Consequences of transplant quality on chronic allograft nephropathy

Using kidneys from expanded-criteria donors to alleviate organ shortage has raised concern on reduced transplant outcomes. In this paper, we review how critical donor-related factors such as donor age, brain death, and consequences of ischemia-reperfusion injury (IRI) determine graft quality and impact chronic allograft nephropathy. We propose that combinatorial effects of organ-intrinsic features associated with increasing age and unspecific injuries related to brain death and IRI will impact innate and adaptive immune responses. Future research will need to explore avenues to optimize donor management, organ preservation, adapted immunosuppressive strategies, as well as modifications of the allocation of suboptimal allografts.     

Exonic duplication of the hepatocyte nuclear factor-1beta gene (transcription factor 2, hepatic) as a cause of maturity onset diabetes of the young type 5

CONTEXT: Maturity onset diabetes of the young (MODY) type 5 has been described as the association of early-onset diabetes and renal disease. Actually, MODY5 encompasses multiple phenotypes, including nondiabetic progressive renal failure, kidney and genital tract malformations, atypical familial hyperuricemic nephropathy, pancreas atrophy, and liver test abnormalities. The occurrence of MODY5 has been associated with various molecular abnormalities of TCF2, including missense, nonsense, small insertion/deletions, and splice site mutations, as well as large genomic deletions or single exonic deletion of TCF2. DESIGN: Using quantitative multiplex PCR amplification of short fluorescent fragments, we have analyzed the TCF2 gene in a French family of which three relatives presented a MODY5 phenotype. The proband had an extended clinical phenotype, including hyperuricemic nephropathy and early gout, chronic renal failure, renal morphological abnormalities, abnormal liver tests, and diabetes. His son had almost no clinical expression of the disease, whereas his grandson had a restricted but severe renal phenotype present from birth. RESULTS: We show that a duplication of the exon 5 of TCF2 is responsible for the MODY5 phenotypes in this family. CONCLUSIONS: Thus, we describe a novel molecular mechanism that may be responsible for MODY5, and we emphasize the wide intrafamilial variability of MODY5 expressivity. These observations suggest that the diagnosis of MODY5 may be raised even in subjects with partial phenotypes. They also confirm that quantitative multiplex PCR amplification of short fluorescent fragments analysis should be the first step of genetic screening in patients with a MODY5 phenotype.     

Pulmonary nodule detection on MDCT images: evaluation of diagnostic performance using thin axial images,maximum intensity projections,and computer-assisted detection

This study aimed at evaluating the diagnostic benefits of maximum intensity projections (MIP) and a commercially available computed-assisted detection system (CAD) for the detection of pulmonary nodules on MDCT as compared with standard 1-mm images on lung cancer screening material. Thirty subjects were randomly selected from our database. Three radiologists independently reviewed three types of images: axial 1-mm images, axial MIP slabs, and CAD system detections. Two independent experienced chest radiologists decided which were true-positive nodules. Two hundred eighty-five nodules ≥1 mm were identified as true-positive by consensus of two independent chest radiologists. The detection rates of the three independent observers with 1-mm axial images were 22 ± 4.8%, 30 ± 5.3%, and 47 ± 2.8%; with MIP: 33 ± 5.4%, 39 ± 5.7%, and 45 ± 5.8%; and with CAD: 35 ± 5.6%, 36 ± 5.6%, and 36 ± 5.6%. There was a reading technique effect on the observers’ sensitivity for nodule detection: sensitivities with MIP were higher than with 1-mm images or CAD for all nodules (F-values = 0.046). For nodules ≥3 mm, readers’ sensitivities were higher with 1-mm images or MIP than with CAD (p < 0.0001). CAD was the most and MIP the less time-consuming technique (p < 0.0001). MIP and CAD reduced the number of overlooked small nodules. As MIP is more sensitive and less time consuming than the CAD we used, we recommend viewing MIP and 1-mm images for the detection of pulmonary nodules. This study was presented at the ECR 2006.