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Biomedical subjects

Jorge Martínez

Publications and source records attributed to Jorge Martínez.

At least 19 recordsLinked to original sources

[Problems and solutions in health care for chronic diseases. A qualitative study with patients and doctors].

BACKGROUND: Chronic diseases represent a challenge for health systems and the professionals most involved in chronic care. Despite biomedical advances, the results of care for chronic problems are not as good as they should be. OBJECTIVE: To find out what doctors and patients think of care for some of the main chronic illnesses; to detect concrete areas of deficit and lack of satisfaction felt by both sides and possible lines of improvement; to raise mutual understanding between patients and doctors. PARTICIPANTS: Forty-one patients with fibromyalgia or diabetes mellitus, carers for people with Alzheimer's and breast cancer patients. Forty-three family doctors involved in health care delivery to this kind of patient. METHODS: Four discussion groups. Transcription and syntactical, semantic and pragmatic contents analysis, with both pre-established and emerging categories of consensus. RESULTS: Patients thought, with different nuances as a function of the problem put forward, that questions of respectful, human and integrated care, clear and suitable information, and consistent follow-up were important and insufficiently covered by doctors and health services. Doctors thought that many of their efforts in caring for these patients were useless, and thought it important to reconsider their clinical responsibilities and the patient-doctor relationship. Doctors highlighted the limitations in the health care resources available for working with these patients. CONCLUSIONS: To tackle prevalent chronic problems requires, in the view of doctors and patients, important modifications that are related mainly to the kind of relationship between the two, with new clinical responsibilities and certain organisational care delivery features.

Adult↗

Dog echinococcosis in northern Spain: comparison of coproantigen and serum antibody assays with coprological exam.

A large sheep-dog population from the province of Alava (northern Spain) has been investigated in order to determine the prevalence of the cestode parasite Echinococcus granulosus. Worms were detected in 14.0% of 721 dog faecal supernatants by coproantigen ELISA, and in 9.1% of 754 dog serum samples by serum antibody ELISA. A weak but statistically significant correlation (Spearman's rho=0.103, 95% CI: 0.023-0.178) between the two immunoassay results was found. In addition, eggs of the family Taeniidae were detected in 10.3% of 726 faecal samples examined by coproparasitological (flotation and sedimentation) tests. The overall E. granulosus infection rate, based on a Bayesian latent class model that accounts for the imperfect sensitivities and specificities of all diagnostic tests used, was estimated to be 8.0% (95% credible interval: 5.4-11.4%), corroborating that sheep-dog is the dog class most vulnerable to acquiring the infection. Dog sex did not influence the prevalence of E. granulosus, independently of the diagnostic test used or the dog region of origin. No significant linear correlation was found between the coproantigen ELISA OD values and the dog age (Spearman's rho=-0.049, 95% CI: -0.234 to 0.135), suggesting that there were no differences in prevalence of E. granulosus between old and young dogs. The obtained results highlight the importance of initiating a control program based on regular treatment of the sheep-dogs with praziquantel in the province of Alava.

Age Factors↗

Carcass condemnation causes of growth retarded pigs at slaughter.

Condemnation causes of growth retarded pigs were studied in a Spanish abattoir. A total of 513 carcasses out of 6017 (8.5%) were rejected during inspection. The main reasons for condemnation were abscesses, cachexia, catarrhal bronchopneumonia, vertebral osteomyelitis, arthritis, pleuritis, peritonitis and pleuropneumonia. Positive relationships were found between tail lesions and arthritis (OR=5.23) or vertebral osteomyelitis (OR=24.81), while no relationships were found between tail lesions and abscesses. Lower risks were observed among carcasses condemned for cachexia, and were as follows: abscesses (OR=0.18), arthritis (OR=0.32), vertebral osteomyelitis (OR=0.06). Arcanobacterium pyogenes, either alone or in combination with other agents, was the main bacterial species isolated from abscesses, osteomyelitis and arthritis (73.5% of lesions). Direct economical losses associated with condemnation were calculated to be 30,000 Euro.

Animals↗

[Appendectomies for suspected acute appendicitis during pregnancy: experience at a Chilean public hospital].

BACKGROUND: Acute appendicitis is the most common non obstetric surgical emergency during pregnancy. AIM: To asses our experience in the diagnosis and management of acute appendicitis occurring during pregnancy. PATIENTS AND METHODS: Data from all pregnant patients who were subjected to an appendectomy for a suspected acute appendicitis from January 1998 to December 2002, were retrospectively analyzed. All pathological, surgical, clinical records and the delivery outcome registry of each patient were reviewed. RESULTS: Among 47,322 deliveries, 46 pregnant women aged 29+/-9 years and with a gestational age of 21+/-7 weeks, were operated because of a presumptive acute appendicitis. Forty (87%) had a histopathologically proven appendicitis; ten (25%) cases had a perforated appendix and 30 (75%) had a non-perforated appendicitis. Five (10.9%) patients had a negative laparotomy and one had a necrotic ovarian tumor. Patients with perforated and non perforated appendices had a similar lapse from the onset of symptoms to operation (69+/-45 and 50+/-34 hours respectively, NS) and a similar white cell count (15,667+/-3,707 and 13,006+/-5,206 cells/mm(3), respectively, NS). Wound infection was the most common surgical complication in 15%. Seven (15%) patients had a premature delivery and there was one fetal death (2.2%). There were no pregnancy complications on negative appendectomy cases. CONCLUSIONS: Acute appendicitis continues to be a challenge in diagnosis and treatment during pregnancy. Maternal and fetal outcome was better than previously reported.

Adult↗

Galectin-8 binds specific beta1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells.

Integrin-mediated encounters of T cells with extracellular cues lead these cells to adhere to a variety of substrates and acquire a spread phenotype needed for their tissue incursions. We studied the effects of galectin-8 (Gal-8), a beta-galactoside binding lectin, on Jurkat T cells. Immobilized Gal-8 bound alpha1beta1, alpha3beta1 and alpha5beta1 but not alpha2beta1 and alpha4beta1 and adhered these cells with similar kinetics to immobilized fibronectin (FN). Function-blocking experiments with monoclonal anti-integrin antibodies suggested that alpha5beta1 is the main mediator of cell adhesion to this lectin. Gal-8, but not FN, induced extensive cell spreading frequently leading to a polarized phenotype characterized by an asymmetric lamellipodial protrusion. These morphological changes involved actin cytoskeletal rearrangements controlled by PI3K, Rac-1 and ERK1/2 activity. Gal-8-induced Rac-1 activation and binding to alpha1 and alpha5 integrins have not been described in any other cellular system. Strikingly, Gal-8 was also a strong stimulus on Jurkat cells in suspension, triggering ERK1/2 activation that in most adherent cells is instead dependent on cell attachment. In addition, we found that patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disorder, produce Gal-8 autoantibodies that impede both its binding to integrins and cell adhesion. These are the first function-blocking autoantibodies reported for a member of the galectin family. These results indicate that Gal-8 constitutes a novel extracellular stimulus for T cells, able to bind specific beta1 integrins and to trigger signaling pathways conducive to cell spreading. Gal-8 could modulate a wide range of T cell-driven immune processes that eventually become altered in autoimmune disorders.

Androstadienes↗

Shared and non-shared antigens from three different extracts of the metacestode of Echinococcus granulosus.

Hydatid cyst fluid (HCF), somatic antigens (S-Ag) and excretory-secretory products (ES-Ag) of Echinococcus granulosus protoscoleces are used as the main antigenic sources for immunodiagnosis of human and dog echinococcosis. In order to determine their non-shared as well as their shared antigenic components, these extracts were studied by ELISA-inhibition and immunoblot-inhibition. Assays were carried out using homologous rabbit polyclonal antisera, human sera from individuals with surgically confirmed hydatidosis, and sera from dogs naturally infected with E. granulosus. High levels of cross-reactivity were observed for all antigenic extracts, but especially for ES-Ag and S-Ag. Canine antibodies evidenced lesser avidity for their specific antigens than antibodies from human origin. The major antigenic components shared by HCF, S-Ag, and ES-Ag have apparent molecular masses of 4-6, 20-24, 52, 80, and 100-104 kDa, including doublets of 41/45, 54/57, and 65/68 kDa. Non-shared polypeptides of each antigenic extract of E. granulosus were identified, having apparent masses of 108 and 78 kDa for HCF, of 124, 94, 83, and 75 kDa for S-Ag, and of 89, 66, 42, 39, 37, and 35 kDa for ES-Ag.

Animals↗

Enzymatic activities of Alternaria alternata allergenic extracts and its major allergen (Alt a 1).

Several allergens from Alternaria alternata have been isolated allowing some of them to be identified and characterised. Despite the fact that the major allergen of A. alternata (Alt a 1) has been extensively produced by recombinant technology, its biological activity still remains unknown. In the present study, extracts from culture filtrates were used to evaluate the intra-specific variability of the enzymes and also as a source for isolating and purifying native Alt a 1. This was purified by affinity chromatography using antibody anti-recombinant Alt a 1 (produced in Escherichia coli). Enzyme activities were analysed by the API-ZYM System screening method. Results demonstrated the high variability of enzyme activities among the different strains. Only activities corresponding to phosphatases, esterases and beta-glucosidase were expressed by 100% of the strains. Both native and recombinant Alt a 1 showed phosphatase and esterase activities, suggesting that the glucidic moiety of this allergen does not significantly affect its enzyme activity.

Allergens↗

Successful liver transplantation and delivery in a woman with fulminant hepatic failure occurring during the second trimester of pregnancy.

BACKGROUND: Severe liver dysfunction occurring during pregnancy is an unusual but dramatic event that poses special technical and ethical issues because it involves two lives. METHODS AND RESULTS: We report the case of a 35-year-old woman with cryptogenic fulminant hepatic failure who underwent successful orthotopic liver transplantation at 22 weeks of pregnancy. After a relatively uneventful post-operative course she delivered a normal offspring at the 27th week of gestation. There were no obstetrical complications and neonatal outcome was excellent. After a year of follow-up, the patient is doing well,and the newborn has exhibited normal psychomotor and weight/height development. CONCLUSION: This case illustrates the challenge of treating fulminant hepatic failure during pregnancy and demonstrates that liver transplantation is a feasible therapeutic option for treatment of patients with this condition, allowing successful completion of pregnancy.

Adult↗

Overexpression of RhoA-GTP induces activation of the Epidermal Growth Factor Receptor, dephosphorylation of focal adhesion kinase and increased motility in breast cancer cells.

Rho GTPases are overexpressed in human tumors and are involved in a variety of cellular processes such as organization of the actin cytoskeleton, cell-cell contact and malignant transformation. EGFR activation plays a key role in the acquisition of motile properties in carcinoma cells, and it has been proposed that downregulation of FAK activity is one of its most relevant consequences. In the present study, using mammary MCF-7 cells, we demonstrated that overexpression of the active form of the small GTPase RhoA induced the activation of EGFR by a phenomenon that depends on the activity of a metalloproteinase (MMP), which presumably cleaves a membrane-bound EGFR ligand. The EGFR tyrosine phosphorylation correlates with ERK1,2 activation and the stimulation of urokinase production. An aggressive mammary cell line (MDA-MB-231) that overexpresses both RhoA and EGFR in their active forms also displayed an MMP-dependent activation mechanism of EGFR. RhoA-GTP-transfected cells showed a cortical array of F-actin, rounded morphology, reduced spreading potential and a dephosphorylation of FAK that was released by integrin-dependent fibronectin adhesion and a specific EGFR tyrosine kinase inhibitor. Our results suggest that the MMP-dependent EGFR activation observed in V14 RhoA cells represents the starting point of a signaling route that promotes cell motility by activation of ERK1,2 and further enhancement of proteases production.

Breast Neoplasms↗

Preliminary study of the presence of antibodies against excretory-secretory antigens from protoscoleces of Echinococcus granulosus in dogs with intestinal echinococcosis.

The aim of the present study was to analyze the antibody response against excretory-secretory antigens (ES-Ag) from Echinococcus granulosus protoscoleces, using sera from dogs infected with E. granulosus and other helminths. ES-Ag were obtained from the first 50 h maintenance of protoscoleces in vitro. Immunochemical characterization was performed by immunoblotting with sera from dogs naturally infected with E. granulosus (n = 12), sera from dogs infected with helminths other than E. granulosus (n = 30), and helminth-free dog sera (n = 20). These findings were compared to those obtained from a somatic extract of protoscoleces (S-Ag). ES-Ag only showed four cross-reacting proteins of 65, 61, 54, and 45-46 kDa. Antigens with apparent masses of 89 and 50 kDa in ES-Ag and of 130 and 67 kDa in S-Ag were identified by sera of dogs infected with E. granulosus only, whereas a protein of 41-43 kDa was recognised by the majority of the sera from dogs with non-echinococcal infection. Employing ELISA to study the same sera, S-Ag revealed higher immunoreactivity than ES-Ag, but also showed higher cross-reactivity levels when sera from dogs with non-echinococcal infection were assayed in immunoblotting.

Animals↗

Septicaemia secondary to infection by Corynebacterium macginleyi in an Indian python (Python molurus).

A seven-year-old female Indian python (Python molurus) weighing about 35kg was euthanased after several clinical episodes of stomatitis, pneumonia, ophthalmitis and dystocia over a period of four years. The animal had been maintained in a terrarium in a circus truck at an adequate temperature. During shows, however, the snake was considered to be exposed to stressful conditions for several hours at a time at low temperatures and with noise and bright lights. A post-mortem examination indicated ulcerative stomatitis, osteomyelitis, severe pneumonia and numerous granulomata and multifocal necrosis in stomach and spleen. Corynebacterium macginleyi was isolated in pure culture from the ulcerative stomatitis, and mixed with Stenotrophomonas maltophilia from the lungs and spleen. The findings indicated that the snake had died from a septicaemic process caused by C. macginleyi, probably originating from the stomatitis. The role of S. maltophilia as a secondary agent is discussed. The stress of the circus show and poor husbandry may have predisposed the animal to infection and septicaemia. This is the first report of C. macginleyi causing disease in a snake.

Animals↗

EGF receptor transactivation by urokinase receptor stimulus through a mechanism involving Src and matrix metalloproteinases.

Urokinase-type plasminogen activator receptor (uPAR) and epidermal growth factor receptor (EGFR) are ubiquitous receptors involved in the control of a variety of cellular processes frequently found altered in cancer cells. The EGFR has been recently described to play a transduction role of uPAR stimuli, mediating uPA-induced proliferation in highly malignant cells that overexpress uPAR. In the present work, we found for the first time that uPAR stimulation with the amino-terminal fragment (ATF) of urokinase devoid of proteolytic activity transactivates the EGFR in mammary MCF-7 cells through a mechanism involving Src and a metalloproteinase, as indicated by its sensitivity to selected inhibitors. In these cells, which express low levels of uPAR and malignancy, both ATF and EGF stimuli induced an interaction of the EGFR with uPAR and ERK activation. However, EGFR activation by uPAR stimuli mediated cellular invasion rather than proliferation, while EGFR activation by EGF led to a proliferative response. These results revealed a complex modulation of EGFR function toward different cellular responses according to the status of uPAR activity. On the other hand, we also found that MMP-mediated activation of EGFR can occur in an autocrine manner in cells which secrete uPA. All this reveals novel regulatory systems operating through autocrine loops involving uPAR stimuli, Src, MMP and EGFR activation which could mediate fine control of physiological processes as well as contribute to the expression of proliferative and invasive phenotypes of cancerous cells.

Adenocarcinoma↗

[Outpatient laparoscopic cholecystectomy. Experience in 357 patients].

BACKGROUND: Laparoscopic cholecystectomy (LC) is a widely used technique in the treatment of gallstone disease. Outpatient laparoscopic cholecystectomy (OLC) is a cost/effective and safe procedure in selected patients. AIM: A pilot program of OLC was conducted in a Chilean Public Hospital to evaluate the feasibility and results, including and patients' satisfaction using OLC. PATIENTS AND METHODS: Patients were eligible for OLC if they were less than 60 years old, had low anesthestetitc risk (ASA I-II), normal liver function tests and an abdominal ultrasound showing gallstones or gallbladder polyps with a normal common bile duct. RESULTS: We performed OLC in 357 patients aged 36 +/- 10 years, 90% female. Intraoperative complications were observed in 4 (1.1%) patients (uncontrolled bleeding in two and minor biliary tree injuries in two, both requiring conversion to the open technique). Four other patients required conversion due to anatomic reasons (overall conversion rate: 2.2%). Ninety two percent of patients were discharged within 6 hours of the operation. Eight (2.2%) were readmitted because of a mild acute pancreatitis (n=1), biliary leakage (n=1), persistent pain (n=2), vomiting (n=2), and retained stones (n=2). Two (0.6%) patients were re-operated. There was no mortality. Ninety-four percent of 277 patients (77.6%), who answered a Satisfaction Survey, evaluated OLC procedure with a high degree of satisfaction. CONCLUSION: OLC is a safe and feasible procedure in selected gallstone patients. The procedure has good outcomes and a high degree of patient satisfaction. A wide use of OLC should reduce both direct and indirect costs of surgical treatment of gallstone disease.

Adolescent↗

Cyclic AMP inhibits TGFbeta1-induced cell-scattering and invasiveness in murine-transformed keratinocytes.

Mouse-transformed keratinocytes cultured in the presence of transforming growth factor beta1 (TGF-beta1) acquire an array of morphologic and functional properties that give rise to a migratory phenotype that expresses mesenchymal molecular markers. This cellular conversion involves activation of the Ras-ERK pathway, enhancement of urokinase (uPA) and matrix metalloproteinase-9 (MMP-9) expression and induction of invasiveness. In our present work, we demonstrate that cAMP and forskolin are able to prevent the expression of these mesenchymal properties, probably due to blockade of the Ras-ERK pathway. Our results also show that cAMP and forskolin are able to abolish the TGF-beta1-induced reorganization of the actin cytoskeleton that is characteristic of the mesenchymal phenotype and also inhibits the disruption of the E-cadherin cell to cell interactions. The latter responses seem to depend on the activity of protein kinase A, as demonstrated by the activation of the Ras-ERK pathway by specific protein kinase A inhibitors.

Animals↗

Transforming growth factor-beta1 modulates matrix metalloproteinase-9 production through the Ras/MAPK signaling pathway in transformed keratinocytes.

Mouse transformed keratinocytes cultured in the presence of transforming growth factor-beta1 (TGF-beta1) acquire a set of morphological and functional properties giving rise to a more motile phenotype that expresses mesenchymal markers. In this work, we present evidence showing that TGF-beta1 stimulates cellular production of MMP-9 (Gelatinase B), a metalloproteinase that plays an important role in tumoral invasion. Our results demonstrate that TGF-beta1stimulates MMP-9 production and MMP-9 promoter activity in a process that depends of the activation of the Ras-ERK1,2 MAP kinase pathway. The latter was demonstrated by cellular transfection of TGF-beta1-sensitive cells with a RasN17 mutant gene, using PD 098059, a MEK 1,2 inhibitor, and treating cells with anti-sense oligodeoxinucleotides. The enhanced MMP-9 production proved to be an important factor in the acquisition of migratory and invasive properties as shown by the use of a specific inhibitor of MMP-9 (GM6001) that inhibits the TGF-beta1-stimulated invasive and migratory properties of these transformed keratinocytes.

Animals↗