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Biomedical subjects

E Pareja

Publications and source records attributed to E Pareja.

At least 19 recordsLinked to original sources

Pancreatic function after severe acute biliary pancreatitis: the role of necrosectomy.

OBJECTIVES: To investigate the recovery of pancreatic function after severe acute biliary pancreatitis (ABP), especially the influence of necrosectomy on endocrine and exocrine functions. METHODS: Prospective cohort study including 39 patients with severe ABP. According to need or no need for surgical necrosectomy, patients were further subdivided into 2 groups. Functional pancreatic evaluation was carried out 12 months after the ABP episode. Endocrine function was evaluated by an oral glucose tolerance test and exocrine function by fecal fat excretion, fecal chymotrypsin (FQ), and secretin-cerulein tests (SCT). RESULTS: Most of the patients with necrosectomy had an abnormal exocrine pancreatic function, with steatorrhea in 25%. In the group without surgery, exocrine function was pathologic in only 13.3% and there were no cases of steatorrhea. Endocrine function was pathologic in 75% of patients undergoing necrosectomy versus 26.7% in the nonoperated group. In this latter group, the patients with abnormal endocrine function did not require insulin therapy, while in 33.3% of patient in the necrosectomy group insulin was necessary. CONCLUSIONS: In our homogeneous series of severe ABP, necrosectomy impaired significantly pancreatic endocrine and exocrine function. On the other hand, most patients with the same origin and severity index, but without surgical debridement, maintained normal pancreatic function.

Aged↗

Main pancreatic duct: morphlogy after acute biliary pancreatitis with magnetic resonance cholangiopancreatography after secretin stimulation.

OBJECTIVE: to assess whether a magnetic resonance cholangiopancreatography performed after an acute biliary pancreatitis leads to pancreatic morphological alterations and if secretin stimulation influences the visualization of the pancreatic tree. METHOD: forty patients with acute biliary pancreatitis, 25 female (62,5/) and 15 male (37,5/), 27 mild and 13 severe, were prospectively and consecutively studied. All patients had undergone cholecystectomy. No altered pancreatic functions were observed. Morphology of the pancreas and of the main pancreatic duct were assessed by magnetic resonance cholangiopancreatography five years after the episode of pancreatitis and a comparative study between patients and case controls was carried out. Secretin was given in 16 cases in whom the visualization of the duct was incomplete or absent. Ductal morphology before and after secretin stimulation was compared. RESULTS: significant differences were observed when the diameter and length of the main pancreatic duct were compared in patients and control cases and was completely visualized in 60% of the cases, and could be seen in all patients after secretin stimulation. The comparative statistical analysis of the length and diameter of the pancreatic duct before and after the secretin stimulation showed significant differences. CONCLUSION: acute biliary pancreatitis leads to morphological alterations, regarded as scar lesions which do not become chronic. Secretin stimulation improves the visualization of the main pancreatic duct.

Acute Disease↗

Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity.

CYP activity and protein contents have been measured in human liver using different techniques. In contrast, CYP mRNA data are scarce and the relationships between CYP mRNA contents and activities have not been established. These studies deserve further attention because mRNA determinations by RT-PCR require a very small amount of material (e.g., liver needle biopsy) and could provide important data regarding CYP expression regulation. In this study we measured in 12 human liver samples the mRNA contents of 10 CYPs by quantitative RT-PCR and the metabolic activities using specific substrates. mRNA contents and activities showed high correlation coefficients for CYP1A1, CYP1A2, CYP3A4, CYP2D6, and CYP2B6 (0.96, 0.94, 0.69, 0.61, and 0.52, respectively), but no significant correlations were found for CYP2C9, CYP2A6, and CYP2E1. The results suggest that the regulation of CYP1A1, CYP1A2, CYP3A4, CYP2D6, and CYP2B6 expression is essentially pretranslational and that their mRNA levels could allow a good estimate of their activity.

Adult↗

Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor.

BACKGROUND/AIMS: Cultured human hepatocytes are considered a close model to human liver. However, the fact that hepatocytes are placed in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism in vitro reflect that of the liver in vivo? This issue was examined by investigating the in vitro and in vivo metabolism of aceclofenac, an analgesic/anti-inflammatory drug. METHODS: Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC. During the course of clinical recovery, patients were given the drug, and the metabolites, largely present in the urine, were analyzed. In vitro and in vivo data of the same individual were compared. RESULTS: The relative abundance of oxidized metabolites in vitro (i.e. 4'OH-aceclofenac + 4'OH-diclofenac vs. total hydroxylated metabolites; Spearman's p = 0.855), as well the hydrolysis of aceclofenac (4'OH-diclofenac vs. 4'OH-aceclofenac + 4'OH-diclofenac; p = 0.691) correlated well with in vivo data. The conjugation of the drug in vitro (24.6 +/- 7.6%) was lower than that in vivo (44.9 +/- 5.3%). The rate of 4'OH-aceclofenac formation in vitro correlated with the amount of metabolites excreted in urine after 16 h (p = 0.95). CONCLUSIONS: The in vitro/in vivo metabolism of the drug was surprisingly similar in each patient. The variability observed in vitro reflected an existing phenotypic variability among donors.

Anti-Inflammatory Agents, Non-Steroidal↗

[Bronchial carcinoid tumors: a prospective study].

We report the results of a study performed in the thoracic surgery department of Hospital General Universitario of Valencia from October 1989 to December 1996. Of the 621 patients diagnosed of lung cancer during this period, 320 underwent the usual surgical excision, 18 were confirmed histologically as bronchial carcinoid tumors, indicating an incidence of 5.6% of all pulmonary neoplasms resected in our department. The symptoms most often reported were recurring infection (44.5%) and chest pain (33.3%). Only one patient presented carcinoid syndrome. The most common radiologic presentation was solitary pulmonary nodule (50%). The tumor was visible by fiberoptic bronchoscopy in 9 cases. Diagnosis was by bronchial biopsy in four cases. Confirmation was by immunohistochemical analysis of the specimen in all cases. Electron microscopy and immunohistochemical techniques using neuroendocrine panmarkers is considered fundamental for differentiating between neuroendocrine neoplasms and typical and atypical carcinoid tumors. Thirteen (72.2%) of the 18 patients studied were diagnosed of typical carcinoids and 5 (27.8%) of atypical carcinoids. Neuroendocrine marking showed neurospecific enolase in 15 patients and chromogranin positivity in 10.

Adolescent↗

Analysis of LMP and TAP polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in rheumatoid arthritis.

OBJECTIVE: The aim of this study was to investigate the relation between the polymorphism of large molecular weight proteasome (LMP) (LMP2-LMP7) and transporter associated with antigen processing (TAP) (TAP1-TAP2) genes and rheumatoid arthritis (RA). METHODS: Sixty RA patients and 102 ethnically matched unrelated healthy subjects were typed for LMP, TAP, and disease associated HLA-DRB1 alleles by using a new strategy based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with amplification created restriction sites. RESULTS: The polymorphism of LMP (LMP2-LMP7) and TAP (TAP1-TAP2) genes was examined in shared epitope positive and negative RA patients and controls. No significant differences in the LMP or TAP allele frequencies were observed between the total patient and control groups or the patients and controls groups or the patients and controls positive or negative for the shared epitope. CONCLUSION: The data suggest that the polymorphisms of LMP and TAP genes do not have an important influence in the pathogenesis of RA, although larger studies will be needed to provide more conclusive evidence on the role of these genes in RA. A new, highly reliable strategy for typing LMP alleles is also described.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Polymorphism at the TNF loci in rheumatoid arthritis.

The purpose of this work was to analyze the possible influence of TNF loci polymorphism on the susceptibility and/or the disease profile of rheumatoid arthritis (RA). Tumor necrosis factor (alpha and beta) genotypes were determined in 60 patients with RA and 102 healthy subjects by a method based on PCR-RFLP with amplification-created restriction sites. The results obtained in the present study showed that there is not a significant association of either TNF alpha promoter variation (at positions -308 and -238) or TNF beta polymorphism with susceptibility to RA. However, a significant difference in the mean age at disease onset was found between -238 TNF alpha genotypes. In addition, a difference in the presence of nodular disease was observed between -308 TNF alpha genotype. The results of this study suggests that the TNF alpha gene may play a role in the disease profile of rheumatoid arthritis.

Alleles↗

Allele walking: a new and highly accurate approach to HLA-DRB1 typing. Application to DRB1*04 alleles.

We have developed a typing method, which can be used even in small laboratories, to produce a highly accurate and reliable allele assignment in any homozygous or heterozygous situation. We have called the method allele walking (AW) and it consists of sequential rounds of PCR-RFLP. After digestion, electrophoresis separates alleles positive for the mutation from the negative alleles; the cleaved fragment is then recovered from the gel and analyzed for mutations at another codon. In this way, AW is able to positively ascertain which mutations are in the same chromosome (cis-linkage) and assigns alleles independently from each other. Artificial sites are created in the PCR step in order to positively detect substitutions not naturally recognized by any of the existing or convenient enzymes. We report the application of AW for typing the 22 DRB1*04 alleles. The first PCR-RFLP round groups DRB1*04 alleles. Subsequently, the mutations at codons 86, 74, 71, 57 and 37 can be analyzed for the unambiguous assignment of the majority of the alleles. Additional polymorphisms at different codons can be assayed to resolve any undetermined alleles. The viability of all the restriction sites used as well as the feasibility of AW were successfully tested.

Alleles↗

Heat shock protein 70 gene polymorphisms in rheumatoid arthritis.

A role for heat shock proteins (hsp) in rheumatoid arthritis has been suggested. In addition, the specific binding of human HSP70 protein to QKRAA and RRRAA motifs within the HV3 region of disease-associated DRB1*0401 and DRB1*1001 molecules, respectively, has been proposed as being relevant to rheumatoid arthritis. The purpose of this work was to analyze the influence of HSP70 gene polymorphism on the susceptibility to or severity of rheumatoid arthritis and to investigate the possible contribution of these HSP70 polymorphisms in determining HLA-DRB1*0401/*1001 disease association. The frequencies of the HSP70-1, HSP70-2 and HSP70-hom genotypes were analyzed by PCR-RFLP using BsrBI, PstI and NcoI enzymes, respectively, in patients with rheumatoid arthritis and in healthy controls. No significant differences were observed when HSP70 allele distribution between the groups under study were compared. Moreover, we did not observe any significant difference in HSP70 allele frequencies between patients positive for HLA-DRB1*0401/*1001 alleles and matched controls. Our data indicate that HSP70 gene polymorphisms do not appear to be relevant in the susceptibility to or severity of rheumatoid arthritis.

Arthritis, Rheumatoid↗

The tetramer model: a new view of class II MHC molecules in antigenic presentation to T cells.

Crystallographic studies suggest a plausible divalent interaction between T-cell receptor (TCR) and MHC class II molecules. In addition, biochemical data suggest that these divalent MHC molecules are preformed at the membrane of the antigen-presenting cell. The tetramer model is based on these preformed tetrameric class II molecules that can be loaded with identical or different peptides in their two grooves. This enables divalent class II molecules to deliver two different messages to T cell: 1) a two-peptide message, in which the tetramer with two identical peptides is able to cross-link two TCRs triggering full activation of a T cell. At the thymic level we propose that this message induces negative selection; or 2) a one-peptide message: only one of the peptides loaded in the class II tetramer is able to interact with that TCR. This message would be involved in triggering partial activation phenomena in mature lymphocytes, whereas in thymocytes this message would mediate positive selection. Since high concentrations of a peptide would favor the load of tetramers with identical peptides, the tetramer could therefore be viewed as a quantitative-qualitative transducer that would trigger different responses depending on the concentration of antigenic peptides.

Animals↗

[The so-called malignant pleural effusion: a new review of direct data obtained with diagnostic pleuroscopy].

We analyze a series of 896 thoracoscopies for pleural effusion, of which 78% (662/896) were due to pleural carcinomatosis, primary or metastatic. Pleural malignancy was observed mainly, in the right hemithorax (65%), arising from tumors within the diaphragm. The likelihood of finding pleural metastasis in lung cancer was 77%. When the pleural effusion is slight (less than 500 ml) the likelihood falls to 22%. We therefore advise thoracoscopy in the former and thoracotomy in the latter. Blood-stained effusion continues to have the worst prognosis (84% stemming from metastasis) and signifies an advanced stage of pleural metastasis. The pleura parietal is involved in 69% of pleural carcinomatosis cases, and in 80% when the lower hemithorax or the area around breast or lung tumors are involved. The cytology yield was 45.9%, though always depending on extent of metastasis. When metastasis was slight, the likelihood of positive cytology was less (19%) and when metastasis was generalized throughout the entire pleura the likelihood increased to 73%. We found no reason to think that the cells in most pleural liquids are able to nest and form tumoral niches. The origin of such cell nests was rather found to be in shedding from the metastases themselves, from lung tumors or from carcinomatous lymphangitis by lymphatic obstruction. The diagnostic yield of thoracoscopy once again proved to be superior to that of pleural biopsy.

Adult↗

HLA antigens in brucellosis.

106 patients diagnosed as having brucellosis were typed for HLA class I and class II antigens. The number of healthy controls was 272 and 102 for classes I and II, respectively. 17 HLA-A, 31 HLA-B, 7 HLA-C and 8 HLA-DR specificities were studied. The most important finding was a highly significant decrease of the HLA-Cw2 antigen frequency in the patient group compared with the controls. The corrected p value was p less than 0.0001 (Fisher's test). This finding is compatible with the idea that HLA-Cw2 antigen could be a protective factor. No other positive or negative association was observed. There was no significant difference in HLA antigen frequencies between patients with and without joint manifestations. In addition, we did not find an HLA-B27 increase in the group of patients with brucellosis associated spondylarthritis when compared with healthy individuals.

Arthritis↗