RESUMEN
Neisseria meningitidis is a major cause of bacterial septicemia and meningitis. Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.
Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Vacunas Bacterianas , Genoma Bacteriano , Neisseria meningitidis/genética , Neisseria meningitidis/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/química , Antígenos Bacterianos/genética , Antígenos de Superficie/química , Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Cápsulas Bacterianas , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Vacunas Bacterianas/genética , Vacunas Bacterianas/inmunología , Secuencia Conservada , Escherichia coli/genética , Humanos , Sueros Inmunes/inmunología , Ratones , Neisseria meningitidis/clasificación , Neisseria meningitidis/patogenicidad , Sistemas de Lectura Abierta , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/aislamiento & purificación , Recombinación Genética , Análisis de Secuencia de ADN , Serotipificación , Vacunación , VirulenciaRESUMEN
We have analyzed transcriptional regulation of the chlamydial plasmid pCT. Transcription of a full-length 2.9-kb ORF1-ORF2 mRNA is likely to be regulated by the sigma 66 transcription factor which recognizes the TATAAT and TNGNCA sequences at the -10 and -35 DNA regions, respectively. RNA synthesis starts 39 nucleotides (nt) upstream from the ATG start codon of ORF1 and terminates within the downstream ORF3 DNA region. A 2.8-kb transcript transverses the ORF3-6 DNA region, while two transcripts of 2.2 and 1.9 kb cover the ORF4-6 DNA region. These mRNAs overlap two abundant transcripts which regulate the expression of the ORF3 and ORF4 genes. The accumulation of transcripts associated with these ORFs is likely to be regulated at the level of RNA synthesis by an unknown sigma factor which could select the RTTTAAA and TTYTTR sequences located at the -10 and -35 DNA regions, respectively. This new promoter consensus sequence could be unique to the gene expression machinery of Chlamydiae.
Asunto(s)
Chlamydia trachomatis/genética , Regulación Bacteriana de la Expresión Génica , Sistemas de Lectura Abierta , Plásmidos/genética , Regiones Promotoras Genéticas , Transcripción Genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Secuencia de Bases , Secuencia de Consenso , ARN Polimerasas Dirigidas por ADN/metabolismo , Escherichia coli , Genes Bacterianos , Datos de Secuencia Molecular , ARN Bacteriano/biosíntesis , ARN Mensajero/biosíntesis , Secuencias Reguladoras de Ácidos Nucleicos , Alineación de Secuencia , Homología de Secuencia de Ácido Nucleico , Factor sigma/genética , Factor sigma/metabolismoRESUMEN
Monoclonal antibodies (Mab) were raised against CRM197, a non-toxic mutant of diphtheria toxin (DT). The ability of four Mabs to bind DT and the six functional mutants CRM197, CRM176, CRM228, CRM1001, CRM45 and CRM30 was assessed by immunoblotting and by a radioimmunoassay in which the protein antigen in solution competes with labeled CRM197 for the Mab binding site. The results show that the peptides recognized by Mab11.3, Mab53 and Mab23 are accessible in the mutant molecules in solution but not when they are part of the native DT structure, which could therefore be described for this purpose as 'closed' in contrast with an 'open' conformation of CRM197, CRM176 and CRM228. In particular, the behaviour of Mab53 indicates that the single amino acid substitutions in the A fragments of CRM197 and CRM176 also affect the conformation of their B fragments.
Asunto(s)
Anticuerpos Monoclonales , Toxoide Diftérico , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Unión Competitiva , Toxoide Diftérico/genética , Toxoide Diftérico/inmunología , Epítopos/inmunología , Ratones , Ratones Endogámicos BALB C , Mutación , Conformación ProteicaRESUMEN
Bacterial immunogens (whole cells of Borrelia burgdorferi, elementary bodies of Chlamydia trachomatis and purified proteins of 22 and 24 kDa of Borrelia hermsii) were emulsified with an excess of complete Freund's adjuvant and injected (i.p.) on days 0, 7, 14 and 21, into BALB/c mice treated with pristane on day 6. This procedure induced the development of antibody-producing ascites tumours which could be serially transplanted in pristane-conditioned mice. Ascites tumours continued to yield a consistent amount of specific polyclonal antibody after ten serial transplants. The method described appears to be particularly useful for the production of a large amount of antibody when only small amounts of immunogen are available.
Asunto(s)
Carcinoma de Ehrlich/inmunología , Animales , Especificidad de Anticuerpos , Borrelia/inmunología , Carcinógenos , Carcinoma de Ehrlich/etiología , Chlamydia trachomatis/inmunología , Adyuvante de Freund , Inmunización , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , TerpenosRESUMEN
A polymerase chain reaction (PCR) amplification assay was developed to detect Coxsackievirus B3 ribonucleic acid (RNA) in blood and myocardial tissue of explanted hearts from 40 patients who underwent cardiac transplantation and in 1 normal heart. Twenty-one patients were affected by idiopathic dilated cardiomyopathy of different duration and 19 by coronary artery disease. Coxsackievirus B3 in vitro infected Vero cells and cells infected by related human enteroviruses (Coxsackievirus B2, B4, and poliovirus 1) were used as reaction controls. PCR was performed using 4 pairs of primers homologous to Coxsackie-virus B3 sequences. Three sets were located in regions of the genome conserved at nucleotide level between several enterovirus species (replicase gene, 5' noncoding region), while one was located in a Coxsackievirus B3-specific region (VP1 gene). Total RNA was prepared by acid guanidinium isothiocyanate extraction from tissue stored frozen at -80 degrees C. One microgram of total RNA was retrotranscribed with either antisense primer or with random hexanucleotide primers and then subjected to 40 cycles of amplification. PCR products were separated by electrophoresis on a 10% polyacrylamide gel, electrotransferred to a nylon membrane and then hybridized to oligonucleotide probes specific for the coxsackievirus B3 genome radiolabeled with radioactive isotope of phosphorous. All pairs of primers yielded specific amplification products when tested on Coxsackievirus B3-infected Vero cells, with a sensitivity of 1 infected cell out of 10(5) to 10(6) cells starting from 1 microgram total RNA. Primer sets for regions of Coxsackievirus B3 genome highly conserved between related enteroviral species gave positive amplification also when challenged with RNA from cells infected by Coxsackievirus B2, B4 and poliovirus 1.
Asunto(s)
Cardiomiopatía Dilatada/microbiología , Enterovirus Humano B/genética , Trasplante de Corazón , ARN Viral/análisis , Adulto , Secuencia de Bases , Southern Blotting , Cardiomiopatía Dilatada/cirugía , Enterovirus Humano B/aislamiento & purificación , Femenino , Corazón/microbiología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Sondas de Oligonucleótidos , Reacción en Cadena de la Polimerasa , ARN Viral/sangreRESUMEN
We analyzed the distribution of DRB1, DQA1, DQB1, and DPB1 allelic variants in 48 rheumatoid arthritis (RA) patients, compared with 109 Italian random controls, using PCR amplification and hybridization with specific oligonucleotides. We confirm the previously reported increase of DR4 specificity, in comparison with healthy Italian individuals. In particular, we find a statistically significant positive association of DRB1*0401 and DRB1*0404 alleles with RA. However, when we compare the DR4+ groups, none of the DRB1*04 alleles is increased in the RA group. By sequence analysis, performed on 10 patients, we demonstrate that the DRB1*04 genes of RA show no difference from the DRB1*04 sequences previously published. From the molecular analysis of the other DRB1 polymorphic variants, we find a trend of positive association of DRB1*0101 in DR4-negative patients versus DR4-negative healthy controls and, in the group of DR4-negative and/or DR1-negative patients, a similar increase of DRB1*06. Also, we observe in RA patients a statistically significant increase of DQA1*0301 and DQB1*0302 accompanied by a significant decrease of DQA1*0201, DQA1*0501 and DQB1*0201. Finally, from the analysis of DPB1 gene, it can be assessed that the distribution of DPB1 alleles does not differ significantly between RA patients and healthy controls.
Asunto(s)
Artritis Reumatoide/genética , Enfermedades Autoinmunes/genética , Genes MHC Clase II , Antígenos HLA-D/genética , Adulto , Anciano , Alelos , Secuencia de Aminoácidos , Artritis Reumatoide/inmunología , Enfermedades Autoinmunes/inmunología , Secuencia de Bases , Susceptibilidad a Enfermedades/inmunología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Italia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
Vascular disease is an underestimated complication of neurofibromatosis type 1 (NF1). The few studies available on this disease are based on case reports. The purpose of this study was to evaluate the relationship between 24-h systolic blood pressure (SBP) and 24-h heart rate obtained by ambulatory blood pressure monitoring and the carotid femoral pulse wave velocity, a widely used index of arterial distensibility, evaluated with Complior. We studied 64 young NF1 patients and 30 healthy subjects. There was no difference in pulse wave velocity between NF1 patients and healthy subjects. Ten of the NF1 patients showed 24-h SBP or 24-h diastolic blood pressure (DBP) >95th percentile for age and sex. We divided the NF1 group into subgroups: NF1 patients with 24-h SBP and 24-h DBP < or = 95th percentile for age and sex (NF1A group) and NF1 patients with mean SBP or DBP >95th percentile for age and sex (NF1B group). The pulse wave velocity of NF1A and NF1B patients were 6.3 +/- 1 m/sec and 6.4 +/- 1 m/sec, respectively (P = not significant). A significant relationship was found between 24-h SBP, 24-h heart rate, and pulse wave velocity in healthy subjects, but not in all NF1 patients and also between the NF1A and NF1B groups. Distensibility of the central arteries may be altered by various environmental or genetic factors. Thus, genetic determinants may play a role in the response of the large arteries to blood pressure. The recent discovery of neurofibromin in aortic smooth muscle may explain the vascular abnormalities present in NF1 patients. We emphasize the importance of a careful vascular evaluation using a noninvasive method, such as Complior and a periodic ambulatory blood pressure monitoring to detect NF1 patients at high risk of vascular complications.
Asunto(s)
Frecuencia Cardíaca/fisiología , Neurofibromatosis 1/fisiopatología , Enfermedades Vasculares/fisiopatología , Adolescente , Adulto , Arterias/fisiopatología , Monitoreo Ambulatorio de la Presión Arterial/métodos , Niño , Preescolar , Elasticidad , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Análisis Multivariante , Neurofibromatosis 1/complicaciones , Análisis de Regresión , Enfermedades Vasculares/complicacionesRESUMEN
We examined long-term changes in cognitive function and quality of life (QL) in hypertensive patients by comparing the antihypertensive effect of hydrochlorothiazide (HCTZ) and losartan. We studied 69 patients (age range, 30 to 73 years) with mild-to-moderate hypertension. All patients, in a double-blind study, were randomly allocated to either treatment with 50 mg losartan once daily or 25 mg HCTZ once daily. The sample in each treatment group was divided by age (younger than 60 years or 60 years or older). At baseline and after 26 months, a QL questionnaire appropriate for the hypertensive patients was given. Cognitive function was evaluated, at baseline and after 26 months, by psychometric tests consisting of items from the Mini-Mental State Examination (MMSE) and the Sandoz Clinical Assessment Geriatric (SCAG). A score of less than 24 on the MMSE and more than 40 on the SCAG was predictive of cognitive impairment. The losartan group had a significant improvement in SCAG (P<.001) and MMSE (P<.001). No significant changes were observed in the HCTZ group (SCAG, P = .1; MMSE, P = .2). Sixty-five percent of the elderly had a MMSE score less than 24 and 70% had a SCAG score greater than 40, v. 35% and 48%, respectively, in younger patients. The health state index of QL improved significantly in both groups (losartan group, P<.01; HCTZ group, P<.02); the improvement in QL scores in patients using HCTZ was significant only in subjects aged 60 years and older (P<.04). These results suggest that losartan can have a positive effect not only on blood pressure but also on impaired cognitive function, reversing even minimal cognitive deficits induced by hypertension. The elderly patients in our sample had worse scores and cognitive performance was lower than in younger patients, even if in the losartan group the score improvement was the same at all ages. The same could not be said for HCTZ.
Asunto(s)
Antihipertensivos/uso terapéutico , Cognición/efectos de los fármacos , Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Losartán/uso terapéutico , Calidad de Vida , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Ritmo Circadiano/fisiología , Diuréticos , Método Doble Ciego , Femenino , Humanos , Hipertensión/fisiopatología , Hipertensión/psicología , Masculino , Persona de Mediana Edad , Pronóstico , Psicometría , Encuestas y CuestionariosRESUMEN
Eighty tissue biopsies from 73 women suspected of having papillomavirus (HPV) infection of the lower genital tract were examined by in situ hybridization with biotinylated DNA probes derived from the complete genomes of four HPV types (6, 11, 16, and 18) and restriction analysis of the extracted DNA on Southern blots. In a subset of 52 samples, the in situ test had a 90.4% sensitivity (47 of 52) in detecting the presence or absence of virus, whereas Southern blot analysis detected HPV with a sensitivity of 98.1% (51 of 52). For 51 samples, in which the viral type was determined by restriction analysis, comparison of the signals separately generated by the four probes after in situ hybridization allowed a correct identification of the infecting HPV type in 86.2% (44 of 51) of cases.
Asunto(s)
Biotina , Sondas de ADN de HPV , Sondas de ADN , ADN Viral/análisis , Hibridación de Ácido Nucleico , Papillomaviridae/aislamiento & purificación , Infecciones Tumorales por Virus/microbiología , Adolescente , Adulto , Anciano , Cuello del Útero/microbiología , Condiloma Acuminado/microbiología , Condiloma Acuminado/patología , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones Tumorales por Virus/patología , Vagina/microbiología , Vulva/microbiologíaRESUMEN
A practical protocol using the polymerase chain reaction (PCR) was designed for detecting Chlamydia trachomatis in clinical samples. DNA was extracted from material collected on urethral swabs and used as substrate for the PCR. The target was a 600 basepair DNA segment of the multicopy plasmid that is common to all strains of the bacterium. Negative samples were checked for loss of DNA or presence of polymerase inhibitors by a second PCR, targeted to a conserved segment of the human genome. The whole procedure was tested on 216 men with non-gonococcal urethritis (NGU). All patients were independently assessed by tissue culture isolation (60 positive samples) and a commercial immunoenzymatic assay. The PCR protocol, while sufficiently simple for routine application, was reliable and, for the diagnosis of urethritis, at least as good as tissue culture isolation.
Asunto(s)
Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/aislamiento & purificación , ADN Bacteriano/análisis , Uretritis/microbiología , Adolescente , Adulto , Secuencia de Bases , Infecciones por Chlamydia/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Uretra/microbiología , Uretritis/diagnósticoRESUMEN
Chromosomal restriction fragments of Corynebacterium ulcerans and C. diphtheriae, containing an integration site for corynephages of the beta family, show homology on Southern blots. Homologous DNA in also found in the soil isolate C. glutamicum, although this strain is not susceptible to beta-corynephages. Three of these DNA fragments, one for each bacterial strain, and a fragment of gamma-corynephage DNA previously shown to contain the phage integration site, were cloned and sequenced. Alignment of the 3 bacterial sequences shows a very high degree of homology in a stretch of ca 120 nucleotides, whereas the rest of the sequences is generally non-homologous. Within this common bacterial portion, a segment of ca. 96 nucleotides (core sequence) is also highly homologous to the phage sequence. The first half (ca. 50 bp) of the core sequence is identical in all aligned sequences whereas the second half, which is largely occupied by a stem-and-loop structure, contains point mutations peculiar to each clone. The described sequences are likely to be involved in phage integration/excision processes.
Asunto(s)
Sitios de Ligazón Microbiológica/genética , Bacteriófagos/genética , Corynebacterium/genética , ADN Bacteriano/genética , Lisogenia/genética , Secuencia de Bases , Corynebacterium diphtheriae/genética , Datos de Secuencia Molecular , Homología de Secuencia de Ácido Nucleico , Especificidad de la EspecieRESUMEN
This is the first European study that has evaluated educational level in a large sample of hypertensive outpatients. We established the educational level of the hypertensive outpatients in our unit, and determined whether the awareness of hypertension and its organ damage was education-related. We analysed data from 812 consecutive outpatients (378 men, mean age 50 +/- 10 years) with essential stage I-II hypertension. Subjects were subdivided into two categories: group A subjects were highly educated; group B subjects had a little education. Data were compared with educational level from the 1991 population census for the Campania region (ISTAT data) and with 200 type 2 diabetes patients (96 men, mean age 51 +/- 9 years) from the nearest diabetes unit. For each hypertensive patient we considered clinical, echocardiographic and biochemical parameters. Data from the last census showed a high percentage (80%) of subjects with low education. The percentage of type 2 diabetic patients with little education was high (190 patients, 95%). Conversely, it is somewhat surprising that most hypertensive patients reached high standards of education and worked at sedentary jobs (group A: 736 patients, 91%; P < 0.0001). Multivariate analysis showed that only diastolic blood pressure (P = 0.03) was independently associated with low educational level. Compared to diabetes, hypertension and its risk factors are relatively unknown to people with little education. Education is associated with greater health care and awareness that may overcome the risk related to low physical activity. Thus, we stress the importance of a sound health policy able to reach out to the uneducated and make them aware of hypertension and the health care services available to them.
Asunto(s)
Atención a la Salud , Hipertensión/terapia , Educación del Paciente como Asunto , Adulto , Anciano , Colesterol/sangre , Ecocardiografía , Escolaridad , Femenino , Fibrinógeno/análisis , Conductas Relacionadas con la Salud , Hemodinámica/fisiología , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores Socioeconómicos , Triglicéridos/sangre , Ácido Úrico/sangreRESUMEN
This study evaluated the anti-hypertensive efficacy, tolerability and effects on left ventricular mass of losartan, a selective angiotensin II receptor antagonist, after 22 months in patients with essential hypertension. The study included 77 hypertensive patients who were randomised at baseline to 22 months double-blind once-daily treatment with losartan 50 mg (L group n = 44 patients, mean age 54+/-9 years) or hydrochlorothiazide 25 mg (HCTZ group, n = 33 patients, mean age 56+/-7 years). Routine haematology, blood chemistry, standard electrocardiography, echocardiography and ambulatory non-invasive 24-h blood pressure (BP) monitoring were performed at baseline and after 10 and 22 months. The results showed good tolerability and a significant mean systolic and diastolic BP reduction in all groups (L group: 22 mm Hg and 11 mm Hg; HCTZ group: 11 mm Hg and 7 mm Hg, respectively for systolic and diastolic mean BP). Moreover, a remarkable reduction in left ventricular mass index was reached after 10 and 22 months only in the L group (L group: delta = -11 g/m2, P<0.02; HCTZ group: delta = -5 g/m2, P= 0.38). In conclusion, losartan was well tolerated and produced a significant reduction in BP and left ventricular mass in hypertensive patients
Asunto(s)
Antihipertensivos/administración & dosificación , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Losartán/administración & dosificación , Adulto , Anciano , Antihipertensivos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Hidroclorotiazida/efectos adversos , Hipertensión/patología , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/patología , Losartán/efectos adversos , Masculino , Persona de Mediana EdadRESUMEN
Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin-dependent mellitus type 1, affecting the sympathetic or parasympathetic sections or both. The different impairment in the two sections might modify left ventricular function early. To evaluate this relationship, we studied 61 patients (mean age 39.6 +/- 7 years) with type 1 diabetes for more than 10 years, without coronary artery disease (CAD); negative ergometric stress test) and without other pathologies that could interfere with ventricular function. All patients underwent MONO-, 2-dimensional and Doppler echocardiographic examination and radionuclide angiography with 99Tc (RNA). According to the outcome of the Ewing tests, patients were divided into two groups: group A with two or more tests altered (26 patients with CAN) and group B with one or no tests altered (35 patients without CAN). No significant differences between the two groups were found in the systolic function parameters with either technique. In contrast, a pattern of abnormal relaxation was found for the diastolic function parameters: in group A a decrease in E-wave velocity and its time-velocity integral and an increase in A-wave and its time-velocity integral were detected with echocardiography. Moreover, RNA showed a reduced peak filling rate and an increased isovolumic relaxation time. When compared with normal values, an abnormal diastolic filling, defined as two independent echocardiography plus one RNA variable impairment, was found in 15 patients (57.6%) in group A and in only 4 patients (11.4%) in group B (P < 0.001). Our findings suggest an early involvement of diastolic function in patients with CAN.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/etiología , Función Ventricular Izquierda/fisiología , Adolescente , Adulto , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Estudios de Cohortes , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Ecocardiografía Doppler , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , ARN/análisis , ARN/genética , Angiografía por RadionúclidosRESUMEN
BACKGROUND: Left atrial enlargement (LAE) is associated with an increased risk of death and cardiovascular (CV) hospitalization. Whether or not LAE reflects early structural change from hypertension is unclear. HYPOTHESIS: The aim of this study was to evaluate the relationship between LA size, 24-h blood pressure measurements, age, body mass index (BMI), and left ventricular mass index (LVMI) in hypertensive patients. METHODS: We studied 164 outpatients (age range 30-76 years, 73 men and 91 women) with mild to moderate hypertension. Physical examination, electrocardiogram, noninvasive blood pressure monitoring (ABPM), Doppler echocardiogram were performed. Left ventricular mass index and LA dimensions were calculated. The sample was divided by age (< 60 and > or = 60 years). RESULTS: Left ventricular hypertrophy (LVH) was present in 45% of patients aged < 60 years and in 70% of patients aged > or = 60 years (p = 0.002). Left atrial enlargement (> 4 cm) was present in 35% of elderly and in 24% of young patients (p = 0.31), and in 36% of patients with and 21% of patients without LVH (p = 0.0057). There was no significant difference in the younger patients with and without LVH. The incidence of obesity was low (31%) in the whole sample. The percentage of overweight in the elderly patients with LVH and higher LA size was equally low. Multivariate analysis showed age (p = 0.044) and LVMI (p = 0.002) as the only significant predictors of LA enlargement. CONCLUSION: Since LAE is associated with a high risk of death and CV hospitalization, we emphasize the importance of development and use of drugs that inhibit LVH.
Asunto(s)
Atrios Cardíacos , Hipertensión , Adulto , Factores de Edad , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Índice de Masa Corporal , Ritmo Circadiano/fisiología , Ecocardiografía , Femenino , Atrios Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Incidencia , Masculino , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
BACKGROUND: In childhood, late cardiotoxicity is characterized by inappropriately thin wall and consequent increased end-systolic wall stress, but the associations of impaired left ventricular geometry and function occurring under these circumstances need further investigation. HYPOTHESIS: The purpose of this study was to assess anthracycline late effects on the relationships occurring between increased end-systolic stress (ESS) and changes in both M-mode systolic measurements (i.e., endocardial and midwall fractional shortening) and Doppler diastolic indices in the pediatric age. METHODS: The population consisted of 101 children treated with anthracyclines for at least 12 months and 91 healthy children. Using M-mode echocardiography, end-systolic wall stress was calculated as index of afterload, and endocardial and midwall fractional shortening as systolic indices. Doppler transmitral measurements were made as diastolic indices. RESULTS: Patients treated with anthracyclines showed significantly lower relative wall thickness and left ventricular mass index, greater end-systolic wall stress, reduced endocardial and midwall fractional shortening and peak E/A ratio, prolonged deceleration, and isovolumic relaxation times. Direct relationships were found between end-systolic wall stress and both endocardial and midwall shortening. The use of midwall shortening in the relation showed a greater, but not significant increase (from 3 to 6%) in the proportion of patients with depressed systolic function than did endocardial shortening. In the anthracycline group, end-systolic wall stress was also inversely related to relative wall thickness and directly to isovolumic relaxation time. CONCLUSIONS: In childhood, reduced myocardial thickness and increased afterload explain much of systolic and diastolic dysfunction of late anthracycline toxicity. Midwall fractional shortening does not seem to add useful information for identifying subsets of children more prone to the development of heart failure.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Diástole/efectos de los fármacos , Sístole/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Adolescente , Niño , Diástole/fisiología , Ecocardiografía Doppler , Femenino , Humanos , Masculino , Sístole/fisiología , Factores de TiempoRESUMEN
Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11 years, range 5-23 years). The calculated mean PWV in the control group was 6.5 +/- 1.15 m/s. The mean PWV of the 64 young patients with NF1 was 6.3 +/- 1.02 m/s. There was no difference between the two groups (p=0.39). Nevertheless, analysis of the linear regression has shown a linear relationship between systolic blood pressure (SBP) and PWV in the control group, while in NF1 patients this relationship is not present. The authors suggest that the coexistence of different factors, such as intimal proliferation, thinning media, fragmentation of the elastic tissue, irregularity, stenosis and tortuosity of the vessels, dysplasia of the small vessels, that counterbalance PWV, normalize the mean value. They emphasize the importance of a careful vascular evaluation, using noninvasive method, such as Complior. This device is well accepted by NF1 patients.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Neurofibromatosis 1/genética , Enfermedades Vasculares/genética , Adolescente , Adulto , Velocidad del Flujo Sanguíneo/genética , Velocidad del Flujo Sanguíneo/fisiología , Presión Sanguínea/genética , Presión Sanguínea/fisiología , Niño , Preescolar , Elasticidad , Femenino , Regulación Neoplásica de la Expresión Génica/fisiología , Pruebas Genéticas , Humanos , Masculino , Músculo Liso Vascular/fisiopatología , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/fisiopatología , Neurofibromina 1 , Flujo Pulsátil/genética , Flujo Pulsátil/fisiología , Valores de Referencia , Procesamiento de Señales Asistido por Computador/instrumentación , Túnica Íntima/fisiopatología , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/fisiopatologíaRESUMEN
The latest research into the prevention of peri- and postoperative thromboembolic disease has found orthopaedic surgery patients to be most at risk. As the genesis of deep venous thrombosis (DVT) is due to haemodynamic, hemorheologic and parietal factors, various prophylactic measures have been considered in the past, measures which have not proved able to provide satisfactory protection in orthopaedics. The results obtained with Defibrotide in a random and controlled clinical study versus calcium heparin involving 211 patients of both sexes candidates to receive total hip arthroplasty and presenting at least one major thromboembolic risk factor are reported. The patients were assigned at random to one of the following treatments: 1) Defibrotide at a dose of 400 mg b.i.d. i.v. in 50 ml phleboclysis in 5 minutes (n = 108); 2) calcium heparin at a dose of 5000 IU t.i.d. subcutaneously (n = 103). The treatment began the day before operation and continued on average up to the eighth day for the Defibrotide group. With the control group it continued until discharge (usually on the 15th day) and at home for about three weeks until the completion of the physiotherapy cycle. In the 108 patients treated with Defibrotide only one case of DVT was reported and in none of these patients were symptoms or signs of pulmonary embolism encountered. In the group treated with calcium heparin 2 cases of clinically and radiologically diagnosed pulmonary embolism and 4 cases of DVT were observed. Although the differences were not statistically significant, the tendency favours Defibrotide. Statistically significant (p less than 0.01) was the difference in postoperative bleeding evaluated with particular attention in patients of advanced age. Further, in the Defibrotide group, scarring was considered excellent in 96% of cases while in the heparin group scarring was excellent in 85% (p less than 0.05). To conclude, the sure clinical effectiveness, tolerance, handiness and lack of interference with clotting functions make Defibrotide a really useful drug for the prevention of thromboembolic episodes in patients undergoing major orthopaedic surgery.
Asunto(s)
Fibrinolíticos/uso terapéutico , Heparina/uso terapéutico , Prótesis de Cadera , Polidesoxirribonucleótidos/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Premedicación , Tromboembolia/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Ensayos Clínicos como Asunto , Femenino , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Distribución Aleatoria , Cicatrización de HeridasRESUMEN
In an open multicenter comparative study aimed at the evaluation of the efficacy of defibrotide in the prophylaxis of postsurgical deep vein thromboses (DVT) an ad interim evaluation has been made on 2626 patients thus far enrolled. 1323 had received defibrotide (200 mg q.i.d. by IV route from day -1 to day +7th postoperative), 941 calcium heparin (5000 IU b.i.d. or t.i.d. by SC route from day 0 to day +7 postoperative) and 362 other treatments (antiaggregating agents, placebo or no therapy). This group has not been included in the final evaluation, due to its limited size. The diagnosis of DVT or pulmonary embolism (PE) was made according to clinical routinary criteria. The incidence of DTV has been 15/1323 (1.13%) in the defibrotide group and 21/941 (2.23%) in the heparin group (chi-square, p = 0.056) while the cases of suspected or ascertained PE have been respectively 3/1323 (0.22%) and 10/941 (1.06%) (p = 0.02). The incidence of adverse effects with defibrotide was less than 1%; occasional cases of increased serum transaminase levels were seen with heparin. These preliminary results supports the effectiveness of defibrotide in the prevention of post-surgery DVT, its effects being similar or more prominent than those of calcium heparin, currently regarded as the standard medication.
Asunto(s)
Fibrinolíticos/uso terapéutico , Polidesoxirribonucleótidos/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Trombosis/prevención & control , Adulto , Anciano , Ensayos Clínicos como Asunto , Femenino , Heparina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/prevención & controlRESUMEN
The effectiveness and tolerability of defibrotide in the prevention of post-surgery deep vein thrombosis (DVT) were compared with those of heparin in a multicentric randomized controlled study. One hundred-eight-four both sexes patients submitted to thoracic surgery were randomly allocated to defibrotide (400 mg b.i.d. by IV route, n = 94) or to calcium heparin (5000 I.U. t.i.d. s.c., n = 90); both treatments were started the day before the operation and withdrawn when patients were allowed to stand up (i.e., after 7 days). No patients developed DVT in the defibrotide group, while a single case of DVT was detected in the heparin group; furthermore, a more prominent bleeding was observed in the latter, in the early post-operative period (normal bleeding: 2nd day: defibrotide 70/92 pts, heparin 53/90 pts, p less than 0.02; 3rd day: defibrotide 87/92 pts, heparin 76/90 pts, p less than 0.05, chi 2 test), while the healing rate of surgical wounds was similar in the two groups. No relevant modifications in laboratory parameters were seen throughout the observation period. Thus, these preliminary data suggest that defibrotide is at least as effective as heparin in the prevention of post-thoracic surgery DVT and that the former drug has a possibly better tolerability profile, due to a lesser tendency to bleeding.