Size reduction of donor organs in pediatric lung transplantation

Mueller C, Hansen G, Ballmann M, Schwerk N, Simon AR, Goerler H, Strueber M. Size reduction of donor organs in pediatric lung transplantation.
Pediatr Transplantation 2010:14: 364–368. © 2009 John Wiley & Sons A/S. Abstract: Lobar transplantation and peripheral segmental resection allow downsizing of larger lungs for use in smaller recipients, particularly with regard to pediatric patients on the high urgency waiting list. We studied the safety and outcome of these techniques in children. All pediatric patients who underwent reduced size LTx between January 2000 and March 2009 were retrospectively reviewed and compared with pediatric patients who underwent full size LTx during the same period. Patient characteristics, intra‐operative variables, and post‐operative morbidity and mortality were compared. Among 28 primary LTxs, 16 (57%) were performed in reduced size technique. Preoperatively, there was a trend toward a higher rate of mechanical ventilation and a higher capillary pCO₂ in the reduced size group. Surgical procedures tended to be longer in that group. Post‐operative complications, survival and functional parameters were comparable between both groups. Our study demonstrates that reduced size LTx in children is a reliable therapeutic option that provides results comparable to full size LTx. This technique might help to reduce waiting list mortality by expanding the donor pool in pediatric LTx.     

PALS1 is essential for retinal pigment epithelium structure and neural retina stratification

The membrane-associated palmitoylated protein 5 (MPP5 or PALS1) is thought to organize intracellular PALS1-CRB-MUPP1 protein scaffolds in the retina that are involved in maintenance of photoreceptor-Müller glia cell adhesion. In humans, the Crumbs homolog 1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, especially PALS1, we generated and analyzed conditional knockdown mice for Pals1. Small irregularly shaped spots were detected throughout the PALS1 deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. The electroretinography a- and b-wave was severely attenuated in the aged mutant retinas, suggesting progressive degeneration of photoreceptors. The histological analysis showed abnormal retinal pigment epithelium structure, ectopic photoreceptor nuclei in the subretinal space, an irregular outer limiting membrane, half rosettes of photoreceptors in the outer plexiform layer, and a thinner photoreceptor synaptic layer suggesting improper photoreceptor cell layering during retinal development. The PALS1 deficient retinas showed reduced levels of Crumbs complex proteins adjacent to adherens junctions, upregulation of glial fibrillary acidic protein indicative of gliosis, and persisting programmed cell death after retinal maturation. The phenotype suggests important functions of PALS1 in the retinal pigment epithelium in addition to the neural retina.     

Chronic Mycoplasma pneumoniae infection in a child after renal transplantation

Schwerk N, Hartmann C, Baumann U, Pape L, Ehrich JHH, Hansen G. Chronic Mycoplasma pneumoniae infection in a child after renal transplantation.
Pediatr Transplantation 2010: 14: E26–E29. © 2009 John Wiley & Sons A/S. Abstract: Mycoplasma pneumoniae has rarely been reported in renal transplant recipients. We present the case of a 10‐yr‐old boy with a six‐month history of chronic cough, recurrent pyrexia, and weight loss three yr after RTx. The patient's post‐transplant course was complicated by recurrence of NS that resolved with plasmapheresis and PTLD, which was successfully treated with an anti‐CD20 monoclonal antibody. Chest X‐ray showed a round mass‐like lesion in the left upper lobe; MRT, PET, and bronchoscopy ruled out a PTLD. BAL fluid revealed M. pneumoniae‐DNA. A three‐wk course of macrolide therapy induced rapid recovery. We conclude that M. pneumoniae infection should be considered in immunosuppressed patients with long‐lasting respiratory complaints and fever of unknown origin. Antibiotic treatment should be given for a minimum of three wk.     

Secondary research use of personal medical data: attitudes from patient and population surveys in The Netherlands and Germany

Making routine clinical-care-data available for medical research requires adequate consent to legitimize use and exchange. While, public interest in supporting medical research is increasing, individuals often find it difficult to actively enable researchers to access their data. In addition to broad consent, the idea of (consent-free) data donation has been brought into play as another way to legitimize secondary research use of medial data. However, flanking the implementation of broad consent policies or data donation, the attitude of patients, and the general public toward different aspects of these approaches needs to be assessed. We conducted two empirical studies to this end among Dutch patients (n = 7430) and representative German citizens (n = 1006). Wide acceptance of broad consent was observed among Dutch patients (92.3%), corroborating previous findings among German patients (93.0%). Moreover, 28.8% of the Dutch patients generally approved secondary data-use for non-academic research, 42.3% would make their decision dependent upon the type of institution in question. In the German survey addressing the general population, 78.8% approved data donation without explicit consent as an alternative model of legitimization, the majority of those who approved (96.7%) would allow donated data to be used by universities and public research institutions. This willingness to support contrasted sharply with the fact that only 16.6% would allow access to the data by industry. Our findings thus not only add empirical evidence to the debate about broad consent and data donation, but also suggest that widespread public discussion and education about the role of industry in medical research is necessary in that context.Subject terms: Medical research, Social sciences     

Transplantation of human umbilical cord blood-derived adherent progenitors into the developing rodent brain

The results of several recent studies suggest that human umbilical cord blood (HUCB)-derived cells have the potential to undergo neural differentiation both in vitro and in vivo. Transplantation into the embryonic ventricular zone provides a unique opportunity to study the migration and differentiation of nonneural somatic progenitor cells in response to instructive cues within the developing neuroepithelium. We isolated an adherently growing population of HUCB-derived cells expressing CD13, CD29, CD49e, CD71, CD73, CD166, Flk-1, and vimentin but lacking CD34 and CD45. On transplantation into the ventricles of embryonic day 16.5 rat embryos, these cells formed subventricular clusters that extended into a variety of host brain regions, including striatum, cortex, hippocampus, thalamus, hypothalamus, tectum, pons, and cerebellum. Donor cells identified with an antibody to human nuclei or human-specific DNA in situ hybridization maintained expression of their original marker antigens and showed no expression of the neural markers MAP2 and NeuN (neurons), GFAP (astrocytes), and CNP (oligodendrocytes). In contrast to grafted primary neural cells, they remained largely confined to subventricular clusters with little evidence for intraparenchymal integration. Thus, the neurogenic environment of the embryonic ventricular zone does not promote the elaboration of a neural phenotype in HUCB-derived cells.