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Biomedical subjects

E de Miguel

Publications and source records attributed to E de Miguel.

At least 19 recordsLinked to original sources
PubMed2001

Withdrawing and withholding life support in the intensive care unit: a Spanish prospective multi-centre observational study.

OBJECTIVE: To determine how frequently life support is withheld or withdrawn from adult critically ill patients, and how physicians and patients families agree on the decision regarding the limitation of life support. DESIGN: Prospective multi-centre cohort study. SETTING: Six adult medical-surgical Spanish intensive care units (ICUs). PATIENTS AND PARTICIPANTS: Three thousand four hundred ninety-eight consecutive patients admitted to six ICUs were enrolled. MEASUREMENTS AND RESULTS: Data collected included age, sex, SAPS II score on admission and within 24 h of the decision to limit treatment, length of ICU stay, outcome at ICU discharge, cause and mode of death, time to death after the decision to withhold or withdraw life support, consultation and agreement with patient's family regarding withholding or withdrawal, and the modalities of therapies withdrawn or withheld. Two hundred twenty-six (6.6%) of 3,498 patients had therapy withheld or withdrawn and 221 of them died in the ICU. Age, SAPS II and length of ICU stay were significantly higher in patients dying patients who had therapy withheld or withdrawn than in patients dying despite active treatment. The proposal to withhold or withdraw life support was initiated by physicians in 210 (92.9%) of 226 patients and by the family in the remaining cases. The patient's family was not involved in the decision to withhold or withdraw life support therapy in 64 (28.3%) of 226 cases. Only 21 (9%) patients had expressed their wish to decline life-prolonging therapy prior to ICU admission. CONCLUSIONS: The withholding and withdrawing of treatment was frequent in critically ill patients and was initiated primarily by physicians.

Adult↗
PubMed2000

Emergence of axonal tracts in the developing brain of the turbot (Psetta maxima).

In this study we have investigated the pattern of morphogenesis and axogenesis in the turbot brain during embryonic and early larval stages with immunohistochemistry using an antibody against acetylated tubulin. The first immunoreactive elements were detected at 74 h post-fertilization in fibers running in the medial and lateral longitudinal fascicles. Newly positive axonal bundles are progressively added during development forming rostrocaudally directed tracts. The tract of the postoptic commissure appears at 86 h post-fertilization located rostrally to the medial longitudinal fascicle. Together, the medial longitudinal fascicle and the tract of the postoptic commissure constitute a major longitudinal axonal pathway, which is extended rostrally in embryos of 98 h post-fertilization by the supraoptic tract. In the forebrain, two vertical tracts, the tract of the posterior commissure (appearing around 98 h post-fertilization) and the tract of the anterior commissure (detected at 110 h post-fertilization) project descending axons to the pre-existing axonal longitudinal pathway. These early tracts are connected by four associated commissures (ventral tegmental, postoptic, posterior and anterior commissure). Some groups of labeled cell bodies are identified either as the origin of the embryonic tracts or contributing axons to the axonal pathways. Additionally, a conspicuous cluster of large cells, not clearly associated with any axonal bundle, was observed from 98 h post-fertilization lining the caudal floor of the presumptive hypothalamus. Several hypotheses are proposed to determine the nature of these cells. A comparison of the emergence of the axonal circuitry in turbot and that of other teleosts reveals significant analogies, suggesting that a common pattern underlies the establishment of the embryonic tracts in this vertebrate group. The minor differences observed between different teleost species, associated with the absence of some axonal fascicles, is also considered.

Animals↗
PubMed1999

Distribution of GABA-immunolabeling in the early zebrafish (Danio rerio) brain.

The spatial and temporal pattern of GABA-expression in the brains of zebrafish (Danio rerio) embryos was studied by means of immunohistochemical techniques. GABA is said to exert neurotrophic actions in the early regulation of the differentiation of the central nervous system. In early stages GABAergic cells form distinct clusters throughout the CNS. As development progresses, more GABAergic clusters appear, and a pattern of GABAergic axonal projections is well defined. Although there is a corresponding pattern of distribution and appearance of GABA-expression in the brain of different teleosts, further studies are needed to establish its role during early morphogenesis of the CNS of vertebrates.

Animals↗
PubMed1999

[Hemodynamics and oxygenation in experimental lung lobe transplantation].

INTRODUCTION: Lung transplantation is the only valid treatment for the severe neonatal pulmonary hypoplasia. The objective of this work is to develop and to establish a model of lobar lung transplantation. MATERIAL AND METHODS: Twenty pigs were used. Neonates 2-3 weeks; adults 10-12 weeks. Donors weighed 15 to 20 kg and recipients 5 to 7. In Group A animals were used to assess surgical anatomy and to develop surgical technique and instrumentation's model. The remainder animals (Group B) underwent left lobar lung transplantation. Hemodynamic and oxygenation data were collected before and after six hours of right lung exclusion. RESULTS: All animals tolerated right lung exclusion. There was a significant increase in mean pulmonary artery pressure and a sustained reduction in cardiac output. Oxygenation values were not affected during unilateral lung perfusion. CONCLUSIONS: The neonatal pig has a good tolerance to reduced-size lung transplantation. Lobar lung transplantation could increase substantially the donor's lung pool.

Animals↗
PubMed1998

An NMR-based identification of peptide fragments mimicking the interactions of the cathepsin B propeptide.

Selected fragments of the 62-residue proregion (or residues 1p-62p) of the cysteine protease cathepsin B were synthesized and their interactions with cathepsin B studied by use of proton NMR spectroscopy. Peptide fragments 16p-51p and 26p-51p exhibited differential perturbations of their proton resonances in the presence of cathepsin B. These resonance perturbations were lost for the further truncated 36p-51p fragment, but remained in the 26p-43p and 28p-43p peptide fragments. Residues 23p-26p or TWQ25A in the N-terminal 1p-29p fragment did not show cathepsin B-induced resonance perturbations although the same residues had strongly perturbed proton resonances within the 16p-51p peptide. Both the 1p-29p and 36p-51p fragments lack a common set of hydrophobic residues 30p-35p or F30YNVDI35 from the proregion. The presence of residues F30YNVDI35 appears to confer a conformational preference in peptide fragments 16p-51p, 26p-51p, 28p-43p and 26p-43p, but the same residues induce the aggregation of peptides 16p-36p and 1p-36p. The peptide fragment 26p-43p binds to the active site, as indicated by its inhibition of the catalytic activity of cathepsin B. The cathepsin B prosegment can therefore be reduced into smaller, but functional subunits 28p-43p or 26p-43p that retain specific binding interactions with cathepsin B. These results also suggest that residues F30YNVDI35 may constitute an essential element for the selective inhibition of cathepsin B by the full-length cathepsin B proregion.

Cathepsin B↗
PubMed1998

Arthritis induced by proteoglycan aggrecan G1 domain in BALB/c mice. Evidence for t cell involvement and the immunosuppressive influence of keratan sulfate on recognition of t and b cell epitopes.

Our previous work showed that the proteoglycan aggrecan can induce erosive polyarthritis and spondylitis in BALB/c mice, and that the G1 domain of the proteoglycan aggrecan (G1) is the arthritogenic region. In this study, two T cell epitopes residing on G1 within residues 70-84 (peptide G5) and 150-169 (peptide G9) were identified using synthetic peptides and aggrecan-specific T cell lines. Two G1-specific T cell hybridomas exclusively responded to peptide G5. When the G5-specific T cell line was injected intraperitoneally into BALB/c mice, it induced acute inflammatory arthritis in joints, but only in those that had been injected with the epitope recognized by these T cells. Furthermore, we also demonstrate that the keratan sulfate chain(s) (KS) on G1 possess immunosuppressive properties with respect to T and B cell epitope recognition. T cell lines that recognize both G1 and peptide G5 show an increased response to G1 after KS is removed. Antibodies in hyperimmune sera of mice immunized with G1 show increased epitope recognition (quantitative and qualitative) after KS removal before immunization. These studies reveal that a T cell line specific to an epitope on the G1 domain of aggrecan, also recognizing a corresponding mouse G1 epitope, can induce arthritis by adoptive transfer and homing to the intraarticular epitope, thereby implicating T cells in arthritis development caused by immunity to the G1 domain of aggrecan. Moreover, the presence of KS on G1 can inhibit arthritis development by suppressing T and B cell epitope recognition.

Aggrecans↗
PubMed1998

Induction of arthritis in BALB/c mice by cartilage link protein: involvement of distinct regions recognized by T and B lymphocytes.

Both type II collagen and the proteoglycan aggrecan are capable of inducing an erosive inflammatory polyarthritis in mice. In this study we provide the first demonstration that link protein (LP), purified from bovine cartilage, can produce a persistent, erosive, inflammatory polyarthritis when injected repeatedly intraperitoneally into BALB/c mice. We discovered a single T-cell epitope, located within residues 266 to 290 of bovine LP (NDGAQIAKVGQIFAAWKLLGYDRCD), which is recognized by bovine LP-specific T lymphocytes. We also identified three immunogenic regions in bovine LP that contain epitopes recognized by antibodies in hyperimmunized sera. One of these B-cell regions is found in the most species-variable domain of LP (residues 1 to 36), whereas the other epitopes are located in the most conserved regions (residues 186 to 230 and 286 to 310). The latter two regions contain an AGWLSDGSVQYP motif shared by the G1 globulin domain of aggrecan core protein, versican, neurocan, glial hyaluronan-binding protein, and the hyaluronan receptor CD44. Our data reveal that the induction of arthritis is associated with antibody reactivities to B-cell epitopes located at residues 1 to 19. Together, these observations show that another cartilage protein, LP, like type II collagen and the proteoglycan aggrecan, is capable of inducing an erosive inflammatory arthritis in mice and that the immunity to LP involves recognition of both T- and B-cell epitopes. This immunity may be of importance in the pathogenesis of inflammatory joint diseases, such as juvenile rheumatoid arthritis, in which cellular immunity to LP has been demonstrated.

Amino Acid Sequence↗
PubMed1998

Morphometric and proliferative effects of growth hormone on radiation enteritis in the rat.

UNLABELLED: Radiation enteritis is a common occurrence after radiotherapy in patients with abdominal tumors. Growth hormone may modify the response of the intestinal mucosa to radiation through its effects on the cell cycle or by increasing cell mass. The aim of this study is to determine the effects of growth hormone in the radiation-induced morphoproliferative changes in the intestinal mucosa. MATERIAL AND METHODS: An intestinal mucosal lesion was induced in adult male Wistar rats by means of abdominal irradiation with a lethal dose (LD50) of 1200 cGy. All animals received treatment with either saline or growth hormone for 7 days after irradiation. The animals were sacrificed on day 7. Body weight was determined the morphoproliferative status of the intestinal mucosa was assessed and the disaccharidase activity was measured. RESULTS: Growth hormone reduced body weight loss and increased mucosal length in irradiated rats. Mucosal proliferation was incremented in both irradiated and nonirradiated growth hormone-treated rats. Disaccharidase activity levels were similar to or higher than control values in all treated groups. CONCLUSION: Administration of growth hormone to irradiated rats reduces intestinal injury, probably as a consequence of an earlier recovery of intestinal morphology and functional status.

Animals↗
PubMed1998

Growth hormone reduces bacterial translocation in radiation enteritis in the rat.

BACKGROUND: Radiotherapy may be considered as one of the most effective treatments for digestive tumours. This procedure has major side effects, especially in fast growing tissues like intestinal mucosa. The administration of drugs that reduce or avoid radiation injury of the intestinal mucosa may be clinically advantageous. Growth hormone is a peptide suitable for this purpose by modifying cell proliferation within the intestinal crypt. MATERIAL AND METHOD: Adult male Wistar rats were used in a model of abdominal irradiation. Each irradiated animal received 1200 cGy under anaesthesia and was sacrificed four and seven days later. The animals were treated with either saline or growth hormone (1 mg/kg/day) beginning immediately after the irradiation treatment. On the day of sacrifice, intestinal samples were taken for morphometric measurements and mesenteric lymph nodes for bacterial translocation. RESULTS: Mortality was of 50% approximately and was not affected by growth hormone treatment in irradiated animals. Bacterial translocation increased (p < 0.05) in irradiated animals whereas no significant increase was observed in rats treated with growth hormone. Growth hormone promotes an earlier growth of intestinal villi in irradiated animals (p < 0.05). CONCLUSIONS: Growth hormone promotes the morphologic adaptation of intestinal mucosa after abdominal irradiation, reducing bacterial translocation in rat.

Animals↗
PubMed1996

Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin and vasoactive intestinal peptide on interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha production by whole blood cells from healthy young and old subjects.

In the present study, we have investigated the effect in vitro of gastrin-releasing peptide (GRP, 10(-10) M), neuropeptide Y (NPY, 10(-10) M), somatostatin (10(-10) M) and vasoactive intestinal peptide (VIP, 10(-9) M) on the production of IL-1 beta, IL-6 and TNF alpha by peripheral whole blood cells from healthy young and old people. We have found that GRP, NPY, somatostatin and VIP stimulated the production of IL-1 beta in old subjects, and NPY, somatostatin and VIP in young ones. In addition, the production of IL-6 was enhanced by GRP, NPY and VIP in young and old people. The TNF alpha production was stimulated by NPY and somatostatin in young subjects, and by NPY, somatostatin and VIP in old ones, whereas GRP produced a decrease of TNF alpha in young persons. GRP in old subjects and VIP in young and old subjects stimulated in a great degree the LPS-induced IL-6 production by whole blood cells. On the contrary, GRP and VIP inhibited highly the LPS-induced TNF alpha production in young controls. Our results show that these neuropeptides, when added to whole blood cells at physiological concentrations, are able to stimulate the production of IL-1 beta, IL-6 and TNF alpha in a differential way according to the subject age.

Adult↗
PubMed1996

[Effects of neurotensin on the development of suckling rats with intestinal resection].

Massive intestinal resection produces malabsorption which, in the suckling rat, reduces growth. Our aim was to determine whether the proliferative action of neurotensin, can reduce the negative effects on growth induced by bowel resection. Fifteen days old suckling Wistar rats were used. Twenty rats underwent 90% midgut resection and twelve were used as controls. Half the animals were treated with neurotensin (600 micrograms/kg-day) until sacrifice 30 days later. Body and bone weight were measured and mucosal samples obtained. All resected animals lost body weight and bone weight. Neurotensin treatment reduced femur weight loss. After bowel resection, significant trophic effects were observed at mucosal level (crypt and villous size) but only in the jejunum of resected animals neurotensin treatment had a trophic effect. In conclusion, neurotensin favors intestinal adaptation after resection without improving mid-term growth in the suckling rat.

Adaptation, Physiological↗
PubMed1996

[Histiocytosis X and ankylosing spondylitis. A common pathogenesis?].

Histiocytosis X is considered a group of diseases of unknown origin. Nevertheless, the presence of certain lymphocytes disorders and immunocomplexes has permitted us to think that it is an immunologic disease. The ankylosing spondylitis is also a disease of unknown origin, but like the histiocytosis X, might be of immunologic origin. In both entities, a defect of T-lymphocytes has been demonstrated. We present a patient in whom both diseases are associated, which is not reported before in the medical literature. We think that these disorders may be related by a common immunologic alteration.

Adult↗
PubMed1996

[An experimental model of hepatointestinal transplant in the pig with clinical applications].

A model of experimental hepatointestinal transplant in pigs, with clinical applications is presented. Ten animals received a graft composed by the liver and the full length of the small bowel. Two pigs died during the transplant and in eight the surgical procedure was well tolerated with a good revascularization of the grafts. The coagulation parameters were normal after the transplant and only minor biochemical disturbances were found. The main difficulties of the surgical technique are related with the poor tolerance of the pig to the portal and caval clamping, and the close relationships of the duodenum, pancreas and distal colon, produced by the 360 degrees anti-clockwise bowel rotation around the mesenteric vessels. Clamping the supraceliac aorta during the implant of the graft keeps the animal hemodynamically stable and makes unnecessary the use of the more complicated veno venous shunt.

Animals↗
PubMed1995

Localized right upper lobe edema.

One of the lesser known atypical forms of radiographic presentation of pulmonary edema is the isolated or predominant affection of the upper right lobe in patients with mitral valve insufficiency. As a possible cause of this distribution, it has been established that the regurgitation jet during the ventricular systole may be directed selectively toward the orifice of the right upper lobe vein, locally accentuating the forces responsible for edema formation. There are few cases with these characteristics in the literature reviewed. We present an additional three cases, concluding that localized pulmonary edema secondary to mitral insufficiency should be suspected in the presence of any type of airspace consolidation in the right upper lobe, with or without associated affection of the middle lobe, in patients with a history of mitral valve insufficiency, especially when there are radiologic signs of left heart failure.

Adult↗
PubMed1995

[Biochemical indicators of primary graft dysfunction in experimental orthotopic liver transplantation].

Aiming at investigating biochemical markers of Primary Graft Nonfunction (PNF) in Orthotopic Liver Transplantation (OLT) an experimental work is made on 21 Large-White pigs randomly distributed in three groups of seven, and two additional groups of seven donors each. In Group I the supra and infrahepatic cava, the portal vein and the hepatic artery were clamped. After 30 minutes the caval and portal clamps were released and 30 minutes later the arterial clamp was also removed. In Group II (viable), OLT was performed. The Collins solution was used as preservation fluid, keeping the cold ischemia time under 2 hours. In Group III (Non-Viable), an OLT was carried out 24 hours of cold ischemia with Collins solution. Blood samples are taken in 8 different moments along the procedure to determinate the values of AST, ALT, LDH, FA, Bilirubin, Uric Acid, Cholesterol, Triglycerides, Urea, Creatinine, Glucose, Total Protein, Calcium, Phosphorus, CPK and Aldolase. The last 5 samples were drawn after reperfusion. In the Group III we found, in the samples drawn after reperfusion of the graft, significant increases in 5 of these parameters, AST, ALT LDH, Aldolase and Uric Acid. We consider that these 5 parameters may be of value in the early diagnosis of PNF of the graft, being the AST and ALT the most reliable, with the higher specificity for the same sensitivity.

Alanine Transaminase↗