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Biomedical subjects

P Delgado

Publications and source records attributed to P Delgado.

At least 19 recordsLinked to original sources

Plasma d-dimer predicts poor outcome after acute intracerebral hemorrhage.

OBJECTIVE: To investigate if systemic d-dimer activation occurs after acute intracerebral hemorrhage (ICH) and to study its influence on clinical outcome. METHODS: The authors determined plasma baseline d-dimer in 98 consecutive acute (<24 hours) ICH patients. Glasgow Coma Scale and NIH Stroke Scale scores were recorded to assess neurologic status on baseline and follow-up visits (24 hours, 48 hours, 7th day, and 3rd month). They also determined the d-dimer temporal profile at follow-up visits in a subgroup of 21 patients. ICH volume was measured on baseline and follow-up CT scans. Early neurologic deterioration (END) and mortality during the 1st week were recorded. RESULTS: ICH patients showed higher plasma d-dimer level than reference laboratory values at baseline (1,780 vs 360 ng/mL; p = 0.013) and 3 months after ICH onset (1,530 vs 470 ng/mL; p = 0.013). The d-dimer level was related to baseline ICH volume (r = 0.23, p = 0.049) and to the presence of intraventricular (2,370 vs 1,360 ng/mL; p = 0.019) or subarachnoid (4,180 vs 1,520 ng/mL; p = 0.001) extension. Nearly one-fourth of patients presented END, and 20% died as a result of ICH. As predictors of END, the authors identified d-dimer level >1,900 ng/mL (odds ratio [OR] 4.5, 95% CI 1.03 to 20.26, p = 0.045) and systolic blood pressure >182 mm Hg (OR 6.8, 95% CI 1.25 to 36.9, p = 0.026). Moreover, ICH volume >30 mL (OR 19.13, 95% CI 2.06 to 177, p = 0.009) and d-dimer levels >1,900 ng/mL (OR 8.75, 95% CI 1.41 to 54.16, p = 0.020) emerged as independent predictors of mortality. CONCLUSION: Increased plasma d-dimer level following acute intracerebral hemorrhage is associated with early neurologic deterioration and poor outcome.

Acute Disease↗

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↗

[Morbimortality in carotid endarterectomy].

OBJECTIVE: To assess perioperative and long-term morbidity in patients diagnosed of carotid stenosis submitted to our Department for surgical endarterectomy. PATIENTS AND METHODS: A retrospective study of 97 endarterectomies performed by six neurosurgeons in 90 patients treated between January 1995 and December 2003. Ten patients were women. Average mean age was 69 years-old (range 38-86). Seven patients were treated bilaterally. Eighty-four stenosis were greater than 70%. Annual number of interventions per surgeon was 3 (range 0-10). The median follow-up was 121 days, (range 8-2106). RESULTS: Four patients died perioperatively and other 4 ones developed new neurologic deficits. The combined morbidity-mortality rate was 8.9% of the patients and 8.2% of the surgeries. Four patients needed reintervention, because of immediate postoperative new deficit (one) and surgical hematoma (three). Transient peripheral nerve palsy occurred in 8 patients and 21 medical complications were registered. In the long term, 7 patients died (6 because of cancer and 1 because of cardiopathy) and 5 presented neurologic events (3 ipsilateral and 2 in other locations). Last postoperative image control, performed on average after 52 days (0-2832), revealed 7 stenosis of the treated artery. CONCLUSIONS: Carotid endarterectomy can be safely performed in low-volume centers with acceptable results and reasonable morbidity and mortality rates when simple techniques are used. We consider crucial to evaluate self complications and results in order to improve them.

Adult↗

[Efficacy and safety of two vitamin supplement regimens on homocysteine levels in hemodialysis patients. Prospective, randomized clinical trial].

UNLABELLED: High levels of homocysteine (tHcy) are frecuent in MHD patients, and recognized as a risk factor for cardiovascular events. Vitamin supplements have been shown to lower serum Hcys, although optimal dose and efficacy is not well defined. Moreover, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism can modulate its prevalence and response to treatment. OBJECTIVE: To evaluate efficacy and safety of two vitamin supplement regimens on Hcys serum levels over a 12 month period. METHODS: We conducted a prospective, randomised, double-blind trial in 60 stable MHD patients (68 +/- 13 years, 48% male, 50% diabetics). Patients were randomly assigned to one of two treatment regimens: 1) daily renal multivitamin containing folate (FA), vitamin B6 and B12 (5 mg, 10 mg and 0.4 mg respectively) (N = 27); and 2) supraphysiological daily doses (15 mg, 100 mg and 1 mg) (N = 33). These regimens were continued throughout the study period. Hcys levels were compared with a control group from the general population (N = 276) matched for age and gender. MEASUREMENTS: demographic and clinical data, serum levels of Hcys, FA, B6, B12 at baseline and after 1, 3, 6 and 12 months of treatment; MTHFR gene polymorphism (PCRRT). RESULTS: At baseline, global prevalence of hyperhomocysteinemia (tHcy > or = 15 micromol/L) was 100% in patients and 22% en controls. Hcys levels were significantly higher in patients versus controls (32.4 +/- 8.9 vs 12.9 +/- 6.8; P < 0.0001). Both regimens were equally effective in reducing Hcys levels. As a whole, Hcys levels were reduced by 23.6% (P < 0.001) after one month of treatment. The highest reduction was observed at the sixth month (28.3%, 32.4 +/- 8.9 vs 22.7 +/- 6.4, P < 0.001) and remained stable thereafter. However, only 12% of patients normalised their plasma levels after 12 months of therapy. The effect of treatment was not influenced by age, gender, diabetes, body weight or time on MHD. Reduction rate of tHcy levels was related to baseline tHcy level (r = 0.500, P < 0.001) and baseline FA levels (r = -0.332, P = 0.009). The MTHFR polimorfism did not significantly modified the effect of the treatment. No side effects were associated with either regimen. CONCLUSIONS: Hyperhomocysteinemia is common in patients with conventional HD schedules and this is not related to vitamin deficiencies. Vitamin supplements significantly reduce Hcys levels in a sustained but suboptimal way. Supraphysiological doses did not improve the results. Further studies are requiered to demonstrate that this effect is associated with an improval in morbidity and mortality.

Aged↗

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↗

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↗

[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↗

(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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗