Selective late steroid withdrawal after renal transplantation

Steroid withdrawal (SW) after paediatric renal transplantation (RTPL) is controversial. Selective late SW has been performed in our unit since 1995. The safety and effects of SW were analysed retrospectively in 47 patients undergoing RTPL between 1995 and 2004. Initial immunosuppression consisted of cyclosporine A, azathioprine or mycophenolate mofetil and steroids. Criteria for SW were: (1) stable renal function, (2) time interval after RTPL ≥ 1year, (3) no rejection or time interval after last rejection ≥ 1year and (4) good compliance. SW was performed in 30 patients at an age of 13.5years (range 4.5-18.5) and 2.2years (range 1-6.6) after RTPL. After SW, one patient experienced a steroid-sensitive rejection. Follow-up after SW (1.3year; range 0.25-7.5) showed maintained renal function: glomerular filtration rate at SW and currently was 82 (65-128) and 82 (42-115) ml/min per 1.73m2, respectively. The number of patients on antihypertensive treatment did not significantly change (at SW: n = 15; currently: n = 11). Height and body mass index (BMI) remained stable: Median standard deviation score (SDS) for height/BMI at SW and currently was −1.1/0.2 and −0.8/0.1, respectively. Selective late SW was safe regarding renal function and had no significant effect on blood pressure and growt

Successful long-term outcome after renal transplantation in a patient with atypical haemolytic uremic syndrome with combined membrane cofactor protein CD46 and complement factor I mutations

Background: Atypical haemolytic uremic syndrome (aHUS) is often associated with a high risk of disease recurrence and subsequent graft loss after isolated renal transplantation. Evidence-based recommendations for a mutation-based management after renal transplantation in aHUS caused by a combined mutation with complement factor I (CFI) and membrane cofactor protein CD46 (MCP) are limited. Case-diagnosis/Treatment: We describe a 9-year-old boy with a first manifestation of aHUS at the age of 9months carrying combined heterozygous mutations in the CFI and MCP genes. At the age of 5years, he underwent isolated cadaveric renal transplantation. Fresh frozen plasma was administered during and after transplantation, tapered and finally stopped after 3years. Conclusions: During the 5-year follow-up after transplantation there have been no signs of aHUS recurrence and graft function has remained good. The combination of heterozygous MCP and CFI mutations with aHUS might have a positive impact on the post-transplant course, possibly predicting a lower risk of aHUS recurrence after an isolated cadaveric renal transplantatio

Towards a Harmonized Terminology: A Glossary for Biocide Susceptibility Testing

Disinfection is a key strategy to reduce the burden of infections. The contact of bacteria to biocides—the active substances of disinfectants—has been linked to bacterial adaptation and the development of antimicrobial resistance. Currently, there is no scientific consensus on whether the excessive use of biocides contributes to the emergence and spread of multidrug resistant bacteria. The comprehensive analysis of available data remains a challenge because neither uniform test procedures nor standardized interpretive criteria nor harmonized terms are available to describe altered bacterial susceptibility to biocides. In our review, we investigated the variety of criteria and the diversity of terms applied to interpret findings in original studies performing biocide susceptibility testing (BST) of field isolates. An additional analysis of reviews summarizing the knowledge of individual studies on altered biocide susceptibility provided insights into currently available broader concepts for data interpretation. Both approaches pointed out the urgent need for standardization. We, therefore, propose that the well-established and approved concepts for interpretation of antimicrobial susceptibility testing data should serve as a role model to evaluate biocide resistance mechanisms on a single cell level. Furthermore, we emphasize the adaptations necessary to acknowledge the specific needs for the evaluation of BST data. Our approach might help to increase scientific awareness and acceptance

Inherited renal tubular dysgenesis: the first patients surviving the neonatal period

Renal tubular dysgenesis (RTD) is a clinical disorder either acquired during fetal development or inherited as an autosomal recessive condition. Inherited RTD is caused by mutations in the genes encoding the components of the renin-angiotensin system angiotensinogen, renin, angiotensin-converting enzyme and angiotensin II receptor type 1. Inherited RTD is characterized by early onset oligohydramnios, skull ossification defects, preterm birth and neonatal pulmonary and renal failure. The histological hallmark is the absence or poor development of proximal tubules. So far, all patients died either in utero or shortly after birth. We report the first patients with inherited RTD surviving the neonatal period and still being alive. Genetic and functional analysis of the renin-angiotensin system contributes to the diagnosis of RTD. In conclusion, the clinical diagnosis of inherited RTD is easily missed after birth without renal biopsy or information on affected family members. Genetic and functional analysis of the renin-angiotensin system contributes to correct diagnosi

Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpopulation changes during development (n = 13) and due to disease and/or treatment (n = 18) in tissues stored in fertility preservation programs, using markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC). Throughout normal prepubertal testicular development, only the density of 5mC-positive spermatogonia significantly increased with age. In comparison, patients affected by disease and/or treatment showed a reduced density of UTF1-, PCNA- and 5mC-positive spermatogonia, whereas the percentage of spermatogonial subpopulations remained unchanged. As an exception, sickle cell disease patients treated with hydroxyurea displayed a reduction in both density and percentage of 5mC- positive spermatogonia. Our results demonstrate that, in general, a reduction in spermatogonial density does not alter the percentages of undifferentiated and proliferating spermatogonia, nor the establishment of global methylation. However, in sickle cell disease patients', establishment of spermatogonial DNA methylation is impaired, which may be of importance for the potential use of this tissues in fertility preservation programs

Land schafft Architektur: Die Lehre der Architektur und die Entstehung der Landschaftsarchitektur an der TUD - Sammlung von Gartenplänen und Zeichnungen aus den Jahren 1870-1900

Land schafft Architektur | Gartenarchitektur um 190

DDRprot: a database of DNA damage response-related proteins

The DNA Damage Response (DDR) signalling network is an essential system that protects the genome’s integrity. The DDRprot database presented here is a resource that integrates manually curated information on the human DDR network and its sub-pathways. For each particular DDR protein, we present detailed information about its function. If involved in post-translational modifications (PTMs) with each other, we depict the position of the modified residue/s in the three-dimensional structures, when resolved structures are available for the proteins. All this information is linked to the original publication from where it was obtained. Phylogenetic information is also shown, including time of emergence and conservation across 47 selected species, family trees and sequence alignments of homologues. The DDRprot database can be queried by different criteria: pathways, species, evolutionary age or involvement in (PTM). Sequence searches using hidden Markov models can be also used.E.A.-L. was supported by the European Commission grant [FP7-REGPOT-2012-2013-1; A.A. was partially supported by the Spanish Ministry of Science and Innovation grant [PS09/02111].Peer reviewe