RESUMEN
BACKGROUND/OBJECTIVES: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the post-thrombotic syndrome (PTS). PATIENTS/METHODS: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. RESULTS: Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2-year SF-36 PCS scores. PTS alone independently predicted 2-year VEINES-QOL (P < 0.0001) and VEINES-Sym (P < 0.0001) scores. CONCLUSIONS: Development of PTS is the principal determinant of health-related QOL 2 years after DVT. Our study provides prognostic information on patient-reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.
Asunto(s)
Calidad de Vida , Trombosis de la Vena/complicaciones , Trombosis de la Vena/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Síndrome Postrombótico/diagnóstico , Síndrome Postrombótico/etiología , Pronóstico , Estudios Prospectivos , Encuestas y Cuestionarios , Trombosis de la Vena/tratamiento farmacológicoRESUMEN
Beta thalassemia is an autosomal recessive disorder characterized by reduced (beta(+)) or absent (beta(0)) beta-globin chain synthesis. In Lebanon it is the most predominant genetic defect. In this study we investigated the religious and geographic distribution of the beta-thalassemia mutations identified in Lebanon, and traced their precise origins. A total of 520 beta-globin chromosomes from patients of different religious and regional backgrounds was studied. Beta thalassemia mutations were identified using Amplification Refractory Mutation System (ARMS) PCR or direct gene sequencing. Six (IVS-I-110, IVS-I-1, IVS-I-6, IVS-II-1, cd 5 and the C > T substitution at cd 29) out of 20 beta-globin defects identified accounted for more than 86% of the total beta-thalassemia chromosomes. Sunni Muslims had the highest beta-thalassemia carrier rate and presented the greatest heterogeneity, with 16 different mutations. Shiite Muslims followed closely with 13 mutations, whereas Maronites represented 11.9% of all beta-thalassemic subjects and carried 7 different mutations. RFLP haplotype analysis showed that the observed genetic diversity originated from both new mutational events and gene flow from population migration. This study provides information about the types and distribution of beta-thalassemia mutations within each religious group and geographic region, which is essential for the implementation of screening and prevention programs.
Asunto(s)
Emigración e Inmigración , Heterogeneidad Genética , Genética de Población , Globinas/genética , Mutación/genética , Talasemia beta/genética , Frecuencia de los Genes , Pruebas Genéticas , Geografía , Haplotipos/genética , Humanos , Líbano , Polimorfismo de Longitud del Fragmento de Restricción , Talasemia beta/epidemiologíaRESUMEN
Beta-thalassemia is the most common genetic disorder in the Lebanese population. Of the 200 different mutations in the beta-globin gene that leads to thalassemia, the IVSI-110 (29.87%), IVSI-6 (20.74%), IVSI-1 (14.07%), IVSII-1 (9.13%), Cd29 (9.13%), and Cd30 (3.95%) mutations are the most frequent among Lebanese thalassemic patients. These mutations are also present at high frequencies in the East Mediterranean region. Due to this high prevalence of certain beta-thalassemia mutations, a rapid technique for the prenatal diagnosis of these mutations was implemented. The technique used is based on Real-Time PCR quantification and melting curve analysis of the amplified fragment using the LightCycler. The DNA samples used for amplification were obtained from CVS or amniotic fluid. Six mutations were easily and efficiently detected using only 3 sets of probes. With this method, mutant genotypes can be easily distinguished from normal alleles. In prenatal diagnosis, the accuracy and the speed of testing are paramount. The method of prenatal beta-thalassemia mutations detection described here is efficient and fast, with the entire procedure including DNA preparation taking less than half a workday. It is safe, does not involve radioactivity, and is accurate showing 100% concordance with conventional DNA sequencing methods.
Asunto(s)
Pruebas Genéticas/métodos , Globinas/genética , Mutación , Diagnóstico Prenatal/métodos , Talasemia beta/diagnóstico , Talasemia beta/genética , Secuencia de Bases , Análisis Mutacional de ADN/métodos , Genotipo , Humanos , Sondas de Oligonucleótidos/genética , Reacción en Cadena de la Polimerasa/métodosRESUMEN
The effect of a number of host and environmental factors on the onset of type 1 diabetes mellitus (DM1) in a group of Lebanese children and young adults was studied. Results showed that DM1 in a group of 253 patients presented no gender preference and that the age of onset was similar in both genders. The overall body mass index reflected good metabolic control. HbA1c had a mean value of 8.98%, suggesting poor glucose control. Family history of DM1 and type 2 diabetes mellitus as well as consanguinity in patients' families were not different from those reported in the literature. Finally, onset of DM1 showed seasonal variation, peaking during winter months. DM1 showed a higher prevalence of onset among children born first and a decreased incidence as birth order increased. This study provides valuable data for the diagnosis, control and prevention of DM1 in children.
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Edad de Inicio , Animales , Orden de Nacimiento , Índice de Masa Corporal , Lactancia Materna/estadística & datos numéricos , Niño , Consanguinidad , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Hemoglobina Glucada/análisis , Humanos , Incidencia , Líbano/epidemiología , Masculino , Leche , Prevalencia , Factores de Riesgo , Estaciones del Año , Distribución por SexoAsunto(s)
Talasemia/complicaciones , Tromboembolia/complicaciones , Tromboembolia/epidemiología , Adolescente , Adulto , Anciano , Alelos , Transfusión Sanguínea , Niño , Preescolar , Factor V/genética , Femenino , Frecuencia de los Genes , Humanos , Líbano , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Talasemia/epidemiologíaRESUMEN
Sickle cell disease (SCD) is an inherited autosomal recessive disorder of the beta-globin chain. Despite the fact that all subjects with SCD have the same single base pair mutation, the severity of the clinical and hematological manifestations is extremely variable. This study examined for the first time in Lebanon the correlation between the clinical manifestation of SCD and the beta-globin gene haplotypes. The haplotypes of 50 patients diagnosed with SCD were determined using polymerase chain reaction amplification of fragments containing nine polymorphic restriction sites around and within the epsilon-Ggamma-Agamma-psibeta-delta-beta-globin gene complex. Most reported haplotypes were found in our population with the Benin haplotype as the most prevalent one. When the patients were divided according to their HbF levels into three groups (Group A: HbF < 5%, Group B: HbF between 5 and 15%, and Group C: HbF > 15%), surprisingly, the highest levels of HbF were associated with the most severe clinical cases. Our findings suggest that fetal hemoglobin levels are important but not the only parameters that affect the severity of the disease. In addition, the high levels of HbF in patients with CAR haplotypes did not seem to ameliorate the severity of symptoms, suggesting that genetic factors other than haplotypes are the major determinants of increased HbF levels in Lebanon.
Asunto(s)
Anemia de Células Falciformes/etiología , Hemoglobina Fetal/metabolismo , Globinas/genética , Haplotipos , Adolescente , Adulto , Anemia de Células Falciformes/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Líbano/epidemiología , Masculino , Familia de Multigenes , Dolor , Fenotipo , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
Type-1 diabetes (T1D) is an autoimmune disease leading to insulin deficiency. Its occurrence is influenced by genetic and environmental factors. The human leukocyte antigen (HLA) region on chromosome 6 accounts for 45% of the genetic susceptibility for the disease, mainly the HLA-DQB1*0201 and HLA-DQB1*0302 alleles. Among the environmental factors involved, early exposure to cow's milk seems to be a trigger. In this study, we investigated the occurrence of T1D in 253 Lebanese Caucasian patients, in relation to HLA-DQB1*0201, HLA-DQB1*0302, HLA-DQB1*0602, gender, and early exposure to cow's milk, as well as to family history of T1D and type-2 diabetes (T2D). Our genetic analysis results show that in the patients studied, 77% and 40% were positive for BQ1*0201 and BQ1*0302, respectively. As for BQ1*0602, only 0.8% of patients were positive for this T1D protective allele, compared with 24% among the controls. Furthermore, our results did not show any gender preference of the disease or any effects of early intake of cow's milk on the age at onset of T1D. When family history of T2D or T1D was studied, our results show a novel finding whereby an immediate family history of T2D, but not T1D, delays the age at onset of T1D.
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/genética , Registros Médicos , Adulto , Edad de Inicio , Animales , Ingestión de Líquidos , Femenino , Genotipo , Antígenos HLA/análisis , Humanos , Masculino , LecheRESUMEN
A balance between circulating and locally released vasoconstrictors, such as endothelin-1 (ET-1), and vasodilators, such as nitric oxide, controls vascular smooth muscle tone. In the study reported here, using the technique of simultaneous measurements of intracellular free calcium ([Ca2+]i) and tension, we investigated the effects of a nitric oxide donor, sodium nitroprusside (NaNP) on endothelin-1- and U46619- [a thromboxane angiotensin-II (TXA-II) mimetic] induced sustained increases in tension and [Ca2+]i in intact and endothelium-denuded rabbit thoracic aortas. Our results showed that, in both intact and endothelium-denuded preparations, the nitric oxide donor NaNP (10(-6) M) reverses the ET-1- (10(-7) M) and U46619- (10(-7) M) induced sustained increase in tension but not in [Ca2+]i. However, it did not reduce the ET-1- and U46619-induced responses. Our data suggest that nitric oxide production modulates vascular smooth muscle tension via a mechanism that is independent of that generated by vasoconstrictors such as ET-1 and TXA-II.
Asunto(s)
Calcio/metabolismo , Endotelina-1/farmacología , Músculo Liso Vascular/efectos de los fármacos , Óxido Nítrico/fisiología , Vasodilatación/efectos de los fármacos , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Animales , GMP Cíclico/fisiología , Femenino , Masculino , Músculo Liso Vascular/fisiología , NG-Nitroarginina Metil Éster/farmacología , Nitroprusiato/farmacología , ConejosRESUMEN
It was reported that neuropeptide Y (NPY) affects cardiac and vascular smooth muscle (VSM) function probably by increasing intracellular Ca2+. In this study, using fura-2 microfluorometry and fluo-3 confocal microscopy techniques for intracellular Ca2+ measurement, we attempted to verify whether the action of NPY receptor's stimulation in heart and VSM cells modulates intracellular Ca2+ and whether this effect is mediated via the Y1 receptor type. Using spontaneously contracting single ventricular heart cells of 10-day-old embryonic chicks and the fluo-3 confocal microscopy Ca2+ measurement technique to localize cytosolic ([Ca]c) and nuclear ([Ca]n) free Ca2+ level and distribution, 10-10 M of human (h) NPY significantly (P < 0.05) increased the frequency of cytosolic and nuclear Ca2+ transients during spontaneous contraction. Increasing the concentration of hNPY (10(-9) M) did not further increase the frequency of Ca2+ transients. The L-type Ca2+ channel blocker, nifedipine (10(-5) M), significantly (P < 0.001) blocked the spontaneous rise of intracellular Ca2+ in the absence and presence of hNPY (10(-10) and 10(-9) M). However, the selective Y1 receptor antagonist, BIBP3226 (10(-6) M), significantly decreased the hNPY-induced (10(-10) and 10(-9) M) increase in the frequency of Ca2+ transients back to near the control level (P < 0.05). In resting nonworking heart and human aortic VSM cells, hNPY induced a dose-dependent sustained increase of basal resting intracellular Ca2+ with an EC50 near 10(-9) M. This sustained increase was cytosolic and nuclear and was completely blocked by the Ca2+ chelator EGTA, and was significantly decreased by the Y1 receptor antagonist BIBP3226 in both heart (P < 0.05) and VSM (P < 0.01) cells. These results strongly suggest that NPY stimulates the resting basal steady-state Ca2+ influx through the sarcolemma and induces sustained increases of cytosolic and nuclear calcium, in good part, via the activation of the sarcolemma membrane Y1 receptor type in both resting heart and VSM cells. In addition, NPY also increased the frequency of Ca2+ transients during spontaneous contraction of heart cells mainly via the activation of the Y1 receptor type, which may explain in part the active cardiovascular action of this peptide.
Asunto(s)
Calcio/metabolismo , Núcleo Celular/metabolismo , Citosol/metabolismo , Músculo Liso Vascular/metabolismo , Miocardio/metabolismo , Neuropéptido Y/farmacología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/fisiología , Embrión de Pollo , Relación Dosis-Respuesta a Droga , Humanos , Músculo Liso Vascular/citologíaRESUMEN
Recent studies in heart cells have shown taurine to induce a sustained increase of both intracellular Ca2+ and Na+. These results led us to believe that the increase in Na+ by taurine could be due to Na+ entry through the taurine-Na+ cotransporter which in turn favours transarcolemmal Ca2+ influx through Na(+)-Ca2+ exchange. Therefore, we investigated the effect of beta-alanine, a blocker of the taurine-Na+ cotransporter and low concentrations of CBDMB (a pyrazine derivative, 5-(N-4chlorobenzyl)-2',4'-dimethylbenzamil), a Na(+)-Ca2+ exchanger blocker on taurine-induced [Ca]i increase in embryonic chick heart cells. Using Fura-2 Ca2+ imaging and Fluo-3Ca2+ confocal microscopy techniques, taurine (20 mM) as expected, induced a sustained increase in [Ca]i at both the cytosolic and the nuclear levels. Preexposure to 500 microM of the blocker of the taurine-Na+ cotransporter, beta-alanine, prevented the amino acid-induced increase of total [Ca]i. On the other hand, application of beta-alanine did not reverse the action of taurine on total [Ca]i. However, low concentrations of the Na(+)-Ca2+ exchanger blocker, CBDMB, reversed the taurine-induced sustained increase of cytosolic and nuclear free calcium (in presence or absence of beta-alanine). Thus, the effect of taurine on [Ca]i in heart cells appears to be due to Na+ entry through the taurine-Na+ cotransporter which in turn favours transarcolemmal Ca2+ influx through the Na(+)-Ca2+ exchanger.