RESUMEN
BACKGROUND: Interferon-ß-1b (IFNß-1b) has been used to prevent exacerbation of relapsing-remitting multiple sclerosis (RRMS) including optic-spinal multiple sclerosis (OSMS) in Japan. We encountered 2 patients with OSMS with unexpectedly severe exacerbation soon after the initiation of IFNß-1b therapy. The experience urged us to retrospectively review the patients with RRMS who had been treated with IFNß-1b to identify similar cases. METHODS: At neurologic departments of 9 hospitals, the medical records of 56 patients with RRMS were reviewed to identify those who showed severe exacerbation soon after the initiation of IFNß-1b therapy. RESULTS: Of 56 patients with RRMS, we identified 7 who experienced severe exacerbation (exacerbation with increased scores of Expanded Disability Status Scale â§7.0) within 90 days of the initiation of IFNß-1b therapy. In all 7 patients, the exacerbations after the initiation of IFNß-1b therapy were more severe than those experienced by the individual patients before the use of IFNß-1b, and seemed to have occurred unexpectedly in a short time after the initiation of INFß-1b therapy. A retrospective analysis revealed that all 7 patients had antibodies toward aquaporin 4, and the clinical features of all 7 patients after the exacerbation were consistent with those of neuromyelitis optica (NMO) spectrum. CONCLUSIONS: Our study suggests that IFNß-1b may trigger severe exacerbation in patients with the NMO spectrum. In INFß-1b therapy, cases in NMO spectrum should be carefully excluded.
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Adyuvantes Inmunológicos/efectos adversos , Interferón beta/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/tratamiento farmacológico , Adulto , Acuaporina 4/inmunología , Pueblo Asiatico/etnología , Evaluación de la Discapacidad , Femenino , Humanos , Interferon beta-1b , Japón/etnología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/inmunología , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Estudios Retrospectivos , Médula Espinal/efectos de los fármacos , Médula Espinal/patologíaRESUMEN
INTRODUCTION: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with conservation of the splenic artery and vein has recently been performed as a minimally invasive surgery to retain splenic function in the treatment of pancreatic diseases. As the branches of the splenic vessels are very delicate, division of these branches increases the risk of bleeding. MATERIALS AND METHODS: To overcome this problem, we have used the electrothermal bipolar vessel sealer (EBVS) to divide branches of the splenic vessels in LSPDP while conserving the splenic vessels themselves. RESULTS: The EBVS reliably provided excellent and safe hemostasis, minimizing the risk of serious blood loss. CONCLUSION: Use of the EBVS is safe and efficient in LSPDP with conservation of the splenic vessels.
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Electrocoagulación/instrumentación , Laparoscopía/métodos , Pancreatectomía/métodos , Bazo/irrigación sanguínea , Arteria Esplénica/cirugía , Vena Esplénica/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Anciano , Pérdida de Sangre Quirúrgica/prevención & control , Diseño de Equipo , Femenino , Humanos , Insulinoma/cirugía , Neoplasias Pancreáticas/cirugía , Hemorragia Posoperatoria/prevención & controlRESUMEN
Effective gene therapy depends on the efficient transfer of therapeutic genes to target cells. None of the current technologies, however, satisfy all of the requirements necessary for gene therapy, because the plasma and nuclear membranes of mammalian cells are tight barriers against gene transfer using synthetic delivery systems. The protein transduction domain (PTD) of human immunodeficiency virus type 1 (HIV-1) Tat protein greatly facilitates protein transfer via membrane destabilisation. We synthesised polylysine peptides containing Tat PTD (TAT-pK), or other sequences, and investigated their potential as agents for gene transfer. The synthesised polypeptide TAT-pK retains DNA binding function and mediates delivery of a reporter gene to cultured cells. RGD motif binds with low affinity to alpha integrins which induce cell activation. Two control polypeptides, GGG-pK and RGD-pK, were synthesised and tested, but their gene transfer abilities were weaker than those of TAT-pK. TAT-pK-mediated gene transfer was enhanced in the presence of chloroquine or ammonium chloride, to a greater extent than that of cationic lipid-mediated gene transfer in most cancer cell lines tested. These data suggest that TAT-pK may be a potent candidate delivery vehicle that promotes gene transfer, dependent on the endocytic pathway. We conclude that the TAT-pK/DNA complex is useful as a minimal unit to package therapeutic genes and to transduce them into mammalian cells.
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Productos del Gen tat , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Polilisina/genética , Carcinoma/patología , Carcinoma de Células Escamosas/patología , Línea Celular , Neoplasias Esofágicas/patología , Genes Reporteros , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pancreáticas/patología , Fragmentos de Péptidos , Proteínas Recombinantes de Fusión , Células Tumorales Cultivadas , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
Cell motility is an important cellular function closely related to the processes of tumour progression and metastasis. Several members of transmembrane 4 superfamily (TM4SF) have been reported to be associated with cell motility and metastatic potential of solid tumour. The aim of this study is to clarify the clinical significance of the member of TM4SF (MRP-1/CD9, KAI1/CD82 and CD151) in human colon cancer. We studied 146 colon cancer patients who underwent curative surgery and studied the expression of MRP-1/CD9, KAI1/CD82 and CD151 using reverse transcriptase - polymerase chain reaction and immunohistochemistry. We found that 64 patients (43.8%) had MRP-1/CD9-positive tumours and that the overall survival rate of patients with MRP-1/CD9-positive tumours was much higher than that of patients with MRP-1/CD9-negative tumours (89.8 vs 50.8%, P<0.001). In contrast, 63 patients (43.2%) had KAI1/CD82-positive tumours and the overall survival rate of patients with KAI1/CD82-positive tumours was also higher than that of patients with KAI1/CD82-negative tumours (84.8 vs 54.9%, P=0.002). On the other hand, positive CD151 expression had a bad effect on the overall survival rate of patients with colon cancer (61.2 vs 74.9%, P=0.022). In a multivariate analysis, MRP-1/CD9 status was a good indicator of the overall survival (P=0.007). We have shown that the reduction of MRP-1/CD9 and KAI1/CD82 expression, and the increasing CD151 expression are indicators for a poor prognosis in patients with colon cancer. This is a first report describing about the relation between CD151 and colon cancer.
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Antígenos CD/biosíntesis , Antígenos CD/farmacología , Antígenos de Neoplasias/farmacología , Biomarcadores de Tumor/análisis , Movimiento Celular , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/farmacología , Anciano , Antígenos de Neoplasias/biosíntesis , Neoplasias del Colon/genética , Femenino , Humanos , Masculino , Proteínas de la Membrana/biosíntesis , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Sobrevida , Tetraspanina 24RESUMEN
Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion (P = 0.0180), lymph node metastasis (P = 0.0033), lymphatic involvement (P = 0.0104), venous involvement (P = 0.0224), perineural involvement (P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification (P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis, possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival (P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216-132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer.
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Antígenos de Neoplasias , Antígenos de Superficie/análisis , Biomarcadores de Tumor/análisis , Carcinoma/química , Neoplasias de la Vesícula Biliar/química , Proteínas de Neoplasias/análisis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/cirugía , Colecistectomía , Progresión de la Enfermedad , Femenino , Enfermedades de la Vesícula Biliar/metabolismo , Enfermedades de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Tablas de Vida , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
A 71-year-old woman showed disorientation 7 days after simple mastectomy for right breast cancer. Computed tomography of the brain was normal. The level of serum sodium was very low (110 mEq/l), while the urine sodium level was normal. The osmolality of urine was higher (342 mosmol/kg) than that of serum (220 mosmol/kg). These data suggested a syndrome of inappropriate secretion of antidiuretic hormone. A fluid restriction, infusion of hypertonic saline and administration of diuretics gradually increased the level of serum sodium. Subsequently, disorientation disappeared. This is a rare case of the syndrome of inappropriate secretion of antidiuretic hormone caused by simple mastectomy, a relatively minor surgical procedure.
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Neoplasias de la Mama/cirugía , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Síndrome de Secreción Inadecuada de ADH/etiología , Mastectomía Simple/efectos adversos , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Síndrome de Secreción Inadecuada de ADH/sangre , Concentración Osmolar , Sodio/sangreRESUMEN
A 75-year-old man was admitted to our hospital with disorientation and progression of speech disturbance and gait disturbance. He had been given a diagnosis of cervical spondylosis about four years previously, and gait disturbance and numbness in his extremities have been gradually increasing. Hyperchloremia and a careful history taking, which led to the discovery of habitual use of an analgesic containing bromvalerylurea, suggested bromism. A high level of bromide in serum yielded a diagnosis of bromism. Disorientation and speech disturbance were treated and improved by infusion diuresis. Gait disturbance only partly improved. There is a possibility that not only cervical spondylosis, but also chronic bromvalerylurea intoxication, may have contributed to the neurological disturbance resulting in gait disturbance and numbness. Bromvalerylurea, which is contained in many commercially available analgesics, should be noted as a possible cause of neurological disturbance.
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Analgésicos/envenenamiento , Bromisovalum/envenenamiento , Discinesia Inducida por Medicamentos/etiología , Medicamentos sin Prescripción/efectos adversos , Anciano , Enfermedad Crónica , Humanos , MasculinoRESUMEN
OBJECTIVES: Neutral endopeptidase modulates the growth of lung cancer, while aminopeptidase N degrades the extracellular matrix and is involved in cell motility. We studied the metastasis mechanism to detect novel metastasis-associated molecules and to evaluate them for clinical application. METHODS: We studied the relationship between the expression of neutral endopeptidase and aminopeptidase N by quantitative reverse transcript-polymerase chain reaction analysis in 132 patients with non-small cell lung cancer undergoing radical surgery from 1991 to 1996. RESULTS: Patients with neutral endopeptidase-positive and aminopeptidase N-negative tumors were defined as group A, those with neutral endopeptidase-positive and aminopeptidase N-positive or neutral endopeptidase-negative and aminopeptidase N-negative tumors as group B, and those with neutral endopeptidase-negative and aminopeptidase N-positive tumors as group C. The 5-year survival of group A patients (92.9%) was significantly better than that of group B patients (64.7%) and much better than that of group C patients (38.2%) (P = 0.0011). Neutral endopeptidase and aminopeptidase N thus have statistically significant P in overall survival in Cox regression (P = 0.019). CONCLUSION: Neutral endopeptidase and aminopeptidase N gene expressions are significant indicators of prognosis.
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Antígenos CD13/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Neprilisina/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de SupervivenciaRESUMEN
Somatic mosaicism of an expanded repeat is present in tissues of patients with triplet repeat diseases. Of the spinocerebellar ataxias associated with triplet repeat expansion, the most prominent heterogeneity of the expanded repeat is seen in dentatorubral-pallidoluysian atrophy (DRPLA). The common feature of this somatic mosaicism is the difference in the repeat numbers found in the cerebellum as compared to other tissues. The expanded allele in the cerebellum shows a smaller degree of expansion. We previously showed by microdissection analysis that the expanded allele in the granular layer in DRPLA cerebellum has less expansion than expanded alleles in the molecular layer and white matter. Whether this feature of lesser expansion in granule cells is common to other types of neurons is yet to be clarified. We used a newly developed excimer laser microdissection system to analyze somatic mosaicism in the brains of two patients, one with early- and another with late-onset DRPLA, and used single cell PCR to observe the cell-to-cell differences in repeat numbers. In the late onset patient, repeat expansion was more prominent in Purkinje cells than in granule cells, but less than that in the glial cells. In the early onset patient, repeat expansion in Purkinje cells was greater than in granule cells but did not differ from that in glial cells. These findings suggest that there is a difference in repeat expansion among neuronal subgroups and that the number of cell division cycles is not the only determinant of somatic mosaicism.
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Disección/métodos , Rayos Láser , Mosaicismo/genética , Epilepsias Mioclónicas Progresivas/genética , Epilepsias Mioclónicas Progresivas/patología , Células de Purkinje/metabolismo , Células de Purkinje/patología , Repeticiones de Trinucleótidos/genética , Análisis Mutacional de ADN/instrumentación , Análisis Mutacional de ADN/métodos , Disección/instrumentación , Genoma , Humanos , Mosaicismo/patología , Mosaicismo/fisiopatología , Epilepsias Mioclónicas Progresivas/fisiopatología , Neuroglía/metabolismo , Neuroglía/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Huntington's disease (HD) is a neurodegenerative disorder characterized by the expansion of CAG repeats in exon 1 of the HD gene. To clarify the instability of expanded CAG repeats in HD patients, an HD model mouse has been generated by gene replacement with human exon 1 of the HD gene with expansion to 77 CAG repeats. Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues. One or two CAG repeat expansion was found in litters from paternal transmission, whereas contraction of CAG repeat in litters was observed through maternal transmission. Elderly mice show greater CAG repeat instability than younger mice, and a unique case was observed of an expanded 97 CAG repeat mouse. Somatic CAG repeat instability is particularly pronounced in the liver, kidney, stomach, and brain but not in the cerebellum of 100-week-old mice. The same results of expanded CAG repeat instability as observed in this HD model mouse were confirmed in the human brain of HD patients. Glial fibrillary acidic protein (GFAP)-positive cells have been found to be increased in the substantia nigra (SN), globus pallidus (GP), and striatum (St) in the brains of 40-week-old affected mice, although without neuronal cell death. The CAG repeat instability and increase in GFAP-positive cells in this mouse model appear to mirror the abnormalities in HD patients. The HD model mouse may therefore have advantages for investigations of molecular mechanisms underlying instability of CAG repeats.
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Modelos Animales de Enfermedad , Enfermedad de Huntington/genética , Ratones Transgénicos , Expansión de Repetición de Trinucleótido , Factores de Edad , Animales , Astrocitos/química , Astrocitos/patología , Exones , Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/análisis , Gliosis/genética , Gliosis/patología , Globo Pálido/patología , Humanos , Enfermedad de Huntington/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Mosaicismo , Neostriado/patología , Sustancia Negra/patologíaRESUMEN
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder that is clinically characterized by cerebellar ataxia and various associated symptoms. The disease is caused by an unstable expansion of the CAG repeat in the MJD gene. This gene is mapped to chromosome 14q32.1. To determine its genomic structure, we constructed a contig composed of six cosmid clones and eight bacterial artificial chromosome (BAC) clones. It spans approximately 300kb and includes MJD. We also determined the complete sequence (175,330bp) of B445M7, a human BAC clone that contains MJD. The MJD gene was found to span 48,240bp and to contain 11 exons. Northern blot analysis showed that MJD mRNA is ubiquitously expressed in human tissues, and in at least four different sizes; namely, 1.4, 1.8, 4.5, and 7.5kb. These different mRNA species probably result from differential splicing and polyadenylation, as shown by sequences of the 21 independent cDNA clones isolated after the screening of four human cDNA libraries prepared from whole brain, caudate, retina, and testis. The sequences of these latter clones relative to the MJD gene in B445M7 indicate that there are three alternative splicing sites and eight polyadenylation signals in MJD that are used to generate the differently sized transcripts.
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Empalme Alternativo/genética , Exones/genética , Perfilación de la Expresión Génica , Intrones/genética , Enfermedad de Machado-Joseph/genética , Proteínas del Tejido Nervioso/genética , Secuencia de Aminoácidos , Ataxina-3 , Secuencia de Bases , Encéfalo/metabolismo , Cromosomas Artificiales Bacterianos , Cromosomas Humanos Par 14/genética , Mapeo Contig , Cósmidos , Humanos , Datos de Secuencia Molecular , Proteínas Nucleares , ARN Mensajero/análisis , ARN Mensajero/genética , Proteínas Represoras , Repeticiones de Trinucleótidos/genéticaRESUMEN
A 65-year-old Japanese woman with dilated cardiomyopathy, hypothyroidism and refractory sustained ventricular tachycardia experienced a near-death hypoglycemic syncope. The attack seemed to be induced by a high level of serum insulin, probably due to cibenzoline and by concomitant use of an angiotensin converting enzyme inhibitor (ACEI). Additionally, decreased food intake because of a severe toothache may have contributed to the deterioration of her condition. This case warns cardiologists that a combined cibenzoline and ACEI therapy can provoke serious adverse effects such as hypoglycemic syncope in the elderly. Therefore, the possibility of a hypoglycemic attack associated with these drugs should be explained to patients who are in poor condition.
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Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antiarrítmicos/efectos adversos , Hipoglucemia/inducido químicamente , Imidazoles/efectos adversos , Síncope/inducido químicamente , Anciano , Cardiomiopatía Dilatada/tratamiento farmacológico , Femenino , Humanos , Hipotiroidismo/tratamiento farmacológico , Taquicardia Ventricular/tratamiento farmacológicoRESUMEN
The molecular basis of cell motility is obviously highly complex and is considered to be controlled by a number of molecular systems including cell adhesion molecules, their receptors, cytoskeletal components, a junctional unit connecting cytoskeletal components and membrane receptors, and various peptide growth factors. The possible involvement of proteins at the cell surface in controlling cell motility has been systematically investigated. Previously, we have addressed this question using functional monoclonal antibodies (MAbs), which inhibit cell motility as probes. In order to further identify cell surface molecules involved in metastasis of gastrointestinal tumors, the present study utilized an approach based on the selection of a colon cancer cell line RPMI4788, which showed high motility out of a large number of human gastrointestinal tumor cell lines. MAb MH8-4 was established after immunization of mice with RPMI4788 and selected on the basis of inhibition of RPMI4788 cell migration in a transwell penetration assay. MH8-4 inhibited the phagokinetic tract motility of various cancer cell lines. A cDNA cloning revealed that MH8-4 recognized a specific protein structure, integrin alpha 3. In order to determine whether these experimental results are of relevance with respect to actual human gastrointestinal tumors, we investigated integrin alpha 3 expression in 40 colon cancers with distant metastases. Our immunohistochemical study showed that in almost 27.5% of the cases, the metastatic tumors had lower integrin alpha 3 levels than their corresponding primary tumors. Moreover, there were no primary tumors with lower integrin alpha 3 expression than their corresponding metastatic tumors. Our data suggest that low integrin alpha 3 expression may be associated with the metastatic potential of certain colon cancers.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígenos CD/fisiología , Movimiento Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Integrinas/fisiología , Anticuerpos Monoclonales/inmunología , Antígenos CD/biosíntesis , Antígenos CD/genética , Antígenos CD/inmunología , Neoplasias del Colon/genética , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Epítopos , Genes Supresores de Tumor , Humanos , Inmunohistoquímica , Integrina alfa3 , Integrinas/biosíntesis , Integrinas/genética , Integrinas/inmunología , Metástasis de la Neoplasia/patología , Fagocitosis/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
Previously we showed that MRP-1/CD9 might prevent tumor metastasis by suppression of cell motility and invasion of tissue barriers. The present study explored the possibility of preventing metastasis of mouse melanoma BL6 by expression of MRP-1/CD9 through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of MRP-1/CD9 cDNA. Intratumor injection of an adenovirus vector (rAd-MRP-1/CD9) expressing MRP-1/CD9 resulted in a 73.7% reduction in the number of pulmonary metastases of mice and the median survival time of mice treated with rAd-MRP-1/CD9 was significantly longer than those treated with the rAd-beta-gal vector (103.2 approximately plus;8.5 days vs 71.2 approximately plus;5.2 days, P<0.001 respectively). These results support the expression of MRP-1/CD9 through gene transfer as a therapeutic strategy for preventing metastases and prolonging survival, and support the feasibility of gene transfer in a clinically relevant setting.
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Adenoviridae/genética , Antígenos CD/fisiología , Técnicas de Transferencia de Gen , Terapia Genética , Neoplasias Pulmonares/secundario , Melanoma/patología , Glicoproteínas de Membrana , Adenoviridae/fisiología , Animales , Antígenos CD/genética , Western Blotting , División Celular , Movimiento Celular , Extremidades , Inmunohistoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Melanoma/genética , Melanoma/terapia , Ratones , Ratones Endogámicos BALB C , Invasividad Neoplásica , Trasplante de Neoplasias , Tasa de Supervivencia , Tetraspanina 29 , Transfección , Transgenes/genética , Células Tumorales CultivadasRESUMEN
The transient U wave inversion during exercise is specific for detecting left anterior descending coronary artery (LAD) disease. In a homogeneous patient group restricted to LAD disease, however, the significance of the electrocardiographic finding has not yet been clarified. Thus, clinical characteristics in patients with angiographically documented one-vessel disease of the LAD and exercise-induced U wave inversion were delineated. Symptom-limited treadmill exercise testing was performed in 60 patients (43 men, 17 women; mean age 64 +/- 8 years) with angina pectoris whose culprit lesion was located only in the LAD. U wave polarity and amplitude were determined before, during, and after exercise with the P-Q segment as the isoelectric line. Exercise-induced transient U wave inversion was defined as positive when there was a discrete negative deflection > or = 0.05 mV within the T-P segment. Of all patients, 16 (27%) had exercise-induced U wave inversion. There were no differences in age, male gender, antianginal medication use, and coronary angiographic data between the two patients groups: patients with and without U wave inversion. Heart rate and double product of heart rate and systemic systolic blood pressure at peak exercise were also similar. Prevalence of abnormal exercise-induced S-T segment shift was 94% (15 of 16 patients) and 61% (27 of 44 patients) of patients with and without U wave inversion, respectively. The difference was statistically significant (p = 0.02). Among patients with exercise-induced S-T segment shift, the proportion of patients with S-T segment elevation to all the patients was larger in patients with U wave inversion than in patients without U wave inversion [3 (20%) of 15 patients vs 0 (0%) of 27 patients, p = 0.03)]. In conclusion, the exercise-induced U wave inversion in patients with one-vessel disease of the LAD indicates the severe degree of myocardial ischemia induced in the territory perfused by the LAD. However, the electrocardiographic finding does not appear to have independent significance since it closely correlates with the presence of S-T segment shift.
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Enfermedad Coronaria/diagnóstico , Electrocardiografía , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Prueba de Esfuerzo , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
To evaluate whether or not beta-blockers can improve the condition of patients with heart failure treated with a combination of diuretics, digitalis and angiotensin-converting enzyme inhibitor (ACEI), 52 patients with chronic heart failure who have been treated with ACEI for more than 6 months were enrolled. They were divided into 2 groups: 26 patients continued the same therapy another 6 months or more (group A), and 26 patients were given oral metoprolol for 6 months or more, in addition to the ACEI (group B). Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured. The left ventricular dimensions at end-diastole and end-systole were significantly decreased and fractional shortening was significantly increased in group B after 6 months' treatment with the beta-blocker, but these parameters remained unchanged in group A. Plasma levels of both ANP and BNP were significantly decreased in group B, but remained unchanged in group A. These results indicate that concomitant beta-blocker therapy can improve left ventricular function and attenuate plasma ANP and BNP levels in patients with chronic heart failure treated with ACEI.
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Antagonistas Adrenérgicos beta/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Factor Natriurético Atrial/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Antagonistas Adrenérgicos beta/administración & dosificación , Adulto , Factor Natriurético Atrial/sangre , Digitalis/uso terapéutico , Diuréticos/uso terapéutico , Ecocardiografía , Femenino , Hemodinámica , Humanos , Masculino , Metoprolol/administración & dosificación , Metoprolol/farmacología , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fitoterapia , Plantas Medicinales , Plantas TóxicasRESUMEN
A 58-year-old male patient had apical hypertrophic cardiomyopathy (HCM) associated with a life-threatening tachycardia due to atrial flutter. Following palpitation and dyspnea for 2-3 h, he became unconscious because of circulatory catastrophe, but was fully resuscitated. An electrocardiogram recorded just before the loss of consciousness revealed atrial flutter at a rate of 260 beats/min with a 2:1 ventricular response. He was diagnosed as having apical HCM based on the echocardiographic and left ventriculographic findings. Atrial stimulation at a rate of 150 pacings/min for 1 min caused a marked drop in systemic systolic blood pressure from 170 to 120 mmHg. The patient was treated with 150 mg of cibenzoline per day to prevent supraventricular tachyarrhythmias and to improve left ventricular diastolic function. At the time of the recent follow-up at 2 and a half years, he felt quite well.
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Aleteo Atrial/complicaciones , Aleteo Atrial/fisiopatología , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/fisiopatología , Función Ventricular Izquierda , Electrocardiografía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We have cloned a tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel alpha subunit from a mouse cDNA library and designated it as NaT. It encodes 1765 amino acid residues and is virtually identical to that of Scn11a, which has been reported recently, except for 40 nt and 14 aa substitutions. The amino acid identity of NaT/Scn11a with rat NaN/SNS2 is 88%. NaT/Scn11a was mapped to mouse chromosome 9F3-F4 by fluorescence in situ hybridization (FISH). While rat NaN/SNS2 has been reported to be expressed specifically in the peripheral sensory neurons, NaT/Scn11a is expressed not only in the peripheral sensory neurons but also in the spinal cord, uterus, testis, ovary, placenta, and small intestine. NaT is detectable in mouse embryos 15 days postcoitus (p.c.), around the phase of organogenesis and gonadal differentiation. These findings demonstrate a unique distribution of NaT/Scn11a and suggest some of its roles in the above-mentioned processes.
Asunto(s)
Mapeo Cromosómico , Neuronas Aferentes/metabolismo , Nervios Periféricos/metabolismo , Canales de Sodio/genética , Tetrodotoxina/farmacología , Secuencia de Aminoácidos , Animales , Clonación Molecular , Desarrollo Embrionario y Fetal , Femenino , Regulación del Desarrollo de la Expresión Génica , Biblioteca de Genes , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Ratones , Datos de Secuencia Molecular , Especificidad de Órganos , Embarazo , Ratas , Proteínas Recombinantes/química , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Canales de Sodio/química , Canales de Sodio/fisiologíaRESUMEN
We have cloned a cDNA encoding a novel human voltage-gated sodium channel alpha subunit gene, SCN12A, from human brain. Two alternative splicing variants for SCN12A have been identified. The longest open reading frame of SCN12A encodes 1791 amino acid residues. The deduced amino acid sequence of SCN12A shows 37-73% similarity with various other mammalian sodium channels. The presence of a serine residue (S360) in the SS2 segment of domain I suggests that SCN12A is resistant to tetrodotoxin (TTX), as in the cases of rat Scn10a (rPN3/SNS) and rat Scn11a (NaN/SNS2). SCN12A is expressed predominantly in olfactory bulb, hippocampus, cerebellar cortex, spinal cord, spleen, small intestine, and placenta. Although expression level could not be determined, SCN12A is also expressed in dorsal root ganglia (DRG). Both neurons and glial cells express SCN12A. SCN12A maps to human chromosome 3p23-p21.3. These results suggest that SCN12A is a tetrodotoxin-resistant (TTX-R) sodium channel expressed in the central nervous system and nonneural tissues.
Asunto(s)
Encéfalo/metabolismo , Cromosomas Humanos Par 3 , Canales de Sodio/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , Cartilla de ADN , ADN Complementario , Femenino , Humanos , Cariotipificación , Masculino , Mamíferos , Datos de Secuencia Molecular , Especificidad de Órganos , Placenta/metabolismo , Embarazo , Ratas , Proteínas Recombinantes/química , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Canales de Sodio/química , Canales de Sodio/fisiología , Médula Espinal/metabolismo , Tetrodotoxina/farmacologíaRESUMEN
It is well recognized that serum creatinine level provides a quick general assessment of renal function. However, we frequently encounter elderly hypertensive patients with renal involvement whose serum creatinine levels are within normal limits. The aim of this study was thus to determine whether serum creatinine level is a sensitive indicator of renal function in elderly hypertensive patients. Study groups were classified according to age: 82 elderly patients (aged 65 yr or older) and 98 middle-aged patients (aged 40-65 yr) with essential hypertension. To assess hypertensive renal involvement, serum creatinine and serum uric acid levels were measured. We also measured the left ventricular mass (LVM) index by using echocardiography as a marker of hypertensive target organ damage. There was no age-related difference in the LVM index, but the serum creatinine level in elderly hypertensive patients was significantly lower than that in middle-aged hypertensive patients. There was no significant difference in serum uric acid level between the two groups. In addition, the LVM index was correlated with the serum uric acid level (r = 0.46, p = 0.0001) but not with the serum creatinine level in elderly hypertensive patients. In middle-aged hypertensive patients, the LVM index was related to both serum uric acid level (r = 0.41, p = 0.007) and serum creatinine level (r = 0.43, p = 0.003). In conclusion, serum creatinine level may underestimate hypertensive renal involvement in elderly hypertensive patients. In contrast, serum uric acid level may be a sensitive indicator of hypertensive target organ damage irrespective of age.