Consultorio de condiciones crónicas complejas, seguimiento de cardiopatías congénitas críticas / Complex chronic conditions clinic, follow-up of critical congenital heart defects

Introducción: Las cardiopatías congénitas representan la segunda causa de mortalidad infantil en menores de un año. Objetivo: Describir la epidemiología, resultados y seguimiento de cardiopatías congénitas críticas (pacientes que requirieron intervención quirúrgica o cateterismo intervencionista antes del año de vida). Resultados: Se incluyeron 316 pacientes operados o intervenidos por cateterismo antes del año de vida con diagnóstico de cardiopatías congénitas, de los cuales el 30,7% eran sindromáticos y solo el 7,7% tuvieron diagnóstico prenatal. Se logró cirugía reparadora en un 86,7% de los casos siendo la CIV la cardiopatía congénita operada más frecuente en menores de un año. Los pacientes quedaron con defectos residuales significativos en un 23,73%, con una tasa de complicaciones de 39,64%. En el seguimiento post-operatorio un 19,62% requirieron reoperación, y un 5,06% cateterismo. Un 15,19% de los pacientes fallecieron. Conclusiones: El Hospital Juan P. Garrahan tiene una población numerosa y heterogénea de pacientes con cardiopatías críticas. Dado que solo un pequeño porcentaje de nuestros pacientes tuvieron diagnóstico prenatal, se debe mejo- rar en este aspecto, ya que el diagnóstico de cardiopatía en el período fetal mejora las posibilidades de sobrevida en el neona- to. Es importante el seguimiento multidisciplinario, coordinado y continuo de estos pacientes, dado que muchos niños operados tienen comorbilidades y lesiones residuales (AU)

Introduction: Congenital heart defects are the second leading cause of infant mortality in children under one year of age. Objective: To describe the epidemiology, results, and follow-up of patients with critical congenital heart defects (patients who required surgical intervention or interventional catheterization before the year of life). Results: 316 patients with congenital heart defects who underwent surgery or catheterization before the life year, of whom 30.7% were syndromic and only 7.7% were diagnosed prenatally. Repair surgery could be performed in 86.7% of cases with SVD being the most commonly operated congenital heart defect in children under one year of age. Of the patients, 23.73% had a significant residual defect with a complication rate of 39.64%. In the post-operative follow-up, 19.62% required reoperation and 5.06% catheterization. Overall, 15.19% of the patients died. Conclusions: The Juan P. Garrahan Hospital has a large and heterogeneous population of patients with critical heart disease. Since only a small percentage of our patients had a prenatal diagnosis, this aspect should be enhanced, as the diagnosis of heart disease in uterus improves the chances of survival of the neonate. Multidisciplinary, coordinated and continuous follow-up of these patients is important, as many children who undergo surgery have comorbidities and residual lesions (AU)

El adolescente con cardiopatía congénita: transición y transferencia / The adolescent with congenital heart defects: transition and transfer

Introducción: Los grandes avances en el diagnóstico y tratamiento de los pacientes con cardiopatías congénitas en las últimas décadas han permitido que mas del 90% lleguen a la adolescencia y edad adulta. Sin embargo, muchos de ellos requirieran seguimiento e intervenciones de por vida, por lo que necesitaran ser transferidos desde el hospital pediátrico al de adultos. Material y Métodos: Se incluyeron los pacientes mayores de 15 años que consultaron en el área ambulatoria del servicio de cardiología del Hospital Garrahan durante el periodo agosto 2017 - agosto 2018. Las variables analizadas fueron: procedencia, cardiopatía de base y variedad pronostica ,procedimientos intervencionistas factores asociados como síndrome genéticos y otras comorbilidades, cobertura social, nivel educativo, terapéutica medicamentosa, clase funcional, embarazos, prevalencia de cardiopatías en la descendencia y transición-transferencia al hospital de adultos. Resultados: Registramos 704 consultas de 309 pacientes con una edad media de 19,17 años (DS +- 4,62; (rango 15- 49,4 años). Fueron 112 mujeres y 197 varones. El 51,1 % provenían de Buenos Aires,40 % de las provincias del interior y 8,1% CABA. El 92% de los pacientes tenía cardiopatías de moderada y severa complejidad, y el 93,5% eran operadas. El 13,2 % eran síndromes genéticos. El 48.5% tenían comorbilidades, siendo los trastornos electrofisiológicos los más frecuentes en el 72,66% de los casos. El 63% tenía cobertura social pero solo el 2,6% prepagos con cobertura en centros alta complejidad. El 23.6% recibía terapia combinada con 2 o más drogas. El 48,78% ya presentaban antecedente de algún tipo de reintervención, 98,5% de estas se vincularon a las cardiopatías moderadas a complejas. Registramos 15 embarazos con 14 recién nacidos vivos, 1 con cardiopatía congénita. El proceso de transición ­ transferencia en el 55% (170 p) se había iniciado, siendo efectiva (8p), frustra (9p), compartida (49 p), y en proceso (103 p). Hubo un solo fallecimiento durante el periodo de estudio, vinculado a cardiopatía compleja, múltiples reintervenciones y endocarditis. Conclusiones: El 92% de los pacientes en nuestro estudio, tienen cardiopatías operadas de moderada y severa complejidad. Los trastornos electrofisiológicos y la necesidad de reintervenciones durante el seguimiento alejado han sido las complicaciones más frecuentes de esta población. El proceso de transición y transferencia desde el hospital pediátrico al de adultos es deficitario, principalmente por falta de cobertura y experiencia sobre todo para la atención continua de las cardiopatías moderadas y complejas (AU)

Introduction: In recent decades, important advances in the diagnosis and treatment of patients with congenital heart defects have allowed more than 90% of them to reach adolescence and adulthood. However, many patients required lifelong follow-up and interventions, and therefore the need to be transitioned from pediatric to adult care. Material and Methods: Patients older than 15 years who consulted at the outpatient clinic of the department of cardiology at Garrahan Hospital from August 2017 to August 2018 were included. The variables analyzed were place of origin, underlying heart disease, and diagnosis, interventions, associated factors, such as genetic syndromes and other comorbidities, insurance coverage, educational level, pharmacological treatment, functional class, pregnancies, prevalence of heart disease in offspring, and transition-transfer to adult hospital. Results: We recorded 704 consultations from 309 patients with an average age of 19.17 years (SD +- 4.62; range 15-49.4 years); 112 patients were female and 197 male. Overall, 51.1% came from the province of Buenos Aires, 40% from the other provinces, and 8.1% from the city of Buenos Aires. Of the patients, 92% had moderate and severe heart disease, and 93.5% had undergone surgery. Genetic syndromes were identified in 13.2%. Overall, 48.5% had comorbidities, of which electrophysiological disorders were the most common in 72.66% of cases. 63% had social insurance coverage but only 2.6% had a prepaid insurance with coverage in tertiary-level centers. Overall, 23.6% received combination therapy with 2 or more drugs. 48.78% had undergone some type of previous reintervention, 98.5% of whom had moderate-to-severe heart disease. We recorded 15 pregnancies with 14 live neonates, one of whom had congenital heart defects. The transition - transfer had been initiated in 55% (170 p) and was effective (8p), frustrated (9p), shared (49 p), or in progress (103 p). There was only one death during the study period, related to severe heart disease, multiple reinterventions, and endocarditis. Conclusions: 92% of patients in our study have moderate or severe operated heart disease. Electrophysiological disorders and the need for reintervention during the long-term follow-up were the most common complications of this population. The process of transition and transfer from pediatric to adult care is deficient, mainly due to lack of insurance coverage and experience especially for the ongoing care of moderate-to-severe heart disease

Increased flexibility, pain reduction and unaltered levels of IL-10 and CD11b + lymphocytes in patients with systemic lupus erythematosus were associated with kinesiotherapy.

The effect of physical activity on the immune system is still poorly understood in cases of systemic lupus erythematosus (SLE). Therefore, our aim was to investigate differences in the serum levels of cytokines (IL-2, IL-5, IL-6, IL-8, IL-10 and TNF-α) and the numbers of CD11b + and CXCR2 + neutrophils and lymphocytes in women with SLE undergoing drug treatment, without ( n = 9) or with ( n = 5) 4 months of kinesiotherapy. Parameters related to functional capacity were also analyzed. In the case of the patients who were not submitted to kinesiotherapy, there were reductions in the levels of IL-5, IL-6 and IL-10, and an increase in the number of CD11b + leukocytes, in addition to an increase in abdominal circumference after the monitoring time. Patients submitted to kinesiotherapy did not present changes in serum cytokines or in the numbers of CD11b + and CXCR2 + neutrophils and lymphocytes, but there were increases of flexibility and strength, as well as a reduction in pain sensation after the monitoring time. In conclusion, kinesiotherapy was able to increase flexibility and reduce pain in SLE patients without influencing immune parameters.

Role of Intracystic Cytokines and Nitric Oxide in Ovarian Neoplasms.

The development of new biomarkers for the diagnosis and prognosis of ovarian cancer may provide an opportunity for new therapies. In this study, we aimed to compare cytokines (interleukin [IL]-2, IL-5, IL-6, IL-8, IL-10 and tumour necrosis factor [TNF]-α) and nitric oxide (NO) metabolite levels in non-neoplastic tumours, benign primary ovarian tumours and malignant primary ovarian neoplasms. The secondary aim was to relate cytokine and intracystic NO metabolite levels to clinical, laboratory and pathologic characteristics for patients with primary ovarian malignancies. We evaluated 110 patients with adnexal masses. Cytokine concentrations were quantified by enzyme-linked immunosorbent assay and nitrate concentrations by enzymatic reduction of nitrite by nitrate reductase. Patients with malignant neoplasms had higher IL-6, IL-8 and NO levels compared to patients with benign neoplasms. Histologic grade 1 tumours were associated with elevated IL-2 levels, whereas anaemia was associated with elevated IL-6 levels. On average, those patients with elevated IL-8 levels also had a neutrophil/lymphocyte ratio (NLR) greater than 2.6 and less than 36 months of disease-free survival (DFS). Patients with normal CA 19-9 levels had elevated IL-10 levels. TNF-α was elevated in patients with two carcinogenesis and those with a platelet/lymphocyte ratio (PLR) less than 300. NO levels were higher in patients with an NLR less than 2.6 and CA 19-9 greater than 35 U/ml. Elevated intracystic cytokine levels, especially IL-6 and IL-8, are associated with worse prognosis in ovarian cancer.

Lack of association between mtDNA haplogroups and Alzheimer's disease in Tuscany.

Mitochondrial DNA (mtDNA) haplogroup-specific polymorphisms were previously related to several neurodegenerative diseases, including Alzheimer's disease (AD). However, the precise role of mtDNA haplogroups in the neurodegenerative cascade leading to AD is still unclear. In this work we have genotyped predefined European mtDNA haplogroups in 209 patients with AD and 191 matched controls. In order to minimise the risk of "genetic contamination", which could lead to false associations between gene markers and disease, we were careful to enrol in the study only patients and controls of clear Tuscan origin (with at least three generations of Tuscanborn relatives). The frequency of the haplogroups did not differ between the two groups, and no correlation with gender, ApoE genotype, age of onset or disease status was observed. Further studies will be required to define the contribution of mtDNA haplogroups, if any, to the pathogenesis of AD. A correct population selection, in order to minimise the risk of genetic contamination, is essential in these studies.

Circulating neutrophils may play a role in the host response in cervical cancer.

Neutrophil migration is a key event in the inflammatory response of any origin, and neutrophils may present antitumor activity. We investigated the number and function of circulating neutrophils obtained from patients with cervical neoplasia at different stages. Patients with preinvasive (cervical intraepithelial neoplasia, CIN3, n= 6) or microinvasive ([MICRO] stage IA1, n= 4) neoplasia were evaluated together as CIN/MICRO group (n= 10), while patients at stages II-IV were evaluated as invasive group (INV, n= 12). Healthy women served as controls (n= 15). For patients, analysis of leukogram on diagnosis showed a significant elevated neutrophil count in INV group compared with that in CIN/MICRO group. A neutrophil/lymphocyte ratio >/=5 was observed in 67% patients from INV group compared with only 10% from CIN/MICRO group. Neutrophil migration, assayed in a microchemotaxis chamber in response to the chemoattractants (10(-7) M) N-formyl-l-methionyl-l-leucyl-l-phenylalanine, leukotriene B(4), or interleukin-8, was reduced in INV group than in controls or CIN/MICRO group. Surgical treatment in randomly selected patients from CIN/MICRO group (four CIN, one MICRO) increased neutrophil migration to all chemoattractants compared with time on diagnosis. The serum levels of nitric oxide (NO) metabolites, assayed by the Griess reaction, were higher in patients (n= 19) than in controls (n= 15), without differences related to tumor stage, but were reduced in patients after surgery compared with pretreatment (n= 10). Taken together, the results suggest that neutrophils play a role in the host response in cervical cancer. Soluble circulating mediators released by tumor cells, such as NO, could interfere early in the capacity of neutrophils to migrate, thus impairing host immune response.

No evidence for allelic association of serotonin 2A receptor and transporter gene polymorphisms with depression in Alzheimer disease.

Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms associated with cognitive impairment. The serotoninergic system may be involved in the development of depressive symptoms in AD patients, as suggested by the evidence that antidepressant drugs having the serotonin transporter as their target are effectively used to treat depressive AD patients. The aim of this study was to investigate the role of serotonin in depression, searching for association of two serotoninergic polymorphisms (T102C of serotonin receptor 5-HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4 gene) with depressive symptoms and considering their possible interactions with Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not associated with AD when separately analysed. However, we found out an interaction between the two polymorphisms in L/L and C/C genotype carriers increasing the risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of the polymorphisms was detected with depression linked to AD. No interaction between 5-HTTLPR and T102C was detected in depressive AD subjects, even after stratification according to the presence of ApoE4 allele. These results suggest that the serotoninergic system may be not involved in the pathogenesis of depressive symptoms in AD patients, and it may be involved in other aspects of disease pathophysiology like cognitive symptoms and psychosis.

Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program.

Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytic leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeloid leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer (EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n=278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.

Serotoninergic polymorphisms (5-HTTLPR and 5-HT2A): association studies with psychosis in Alzheimer disease.

Patients with Alzheimer disease (AD) often exhibit psychotic symptoms associated with cognitive impairment. A few association studies have been carried out to determine if the serotonin transporter and receptor genes are potential risk factors for AD and/or associated psychopathology. The aim of this study was to investigate the association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with the risk of developing dementia and/or psychotic symptoms in a group of sporadic AD patients from Italy. No significant differences in the distribution of allele and genotype frequencies of 5-HTTLPR and 5-HT2A T102C were found between patient and control groups. However, a significant association between the C102/C102 5-HT2A genotype and psychotic symptoms (p < 0.001) was observed. Our data strongly confirm results from previous studies suggesting that the C102 allele of the 5-HT2A receptor is associated with the occurrence of psychotic symptoms in AD. On the contrary, the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of the disease.

Quantitative assessment of WT1 expression by real time quantitative PCR may be a useful tool for monitoring minimal residual disease in acute leukemia patients.

In order to verify if quantitative assessment of the WT1 transcript amount by the real time quantitative PCR (RQ-PCR) can be used as a marker for minimal residual disease detection, the WT1 transcript amount was determined in BM and PB samples of patients with myeloid and lymphoid acute leukemia, in normal controls, in regenerating bone marrow samples and in purified CD34-positive cells from normal subjects. In 10 patients bearing a fusion gene transcript suitable for minimal residual disease quantitative assessment, we performed a simultaneous analysis of the WT1 and of the fusion-gene transcript at sequential time intervals during follow-up. Sequential WT1 analysis was also performed in five AML patients lacking additional molecular markers. The data obtained show that normal and regenerating BM samples and purified CD34-positive cells consistently express minimal amounts of WT1 transcript and that this is extremely low and frequently undetectable in normal PB. By contrast, high levels of WT1 expression are present in the BM and PB samples of all acute leukemia (AL) cases at diagnosis. The WT1 levels during follow-up were found to follow the pattern of the other molecular markers (fusion gene transcripts) used for MRD monitoring and increased WT1expression in the BM and/or PB during follow-up of AL patients was always found to be predictive of an impending hematological relapse.

Assessment of minimal residual disease (MRD) in CBFbeta/MYH11-positive acute myeloid leukemias by qualitative and quantitative RT-PCR amplification of fusion transcripts.

The inv(16)(p13q22) chromosomal rearrangement associated with FAB M4Eo acute myeloid leukemia (AML) subtype is characterized by the presence of the CBFbeta/MYH11 fusion transcript that can be used to detect minimal residual disease (MRD). However, qualitative RT-PCR studies of MRD have so far produced conflicting results and seem of limited prognostic value. We have evaluated retrospectively MRD in a large series of CBFbeta/MYH11-positive patients employing both qualitative and quantitative (real-time PCR) approaches. 186 bone marrow samples from 36 patients were examined with a median follow-up of 27.5 months; 15 patients relapsed during follow-up. In qualitative studies, carried out by 'nested' RT-PCR assay, all patients in complete remission (CR) immediately after induction/consolidation therapy were found to be PCR positive. However, follow-up samples at later time points were persistently negative (except one case) in patients remaining in continuous CR (CCR) for more than 12 months. 16 patients were evaluated by quantitative real-time PCR assay: CBFbeta/MYH11 transcript copy number was normalized for expression of the housekeeping gene ABL, expressed as fusion gene copy number per 10(4) copies of ABL. A 2-3 log decline in leukemic transcript copy number was observed after induction/consolidation therapy. After achieving CR, the mean copy number was significantly higher in patients destined to relapse compared to patients remaining in CCR (151 vs 9, P < 0.0001 by Mann-Whitney test). Moreover, in CCR patients, the copy number dropped below the detection threshold after the treatment protocol was completed and remained undetectable in subsequent MRD analysis in accordance with results obtained by qualitative RT-PCR. On the contrary, in the seven patients who relapsed, the copy number in CR never declined below the detection threshold; thus a cut-off value discriminating these two groups of patients could be established. The findings of our study, if confirmed, might confer an important predictive value to quantitative real-time PCR determinations of MRD in patients with inv(16) leukemia.

Novel type of BCR-ABL transcript in a chronic myelogenous leukaemia patient relapsed after bone marrow transplantation.

We identified a novel BCR-ABL transcript in a chronic myelogenous leukaemia (CML) patient who relapsed after bone marrow transplantation (BMT), containing a fusion between part of BCR exon 3, 44 nucleotides derived from ABL intron 1b and ABL exon 2. The breakpoints were located within BCR exon 3 on chromosome 22 and within the ABL intron 1b on chromosome 9, and the transcript derives from a splicing of ABL exon 2 to a putative splicing acceptor site 44 nucleotides downstream to the breakpoint on chromosome 9. The patient's clinical course strengthens the idea that short forms of BCR-ABL transcripts are associated with a more aggressive disease.

Screening of drug use in a teenage Brazilian sample using the Drug Use Screening Inventory (DUSI).

The Brazilian translation of the Drug Use Screening Inventory (DUSI) was applied to 213 Brazilian teenagers who were classified according to their alcohol and/or drug dependence level (DSM-III-R) as: 71 nondrug users (Group 1), 71 with light/moderate dependence (Group 2) and 71 with severe dependence (Group 3). The DUSI was applied and the absolute density in each of 10 areas was calculated. The three groups presented statistically significant differences (p < .001) in the "substance use" area, with the following values (medians +/- interquartile range): Group 1: 0+/-7; Group 2: 20+/-33 and Group 3: 80+/-33. The groups also presented significant differences in behavior pattern, social competency, family system, work adjustment, peer relationships and leisure/recreation. Other differences detected among the groups indicated an important relationship between drug use and school delay. A good Spearman rank correlation (0.86, p < .0001) was observed between Composite International Diagnostic Interview (CIDI) diagnosis and DUSI, indicating that this instrument can be useful in the screening of substance use among Brazilian teenagers.

Consistent amounts of acute leukemia-associated P190BCR/ABL transcripts are expressed by chronic myelogenous leukemia patients at diagnosis.

In chronic myelogenous leukemia (CML), the Philadelphia (Ph) chromosome translocation results in the formation of BCR/ABL genes, normally transcribed in two types of hybrid transcripts with a b2a2 or b3a2 BCR/ABL junction, which give origin to 210-kD fusion proteins (P210). A third type of BCR/ABL (with e1a2 type of junction) has been identified in approximately 50% of the Ph-positive acute lymphoblastic leukemia (Ph+ALL) cases and results in the production of a BCR/ABL protein of 190 kD (P190). The presence of this transcript has been associated almost exclusively with the presence of an acute leukemia phenotype. By contrast, here we describe that in addition to transcripts with the b2a2 and b3a2 types of junction corresponding to the P210 proteins, virtually all CMLs at diagnosis bear also BCR/ABL transcripts showing the e1a2 type of junction, which correspond to the acute leukemia-associated P190 protein. With a quantitative polymerase chain reaction assay we found that the amount of the e1a2 mRNA present in CMLs in chronic phase, although in absolute amount much lower than that present in Ph+ ALLs, represents in most cases approximately 20% to 30% of the total BCR/ABL transcripts. Moreover, using a novel and very sensitive Western blot technique, we detected relevant amounts of P190 protein in addition to P210 from peripheral cells of two of the patients.

Recent developments in the use of calcium antagonists in myocardial protection.

For more than two decades calcium antagonists (CEBs) have been widely used for the treatment of myocardial ischaemia (angina pectoris). Amongst the classes of CEBs, the 1,4-dihydropyridines (DHPs), like nifedipine, have been used for this indication because of their haemodynamic and electrophysiological properties. The ability of nifedipine to reduce afterload and to induce coronary vasodilation, as well as to increase collateral blood supply, has supported its extensive use in the treatment of angina pectoris. However, its short duration of action also provokes reflex tachycardia, which often limits its beneficial effect and may actually precipitate pain. The newer DHPs, such as amlodipine and lacidipine, are endowed with slow onset and long duration of vasodilatory activity; they are able to reduce coronary resistance with little or no effect on heart rate. The more lipophilic DHP, lacidipine, shows also a pronounced vascular protection, on both smooth muscle and endothelium, and is able to reduce the formation of atheroma plaque in animal models at therapeutic doses. This protective activity might be explained in terms of both the effective CEB activity of lacidipine together with antioxidant properties that this DHP has shown.

Resultados del cierre de la comunicación interventricular supracristal por vía transpulmonar / Result of transpulmonary closure of supracristal interventricular comunication

Entre noviembre de 1988 y marzo de 1993, 17 pacientes portadores de comunicación interventricular (CIV) supracristal (Conal) cuyas edades oscilaron entre 45 días y 6 años, fueron sometidos a cirugía correctora con circulación extracorpórea utilizando la vía de abordaje transpulmonar. La sobrevida quirúrgica y durante el seguimiento, cuyo tiempo promedio fue de 18,5 meses (rango 2-54 meses), es del 100 por ciento encontrándose los pacientes asintomáticos, libres de medicación, con ritmo sinusal y sin evidencias de cortocircuito residual. Solo un paciente presentó insuficiencia aórtica (IA) mínima, la que había sido detectada en el preoperatorio y que no requirió plástica valvular. El cierre temprano de la CIV supracristal previene la instalación de insuficiencia aórtica por elongación y prolapso de las cúspides valvulares aórticas. El abordaje transpulmonar es la vía de elección en el cierre quirúrgico de la CIV supracristal. (AU)

Resultados del cierre de la comunicación interventricular supracristal por vía transpulmonar / Result of transpulmonary closure of supracristal interventricular comunication

Entre noviembre de 1988 y marzo de 1993, 17 pacientes portadores de comunicación interventricular (CIV) supracristal (Conal) cuyas edades oscilaron entre 45 días y 6 años, fueron sometidos a cirugía correctora con circulación extracorpórea utilizando la vía de abordaje transpulmonar. La sobrevida quirúrgica y durante el seguimiento, cuyo tiempo promedio fue de 18,5 meses (rango 2-54 meses), es del 100 por ciento encontrándose los pacientes asintomáticos, libres de medicación, con ritmo sinusal y sin evidencias de cortocircuito residual. Solo un paciente presentó insuficiencia aórtica (IA) mínima, la que había sido detectada en el preoperatorio y que no requirió plástica valvular. El cierre temprano de la CIV supracristal previene la instalación de insuficiencia aórtica por elongación y prolapso de las cúspides valvulares aórticas. El abordaje transpulmonar es la vía de elección en el cierre quirúrgico de la CIV supracristal.

Protective action of lacidipine in cardiac hypertrophy of the spontaneously hypertensive stroke-prone rat: an ultrastructural study.

We investigated the effect on cardiac hypertrophy of a once-daily treatment with lacidipine, at doses that do not reduce systolic blood pressure. Spontaneously hypertensive stroke-prone rats (SHR-SP) were fed a 1% NaCl enriched diet and treated daily by gastric gavage with lacidipine at doses of 0.3, 1, or 3 mg/kg/die or vehicle. At 15 weeks of age the rats were sacrificed. The heart was removed, weighed and processed for transmission electron microscopy, scanning electron microscopy and ultrastructural morphometry. Though the treatment did not reduce systolic blood pressure, heart weight and heart weight/body weight ratio were lower in the lacidipine-treated rats than in those treated with vehicle alone. Medial and subendothelial lesions were visible in coronaries of vehicle-treated SHR-SP but not in animals treated with lacidipine. In the cardiocytes of the lacidipine-treated rats, the myofibrils had a more regular arrangement and the intercalated discs did not show the irregular course and infoldings seen in the vehicle-treated rats. Morphometry showed a significantly higher density of mitochondria in the cardiocytes of lacidipine-treated SHR-SP. Scanning electron microscopy identified a decrease in the width of cardiocytes and in the number and length of lateral branches following lacidipine-treatment. The cardio-protective action of this calcium-antagonist at doses that do not reduce systolic blood pressure is attributable both to its vascular activity and to improvement in cytoplasmic organization of cardiocytes.

Quantification of the calcium antagonism of lacidipine by kinetic analysis.

The calcium antagonist activity of the long-acting 1,4-dihydropyridine (DHP) lacidipine has been analyzed in rabbit basilar artery using a washout design in constant depolarizing conditions. From the kinetics of the loss of effect with washing, it was possible to fit a model that included the rate constant for dissociation of the DHP from the membrane (k-1) together with its affinity for the voltage-activated channel (K2). The k-1 values for lacidipine and two other DHPs (amlodipine and nifedipine) have been calculated as 0.0098, 0.0182 and 0.166 min-1, respectively. Assuming that the externally applied concentration of the DHP reflected the concentration in the membrane, the apparent pK2 values of 9.80, 9.0 and 9.25 were calculated for the three calcium antagonists. These values are in good agreement with those estimated in a previous study. When the partition of lacidipine into the membrane was taken into consideration, its apparent pK2 was reduced to 4.85. Thus, the study reinforces the concept that the high membrane partition of lacidipine contributes not only to its duration of action but also to its very high potency.

Lacidipine: experimental evidence of vasculoprotective properties.

Lacidipine is a second-generation 1,4-dihydropyridine calcium antagonist, whose potent and long-lasting antihypertensive properties prompted us to investigate whether its chronic administration to Dahl-S rats prevented salt-induced hypertension, vasculopathy, and accelerated mortality. These studies revealed that lacidipine proved vasoprotective when administered both prophylactically and therapeutically at doses of 0.1 and 0.3 mg/kg p.o. once a day, largely equivalent to the therapeutic doses. A generalized dose-related protection against necrotizing vasculopathy and brain damage was detected, although only the highest dose used (10 mg/kg) controlled the development of hypertension. These protective properties were further confirmed in stroke-prone spontaneously hypertensive rats, which develop accelerated mortality as a result of salt-induced cerebral apoplexy and renal lesions. All untreated controls died within 12 weeks of salt-rich diet, whereas all animals survived during the same period when treated prophylactically with lacidipine at 0.3 and 1 mg/kg p.o. once a day, although a slight reduction in systolic blood pressure was measured only with the highest dose. No cerebral lesions and a clear protection against renal damage were detected in lacidipine-treated animals. In conclusion, these findings reinforce the concept that the beneficial effects of calcium antagonists are not simply restricted to a reduction in blood pressure.