantation in this period (non-TIPS carriers). Both groups were homogeneous with no significant differences between age, sex United Network for Organ Sharing (UNOS) score, Child stage, or etiology. RESULTS: Actuarial survival rates at 1 and 3 years: TIPS group 96.15% and 89.29% versus control cohort 87.8% and 81%, respectively. In 73.9%, the TIPS was clearly effective; in 88.9%, a postoperative Doppler revealed normal flow. There were no statistically significant differences compared with time on the waiting list for transplant, duration of the operation, ischemia times, intraoperative consumption of hemoderivates, vascular or nonvascular postoperative complications, duration of stay in the intensive care unit, hospital stay, or retransplantation rate. CONCLUSIONS: In our experience, TIPS insertion does not affect either the intraoperative or postoperative evolution and is not associated with an increased time on the liver transplant waiting list.

Actuarial Analysis↗

[Chronic pancreatitis as the initial presentation of Crohn's disease].

It has been suggested that pancreatitis could be an extrahepatic manifestation of inflammatory bowel disease, since its incidence in this disease is greater than that in the general population and in many cases no etiological factor is found. We present a case of chronic idiopathic pancreatitis as the initial presentation of Crohn's disease of the colon.

Adult↗

Regulation of Brucella virulence by the two-component system BvrR/BvrS.

The Brucella BvrR/BvrS two-component regulatory system is highly similar to the regulatory and sensory proteins of Sinorhizobium and Agrobacterium necessary for endosymbiosis and pathogenicity in plants, and very similar to a putative system present in the animal pathogen Bartonella. Mutations in the bvrR or bvrS genes hamper the penetration of B. abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. In contrast to virulent Brucella, BvrR/BvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrR/BvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B. abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrR/BvrS mutants. We hypothesize that the Brucella BvrR/BvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism.

Amino Acid Sequence↗

The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae.

The Brucella BvrR/BvrS two-component regulatory system is homologous to the ChvI/ChvG systems of Sinorhizobium meliloti and Agrobacterium tumefaciens necessary for endosymbiosis and pathogenicity in plants. BvrR/BvrS controls cell invasion and intracellular survival. Probing the surface of bvrR and bvrS transposon mutants with monoclonal antibodies showed all described major outer membrane proteins (Omps) but Omp25, a protein known to be involved in Brucella virulence. Absence of Omp25 expression was confirmed by two-dimensional electrophoresis of envelope fractions and by gene reporter studies. The electrophoretic analysis also revealed reduction or absence in the mutants of a second set of protein spots that by matrix-assisted laser desorption ionization MS and peptide mass mapping were identified as a non-previously described Omp (Omp3b). Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface-targeted bactericidal peptides, it is proposed that BvrR/BvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments. A genomic search revealed that Omp25 (Omp3a) and Omp3b belong to a family of Omps of plant and animal cell-associated alpha-Proteobacteria, which includes Rhizobium leguminosarum RopB and A. tumefaciens AopB. Previous work has shown that RopB is not expressed in bacteroids, that AopB is involved in tumorigenesis, and that dysfunction of A. tumefaciens ChvI/ChvG alters surface properties. It is thus proposed that the BvrR/BvrS and Omp3 homologues of the cell-associated alpha-Proteobacteria play a role in bacterial surface control and host cell interactions.

Bacterial Outer Membrane Proteins↗

Long-term follow-up of bone mass after orthotopic liver transplantation: effect of steroid withdrawal from the immunosuppressive regimen.

Glucocorticoids have been suggested to play a major role in transplantation-related osteopenia. In this study we assess the long-term changes and the effect of steroid withdrawal from the standard immunosuppressive regimen on bone mineral density (BMD) after orthotopic liver transplantation (OLT). Sixty-nine non-osteoporotic patients (20 women, 49 men), aged 48 +/- 9.5 years (mean +/- SD), and with a follow-up of 58.3 +/- 23.2 months (range 24-121 months) were studied. Immunosuppressive treatment consisted of prednisone, cyclosporin A and azathioprine. In 41 patients (group A), prednisone was tapered and withdrawn after 36.2 +/- 19.3 months (range 13-79 months), whereas in 28 patients (group B) prednisone was maintained. BMD in the spine (L1-L4) was serially measured by dual-energy X-ray absorptiometry (Hologic QDR 1,000w) at baseline, before steroid withdrawal and at the end of study. Age- and sex-matched Z-scores of BMD were calculated. No differences were found in age, body mass index, time since OLT, or baseline BMD between the two groups. BMD had significantly increased in both groups at the end of follow-up period (group A, +8.1 +/- 8.7%; group B, +3.2 +/- 8.0%, p < 0.05). However, the Z-score was significantly higher in group A than in group B at the end of study (-0.44 +/- 1.05 vs -0.99 +/- 0.77; p<0.05). BMD recovery was lower in pre-OLT biliary cirrhosis patients. Bone mass improvement was independent of the time since OLT in both groups, and of the time of steroid withdrawal in group A. Our data confirm that steroid withdrawal accelerates the recovery of bone mass in patients who have undergone a successful liver transplantation.

Adult↗

GTPases of the Rho subfamily are required for Brucella abortus internalization in nonprofessional phagocytes: direct activation of Cdc42.

Members of the genus Brucella are intracellular alpha-Proteobacteria responsible for brucellosis, a chronic disease of humans and animals. Little is known about Brucella virulence mechanisms, but the abilities of these bacteria to invade and to survive within cells are decisive factors for causing disease. Transmission electron and fluorescence microscopy of infected nonprofessional phagocytic HeLa cells revealed minor membrane changes accompanied by discrete recruitment of F-actin at the site of Brucella abortus entry. Cell uptake of B. abortus was negatively affected to various degrees by actin, actin-myosin, and microtubule chemical inhibitors. Modulators of MAPKs and protein-tyrosine kinases hampered Brucella cell internalization. Inactivation of Rho small GTPases using clostridial toxins TcdB-10463, TcdB-1470, TcsL-1522, and TcdA significantly reduced the uptake of B. abortus by HeLa cells. In contrast, cytotoxic necrotizing factor from Escherichia coli, known to activate Rho, Rac, and Cdc42 small GTPases, increased the internalization of both virulent and non-virulent B. abortus. Expression of dominant-positive Rho, Rac, and Cdc42 forms in HeLa cells promoted the uptake of B. abortus, whereas expression of dominant-negative forms of these GTPases in HeLa cells hampered Brucella uptake. Cdc42 was activated upon cell contact by virulent B. abortus, but not by a noninvasive isogenic strain, as proven by affinity precipitation of active Rho, Rac, and Cdc42. The polyphasic approach used to discern the molecular events leading to Brucella internalization provides new alternatives for exploring the complexity of the signals required by intracellular pathogens for cell invasion.

Actins↗

Clinical significance of donor-unrecognized bacteremia in the outcome of solid-organ transplant recipients.

We evaluated the clinical significance of unrecognized bacteremia in the organ donor (i.e., blood culture results that were reported to be positive after transplantation) on the outcome of transplant recipients. Twenty-nine of 569 liver and heart donors (5%) had bacteremia at the time of organ procurement, but there were no documented instances of transmission of the isolated bacteria from the donor to the recipient. Unrecognized bacteremia in the donor does not have a negative clinical impact on the outcome of organ transplant recipients.

Adolescent↗

In vivo proteolytic degradation of the Escherichia coli acyltransferase HlyC.

Escherichia coli hemolysin (HlyA) is the prototype toxin of a major family of exoproteins produced by Gram-negative bacteria known as "repeats in toxins." Only fatty acid-acylated HlyA molecules at residues Lys564 and Lys690 are able to damage the target cell membrane. Fatty acylation of pro-HlyA is dependent on the co-synthesized acyltransferase HlyC and the acylated form of acyl-carrier protein. By using a collection of hlyA and hlyC mutant strains, the processing of HlyC was investigated. HlyC was not detected by Western blot in an E. coli strain encoding hlyC and hlyA, but it was present in a strain encoding only hlyC. The hlyC mRNA pattern, however, was similar in both strains indicating that the turnover of HlyC does not occur at the transcriptional level. HlyC was detected in Western blots of cell lysates from an E. coli strain encoding HlyC and a HlyA derivative where both acylation sites were substituted. Similar results were obtained when HlyC was expressed in a hlyA mutant strain lacking part of a putative HlyC binding domain, indicating that this particular HlyA region affects HlyC stability. We did not detect HlyC in cell lysates from hlyC mutants with different abilities to acylate pro-HlyA, suggesting that the degradation of HlyC is not related to the HlyA acylation process. The protease systems ClpAP, ClpXP, and FtsH were found to be responsible for the HlyA-dependent processing of HlyC.

Acylation↗

Respiratory effects of halothane in a patient with refractory status asthmaticus.

We describe the case of a 36 year old patient who was admitted to the intensive care unit (ICU) for an acute asthma attack that failed to respond to conventional treatment and required mechanical ventilation. The patient's condition improved after halothane was administered; treatment with this inhalational anaesthetic lasted 7 h, and the beneficial effect was obtained by employing concentrations between 0.5 and 2%. Under constant mechanical ventilator settings, a highly significant linear correlation between peak airway pressure and arterial pCO(2)(r: 0.98 P<0.001) was observed. The decrease in p(a)CO(2)induced by halothane may be explained by the diminished dead space that results from the drop in peak airway pressure. Arterial hypotension, which improved with inotropic agents, was the only complication that seemed related to the inhaled anaesthetic. The patient was extubated 24 h after her arrival to the ICU and discharged 72 h later. A causal relationship between the administration of halothane and clinical improvement is suggested.

Administration, Inhalation↗

Choledochocholedochostomy conversion to hepaticojejunostomy due to biliary obstruction in liver transplantation.

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.

Adult↗