ABSTRACT
Paediatric cardiomyopathies are a heterogenous group of rare disorders, characterised by mechanical and electrical abnormalities of the heart muscle. The overall annual incidence of childhood cardiomyopathies is estimated at about 1 per 100,000 children and is significantly higher during the first 2 years of life. Dilated cardiomyopathies account for approximately half of the cases. Hypertrophic cardiomyopathies form the second largest group, followed by the less common left ventricular non-compaction and restrictive phenotypes. Infectious, metabolic, genetic, and syndromic conditions account for the majority of cases. Congestive heart failure is the typical manifestation in children with dilated cardiomyopathy, whereas presenting symptoms are more variable in other phenotypes. The natural history is largely influenced by the type of cardiomyopathy and its underlying aetiology. Results from a national population-based study revealed 10-year transplant-free survival rates of 80, 62, and 48% for hypertrophic, dilated and left ventricular non-compaction cardiomyopathies, respectively. Long-term survival rates of children with a restrictive phenotype have largely been obscured by early listing for heart transplantation. In general, the majority of adverse events, including death and heart transplantation, occur during the first 2 years after the initial presentation. This review provides an overview of childhood cardiomyopathies with a focus on epidemiology, natural history, and outcomes.
ABSTRACT
Cell replacement therapy by intracerebral transplantation of fetal dopaminergic neurons has become a promising therapeutic option for patients suffering from Parkinson's disease during the last decades. However, limited availability of human fetal tissue as well as ethical issues, lack of alternative nonfetal donor cells, and the absence of standardized transplantation protocols have prevented neurorestorative therapies from becoming a routine procedure in patients suffering from neurodegenerative diseases. Improvement of graft survival, surgery techniques, and identification of the optimal target area are imperative for further optimization of this novel treatment. In the present study, human primary fetal ventral mesencephalon-derived tissue from 7- to 9-week-old human fetuses was transplanted into 6-hydroxydopamine-lesioned adult Sprague-Dawley rats. Graft survival, fiber outgrowth, and drug-induced rotational behavior up to 14 weeks posttransplantation were compared between different intrastriatal transplantation techniques (full single cell suspension vs. partial tissue pieces suspension injected by glass capillary or metal cannula) and the intranigral glass capillary injection of a full (single cell) suspension. The results demonstrate a higher survival rate of dopamine neurons, a greater reduction in amphetamine-induced rotations (overcompensation), and more extensive fiber outgrowth for the intrastriatally transplanted partial (tissue pieces) suspension compared to all other groups. Apomorphine-induced rotational bias was significantly reduced in all groups including the intranigral group. The data confirm that human ventral mesencephalon-derived cells serve as a viable cell source, survive in a xenografting paradigm, and functionally integrate into the host tissue. In contrast to rat donor cells, keeping the original (fetal) neuronal network by preparing only a partial suspension containing tissue pieces seems to be beneficial for human cells, although a metal cannula that causes greater tissue trauma to the host is required for injection. In addition, homotopic intranigral grafts may represent a complimentary grafting approach to the "classical" ectopic intrastriatal target site in PD.
