RESUMEN
PURPOSE OF REVIEW: Patients with hypertrophic cardiomyopathy (HCM) who have left ventricular outflow tract obstruction (LVOTO) often experience severe symptoms and functional limitation. Relief of LVOTO can be achieved by two invasive interventions, i.e., surgery myectomy and alcohol septal ablation (ASA), leading in experienced hands to a dramatic improvement in clinical status. Despite extensive research, however, the choice of the best option in individual patients remains challenging and poses numerous clinical dilemmas. RECENT FINDINGS: Invasive strategies have been recently incorporated in recommendations for the diagnosis and treatment of HCM on both sides of the Atlantic. These guidelines are based on a bulk of well-designed but retrospective studies as well as on expert opinions. Evidence now exists that adequate evaluation and management of HCM requires a multidisciplinary team capable of choosing the best available options. Management of LVOTO still varies largely based on local expertise and patient preference. Following the trend that has emerged for other cardiac diseases amenable to invasive interventions, the concept of a "HCM heart team" is coming of age.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cardiomiopatía Hipertrófica , Ablación por Catéter , Miomectomía Uterina , Cardiomiopatía Hipertrófica/cirugía , Femenino , Humanos , Estudios RetrospectivosRESUMEN
We aimed to evaluate efficacy and tolerability of a protocol including lifestyle modifications and a novel combination of dietary supplements in prehypertension. A prospective, double-blind, randomised, placebo-controlled trial was conducted in 176 subjects (103 men, aged 52±10 years), with blood pressure (BP) of 130-139 mm Hg systolic and/or 85-89 mm Hg diastolic entered. After a single-blind run-in period, participants were randomised to twice daily placebo (n=88) or a commercially available combination pill (n=88). Primary endpoints were the differences in clinic BP between the two groups at the end of the trial. Secondary endpoints included intragroup differences in clinic BP during the study period and response rates (that is, BP <130/85 mm Hg or a BP reduction >5 mm Hg on week 12). Baseline characteristics were similar among the treatment groups. At 12 weeks, the supplement group had lower systolic BP (124±9 versus 132±7 mm Hg, P<0.0001) and similar diastolic BP (81±8 versus 82±7 mm Hg, P=0.382) compared to the placebo group. With respect to baseline measures, changes in BP with supplements were statistically significant for systolic (-9.3±4.2 mm Hg, P<0.0001) and diastolic values (-4.2±3.6 mm Hg, P<0.0001). Changes versus baseline in systolic and diastolic BP, conversely, were not different on placebo. The overall response rate at week 12 was significantly greater with supplements than placebo (58% (51 of 88) and 25% (22 of 88), respectively, P<0.0001). This randomised trial shows that combination of supplements with BP-lowering effect is an effective additional treatment to conventional lifestyle modifications for a better control of systolic BP in prehypertension.
Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Suplementos Dietéticos , Prehipertensión/tratamiento farmacológico , Adulto , Antihipertensivos/efectos adversos , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Prehipertensión/diagnóstico , Prehipertensión/fisiopatología , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD. We examined three polymorphisms of the TERT gene (VNTR MNS16A, rs2853691, rs33954691) and three polymorphisms of the TERC gene (rs12696304, rs3772190, rs16847897) in a sample of 220 AD patients and 146 controls. MNS16A LL genotype was found to be associated with an increased risk of AD only in males [interaction term adjusted OR=3.55 (95% CI 1.2-10.2)]. The three TERC single nucleotide polymorphisms are in strict linkage disequilibrium and their genotype combinations influenced the age at AD onset (AAO). The combined genotype GG-TT-CC was associated with a mean AAO six years lower (70.5±6.7) than that associated with the other genotype combinations (76.04±6.7, p=0.01). The fact that the MNS16 L allele has been reported to lower TERT expression, and that the TERC alleles G, T, C (rs12696304, rs3772190, rs16847897 in this order have been repeatedly found associated with shorter LTL, seems to corroborate the hypothesis of a role of telomere length and telomerase in AD susceptibility.
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Enfermedad de Alzheimer/genética , Longevidad/genética , Polimorfismo de Nucleótido Simple , ARN/genética , Telomerasa/genética , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Humanos , Italia , Modelos Lineales , Modelos Logísticos , Masculino , Acortamiento del TelómeroRESUMEN
BACKGROUND: Over the last two decades the interest on patent foramen ovale (PFO) as a cause of cardioembolism in cryptogenic stroke has tremendously increased, thanks to the availability of better techniques to diagnose cardiac right-to-left shunt by ultrasounds and of percutaneous means of PFO treatment with interventional techniques. Many studies have been published that have attempted to define diagnostic methodology, prognosis, and optimal treatment (pharmacological or percutaneous closure) of PFO patients with cryptogenic stroke. Unfortunately, even today, definitive evidence is still lacking, and clinical management is not consistent among cardiologists. AIMS: This review aims to evaluate the role of PFO in cryptogenic stroke, the diagnostic accuracy of transcranial Doppler, contrast transthoracic and transesophageal echocardiography in the diagnosis of left-fright shunt and PFO; and discuss the indications to medical treatment and percutaneous closure of PFO. METHODS: All studies published in the literature on PFO and cryptogenic stroke are considered and discussed. RESULTS: We define an appropriate diagnostic and clinical management of PFO patients with cryptogenic stroke. CONCLUSION: After many years of interest on PFO and many concluded studies, there are still no definitive data. However, we are on good track for an appropriate management of PFO patients and cryptogenic stroke.
Asunto(s)
Foramen Oval Permeable/complicaciones , Accidente Cerebrovascular/etiología , Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Cateterismo Cardíaco/métodos , Ecocardiografía/métodos , Embolia Paradójica/diagnóstico por imagen , Embolia Paradójica/etiología , Embolia Paradójica/terapia , Foramen Oval Permeable/diagnóstico por imagen , Foramen Oval Permeable/terapia , Humanos , Recurrencia , Medición de Riesgo/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Warfarina/uso terapéuticoRESUMEN
Androgens play a pivotal role in cardiovascular function and their effects differ between men and women. In postmenopausal women, testosterone replacement within physiological levels is associated with overall well-being. However, a definitive explanation as to how androgens have an impact on cardiovascular health in postmenopausal women and whether they may be used for cardiovascular treatment has yet to be established. With these aims, a systematic review of the existing studies on the link between androgens and cardiovascular disease and the effects of testosterone therapy on cardiovascular outcomes in postmenopausal women has been conducted. The few existing studies on cardiovascular outcomes in postmenopausal women indicate no effect or a deleterious effect of increasing androgens and increased cardiovascular risk. However, there is evidence of a favorable effect of androgens on surrogate cardiovascular markers in postmenopausal women, such as high density lipoprotein cholesterol, total cholesterol, body fat mass and triglycerides. Further studies are therefore needed to clarify the impact of therapy with androgens on cardiovascular health in postmenopausal women. The cardiovascular effect of testosterone or methyltestosterone with or without concomitant estrogens needs to be elucidated.
Asunto(s)
Andrógenos , Enfermedades Cardiovasculares , Posmenopausia , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/prevención & control , Sistema Cardiovascular/efectos de los fármacos , Terapia de Reemplazo de Estrógeno , Femenino , Humanos , MEDLINE , Metiltestosterona/uso terapéutico , Persona de Mediana Edad , Factores de Riesgo , Testosterona/efectos adversos , Testosterona/fisiología , Testosterona/uso terapéuticoRESUMEN
Noninvasive coronary angiography with multislice computed tomography (CT) scanners is feasible with high sensitivity and negative predictive value. The radiation exposure associated with this technique, however, is high and concerns in the widespread use of CT have arisen. We evaluated the diagnostic accuracy of coronary angiography using 320-row CT, which avoids exposure-intensive overscanning and overranging. We prospectively studied 118 unselected consecutive patients with suspected coronary artery disease (CAD) referred for invasive coronary angiography (ICA). All patients had 320-row CT within 1 week of ICA, which, together with quantitative analysis, served as the reference standard. Of the 65 out of 118 patients who were diagnosed as having CAD by ICA, 64 (98 %) were correctly identified at 320-row CT. Noteworthy, 320-row CT correctly detected CAD in 3 patients with atrial fibrillation and ruled out the disease in the other 8 patients. From 151 significant coronary stenoses detected on ICA, 137 (91 %) were correctly identified with 320-row CT. In the per-patient analysis, sensitivity and specificity of 320-row CT were 98 and 91 %, respectively. In the per-vessel analysis, sensitivity and specificity of 320-row CT were 93 and 95 %, respectively. In the per segment analysis, sensitivity and specificity of 320-row CT were 91 and 99 %, respectively. Diameter stenosis determined with the use of CT showed good correlation with ICA (P < 0.001, R = 0.81) without significant underestimation or overestimation (-3.1 ± 24.4 %; P = 0.08). Comparison of CT with ICA revealed a significantly smaller effective radiation dose (3.1 ± 2.3 vs. 6.5 ± 4.2 mSv; P < 0.05) and amount of contrast agent required (99 ± 51 vs. 65 ± 42 ml, P < 0.05) for 320 row CT. The present study in an unselected population including patients with atrial fibrillation demonstrates that 320-row CT may significantly reduce the radiation dose and amount of contrast agent required compared with ICA while maintaining a very high diagnostic accuracy.
Asunto(s)
Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Tomografía Computarizada Multidetector , Anciano , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Estudios Prospectivos , Dosis de Radiación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Middle-aged women have a lower prevalence of coronary artery disease (CAD) compared with age-matched men, but mechanisms underlying this phenomenon remain controversial. To verify whether there is a link between circulating endothelial progenitor cells (EPCs) and gender-specific difference of CAD, we compared subpopulations of EPCs among postmenopausal normal women, patients with CAD, and age-matched men. METHODS: We studied 71 consecutive middle-aged patients with stable CAD (30 postmenopausal women and 41 men) and 40 middle-aged normal controls (20 postmenopausal women and 20 men). Blood samples were drawn at time of coronary angiography and subpopulations of EPCs were measured by flow cytometry. RESULTS: Women and men with CAD had similar age, risk factors, clinical presentation, left ventricular function, extension of CAD, and medical therapy at time of coronary angiography. Hematologic analysis showed that men and women with CAD had similar white cell count, mononuclear cells, and subpopulations of EPCs. Postmenopausal normal women, conversely, had significantly higher absolute numbers of CD34+, CD133+, CD105+ and CD14+ cells than other groups. CONCLUSIONS: Increased numbers of subpopulations of EPCs in normal postmenopausal women might contribute to the gender-specific difference of CAD in middle age. Lack of difference in EPCs between women and men with CAD suggests that stem cells become unable to play a protective role when the disease is clinically evident.
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Células Endoteliales/metabolismo , Posmenopausia/metabolismo , Células Madre/metabolismo , Antígeno AC133 , Antígenos CD/metabolismo , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/metabolismo , Endoglina , Femenino , Citometría de Flujo , Glicoproteínas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Péptidos/metabolismo , Receptores de Superficie Celular/metabolismoRESUMEN
The mammalian chromosomes present specific sites of gaps or breaks, the common fragile sites (CFSs), when the cells are exposed to DNA replication stress or to some DNA binding compounds. CFSs span hundreds or thousands of kilobases. The analysis of these sequences has not definitively clarified the causes of their fragility. There is considerable evidence that CFSs are regions of late or slowed replication in the presence of sequence elements that have the propensity to form secondary structures, and that the cytogenetic expression of CFSs may be due to unreplicated DNA. In order to analyse the relationship between DNA replication time and fragility, in this work we have investigated the timing of replication of sequences mapping within two CFSs (FRA1H and FRA2G), of syntenic non-fragile sequences and of early and late replicating control sequences by using fluorescent in situ hybridization on interphase nuclei, conventional fluorescence microscopy and confocal microscopy. Our results indicate that the fragile sequences are slow replicating and that they enter G2 phase unreplicated with very high frequency. Thus these regions could sometimes reach mitosis unreplicated or undercondensed and be expressed as chromosome gaps/breakages.
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Sitios Frágiles del Cromosoma , Replicación del ADN , Células Cultivadas , Cromosomas Artificiales Bacterianos , Humanos , Hibridación Fluorescente in Situ , Microscopía Confocal , Microscopía FluorescenteRESUMEN
Common fragile sites are nonrandom loci that show gaps and breaks when cells are exposed to specific compounds. They are preferentially involved in recombination, chromosomal rearrangements, and foreign DNA integration. These sites have been suggested to play a role in chromosome instability observed in cancer. In this work we used a FISH-based approach to identify a BAC contig that spans the FRA2G fragile site located at the 2q31 region. Our observations indicate that a very fragile region spanning at least 450 kb is present within a large fragile region that extends over 1 Mb. At least seven genes are mapped in the fragile region. One of these seems to be a good candidate as a potential tumor suppressor gene impaired by the recurrent deletions observed at the 2q31 region in some neoplasms. In the fragile region, a considerable number of regions of high flexibility that may be related to the fragility are present.
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Fragilidad Cromosómica , Cromosomas Artificiales Bacterianos , Islas de CpG/genética , Humanos , Hibridación Fluorescente in SituRESUMEN
We investigated the 5S ribosomal RNA (rRNA) genes of the isopod crustacean Asellus aquaticus. Using PCR amplification, three different tandemly repeated units containing 5S rDNA were identified. Two of the three sequences were cloned and sequenced. One of them was 1842 bp and presented a 5S rRNA gene and a U1 small nuclear RNA (snRNA) gene. This type of linkage had never been observed before. The other repeat consisted of 477 bp and contained only an incomplete 5S rRNA gene lacking the first eight nucleotides and a spacer sequence. The third sequence was 6553 bp long and contained a 5S rRNA gene and the four core histone genes. The PCR products were used as probes in fluorescent in situ hybridization (FISH) experiments to locate them on chromosomes of A. aquaticus. The possible evolutionary origin of the three repeated units is discussed.
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Crustáceos/genética , ADN Ribosómico/genética , Ligamiento Genético/genética , ARN Ribosómico 5S/genética , ARN Nuclear Pequeño/genética , Secuencias Repetidas en Tándem/genética , Animales , Secuencia de Bases , Genes , Genoma , Hibridación Fluorescente in Situ , Masculino , Metafase/genética , Datos de Secuencia Molecular , Homología de Secuencia de Ácido Nucleico , Espermatogonias/citología , Espermatogonias/metabolismoRESUMEN
BACKGROUND: It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers. METHODS: Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo. RESULTS: All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia. CONCLUSIONS: PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.
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Antagonistas Adrenérgicos beta/uso terapéutico , Angina de Pecho/tratamiento farmacológico , Atenolol/uso terapéutico , Isquemia Miocárdica/fisiopatología , Inhibidores de Fosfodiesterasa/farmacología , Piperazinas/farmacología , Adulto , Anciano , Angina de Pecho/complicaciones , Presión Sanguínea/efectos de los fármacos , Enfermedad Crónica , Contraindicaciones , Interacciones Farmacológicas , Prueba de Esfuerzo , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/etiología , Purinas , Citrato de Sildenafil , SulfonasRESUMEN
In this study we have used FISH to examine the relationship between a group of homeobox genes, namely DLX1/DLX2, EVX2 and four HOXD genes (10, 11, 12, 13), that map to region q31 on chromosome 2, and the FRA2G and FRA2H fragile sites located at 2q31 and 2q32.1 respectively. Our results indicate that these homeobox genes lie between the two fragile regions.
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Fragilidad Cromosómica/genética , Cromosomas Humanos Par 2/genética , Genes Homeobox/genética , Proteínas de Homeodominio , Familia de Multigenes/genética , Afidicolina/farmacología , Rotura Cromosómica/genética , Sitios Frágiles del Cromosoma , Sondas de ADN , Humanos , Hibridación Fluorescente in Situ , Indoles , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Mapeo Físico de CromosomaRESUMEN
In this work, genomic in-situ hybridization (GISH) was used to study the sex chromosome molecular differentiation on chromosomes of male and female individuals of the isopod crustacean Asellus aquaticus. As a composite hybridization probe, we contemporaneously used male and female whole genomic DNA differently labelled in the presence of an excess of unlabelled DNA of the female homogametic sex. The karyotype of A. aquaticius normally displays eight homomorphic chromosome pairs, but a heteromorphic sex chromosome pair is present in about a quarter of the males of a natural population previously identified by us. GISH did not reveal any sex chromosome molecular differentiation on the male and female homomorphic sex chromosome pair, and the karyotypes of these individuals were equally labelled by the male- and female-derived probe, while the heteromorphic Y chromosome showed a differentially labelled region only with the male-derived probe. This region evidently contains male-specific sequences but, because no similar hybridized region is observed on the male homomorphic chromosome pair, they are probably not important for sex determination but represent a molecular differentiation acquired from the Y chromosome.
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Hibridación in Situ , Cromosomas Sexuales , Animales , Crustáceos , Sondas de ADN , Femenino , Masculino , Diferenciación Sexual/genéticaRESUMEN
A tandemly repeated unit of 6553 bp containing a copy of the four core histone genes H2B, H2A, H3, and H4, and also a 5S rRNA gene, was amplified by PCR from genomic DNA of the isopod crustacean Asellus aquaticus. The linkage between 5S rRNA genes and histone genes has been so far observed in only one other organism, the anostrac crustacean Artemia salina. The gene cluster was cloned and sequenced. The histone genes, in their 3' flanking region, have the interesting feature of possessing two different mRNA termination signals, the stem-loop structure and the AATAAA sequence. A part of the PCR product was used as a probe in FISH experiments to locate the gene cluster on an inter-individually variable number of chromosomes from 6 to 12 per diploid cell, always in a terminal position and never associated with the heterochromatic areas. Fluorescence in situ hybridization (FISH) was also performed on preparations of released chromatin and the reiteration level of the gene cluster was determined as approximately 200-300 copies per haploid genome.
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Mapeo Cromosómico , Crustáceos/genética , ARN Ribosómico 5S/genética , Secuencias Repetidas en Tándem , Animales , Southern Blotting , Histonas/genética , Hibridación in Situ , Hibridación Fluorescente in Situ , Modelos Genéticos , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: The role of testosterone on the development of coronary artery disease in men is controversial. The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone. Conversely, recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men. Accordingly, the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men. METHODS AND RESULTS: After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order). The exercise tests were performed 30 minutes after administration of testosterone (2.5 mg IV in 5 minutes) or placebo. All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo, whereas only 10 patients had a positive exercise test after testosterone. Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone. Compared with placebo, testosterone increased time to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression (135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus 132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST-segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05). CONCLUSIONS: Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease. This effect may be related to a direct coronary-relaxing effect.
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Fármacos Cardiovasculares/farmacología , Enfermedad Coronaria/complicaciones , Isquemia Miocárdica/prevención & control , Testosterona/farmacología , Anciano , Fármacos Cardiovasculares/uso terapéutico , Electrocardiografía , Prueba de Esfuerzo/efectos adversos , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/etiología , Testosterona/uso terapéuticoRESUMEN
In this investigation we analysed the 5S rRNA genes of the isopod crustacean Proasellus coxalis, 5S rDNA hybridization of digested genomic DNA and amplification by PCR demonstrate that these genes are organized in tandem repeats of 589 bp, 120 of which represent the coding sequence and 469 the spacer sequence. Proasellus coxalis is the first crustacean species in which 5S rRNA genes have been found tandemly arranged without being linked to other repeated genes. The PCR product has been used as a probe in FISH to locate the 5S rRNA genes on two chromosome pairs of the P. coxalis karyotype. Comparison of the 5S rRNA sequence of this species with previously published sequences of six other crustacean species shows the existence of a good correlation between phylogenetic relationships and sequence identity.