RESUMEN
Pulse transit time (PTT) is defined as the time it takes the blood pressure (BP) wave to propagate from the heart to a specified point on the body. After an initial BP measurement, PTT can track BP over short periods of time. This paper evaluates two PTT algorithms: Chen's and Poon's algorithm; two of the most cited works in the area. The criteria for evaluating them were: which was capable of best tracking changes in BP and which provided the longest time between subsequent BP measurements. These establish the suitability of the PTT method for practical applications, which has not been examined previously. Accuracy was evaluated using the Association of Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society's (BHS) standards. Results show that Chen's algorithm is dependent on its lookup table at short intervals but remains accurate using a 6-min calibration interval, with r=0.96 and r(2)=0.98. Poon's algorithm fails when using a 2-min calibration interval, but is more capable of reflecting changes in BP. The short calibration interval and accuracy limit the usefulness of calculating BP using PTT. Therefore, neither of the algorithms can be recommended because of their shortcomings when estimating BP.
Asunto(s)
Análisis de la Onda del Pulso/métodos , Algoritmos , Calibración , HumanosRESUMEN
INTRODUCTION: Warfarin is used for the treatment of thromboembolic disease. It requires careful and sustained monitoring due to its narrow therapeutic index and potentially life-threatening complications. Patient education and knowledge is, therefore, vital. AIMS: To assess, in a specialised anticoagulation clinic, the extent of patients' knowledge of their warfarin treatment. METHODS: Ethical approval was obtained. All patients, aged over 18 years, attending our anticoagulation clinic during our study period were asked to participate. RESULTS: We enrolled 181 patients, 47.9% of respondents were unaware of any potential drug interactions, 57.7% of patients were unaware of any potential side effects, 20% of patients had experienced side effects, 10.9% of patients had been hospitalised due to side effects, 58% of which were due to Haemorrhage and 79% of patients kept a personal record of their INR. CONCLUSIONS: Patients' understanding of warfarin treatment was poor, despite their high level of compliance.
Asunto(s)
Anticoagulantes/uso terapéutico , Conocimientos, Actitudes y Práctica en Salud , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Educación del Paciente como Asunto , Encuestas y Cuestionarios , Warfarina/efectos adversosRESUMEN
Hypercholesterolemia has not traditionally been considered an important risk factor in the pathogenesis of stroke. However, recent studies show that statin therapy significantly reduces ischemic stroke for patients with established coronary artery disease. Statin therapy may reduce stroke through amelioration of precerebral atherosclerosis in the carotid artery and the aorta. Anti-atherosclerotic, anti-inflammatory, and antithrombotic actions of statins occur within the blood and in plaque. Statins may also protect against cerebral ischemia through beneficial modulation of the brain endothelial nitric oxide system. Ongoing studies are exploring the role of statin therapy in the primary prevention of stroke and in the prevention of cognitive decline and multi-infarct cerebrovascular disease.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Ácidos Heptanoicos/uso terapéutico , Lovastatina/uso terapéutico , Pirroles/uso terapéutico , Accidente Cerebrovascular/prevención & control , Antiinflamatorios/uso terapéutico , Anticolesterolemiantes/farmacología , Atorvastatina , Isquemia Encefálica/complicaciones , Encefalitis/prevención & control , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/enzimología , Fibrinolíticos/farmacología , Ácidos Heptanoicos/farmacología , Humanos , Lovastatina/farmacología , Óxido Nítrico Sintasa/metabolismo , Pirroles/farmacología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatologíaRESUMEN
An emerging body of evidence indicates that beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or 'statins', provide neuroprotection in addition to reducing ischaemic stroke. Statins reduce the incidence of ischaemic stroke by stabilising atherosclerotic plaques in the precerebral vasculature and through antithrombotic actions, and the neuroprotective effects of statins may confer significant clinical benefit. Some of these neuroprotective effects are likely to be cholesterol independent and mediated by the interruption of isoprenoid biosynthesis. Therapy with statins may modulate endothelial function and preserve blood flow to regions exposed to an ischaemic insult. In particular, statin-mediated preservation of endothelial nitric oxide synthase activity in cerebral vasculature, especially in the ischaemic penumbra, may limit neurological deficit. Moreover, putative anti-inflammatory and antioxidant properties of statins may confer additional neuroprotection. Further large clinical trials are necessary to address the role of statin therapy in the primary prevention of stroke, small vessel cerebrovascular disease and vascular dementia.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Antioxidantes/farmacología , Citocinas/biosíntesis , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Antígeno de Macrófago-1/análisis , Óxido Nítrico Sintasa/fisiologíaRESUMEN
BACKGROUND: Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively. Other gene defects that cause isolated aneurysms, however, have not thus far been described. METHODS AND RESULTS: We studied 3 families affected by FAA. No family met the diagnostic criteria for either Marfan or Ehlers-Danlos syndrome. Echocardiography defined involvement of both the thoracic and abdominal aorta. In family ANA, candidate gene analysis excluded linkage to loci associated with aneurysm formation, including fibrillin-1, fibrillin-2, and type III procollagen, and chromosome 3p24.2-p25. Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4. In family ANB, FAA was linked to fibrillin-1. In family ANF, however, FAA was not linked to any locus previously associated with aneurysm formation, including fibrillin-1 and FAA1. CONCLUSIONS: FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.
Asunto(s)
Aneurisma de la Aorta/genética , Cromosomas Humanos Par 11/genética , Adolescente , Adulto , Anciano , Aneurisma de la Aorta/patología , Niño , Preescolar , Bandeo Cromosómico , Mapeo Cromosómico , Salud de la Familia , Femenino , Heterogeneidad Genética , Predisposición Genética a la Enfermedad/genética , Humanos , Lactante , Escala de Lod , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , LinajeRESUMEN
BACKGROUND: Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of the aortic media, called medial necrosis. Families identified with dominant inheritance of thoracic aortic aneurysms and dissections (TAA/dissections) indicate that single gene mutations can cause medial necrosis in the absence of an associated syndrome. METHODS AND RESULTS: Fifteen families were identified with multiple members with TAAs/dissections. DNA from affected members from 2 of the families was used for a genome-wide search for the location of the defective gene by use of random polymorphic markers. The data were analyzed by the affected-pedigree-member method of linkage analysis. This analysis revealed 3 chromosomal loci with multiple markers demonstrating evidence of linkage to the phenotype. Linkage analysis using further markers in these regions and DNA from 15 families confirmed linkage of some of the families to 5q13-14. Genetic heterogeneity for the condition was confirmed by a heterogeneity test. Data from 9 families with the highest conditional probability of being linked to 5q were used to calculate the pairwise and multipoint logarithm of the odds (LOD) scores, with a maximum LOD of 4.74, with no recombination being obtained for the marker D5S2029. In 6 families, the phenotype was not linked to the 5q locus. CONCLUSIONS: A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.
Asunto(s)
Aneurisma de la Aorta Torácica/genética , Disección Aórtica/genética , Proteínas de la Matriz Extracelular , Proteoglicanos , Disección Aórtica/patología , Aneurisma de la Aorta Torácica/patología , Proteoglicanos Tipo Condroitín Sulfato/genética , Mapeo Cromosómico , Cromosomas Humanos Par 5/genética , Salud de la Familia , Femenino , Heterogeneidad Genética , Genoma Humano , Genotipo , Haplotipos , Humanos , Lectinas Tipo C , Escala de Lod , Masculino , Repeticiones de Microsatélite , Linaje , Polimorfismo de Nucleótido Simple , Proteínas/genética , Análisis de Secuencia de ADN , Trombospondinas/genética , VersicanosRESUMEN
Recent molecular genetic investigations of primary cardiac tumors (myxomas, lipomas, rhabdomyomas, and fibromas) have provided insight into fundamental mechanisms of cardiac cell growth. Myxomas are the most common adult cardiac tumor, and familial cardiac myxomas are now appreciated to be caused by mutations in the PRKAR1alpha gene that encodes a regulatory subunit of protein kinase A. Cytogenetic studies have targeted candidate chromosomal loci that may be perturbed during cardiac lipoma pathogenesis. Rhabdomyomas, the most common pediatric cardiac neoplasm, are frequently associated with tuberous sclerosis, caused by mutations in the TSC-1 and TSC-2 genes. The study of Gorlin syndrome has shed light on the etiology of cardiac fibromas. This disorder is caused by mutation of the PTC gene, which regulates cell growth, commitment and differentiation. In the future, manipulation of PRKAR1alpha-, TSC-, and PTC-dependent pathways may foster new strategies to regenerate myocardium in the ischemic or myopathic heart.
Asunto(s)
Neoplasias Cardíacas , Fibroma/genética , Neoplasias Cardíacas/genética , Humanos , Lipoma/genética , Biología Molecular/tendencias , Mixoma/genética , Rabdomioma/genéticaRESUMEN
The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of evidence suggests that statins also possess important additional clinical benefits, such as stroke risk reduction. In this article we review the evidence that statins may be neuroprotective, especially in the brain parenchyma during stroke. We also review the observational data that statins may prevent the onset of dementia.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Animales , Demencia/tratamiento farmacológico , Demencia/patología , Humanos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/patologíaRESUMEN
Cardiac myxomas are benign mesenchymal tumors that can present as components of the human autosomal dominant disorder Carney complex. Syndromic cardiac myxomas are associated with spotty pigmentation of the skin and endocrinopathy. Our linkage analysis mapped a Carney complex gene defect to chromosome 17q24. We now demonstrate that the PRKAR1alpha gene encoding the R1alpha regulatory subunit of cAMP-dependent protein kinase A (PKA) maps to this chromosome 17q24 locus. Furthermore, we show that PRKAR1alpha frameshift mutations in three unrelated families result in haploinsufficiency of R1alpha and cause Carney complex. We did not detect any truncated R1alpha protein encoded by mutant PRKAR1alpha. Although cardiac tumorigenesis may require a second somatic mutation, DNA and protein analyses of an atrial myxoma resected from a Carney complex patient with a PRKAR1alpha deletion revealed that the myxoma cells retain both the wild-type and the mutant PRKAR1alpha alleles and that wild-type R1alpha protein is stably expressed. However, in this atrial myxoma, we did observe a reversal of the ratio of R1alpha to R2beta regulatory subunit protein, which may contribute to tumorigenesis. Further investigation will elucidate the cell-specific effects of PRKAR1alpha haploinsufficiency on PKA activity and the role of PKA in cardiac growth and differentiation.
Asunto(s)
Anomalías Múltiples/genética , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Mutación del Sistema de Lectura , Neoplasias Cardíacas/genética , Mixoma/genética , Trastornos de la Pigmentación/genética , Anomalías Múltiples/etiología , Cromosomas Humanos Par 17 , Clonación Molecular , Femenino , Neoplasias Cardíacas/etiología , Humanos , Masculino , Mixoma/etiología , Trastornos de la Pigmentación/etiología , Análisis de Secuencia de ADNRESUMEN
A hypertensive emergency is a situation in which uncontrolled hypertension is associated with acute end-organ damage. Most patients presenting with hypertensive emergency have chronic hypertension, although the disorder can present in previously normotensive individuals, particularly when associated with pre-eclampsia or acute glomerulonephritis. The pathophysiological mechanisms causing acute hypertensive endothelial failure are complex and incompletely understood but probably involve disturbances of the renin-angiotensin-aldosterone system, loss of endogenous vasodilator mechanisms, upregulation of proinflammatory mediators including vascular cell adhesion molecules, and release of local vasoconstrictors such as endothelin 1. Magnetic resonance imaging has demonstrated a characteristic hypertensive posterior leucoencephalopathy syndrome predominantly causing oedema of the white matter of the parietal and occipital lobes; this syndrome is potentially reversible with appropriate prompt treatment. Generally, the therapeutic approach is dictated by the particular presentation and end-organ complications. Parenteral therapy is generally preferred, and strategies include use of sodium nitroprusside, beta-blockers, labetelol, or calcium-channel antagonists, magnesium for pre-eclampsia and eclampsia; and short-term parenteral anticonvulsants for seizures associated with encephalopathy. Novel therapies include the peripheral dopamine-receptor agonist, fenoldapam, and may include endothelin-1 antagonists.
Asunto(s)
Hipertensión , Antihipertensivos/uso terapéutico , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/fisiopatología , Encefalopatía Hipertensiva/tratamiento farmacológico , Encefalopatía Hipertensiva/etiología , Encefalopatía Hipertensiva/fisiopatologíaRESUMEN
Dopamine (DA) is regarded as an important modulator of enteric function. Recent experiments have suggested that newly cloned DA receptor subtypes are widely expressed in peripheral organs, including the gastrointestinal tract. In the present studies, the D(1A) receptor subtype was identified in rat gut regions through localization of receptor protein by means of light microscopic immunohistochemistry and Western blot analysis and receptor mRNA by RT-PCR and in situ amplification and hybridization (3SR in situ). D(1A) receptor immunoreactivity was shown to have a diverse distribution in the gastrointestinal tract, being present in the gastroesophageal junction, stomach, pylorus, small intestine, and colon. The receptor has a transmural distribution present in both epithelial and muscle layers as well as in blood vessels and lamina propria cells of different gastrointestinal regions. Western blot analysis demonstrated a single 50-kDa band for esophagus, stomach, duodenum, jejunum, and colon. The in situ hybridization signal was localized to the same sites revealed by D(1A) receptor immunoreactivity. RT-PCR revealed an appropriate sized signal in similar regions. This study is the first to identify expression of the central D(1A) receptor throughout the normal mammalian gastrointestinal tract.
Asunto(s)
Sistema Digestivo/metabolismo , Receptores de Dopamina D1/metabolismo , Animales , Western Blotting , Inmunohistoquímica , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Dopamina D1/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Distribución TisularRESUMEN
Cardiac lipomas occur infrequently but account for a significant portion of rare cardiac tumors. Common cutaneous lipomas have previously been associated with rearrangements of chromosome band 12q15, which often disrupt the high-mobility-group protein gene HMGIC. In this report, we describe the cytogenetic analysis of an unusual giant cardiac lipoma that exhibited myocardial invasion in a patient with a history of multiple lipomatosis (cutaneous lipoma, lipomatous gynecomastia, lipomatous hypertrophy of the interatrial septum, and dyslipidemia). Cytogenetic studies of cells derived from the cardiac lipoma demonstrated no abnormalities of chromosome 12, but did reveal a t(2;19)(p13;p13.2). A liposarcoma-derived oncogene (p115-RhoGEF) previously mapped to chromosome 19 and the low-density lipoprotein receptor gene (LDLR) previously mapped to chromosome band 19p13 were evaluated to determine whether they were disrupted by this translocation. Fluorescence in situ hybridization analyses assigned p115-RhoGEF to chromosome 19 in bands q13.2-q13.3 and mapped the LDLR to chromosome arm 19p in segment 13.2, but centromeric to the t(2;19) breakpoint. Thus, these genes are unlikely to be involved in the t(2;19)(p13;p13.2). Further studies of the regions of chromosomes 2 and 19 perturbed by the translocation in this unusual infiltrating cardiac lipoma will identify gene(s) that participate in adipocyte growth and differentiation and may provide insight into syndromes of multiple lipomatosis.
Asunto(s)
Cromosomas Humanos Par 19/genética , Cromosomas Humanos Par 2/genética , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/patología , Lipoma/genética , Lipoma/patología , Lipomatosis Simétrica Múltiple/genética , Lipomatosis Simétrica Múltiple/patología , Translocación Genética/genética , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana Edad , Invasividad NeoplásicaRESUMEN
Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors--"statins." Initial studies explored the impact of statin therapy on coronary artery disease (CAD) progression and regression. Although the angiographic changes were small, associated clinical responses appeared significant. Subsequent large prospective placebo-controlled clinical trials with statins demonstrated benefit in the secondary and primary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary prevention of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in patients with evidence of vascular disease. In addition to lowering low-density lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotropic effects on many components of atherosclerosis including plaque thrombogenicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial actions of statins occur rapidly and yield potentially clinically important anti-ischemic effects as early as one month after commencement of therapy. Future investigations are warranted to determine threshold LDL values in primary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determinants of platelet reactivity, coagulation, and endothelial function, further research may establish a role for statin therapy in acute coronary syndromes.
Asunto(s)
Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , LDL-Colesterol/sangre , Ensayos Clínicos como Asunto , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hipercolesterolemia/sangre , Hipercolesterolemia/complicaciones , Hipolipemiantes/efectos adversos , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
Septation defects and patent ductus arteriosus are the most common human cardiovascular malformations (CVMs). Genetic factors play a major part in the origin of these malformations. Recent molecular analyses have shed light on several mendelian forms. In the autosomal dominant Holt-Oram syndrome, both atrial and ventricular septal defects are inherited in association with limb deformity as a result of mutations in the gene encoding the TBX5 transcription factor. Mutations in the NKX2.5 transcription factor gene cause autosomal dominant familial atrial septal defects in association with progressive atrioventricular block as well as complex congenital heart disease. Common atrial syndromes in autosomal dominant Ellis-van Creveld syndrome arise in the context of axial skeletal and limb malformation as a result of mutations in the EVC gene, whose function is unknown. Patent ductus arteriosus occurs in several syndromic forms of congenital heart disease, including Holt-Oram syndrome. Recent analyses of autosomal dominant Char syndrome, which includes, with variable penetrance, patent ductus arteriosus as well as craniofacial and hand malformations, have shown that the syndrome is caused by mutations in the TFAP2B transcription factor gene. Ongoing analyses are poised to determine the contribution of these genes as well as others yet to be identified to common, sporadic forms of congenital heart disease.
Asunto(s)
Conducto Arterioso Permeable/genética , Defectos del Tabique Interatrial/genética , Defectos del Tabique Interventricular/genética , Proteínas de Xenopus , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Animales , Movimiento Celular , Embrión de Pollo , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/fisiología , Síndrome de Down/patología , Conducto Arterioso Permeable/embriología , Conducto Arterioso Permeable/epidemiología , Síndrome de Ellis-Van Creveld/genética , Síndrome de Ellis-Van Creveld/patología , Defectos de la Almohadilla Endocárdica/embriología , Defectos de la Almohadilla Endocárdica/genética , Femenino , Corazón Fetal/patología , Regulación del Desarrollo de la Expresión Génica , Genes Dominantes , Ligamiento Genético , Defectos del Tabique Interatrial/embriología , Defectos del Tabique Interventricular/embriología , Proteína Homeótica Nkx-2.5 , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/fisiología , Humanos , Masculino , Proteínas de la Membrana , Ratones , Modelos Animales , Cresta Neural/citología , Linaje , Proteínas/genética , Proteínas/fisiología , Síndrome , Proteínas de Dominio T Box/deficiencia , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/fisiología , Factor de Transcripción AP-2 , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Factores de Transcripción/fisiologíaRESUMEN
BACKGROUND: The atheroma-retarding properties of beta-hydroxy-beta-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitors, or "statins," in both the coronary and carotid arterial beds are well established. However, a growing body of recent data suggests that statins possess important adjunctive properties that may confer additional benefit beyond the retardation of atherosclerosis. In this article, we review the emerging evidence that statins have beneficial effects within the cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. SUMMARY OF REVIEW: Clinical studies show that statins reduce the incidence of ischemic stroke through probable effects on precerebral atherosclerotic plaque and through antithrombotic mechanisms. Additionally, statins have been shown to reduce infarct size in experimental animal models of stroke. Statins both upregulate endothelial nitric oxide synthase (eNOS) and inhibit inducible nitric oxide synthase (iNOS), effects that are potentially neuroprotective. The preservation of eNOS activity in cerebral vasculature, particularly in the ischemic penumbra, may be especially important in preserving blood flow and limiting neurological loss. Statins may also attenuate the inflammatory cytokine responses that accompany cerebral ischemia, and they possess antioxidant properties that likely ameliorate ischemic oxidative stress in the brain. CONCLUSIONS: In addition to reducing stroke, the statin class of drugs exhibits a number of important neuroprotective properties that likely attenuate the effects of ischemia on the brain vasculature and parenchyma. Further investigation of the role of statins in human neuroprotection by use of neuroimaging and cognitive studies is warranted to explore these preliminary observations. In addition to reducing ischemic stroke, early evidence indicates that statins may also be neuroprotective.
Asunto(s)
Isquemia Encefálica/patología , Trastornos Cerebrovasculares/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Isquemia Encefálica/fisiopatología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , HumanosRESUMEN
Molecular genetic analyses have generated significant advances in our understanding of congenital heart disease. Techniques of genetic mapping with polymorphic microsatellites and fluorescence in situ hybridization (FISH) have provided informative tools for localization and identification of disease genes. Some cardiovascular diseases have proven to result from single gene defects. Others relate to more complex etiologies involving several genes and their interactions. Elucidation of the molecular genetic etiologies of congenital heart disease prompts consideration of DNA testing for cardiac disorders. Future integration of these diagnostic modalities with improved treatments may ultimately decrease morbidity and mortality from congenital heart diseases.
Asunto(s)
Cardiopatías Congénitas/genética , Animales , Femenino , Neoplasias Cardíacas/genética , Defectos de los Tabiques Cardíacos/genética , Válvulas Cardíacas/anomalías , Humanos , Masculino , Ratones , Biología Molecular , SíndromeRESUMEN
The dopamine D3 receptor subtype was identified in rat kidney using both light microscopic immunohistochemistry and electron microscopic immunocytochemistry. Antipeptide polyclonal antisera were directed to both extracellular and intracellular regions of the native D3 receptor. Selectivity of the antipeptide antisera was validated by their ability to recognize native receptor protein expressed in permanently transfected mouse LTK- cells or Spodoptera fragiperda (Sf9) cell membranes. Light microscopic immunohistochemical staining for the D3 receptor was observed only in the cortex. Specific staining was present in proximal and distal tubules, cortical collecting ducts, glomeruli, and renal vasculature. Immunostaining was observed predominantly in the apical portion of both the proximal and distal tubules. Renal arterial staining was prominent in the medial and adventitial layers. Electron microscopic immunocytochemistry revealed immunogold particles in arteriolar smooth muscle cells of the renal vasculature. In proximal and distal tubules and cortical collecting duct, immunogold staining was localized to apical portions of tubule cells. D3 receptor immunogold staining in the glomeruli was clearly present in podocytes. Western blot analysis demonstrated a single D3 receptor band in infected Sf9 cell membranes, in transfected LTK- cells, and in kidney and brain but not in noninfected Sf9 cell membranes or in D2 or D3 receptor transfected or nontransfected LTK- cells. The use of receptor subtype-selective antibodies allows for the tissue localization of specific dopamine receptors that are not distinguished by current pharmacological or ligand-binding technology. The rat kidney expresses the D3 receptor at sites previously deemed to have D2-like receptors.
Asunto(s)
Riñón/metabolismo , Receptores de Dopamina D2/metabolismo , Secuencia de Aminoácidos , Animales , Western Blotting , Inmunohistoquímica , Masculino , Microscopía Electrónica , Datos de Secuencia Molecular , Ratas , Ratas Endogámicas WKY , Ratas Sprague-Dawley , Receptores de Dopamina D3RESUMEN
Seizures are commonly encountered in patients who do not have epilepsy. Factors that may provoke such seizures include organ failure, electrolyte imbalance, medication and medication withdrawal, and hypersensitive encephalopathy. There is usually one underlying cause, which may be reversible in some patients. A full assessment should be done to rule out primary neurological disease. Treatment of seizures in medically ill patients is aimed at correction of the underlying cause with appropriate short-term anticonvulsant medication. Phenytoin is ineffective in the management of seizures secondary to alcohol withdrawal, and in those due to theophylline or isoniazid toxicity. Control of blood pressure is important in patients with renal failure and seizures. Non-convulsive status epilepticus should be considered in any patient with confusion or coma of unclear cause, and electroencephalography should be done at the earliest opportunity. Most ill patients with secondary seizures do not have epilepsy, and this should be explained to patients and their families. Only those patients with recurrent seizures and uncorrectable predisposing factors need long-term treatment with anticonvulsant medication.
Asunto(s)
Convulsiones/etiología , Lesión Renal Aguda/complicaciones , Anticonvulsivantes/uso terapéutico , Antituberculosos/efectos adversos , Presión Sanguínea , Encefalopatías/complicaciones , Broncodilatadores/efectos adversos , Coma/diagnóstico , Confusión/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Electroencefalografía , Etanol/efectos adversos , Humanos , Isoniazida/efectos adversos , Insuficiencia Multiorgánica/complicaciones , Fenitoína/uso terapéutico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Estado Epiléptico/diagnóstico , Síndrome de Abstinencia a Sustancias , Teofilina/efectos adversos , Desequilibrio Hidroelectrolítico/complicacionesRESUMEN
In a young woman with primary pulmonary hypertension, treatment with low-dose nifedipine resulted in resolution of symptoms and of tricuspid regurgitation. On withdrawal of nifedipine, symptomatic pulmonary hypertension recurred within 48 hours and was controlled by reintroduction of low-dose nifedipine.