Analysis of the quality of clinical practice guidelines on established ischemic stroke.
Int J Technol Assess Health Care. 2008;24(3):333-41
Authors: Navarro Puerto MA, Ibarluzea IG, Ruiz OG, Alvarez FM, Herreros RG, Pintiado RE, Dominguez AR, LeÃ³n IM
OBJECTIVES: To catalogue and comparatively assess the quality of Clinical Practice Guidelines (CPG) for ischemic stroke taking into account format and development methodology. METHODS: We performed a comprehensive, systematic bibliographic search of CPGs addressing the management of ischemic stroke. We designed a sensitive strategy, using methodological filters in the following databases: Medline, IME and Lilacs, National Guidelines Clearinghouse, National electronic Library for Health, NICE, Guidelines International Network (GIN), Canadian Medical Association Infobase, development groups such as Scottish Intercollegiate Guidelines Network (SIGN), New Zealand Guidelines Group (NZGG), Agency for Healthcare Research and Quality (AHRQ), Ministry of Health Singapore, Institute for Clinical Systems Improvement (ICSI); and scientific societies: American Heart Association, American Medical Association, Royal College of Physicians London. We included all CPGs published in English, French, Italian, Portuguese, or Spanish from 1999 to 2005 and excluded those CPGs whose scope was primary prevention and rehabilitation from ischemic stroke. Four researchers independently assessed the structure and methodologies followed in drafting the CPGs using the Changing Professional Practice (CPP) and Appraisal of Guidelines Research & Evaluation (AGREE) instruments. RESULTS: We retrieved 117 documents; following application of exclusion criteria, twenty-seven CPGs were appraised. With regard to methodological quality (using the AGREE instrument), the domains that scored highest were "Scope and purpose" and "Clarity and presentation." The lowest scoring domains were "Stakeholder involvement," "Rigor of development," and "Applicability." Most guidelines received an overall score of "would not recommend" (77.8 percent). Finally, based on the CPP instrument, most of the CPGs evaluated were aimed at secondary care and did not provide updating procedures. CONCLUSIONS: The overall quality of the CPGs published for ischemic stroke management did not have minimum methodological quality. Quality improvement has been observed in more recent CPGs and may be due to the publication of new tools such as the AGREE or CPP instruments, as well as international initiatives for CPG improvement.
PMID: 18601802 [PubMed - indexed for MEDLINE]
Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic.
Curr Opin Drug Discov Devel. 2008 Jul;11(4):533-43
Authors: Medina M, Castro A
It is just over a quarter of a century since the original identification and characterization of glycogen synthase kinase-3 (GSK-3), a major protein kinase that is involved in the regulation of glucose metabolism. GSK-3 modulates the function of a diverse series of proteins, as well as being associated with a wide variety of human disorders, including neurodegenerative diseases, stroke, bipolar disorder, diabetes and cancer. Not surprisingly, GSK-3 has attracted significant attention as a therapeutic target and as a means to understand the molecular basis of these disorders. Small-molecule GSK-3 inhibitors have now started to reach clinical development for the treatment of various disorders.
PMID: 18600569 [PubMed - indexed for MEDLINE]
Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing.
Am J Hypertens. 2008 Aug;21(8):948-54
Authors: Hermida RC, Ayala DE, MojÃ³n A, FernÃ¡ndez JR
BACKGROUND: Previous studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium-channel blockers (CCBs), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the administration-time dependent antihypertensive efficacy of the slow-release, once-a-day nifedipine gastrointestinal-therapeutic-system (GITS) formulation. METHODS: We studied 180 untreated hypertensives (86 men and 94 women), 52.5 +/- 10.7 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment. RESULTS: The BP reduction after treatment was significantly larger with bedtime dosing mainly during night time sleep (P < 0.012). The number of patients with controlled ambulatory BP after treatment was greater with bedtime than morning treatment (P = 0.016). The baseline prevalence of nondipping was unaltered after ingestion of nifedipine on awakening, but reduced from 51 to 35% after bedtime dosing (P = 0.025). The morning surge of BP, a risk factor for stroke, was significantly reduced (P < 0.001) only after bedtime administration of nifedipine. Bedtime in comparison to awakening-time ingestion of nifedipine was also associated with a reduction in the incidence of edema from 13 to 1% (P < 0.001). CONCLUSIONS: The increased efficacy on ambulatory BP as well as the significantly reduced prevalence of edema after bedtime as compared to morning ingestion of nifedipine should be taken into account when prescribing this medication to patients with essential hypertension.
PMID: 18600215 [PubMed - indexed for MEDLINE]
Genetics of stroke: a review of recent advances.
Expert Rev Mol Diagn. 2008 Jul;8(4):495-513
Authors: Domingues-Montanari S, Mendioroz M, del Rio-Espinola A, FernÃ¡ndez-Cadenas I, Montaner J
Stroke is a multifactorial disease responsible for nearly 10% of deaths each year in industrialized countries. While some monogenic forms of stroke have been described, the vast majority result from the common polygenic form of the disease. Progress in molecular genetics has allowed the identification, through genome-wide linkage analysis, of various candidate genes, including the genes encoding PDE4D and ALOX5AP. Since then, genetic research has been extensively performed from single candidate genes to whole-genome scan studies, in parallel with the development of high-throughput technologies in molecular diagnostics. Additionally, the safety and efficacy of tissue plasminogen activator, the only approved therapy for the acute phase of stroke, is modulated by genetic background associated with the occurrence of hemorrhagic transformations and with the revascularization of the cerebral arteries. In the near future, understanding the contribution of stroke genetic factors will lead to improvements in prevention and treatments for neurovascular diseases.
PMID: 18598230 [PubMed - indexed for MEDLINE]
Bispectral index monitoring for early detection of brain death.
Transplant Proc. 2008 Jun;40(5):1279-81
Authors: Misis M, Raxach JG, Molto HP, Vega SM, Rico PS
OBJECTIVE: We sought to determine the utility of the bispectral index (BIS) as a tool for clinical evaluation of the moment of brain death (BD). MATERIALS AND METHODS: During a period of 12 months, 54 BDs were registered in our unit, of which 28 were included in the organ donation protocol; 24 fulfilled the requirements of our retrospective observational study. Continuous BIS monitoring was performed using an XP BIS monitor and BIS Quatro sensor evaluating the BIS and the suppression ratio (SR). In almost all cases, sonographic monitoring with transcranial Doppler ultrasound (TCD) was performed every 8 to 12 hours until the diagnosis of BD. RESULTS: We detected a gradual decrease in BIS and increase in SR when the patients underwent clinical progression to BD. At the moment of BD diagnosis, all cases showed BIS 0 and SR 100. In 9 cases the follow-up TCD showed a BD pattern, moments before a BIS 0 and SR 100 appeared. In 18 cases, at the moment of BIS 0/SR 100, TCD showed BD. In all 24 cases, BD diagnosis was confirmed by means of neurological examination and electroencephalogram (EEG). CONCLUSIONS: BIS monitoring is a continuous, simple method that is easy to interpret. It can help in clinical evolution and the decision of the BD moment. In our series, cerebral circulatory cessation (TCD) preceded BIS 0 and SR 100 values. The BIS prematurely detected the start of cerebral circulatory cessation, alerting us of BD.
PMID: 18589087 [PubMed - indexed for MEDLINE]
Cardiac dysfunction during liver transplantation: incidence and preoperative predictors.
Transplantation. 2008 Jun 27;85(12):1766-72
Authors: Ripoll C, Catalina MV, Yotti R, Olmedilla L, PÃ©rez-PeÃ±a J, Lo Iacono O, RincÃ³n D, GarcÃa-FernÃ¡ndez MA, Bermejo J, BaÃ±ares R
BACKGROUND: The aim was to investigate the cardiac response during liver transplantation (LT) and analyze its relationship with clinical factors, echocardiographic, and hemodynamic findings. METHODS: All patients undergoing LT for cirrhosis from 1998 to 2004 were included. Clinical data, comprehensive echocardiography, hepatic, and right heart hemodynamic measurements were analyzed. During LT patients underwent continuous right-heart pressure monitorization. Measurements 10 min after reperfusion were compared with baseline values. Abnormal cardiac response was defined as a decrease in left ventricular stroke work index despite a rise in pulmonary wedge capillary pressure. Predictors of abnormal cardiac response were investigated using logistic regression. RESULTS: Data were available from 209 patients (mean age 52 (9) yrs; Child A 27; B 93; C 89) with a mean model for end-stage liver disease score 16.3 (4.7). Abnormal cardiac response was observed in 47 (22.5%) patients after reperfusion. Patients who developed this response had hyponatremia, lower central venous pressure, lower pulmonary artery pressure, and lower pulmonary wedged capillary pressure. Abnormal cardiac response was related to a longer postoperative intubation time. CONCLUSION: Abnormal cardiac response is observed during LT and may be a manifestation of occult cirrhotic cardiomyopathy. This finding is underestimated with usual diagnostic tools and could be related to indirect signs of circulatory dysfunction of advanced liver disease.
PMID: 18580469 [PubMed - indexed for MEDLINE]
Calculation of prevalence estimates through differential equations: application to stroke-related disability.
Authors: Mar J, Sainz-Ezkerra M, Moler-Cuiral JA
BACKGROUND: Neurological diseases now make up 6.3% of the global burden of disease mainly because they cause disability. To assess disability, prevalence estimates are needed. The objective of this study is to apply a method based on differential equations to calculate the prevalence of stroke-related disability. METHODS: On the basis of a flow diagram, a set of differential equations for each age group was constructed. The linear system was solved analytically and numerically. The parameters of the system were obtained from the literature. The model was validated and calibrated by comparison with previous results. RESULTS: The stroke prevalence rate per 100,000 men was 828, and the rate for stroke-related disability was 331. The rates steadily rose with age, but the group between the ages of 65 and 74 years had the highest total number of individuals. DISCUSSION: Differential equations are useful to represent the natural history of neurological diseases and to make possible the calculation of the prevalence for the various states of disability. In our experience, when compared with the results obtained by Markov models, the benefit of the continuous use of time outweighs the mathematical requirements of our model.
PMID: 18560244 [PubMed - indexed for MEDLINE]
Influence of antiplatelet pre-treatment on the risk of symptomatic intracranial haemorrhage after intravenous thrombolysis.
Cerebrovasc Dis. 2008;26(2):126-33
Authors: Bravo Y, MartÃ-FÃ bregas J, Cocho D, RodrÃguez-YÃ¡Ã±ez M, Castellanos M, de la Ossa NP, Roquer J, Obach V, Maestre J, MartÃ-Vilalta JL
BACKGROUND: The influence of antiplatelet agents (AP) in the development of a symptomatic intracranial haemorrhage (SICH) after intravenous rt-PA is not well known. We assessed the hypothesis that pre-treatment with AP may increase that risk. METHODS: We studied data from consecutive patients with ischaemic stroke treated with intravenous rt-PA within the first 3 h after symptom onset. We recorded the antecedent of any AP therapy previous to thrombolysis. A follow-up CT was performed routinely 24-36 h after the infusion of rt-PA. Intracranial bleeding was categorized according to the criteria of the European Cooperative Acute Stroke Study II (ECASS II) into haemorrhagic infarction type 1 and 2 and parenchymal haemorrhage type 1 and 2. SICH was diagnosed if it was of the parenchymal haemorrhage type, occurred within the first 36 h and was associated with neurological deterioration. RESULTS: Of a total of 605 patients, 137 (22.6%) were pre-treated with AP, most of them (n = 106) with aspirin. Any type of intracranial haemorrhage was observed in 119 patients (19.7%), without differences between the AP (18.4%) and the non-AP (20.2%) groups. Parenchymal haemorrhage was observed in 41 patients (8.5%) and SICH in 26 (4.3%). There was a non-significant rise in the frequency of SICH in the AP group compared with the non-AP group (6.6 vs. 3.6% p = 0.10). CONCLUSIONS: Pre-treatment with AP non-significantly increases the risk of SICH and therefore this antecedent should not be a contraindication for intravenous thrombolysis.
PMID: 18560215 [PubMed - indexed for MEDLINE]
Risk factors for dementia of Alzheimer type and aging-associated cognitive decline in a Spanish population based sample, and in brains with pathology confirmed Alzheimer's disease.
J Alzheimers Dis. 2008 Jun;14(2):179-91
Authors: Ampuero I, Ros R, Royuela A, Abraira V, del Ser T, GarcÃa-Ribas G, GarcÃa de YÃ©benes J
We investigated the environmental and genetic factors for Alzheimer's disease (AD) in Spain and performed a door to door study of a cohort of more than 500 subjects, over 70 years old, from LeganÃ©s, a suburban area near Madrid. The cohort was followed for 6 years by neurologists and other health workers and was divided in three groups: normal controls, subjects with aging-associated cognitive decline (AACD) and probable AD or dementia of Alzheimer's type (DAT). Biological variables and polymorphisms of different genes, important in neurodegeneration or reported to be associated with AD, were investigated as putative risk modifiers. These polymorphisms have also been analyzed in 94 brains, 39 from patients with pathologically confirmed AD and 55 controls. The statistical investigation included the evaluation of different individual risks and a multinomial logistic regression analysis to detect predictive factors. The risk of AACD and AD increased with age, feminine gender and history of stroke and decreased with education. The allele ApoE4 increased the risk of AD but not of AACD. When the impact of ApoE4 was added to the model, the effect of education and stroke disappeared as risk modifiers.
PMID: 18560129 [PubMed - indexed for MEDLINE]
Prognostic significance of blood pressure variability after thrombolysis in acute stroke.
Neurology. 2008 Aug 19;71(8):552-8
Authors: Delgado-Mederos R, Ribo M, Rovira A, Rubiera M, Munuera J, Santamarina E, Delgado P, Maisterra O, Alvarez-Sabin J, Molina CA
OBJECTIVE: To evaluate the impact of early blood pressure (BP) changes on diffusion-weighted imaging (DWI) lesion evolution and clinical outcome in patients with stroke treated with IV tissue plasminogen activator (tPA). METHODS: We prospectively evaluated 80 patients with stroke with a documented middle cerebral artery occlusion treated with IV tPA. Multiple repeated systolic (SBP) and diastolic (DBP) BP measurements were obtained during 24 hours after admission. All patients underwent DWI, perfusion-weighted imaging, and magnetic resonance angiography before and 36-48 hours after thrombolysis. Recanalization was assessed on transcranial Doppler at 6 hours of stroke onset. NIH Stroke Scale scores were recorded at baseline and 24 hours. Modified Rankin Scale was used to assess 3-month outcome. RESULTS: Recanalization occurred in 44 (55%) patients. BP variability, estimated as the SD of the mean, was associated with DWI lesion growth (r = 0.46, p = 0.0003 for SBP and r = 0.26, p = 0.02 for DBP), early clinical course (p = 0.06 for SBP and p = 0.01 for DBP), and 3-month outcome (p = 0.002 for SBP and 0.07 for DBP). However, the prognostic significance of BP changes differed depending on the presence of recanalization. SBP variability emerged as an independent predictor of DWI lesion growth (beta: 6.9; 95% CI, 3.2 to 10.7, p = 0.003) and worse stroke outcome (OR: 11; 95% CI: 2.2 to 56.1; p = 0.004) in patients without recanalization, but not in recanalized patients. CONCLUSION: Blood pressure variability is associated with greater diffusion-weighted imaging lesion growth and worse clinical course in patients with stroke treated with IV tissue plasminogen activator. However, its impact varies depending on the occurrence of early recanalization after thrombolysis.
PMID: 18550860 [PubMed - indexed for MEDLINE]
The Spanish National Transplant Organization (ONT) tumor registry.
Transplantation. 2008 Apr 27;85(8 Suppl):S61-3
Authors: Garrido G, Matesanz R
BACKGROUND: It is important to know the actual risk of tumor transmission from donor to recipient and the serious consequences for the recipient. Tumor registries can help us to improve our knowledge about this problem. METHODS: We have studied all the donors registered in the Spanish National Transplant Organization from January 1, 1990, to December 31, 2006, and especially the donors with a malignant tumor as well as the recipients who have received an organ from these donors. RESULTS: We found 117 donors with a malignant tumor (5.8 per 1000 donors). One hundred fifty-five recipients were transplanted with an organ from these donors. The average age (SD) of donors with tumor was 53 (17) years. The most frequent cause of death was cerebral stroke in 81 donors. Donors with tumor are older than donors without tumor. The cause of death was cerebral stroke more frequently in donors with tumor than donors without tumor. Twenty-two of the recipients who received an organ from a donor with a tumor are dead. In 7 of these 22 recipients the death was cancer-related. Only 13 of the 100 recipients studied developed a malignant tumor, and only 10 of these tumors were donor-related. CONCLUSIONS: The profile of a donor who could have a tumor was most frequently an elderly person who had died of a cerebral stroke. In our experience, the risk of tumor transmission from donors to recipients is low and depends on the aggressiveness of the donor tumor.
PMID: 18425039 [PubMed - indexed for MEDLINE]
Variability in the diagnosis and management of patients with Alzheimer's disease and cerebrovascular disease: results from the GALATEA multicentre, observational study.
Clin Drug Investig. 2008;28(7):429-37
Authors: Gil P, Ayuso JL, Marey JM, AntÃ³n M, Quilo CG
BACKGROUND AND OBJECTIVES: There is frequently a degree of variability among different types of dementia specialists in clinical practice in both the clinical diagnosis and the management of patients with Alzheimer's disease and cerebrovascular disease (CVD). This variability may have an adverse effect on the use of medical resources as well as on patients' well-being. The main objective of this study was to describe the current diagnosis and management of patients with Alzheimer's disease and CVD in Spain. Other objectives were to determine whether there were significant differences in the diagnosis and management of these patients depending on physician characteristics and/or patient profile. METHODS: This was an epidemiological, cross-sectional, multicentre study in which 107 physicians participated and recruited patients with Alzheimer's disease and CVD. During a 1-month period, physicians collected data on diagnosis, treatment, follow-up, adverse events and other characteristics of these patients. This study was performed under naturalistic conditions, and no restrictions were imposed on the physicians. RESULTS: Physicians were mainly neurologists (76%), geriatricians (14%) and psychiatrists (8%) with a median age of 42 years. A total of 720 patients with a diagnosis of Alzheimer's disease and CVD were recruited. The median age of the patients was 78 years. Almost all patients were diagnosed by neuroimaging (98%) together with medical history (87%). The existence of a previous stroke coincident with cognitive deterioration was used as a diagnostic method in only 27% of patients. Among non-pharmacological treatment measures, diet was the most frequently recommended (61%), followed by cognitive stimulation (50%) and physical exercise (44%). The most commonly used pharmacological treatments were galantamine (59%), donepezil (14%) and rivastigmine (11%). The incidence of adverse events was low (3%), and all were considered non-severe. There were no significant correlations between physician age or physician years of practice and the diagnostic method used. The diagnostic method most frequently used by psychiatrists (100%) and geriatricians (97%) was medical history whereas this method was not used as much by neurologists (85%) [p = 0.0150]. Neuroimaging methods were more frequently used by neurologists (99%) and geriatricians (96%) compared with psychiatrists (84%) [p < 0.0001]. Patients with attention disorders had a higher frequency of follow-up visits (p = 0.0145) and were treated less frequently with donepezil (p = 0.0118). CONCLUSIONS: Several possible areas of improvement in the management of patients with Alzheimer's disease and CVD were identified. These included better control of cardiovascular risk factors, such as hypertension and hyperlipidaemia, which have a high prevalence in this population, as has been shown in the present study. These potentially modifiable risk factors may assist in the prevention of Alzheimer's disease. Also identified was the need to emphasize the role of general practitioners in decreasing the time to diagnosis of Alzheimer's disease. Development of well designed clinical practice guidelines may help physicians decide on the most appropriate ways of diagnosing and managing patients with Alzheimer's disease and CVD and reduce practice variations between different medical specialities.
PMID: 18544003 [PubMed - indexed for MEDLINE]
Clopidogrel in secondary ischemic stroke prevention.
Recent Pat Cardiovasc Drug Discov. 2008 Jun;3(2):119-25
Authors: BelvÃs R, Pagonabarraga J, SantamarÃa A, Kulisevsky J
The results obtained in the CAPRIE study in 1996 led to the introduction of the clopidogrel as a new antiplatelet drug in the secondary prevention of acute myocardial infarct (AMI), ischemic stroke (IS) and symptomatic peripheral artery disease (PAD). Clopidogrel showed a similar efficacy and safety than acetylsalicylic acid (ASA). More recently, the combined use of clopidogrel with ASA has evidenced a better protection than ASA alone in some patients: patients with past history of AMI, angina pectoris, intermittent claudication or PAD, IS or TIA, coronary bypass, and diabetes mellitus, patients on treatment with statins, and patients with symptomatic carotid stenosis >/=50%. We review the reported evidence on the efficacy of clopidogrel in the secondary prevention of ischemic stroke.
PMID: 18537762 [PubMed - indexed for MEDLINE]
Etiologic diagnosis of ischemic stroke subtypes with plasma biomarkers.
Stroke. 2008 Aug;39(8):2280-7
Authors: Montaner J, Perea-Gainza M, Delgado P, RibÃ³ M, ChacÃ³n P, Rosell A, Quintana M, Palacios ME, Molina CA, Alvarez-SabÃn J
BACKGROUND AND PURPOSE: Because there is no biologic marker offering precise information about stroke etiology, many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done, precluding correct treatment. METHODS: To examine the diagnostic value of a panel of biochemical markers to differentiate stroke etiologies, consecutive acute stroke patients were prospectively evaluated. Brain computed tomography, ultrasonography, cardiac evaluations, and other tests were done to identify an etiologic diagnosis according to TOAST classification. Blood samples were drawn on Emergency Department arrival (<24 hours) to test selected biomarkers: C-reactive protein, D-dimer, soluble receptor for advanced glycation end products, matrix metalloproteinase-9, S-100b, brain natriuretic peptide (BNP), neurotrophin-3, caspase-3, chimerin, and secretagogin (assayed by ELISA). RESULTS: Of 707 ischemic stroke patients included, 36.6% were cardioembolic, 21.4% atherothrombotic, 18.1% lacunar, and 23.9% of undetermined origin. High levels of BNP, soluble receptor for advanced glycation end products, and D-dimer (P<0.0001) were observed in patients with cardioembolic stroke. Independent predictors (odds ratios with CIs are given) of cardioembolic stroke were as follows: atrial fibrillation 15.3 (8.4-27.7, P<0.001); other embolic cardiopathies 14.7 (4.7-46, P<0.001); total anterior circulation infarction 4 (2.3-6.8, P<0.001); BNP >76 pg/mL 2.3 (1.4-3.7, P=0.001); and D-dimer >0.96 microg/mL 2.2 (1.4-3.7, P=0.001). Even among patients with transient symptoms (n=155), a high BNP level identified cardioembolic etiology (6.7, 2.4-18.9; P<0.001). A model combining clinical and biochemical data had a sensitivity of 66.5% and a specificity of 91.3% for predicting cardioembolism. CONCLUSIONS: Using a combination of biomarkers may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase, thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention.
PMID: 18535284 [PubMed - indexed for MEDLINE]
Prevalence of stroke and transient ischemic attack in three elderly populations of central Spain.
Authors: DÃaz-GuzmÃ¡n J, Bermejo-Pareja F, Benito-LeÃ³n J, Vega S, Gabriel R, Medrano MJ,
OBJECTIVE: Our aim was to assess prevalence rates of cerebrovascular disease (CVD; stroke and transient ischemic attacks) according to age and gender in three populations in central Spain using data from the Neurological Disorders in Central Spain (NEDICES) study, a population-based survey of elderly participants. METHODS: Individuals from one suburban municipality of Greater Madrid (Las Margaritas neighborhood, Getafe), one urban district of Madrid (Lista) and one rural site (ArÃ©valo county, Avila) were evaluated at baseline (n = 5,278). The evaluation included a screening questionnaire and a neurological assessment when possible. We used point prevalence with a reference date of May 1, 1994. RESULTS: Of the 5,278 subjects, there were 186 prevalent stroke cases and 71 cases of transient ischemic attacks. Prevalence rates, adjusted to the standard European populations, were 4.9% for CVD (95% confidence interval [CI] = 4.3-5.4), 3.4% for stroke (95% CI = 2.9-3.9) and 1.3% for transient ischemic attacks (95% CI = 1.0-1.6) in the total population. Age-specific prevalence rates of CVD, stroke and transient ischemic attacks increased exponentially with advancing age. The prevalence rates of CVD, stroke and transient ischemic attacks were higher for men than for women. Prevalence figures were higher in the suburban area of Margaritas compared to the rural region. CONCLUSIONS: In this study, the prevalence of stroke and transient ischemic attacks were higher in men and in urban areas. Central Spain would be a medium stroke prevalence zone.
PMID: 18515974 [PubMed - indexed for MEDLINE]
Effect of cervical spinal cord stimulation on cerebral glucose metabolism.
Neurol Res. 2008 Jul;30(6):652-4
Authors: Clavo B, Robaina F, Montz R, Carames MA, Otermin E, Carreras JL
OBJECTIVE: Syndromes resulting from decreased cerebral blood flow and metabolic activity have significant clinical and social repercussion. However, treatment options are limited. Cervical spinal cord stimulation has shown clinical benefit in the management of several ischemic syndromes. The aim of this report was to assess the effect of cervical spinal cord stimulation on cerebral glucose metabolism. MATERIALS AND METHODS: Between April 2000 and December 2005, 16 patients with brain tumors were assessed. Before and during spinal cord stimulation, they had cerebral glucose metabolism evaluated using 18fluoro-2-deoxyglucose positron emission tomography (18FDG-PET) in the healthy cerebral hemisphere contralateral to the lesion area. RESULTS: Following cervical spinal cord stimulation, there was a significant (p<0.001) increase in glucose metabolism in healthy cerebral hemisphere. The measured increase was 37.7%, with an estimated potential maximal contribution of the first 18fluoro-2-deoxyglucose injection to the quantification of the second positron emission tomography study (carry-over effect)<or=16.6%. CONCLUSION: Cervical spinal cord stimulation can increase cerebral glucose metabolism. This result supports the potential usefulness of this neurosurgical technique as an adjuvant treatment in stroke and brain disorders that result from decreased blood flow and metabolism.
PMID: 18513465 [PubMed - indexed for MEDLINE]
Relationship between bone quantitative ultrasound and mortality: a prospective study.
Osteoporos Int. 2009 Feb;20(2):257-64
Authors: GonzÃ¡lez-MacÃas J, MarÃn F, Vila J, Carrasco E, Benavides P, Castell MV, MagaÃ±a JE, Chavida F, DÃez-PÃ©rez A,
In a cohort of 5,201 women [72.3 +/- 5.3 years] from 58 primary care centers in Spain, followed for three years, no relationship between heel QUS parameters and overall mortality was found. However, a significant relationship between a low speed of sound (SOS) and vascular mortality was observed. INTRODUCTION: An inverse relationship between mortality and bone mineral density measured by dual-energy absorption densitometry or quantitative bone ultrasound (QUS) has been described. The aim of the present study was to test this relationship in the ECOSAP cohort, a 3-year prospective study designed to assess the ability of heel QUS and clinical risk factors to predict non-vertebral fracture risk in women over 64. METHODS: A cohort of 5,201 women [72.3 +/- 5.3 years] was studied. QUS was assessed with the Sahara(R) bone sonometer. Women attended follow-up visits every 6 months. Physicians recorded if the patient died and cause of death. Hazard rates (HR) of all-cause and vascular mortality per one standard deviation reduction in QUS parameters were determined. RESULTS: One hundred (1.9%) women died during a median of 36.1 months follow-up, for a total of 14,999 patient-years, 42 because of vascular events (both cardiovascular and cerebrovascular). After adjusting for age, none of the QUS variables showed statistically significant differences between the patients who died and the survivors. In the final multivariate model, adjusted for age, current thyroxine and hypoglycaemic drug use, chronic obstructive pulmonary disease and decreased visual acuity, SOS was marginally non-significant: (HR: 1.19; 0.97-1.45). However, each 1 SD reduction in SOS was associated with a 39% increase in vascular mortality (HR: 1.39; 1.15-1.66). CONCLUSIONS: In our cohort, SOS was related with vascular mortality, but not overall mortality.
PMID: 18512114 [PubMed - indexed for MEDLINE]
The normal cellular prion protein and its possible role in angiogenesis.
Front Biosci. 2008;13:6491-500
Authors: Turu M, Slevin M, Ethirajan P, Luque A, Elasbali A, Font A, Gaffney J, Cairols M, Kumar P, Kumar S, Krupinski J
Cellular Prion Protein (PrPc) is a ubiquitous glycoprotein present on the surface of endothelial cells. Resting vascular endothelial cells show minimum expression of PrPc and can constitutively release PrPc. PrPc participates in cell survival, differentiation and angiogenesis. During development, neonatal brain endothelial cells transiently express PrPc. Our group recently reported upregulation of PrPc in microvessels from ischemic brain regions in stroke patients. Ischemia/hypoxia induces PrPc expression through the activation of extracellular signal-regulated kinase (ERK). All these data suggest that PrPc plays an important role in angiogenic responses. In addition, PrPc participates in cellular function in the central nervous system, since PrPc is also highly expressed in neurons. PrPc binds copper, suggesting a role in copper metabolism. PrPc also protects cells against oxidative stress and it seems to be involved in neuroprotection. Several studies have demonstrated that PrPc prevents cells from apoptosis and subsequent tissue damage. Moreover, PrPc plays an important role in the immune response. Here, we review the multiple functions of PrPc with a special attention to its recently reported role in angiogenesis.
PMID: 18508675 [PubMed - indexed for MEDLINE]
Overexpression of hypoxia/inflammatory markers in atherosclerotic carotid plaques.
Front Biosci. 2008;13:6483-90
Authors: Luque A, Turu M, Juan-Babot O, Cardona P, Font A, Carvajal A, Slevin M, Iborra E, Rubio F, Badimon L, Krupinski J
Hypoxia, angiogenesis and inflammation leads to plaque progression and remodelling and may significantly contribute towards plaque rupture and subsequent cerebrovascular events. Our aim was to study, markers of hypoxia and inflammation previously identified by microarray analysis, in atherosclerotic carotid arteries with low to moderate stenosis. We hoped to describe different cellular populations expressing the studied markers. The location of selected inflammatory molecules obtained as vascular transplants from organ donors were analysed by immunohistochemistry with monoclonal and polyclonal antibodies. Paraffin-embedded sections were cut and probed with antibodies recognizing active B and T-lymphocytes (CD30), hypoxia-inducible factor-1alpha, endoglin (CD105), Interleukin-6 and C-reactive protein. We observed a notable overexpression of HIF-1alpha in inflammatory and hypoxic areas of carotid arteries in all types of lesions from type II-V taken from the patients with carotid stenosis less than 50%. This suggests that HIF-1alpha may have a putative role in atherosclerosis progression and angiogenesis. Dynamic changes in the non-occluding plaques may explain some of the clinical events in patients with low to moderate carotid stenosis.
PMID: 18508674 [PubMed - indexed for MEDLINE]
Angiogenesis and inflammation in carotid atherosclerosis.
Front Biosci. 2008;13:6472-82
Authors: Krupinski J, Font A, Luque A, Turu M, Slevin M
Carotid atherosclerosis is a leading cause of cerebrovascular events. The control of cardiovascular risk factors, i.e. tobacco smoking, alcohol abuse, hypertension, dyslipidemia, diabetes and obesity proved to reduce number of fatal and non-fatal strokes but failed to prevent important number of them. Screening for biomarkers in individuals at high risk of symptomatic vascular disease helped to identify some of them. However, as disease is by its nature multifocal, global testing for biomarkers may have limited practical application. New imaging techniques, including direct visualization of artery metabolism, by 18-FDG-PET, has brought new tools to study local atherosclerosis progression and individual plaque metabolic activity. Advances in molecular biology helped to identify inflammatory genes and its strong link to angiogenesis. The later, is thought to play a key role in the transformation to unstable plaque. Studies of the complex role that plays angiogenesis in plaque development will help in future to design effective therapies addressed at the individual cell level. The purpose of the review is to bring new insights into complicated pathophysiology of carotid atherosclerosis.
PMID: 18508673 [PubMed - indexed for MEDLINE]