895 research outputs found
Why multidisciplinary clinics should be the standard for treating chronic kidney disease
In adults, strong evidence indicates that slowing progression of chronic kidney disease (CKD) requires an integrated, multidisciplinary approach. In children, however, this approach has not been studied. This editorial commentary to the study by Ajarmeh et al in this volume of Pediatric Nephrology highlights how a dedicated, multidisciplinary team of physicians, nurses, pharmacists, dieticians, social workders and clinic data managers slowed the progression of CKD in children to a remarkable degree. We discuss the strengths and limitations of the study and its cost implications, as well as the issue of determining the optional complement of physicians and allied health care professionals in such clinics. Our calculations indicate that the additional costs of such clinics would be recovered in one year, even if the progession of CKD were to be delayed by 1 year in only 2% of affected children. Here, we call on the international pediatric nephrology community to establihs guidelines for forming multidisciplinary clinics throughout the world. © IPNA 2012
Perinatal Factors Associated with Cardiovascular Disease Risk among Preschool-Age Children in the United States: An Analysis of 1999–2008 NHANES Data
We examined the relationships between selected perinatal and early infancy factors (maternal smoking during pregnancy, infant low birthweight, breastfeeding, and early introduction of solid foods [<6 months of age] and increased BMI [≥85th, ≥95th percentiles for age, sex]), waist circumference (WC), C-reactive protein (CRP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and decreased HDL cholesterol during early childhood. The population-based sample included 3,644 3-to-6-year-old Non-Hispanic White (NHW), Hispanic, and Non-Hispanic Black (NHB) children who participated in the 1999–2008 National Health and Nutrition Examination Surveys. Analysis showed that breastfeeding was significantly protective against early childhood obesity (OR 0.43, 95% CI, 0.27–0.69) and the highest quintile for WC (OR 0.58, 95% CI, 0.37–0.32) among NHW, and against the highest quintile of non-HDL cholesterol among NHB (OR 0.56, 95% CI, 0.32–0.98). Additionally, NHW children were significantly more likely to be obese (OR 2.22, 95% CI 1.30–3.78) and have higher CRP levels (OR 1.63, 95% CI, 1.05–2.51) if their mothers smoked during pregnancy. These results support the observation that breastfeeding may be protective against early childhood obesity while maternal smoking during pregnancy is a risk factor for obesity and increased CRP levels among NHW young children
Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial
Background:
Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease.
Methods:
A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype.
Conclusions:
The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained
Microsatellite instability and defects in mismatch repair proteins: a new aetiology for Sertoli cell‐only syndrome
Microsatellite instability is characteristic of certain types of cancer, and is present in rodents lacking specific DNA mismatch repair proteins. These azoospermic mice exhibit spermatogenic defects similar to some human testicular failure patients. Therefore, we hypothesized that microsatellite instability due to deficiencies in mismatch repair genes might be an unrecognized aetiology of human testicular failure. Because these azoospermic patients are candidates for testicular sperm extraction and ICSI, transmission of mismatch repair defects to the offspring is possible. Seven microsatellite loci were analysed for instability in specimens from 41 testicular failure patients and 20 controls. Blood and testicular DNA were extracted from patient and control specimens, and amplified by PCR targeting seven microsatellite loci. DNA fragment length was analysed with an ABI Prism 310 Genotyping Machine and GeneScan software. Immunohistochemistry was performed on paraffinized testis biopsy sections and cultured testicular fibroblasts from each patient to determine if expression of the mismatch repair proteins hMSH2 and hMLH1 was normal in both somatic and germline cells. Results demonstrate that microsatellite instability and DNA mismatch repair protein defects are present in some azoospermic men, predominantly in Sertoli cell‐only patients (P < 0.01 and P < 0.05 respectively). This provides evidence of a previously unrecognized aetiology of testicular failure that may be associated with cancer predispositio
Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation
AbstractObjectivesWe studied the outcomes of pediatric patients diagnosed with dilated cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic variables at the time of presentation.BackgroundThe outcome of pediatric DCM patients ranges from recovery to a 50% to 60% chance of death within five years of diagnosis. The impact of heart transplantation and other emerging therapies on the outcomes of pediatric DCM patients is uncertain.MethodsWe performed a retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM from 1990 to 1999. Routine therapy included use of digoxin, diuretics, angiotensin-converting enzyme inhibitors, and heart transplantation.ResultsAt the time of last follow-up, 11 patients (12%) had died without transplantation; 20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and 33 (36%) had recovery of left ventricular systolic function. Overall actuarial one-year survival was 90%, and five-year survival was 83%. However, actuarial freedom from “heart death” (death or transplantation) was only 70% at one year and 58% at five years. Multivariate analysis found age <1 year (hazard ratio 7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to be significantly associated with a greater risk of death or transplantation and a higher left ventricular shortening fraction at presentation (hazard ratio 0.92), with a slightly decreased risk of death or transplantation.ConclusionsPediatric DCM patients continue to have multiple outcomes, with recovery of left ventricular systolic function occurring most frequently. Utilization of heart transplantation has led to improved survival after the diagnosis of pediatric DCM
Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood
Introduction Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier.
Methods Seventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m(2) and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n=19) or 240 mg/m(2) (n=18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI.
Results No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls.
Conclusion and implications for cancer survivors At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m(2), no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients
Myocardial Alternative RNA Splicing and Gene Expression Profiling in Early Stage Hypoplastic Left Heart Syndrome
Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS. Splicing of mRNA transcripts is an important regulatory mechanism of gene expression. Tissue specific alterations of this process have been associated with several cardiac diseases, however, transcriptional signature profiles related to HLHS are unknown. In this study, we performed genome-wide exon array analysis to determine differentially expressed genes and alternatively spliced transcripts in the right ventricle (RV) of six neonates with HLHS, compared to the RV and left ventricle (LV) from non-diseased control subjects. In HLHS, over 180 genes were differentially expressed and 1800 were differentially spliced, leading to changes in a variety of biological processes involving cell metabolism, cytoskeleton, and cell adherence. Additional hierarchical clustering analysis revealed that differential gene expression and mRNA splicing patterns identified in HLHS are unique compared to non-diseased tissue. Our findings suggest that gene expression and mRNA splicing are broadly dysregulated in the RV myocardium of HLHS neonates. In addition, our analysis identified transcriptome profiles representative of molecular biomarkers of HLHS that could be used in the future for diagnostic and prognostic stratification to improve patient outcome
Cardiovascular Effects in Childhood Cancer Survivors Treated with Anthracyclines
Anthracyclines are commonly used to treat childhood leukemias and lymphomas, as well as other malignancies, leading to a growing population of long-term childhood cancer survivors. However, their use is limited by cardiotoxicity, increasing survivors' vulnerability to treatment-related complications that can markedly affect their quality of life. Survivors are more likely to suffer from heart failure, coronary artery disease, and cerebrovascular accidents compared to the general population. The specific mechanisms of anthracycline cardiotoxicity are complex and remain unclear. Hence, determining the factors that may increase susceptibility to cardiotoxicity is of great importance, as is monitoring patients during and after treatment. Additionally, treatment and prevention options, such as limiting cumulative dosage, liposomal anthracyclines, and dexrazoxane, continue to be explored. Here, we review the cardiovascular complications associated with the use of anthracyclines in treating malignancies in children and discuss methods for preventing, screening, and treating such complications in childhood cancer survivors
Assessing Latent Effects of Prenatal Cocaine Exposure on Growth and Risk of Cardiometabolic Disease in Late Adolescence: Design and Methods
Prenatal cocaine exposure has been linked to neurocognitive and developmental outcomes throughout childhood. The cardiovascular toxicity of cocaine is also markedly increased in pregnancy, but it is unknown whether this toxicity affects anthropometric growth and the development of cardiometabolic disease risk factors in the offspring across the lifespan. During the early 1990s, the Miami Prenatal Cocaine Study enrolled a cohort of 476 African American children (253 cocaine-exposed, 223 non-cocaine-exposed) and their biological mothers at delivery in a prospective, longitudinal study. The MPCS has collected 12 prior waves of multidomain data on over 400 infants and their mothers/alternate caregivers through mid-adolescence and is now embarking on an additional wave of data collection at ages 18-19 years. We describe here the analytical methods for examining the relationship between prenatal cocaine exposure, anthropometric growth, and cardiometabolic disease risk factors in late adolescence in this minority, urban cohort. Findings from this investigation should inform both the fields of substance use and cardiovascular research about subsequent risks of cocaine ingestion during pregnancy in offspring
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