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Biomedical subjects

P Delgado

Publications and source records attributed to P Delgado.

At least 19 recordsLinked to original sources
PubMed2005

Surgical activity by Spanish Residents in Neurosurgery under the Training Programme in place since 1984 and changes to be implemented under the New Training Programme.

The Spanish National Committee for Neurosurgery has recently approved a new training programme which will shortly replace the former programme, which dates from 1984. The object of this report was to evaluate training in neurosurgery in Spain under the extant programme as perceived by the residents themselves. Assessment of any educational shortcomings might help in designing and evaluating the new one. Secondary objects were to present and discuss the principal changes to be implemented by the new programme.A questionnaire was circulated to the entire population of Spanish neurosurgical residents nation-wide (N = 62) in 2000, and this was repeated using the same group in 2001 and 2002. Residents were to answer questions concerning their experience during the reporting year and the preceding years, the results compiling information for 1996 to 2002. The questionnaire covered 72 surgical procedures listed in ascending order of complexity, with a five-point scale of surgical responsibility for each type. Responses were received from 48 residents. Spanish residents appeared to uniformly fulfil the general requirements of the former programme. The main shortcomings identified were low levels of surgical activity for certain special operations, especially functional and skull base approaches, and the absence of a log book specific to neurosurgery. The new training programme developed by the Spanish National Committee for Neurosurgery has taken these shortcomings into consideration and has introduced major changes in order to ensure that training will be improved on an ongoing basis.

Attitude of Health Personnel↗
PubMed2004

Patterns of dermal exposure to hazardous substances in European union workplaces.

Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other types) in five countries in Europe. In order to optimize data collection and to develop a representative picture of dermal exposure, scenarios (tasks made up of a series of activities) were grouped together into dermal exposure operation units (DEOs). The allocation of scenarios to relevant DEOs was achieved on the basis of similarities of exposure routes, tasks and professional judgement. Sampling and quantification procedures were based on the approaches recommended by the OECD protocol. The laboratories involved in the analysis of the samples participated in quality assurance programmes. This exercise resulted in 419 body measurements and 437 measurements on hands expressed in terms of formulation (product) in use. Exposures for a given scenario varied by several orders of magnitude. The extent and patterns of exposure were found to be dependent on various exposure determinants, including inter- and intra-scenario variations. Hands were found to be the most contaminated parts of the body. Exposure patterns for liquid and solid contaminants were different. On the basis of the analysis of the data presented here, the averaged results (median and 95th percentile) for a given DEO unit should not be used as a representative measure of dermal exposure for all scenarios within that DEO without taking the exposure determinants into account. However, the data could be used to develop an exposure matrix (indicative exposure distributions) for different types of scenario and workplace, using determinants of exposure and a Bayesian approach to integrating expert opinion.

European Union↗
PubMed2003

Transvascular ethanol embolization: first option for the management of symptomatic nonfunctioning renal allografts left in situ.

BACKGROUND: Transplantectomy has been the conventional therapy for symptomatic failed grafts left in situ (FGLIS). Graft intolerance syndrome (GIS) is a common complication after withdrawal of immunosuppression. Our group first reported transvascular ethanol embolization (TVEE) as an alternative for the management of GIS. OBJECTIVE: Our goal was to evaluate the efficacy and safety of TVEE in a large series of patients with symptomatic FGLIS. PATIENTS AND METHODS: From January 1989 to December 2001, 944 patients received cadaveric renal transplants in our center. During this period, 59 patients with FGLIS underwent TVEE (50+/-7 years, 71% men, 15% diabetics). TVEE was performed using a transfemoral approach. A balloon occlusion catheter was inflated in the renal artery before ethanol injection (10-12 cc). The position of coils completed the procedure. No systematic prophylactic antibiotic or steroid treatment was administered. RESULTS: The main indication for TVEE was GIS (51 patients, 86%). TVEE was initially successful in 39 patients (66%). A second TVEE, which was performed in 9 of 20 unresolved cases, was successful in six. After a second TVEE, the efficacy increased to 76%. The most frequent complication was postembolization syndrome (62%), which was manifested by fever, local pain, and inflammation that generally resolved in 48-72 hours. No major complications or deaths were observed. One of four patients underwent transplantectomy. Histologic examination of the removed graft showed renal tissue necrosis (10 cases) and pyonephrosis (4 cases). CONCLUSIONS: TVEE, a safe and effective technique, may be considered as the treatment of choice for symptomatic FGLIS.

Balloon Occlusion↗
PubMed2003

[First steps in neuronavigation].

INTRODUCTION: We try to evaluate the introduction of a neuronavigation system widely used in a neurosurgical department. MATERIAL AND METHODS: We analyze the surgical procedures performed since the introduction of a neuronavigator in our hospital, the advantages and the problems related with its use. RESULTS: From 21/12/00 to 31/12/01, 64 cranial and 5 spinal procedures were performed in our centre with the aid of the BrainLAB neuronavigation system. They were 19.37% of the elective surgeries: 45.7% of cranial and 2.8% of spinal procedures. The accuracy of registration was 1.6 mm; the number of trials for registration was 2.8 on average, although in 3 cases it was not possible; there were disarrangements during 9 surgical procedures (two of them after the lesions were reached). Magnetic resonance imaging (MRI) was used in 54 instances, computerized tomography (CT) in 5, fluoroscopy (Rx) in 1, CT plus MRI in 8, CT plus Rx in 1. Since Z-Touch localization system and software was available, it was used exclusively, disregarding the use of external fiducials. DISCUSSION AND CONCLUSIONS: In our experience, neuronavigation needs extra time, but it helps in the election of the best position for the surgical approach, reduces the time required for scalp incision and craniotomy planning, and is useful for the opening of the dura and the corticectomy. As the operation proceeds, we found it less truhstworthy and necessary. The Z-touch system frees the imaging from the surgery. Its use in spinal operation is scarce and with limited results in our practice. We found the neuronavigation useful, and we employ it on a regular basis in every cranial procedure whenever it is possible.

Humans↗
PubMed2001

(AC)n dinucleotide repeat polymorphism in 5' beta-globin gene in native and Mestizo Mexican populations.

Repeated sequences are dispersed along the human genome. These sequences are useful as markers in diagnosis of inherited diseases, in forensic medicine, and in tracking the origin and evolution of human populations. The (AC)n repeated element is the most frequent in the human genome. In this paper, the (AC)n repeated element located in the 5' flanking region of the beta-globin gene was studied by single-strand conformation polymorphism (SSCP). Four ethnic Mexican groups (Mixteca, Nahua, Otomí, Purépecha) and a Mestizo population were analyzed. We observed three alleles, A [(AC)16, B [(AC)14], and C [(AC)18], with a frequency of between 68.2% and 86.9%, 13.1% and 18.2%, and 6.7% and 13.7%, respectively. Allele C was present only in Purépecha and Mestizo groups. The absence of this allele in the other ethnic groups studied suggests that there is low genetic admixture of Purépecha and that this is a relatively isolated population. However, it could be that the C allele occurs in low frequencies in the other groups as a result of small sample sizes. The (AC)n repeat polymorphism in the beta-globin gene has not been previously studied in Amerindian populations.

Alleles↗
PubMed2000

CD3delta couples T-cell receptor signalling to ERK activation and thymocyte positive selection.

Thymocytes from mice lacking the CD3delta chain of the T-cell receptor (TCR), unlike those of other CD3-deficient mice, progress from a CD4- CD8- double-negative to a CD4+ CD8+ double-positive stage. However, CD3delta-/- double-positive cells fail to undergo positive selection, by which double-positive cells differentiate into more mature thymocytes. Positive selection is also impaired in mice expressing inactive components of the Ras/mitogen activated protein (MAP) kinase signalling pathway. Here we show that CD3delta-/- thymocytes are defective in the induction of extracellular signal-regulated protein kinase (ERK) MAP kinases upon TCR engagement, whereas activation of other MAP kinases is unaffected. The requirement for CD3delta maps to its extracellular or transmembrane domains, or both, as expression of a tail-less CD3delta rescues both ERK activation and positive selection in CD3delta-/- mice. Furthermore, the defect correlates with severely impaired tyrosine phosphorylation of the linker protein LAT, and of the CD3zeta chain that is localized to membrane lipid rafts upon TCR engagement. Our data indicate that the blockade of positive selection of CD3delta-/- thymocytes may derive from defective tyrosine phosphorylation of CD3zeta in lipid rafts, resulting in impaired activation of the LAT/Ras/ERK pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Rho regulates T cell receptor ITAM-induced lymphocyte spreading in an integrin-independent manner.

T cell receptor (TCR) engagement increases integrin-mediated adhesion to APC, resulting in the stabilization of the T cell : APC interaction and the close apposition of the two cell membranes. Here we show that engagement of either the TCR or CD3 chimeras with immobilized antibodies causes the rapid spreading of T cells in an integrin-independent fashion. This effect concurs with the polymerization of the actin cytoskeleton and is dependent on the integrity of the immunoreceptor tyrosine-based activation motifs of the CD3 subunits. Expression of a dominant negative mutant of RhoA, as well as the Rho-specific inhibitor C3 toxin, abolished TCR-induced spreading. In contrast, constitutively active or dominant negative forms of Rac and Cdc42 did not affect cell spreading. We conclude that signals emanating from the TCR can directly induce T cell spreading, independently of integrins, and via a Rho-dependent reorganization of the actin cytoskeleton.

Actins↗
PubMed2000

Sexual side effects of antidepressant drugs.

Sexual functioning often suffers during depression, although depressed people continue to value sex. Many popular antidepressants further impair sexual functioning, with highly serotonergic agents affecting orgasm and libido prominently. This paper addresses clinical assessment of sexual side effects from antidepressant drugs and reviews treatment strategies, including purported antidotes. We pay particular attention to sildenafil, on which there are impressive data and ongoing controlled studies.

Antidepressive Agents↗
PubMed2000

Mirtazapine substitution in SSRI-induced sexual dysfunction.

BACKGROUND: Sexual side effects are a common and bothersome reaction to selective serotonin reuptake inhibitors (SSRIs), frequently leading to cessation of treatment. Mirtazapine, an alpha2-adrenoceptor and serotonin-2/3 receptor antagonist, appears to cause few sexual problems. METHOD: Nineteen patients (12 women and 7 men), with SSRI-induced sexual dysfunction who were in remission from major depressive disorder (total Hamilton Rating Scale for Depression [HAM-D] score < or = 10), were switched to open-label mirtazapine for up to 6 weeks. Mirtazapine was titrated from 7.5 mg to 45 mg daily, as tolerated. Sexual functioning was measured weekly with the Arizona Sexual Experiences Scale (ASEX), and depression was measured weekly with the HAM-D. RESULTS: Eleven patients (58%) had a return of normal sexual functioning (mean +/- SD ASEX score = 12+/-3), and another 2 (11%) reported significant improvement in sexual functioning (mean ASEX score reduced from 24+/-1 to 20+/-0). All nineteen patients maintained their antidepressant response (HAM-D score after 6 weeks of mirtazapine = 6+/-3). The most commonly reported side effects (using moderate/severe rating on a symptom checklist) were initial sedation (N = 3), irritability (N = 6), and muscle soreness and stiffness (N = 3). Weight gain of 10 to 20 lb (4.5-9 kg) was seen in 3 patients (2 women and 1 man). CONCLUSION: Mirtazapine is an effective antidepressant for many patients experiencing SSRI-induced sexual dysfunction.

Adrenergic alpha-Antagonists↗
PubMed2000

Immediate and delayed stimulus repetitions evoke different ERPs in a serial-probe recognition task.

In this study we examined whether event-related potentials (ERPs) associated with stimulus repetition and recognition in a serial-probe recognition task were comparable to ERPs in other tasks that are more typically used to investigate old/new ERP effects. The experiment consisted of 320 trials in which a recognition probe followed a four-item memory set; 160 trials consisted of images depicting common objects that were easy to label (EL task), and 160 trials consisted of images depicting abstract patterns that were difficult to label (DL task). Nineteen participants indicated whether a probe that followed each memory set was or was not presented in the memory set. Half of the probes matched, and half did not match, an item in the preceding memory set. ERPs appeared to reflect two processes--one that differentiated between recently presented stimuli and other stimuli and another that distinguished between repeated stimuli and new stimuli. ERPs to recent probes were more positive than ERPs to other probes in the EL and DL tasks. ERPs to match (old) probes were more positive than ERPs to nonmatch (new) probes only in the EL task.

Adult↗
PubMed1999

Novel esters and amides of nonsteroidal antiinflammatory carboxylic acids as antioxidants and antiproliferative agents.

A series of phenolic antioxidant ester and amide derivatives of the nonsteroidal antiinflammatory drug naproxen was designed to have both antiinflammatory and cytoprotective activity. Compounds were evaluated in vitro both for antioxidant activity, as assessed indirectly by thiobarbituric acid reactive substance (TBARS) formation in a membrane lipid peroxidation assay, and for antiproliferative activity, as indexed by the inhibition of DNA synthesis in cultured human vascular endothelial cells. Compounds of this series exhibited potent antioxidant activity, with IC50 values (1.6-11.63 microM) 2-6-fold lower than that of Trolox (6-hydroxy-2,5, 7,8-tetramethylchroman-2-carboxylic acid) and 400-1300-fold lower than that of vitamin E. Structural modifications of the ester or amide substructure (5a and 6a) did not affect antioxidant activity, but methylation of the 6-hydroxy substituent resulted in compound 6f which was devoid of antioxidant activity. Although indistinguishable in antioxidant activity, the amide derivatives tended to be more potent as antiproliferative agents than the corresponding esters. The IC50's for the amide derivatives (3, 5a-e, 8) ranged from 2 to 7 microM, while the IC50's for the structurally related esters (1, 2a-c, 6a-e) ranged from 9 to 22 microM. Moreover, studies with compound 6a indicate that the observed inhibition of DNA synthesis is reversible, suggesting that the antiproliferative activity is due to a cytostatic rather than cytotoxic activity of the compounds. Thus, the antioxidant-naproxen derivatives represent a novel series of agents that both protect against free-radical damage and possess cytostatic activity in vascular endothelial cells. Studies are in progress to assess the utility of these compounds as potential components of an ocular irrigating solution.

Amides↗
PubMed1999

Antidepressants and the brain.

The pathophysiology and effects of antidepressants in the brain are still poorly understood. While it is generally accepted that increasing the levels of monoamine in the brain is an effective way to alleviate depression, the precise neurobiological mechanisms are unclear. The evidence that monoamine function is impaired in individuals with depression is largely indirect. However, the neurotransmitter depletion model allows a more direct investigation of the role of the monoamines. In this model, tryptophan depletion is used to lower levels of serotonin and alpha-methylparatyrosine is used to induce catecholamine depletion in the brain. Studies have shown that such depletion transiently reverses antidepressant responses in the majority of patients, the response being dependent on the type of antidepressant used. However, depletion in unmedicated patients with depression did not worsen the depressive symptoms, neither did it cause depression in healthy subjects with no history of mental illness. The cause(s) of depression therefore appears to be more complex than simply a reduction in levels of monoamine or diminished function in these systems. The pathophysiology of depression may relate to dysfunction in brain areas modulated by monoamine systems. Antidepressant drugs may mediate their effects by causing adaptive changes in neurones localised in these brain areas.

Animals↗
PubMed1999

[ Magnetic resonance imaging in the early diagnosis of bone marrow necrosis].

Bone marrow necrosis (BMN) is a rare entity characterised by fever and bone pain, accompanied by hypercalcemia and increased LDH. Amorphous eosinophilic material is present in the bone marrow aspirate, with isolated cells in different degrees of necrobiosis. These are frequently post-mortem findings, appearing in up to 19.8% of all autopsies, mostly after haematological malignancies with proliferative features (acute leukaemia, lymphoma). In general terms, BMN is regarded as a poor prognosis sign. Bone gammography with Tc has been included among the diagnostic procedures, in an attempt to carry out an early detection of BMN and to determine its spread. Magnetic resonance imaging (MRI) has recently been regarded useful to evaluate bone marrow involvement in this condition. A 53 year-old woman is presented here who, two and a half years after being diagnosed of mantle cell lymphoma, and having a relapse on her neck lymph nodes, presented severe bone pain showing no radiological evidence of osseous involvement. MRI showed ample spongy marrow involvement of her lower spine, sacrum and pelvic bones. Both femoral heads were preserved, hypointense images being observed in T1, whereas subcortical, hyperintense ones appeared in T2. Bone marrow aspirate showed poor cellularity, with different degrees of necrobiosis on a stippled background. The picture was interpreted as BMN secondary to non-Hodgkin's lymphoma.

Bone Marrow↗
PubMed1999

High population differentiation and genetic variation in the endangered Mexican pine Pinus Rzedowskii (Pinaceae).

Pinus rzedowskii is an endangered pine species from Michoacán (central México), which has been previously reported from only three localities. Classified within the subgenus Strobus, it exhibits intermediate morphological characters between subgenera Strobus and Pinus. We analyzed genetic aspects that could shed light on the evolution and conservation of this species. The genetic structure of nine populations was examined using 14 isozyme loci. Pinus rzedowskii has a relatively high level of genetic variation with 46.8% of the loci assayed being polymorphic, a total of 35 alleles, and a mean heterozygosity per population of 0.219. We calculated Wright's F(ST) statistic to estimate gene flow indirectly and to evaluate whether or not there was genetic structuring among populations. We found a marked differentiation among populations (F(ST) = 0.175) and significant inbreeding (F(IS) = 0.247). No pattern of isolation by distance was found. We also constructed a dendrogram based on a genetic distance matrix to obtain an overview of the possible historical relationships among populations. Finally, we found a convex relationship between the genetic distance among populations and the number of ancestral lineages, suggesting that demographically this species has not been at risk recently. Although endangered, with small and fragmented populations, P. rzedowskii shows higher levels of genetic variation than other conifer species with larger populations or similar conservation status.

Journal Article↗
PubMed1998

CD26 expression and dipeptidyl peptidase IV activity in an aggressive hepatosplenic T-cell lymphoma.

The transmembrane serine aminopeptidase dipeptidyl peptidase IV (DPP IV) (also known as CD26) participates in several immunological functions and has a binding affinity for several molecules, including collagen, which may be an integral mechanism for T cells to traverse endothelial barriers. Since CD26 is phenotypically expressed in certain T-cell malignancies, this study utilized a novel four-color cytofluorographic procedure to measure DPP IV enzymatic activity concurrently with the expression of other surface markers in an aggressive hepatosplenic T-cell lymphoma. Immunophenotypic analysis by flow cytometry revealed the tumor to be CD2+, CD3+, CD5-, CD7+, TcR-gamma/delta+, CD4-, CD8+/-, CD56+, and CD11c+. The CD26 molecule was also expressed, and DPP IV activity was present, with the maximal activity detectable after 10 min of incubation. These results represent the initial description of enzymatically active CD26 in a T-cell malignancy, and raise the possibility that this molecule may be a participant in the pathogenetic mechanisms utilized by the neoplastic cells.

Adolescent↗
PubMed1998

Structural analysis of inhibitor binding to human carbonic anhydrase II.

X-ray crystal structures of carbonic anhydrase II (CAII) complexed with sulfonamide inhibitors illuminate the structural determinants of high affinity binding in the nanomolar regime. The primary binding interaction is the coordination of a primary sulfonamide group to the active site zinc ion. Secondary interactions fine-tune tight binding in regions of the active site cavity >5 A away from zinc, and this work highlights three such features: (1) advantageous conformational restraints of a bicyclic thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison with a monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal substituents attached to a secondary sulfonamide group targeted to interact with hydrophobic patches defined by Phe131, Leu198, and Pro202; and (3) optimal stereochemistry and configuration at the C-4 position of bicyclic thienothiazene-6-sulfonamides; the C-4 substituent can interact with His64, the catalytic proton shuttle. Structure-activity relationships rationalize affinity trends observed during the development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for the treatment of glaucoma.

Binding Sites↗