Further characterization of ATP6V0A2-related autosomal recessive cutis laxa.

Autosomal recessive cutis laxa (ARCL) syndromes are phenotypically overlapping, but genetically heterogeneous disorders. Mutations in the ATP6V0A2 gene were found to underlie both, autosomal recessive cutis laxa type 2 (ARCL2), Debré type, and wrinkly skin syndrome (WSS). The ATP6V0A2 gene encodes the a2 subunit of the V-type H(+)-ATPase, playing a role in proton translocation, and possibly also in membrane fusion. Here, we describe a highly variable phenotype in 13 patients with ARCL2, including the oldest affected individual described so far, who showed strikingly progressive dysmorphic features and heterotopic calcifications. In these individuals we identified 17 ATP6V0A2 mutations, 14 of which are novel. Furthermore, we demonstrate a localization of ATP6V0A2 at the Golgi-apparatus and a loss of the mutated ATP6V0A2 protein in patients' dermal fibroblasts. Investigation of brefeldin A-induced Golgi collapse in dermal fibroblasts as well as in HeLa cells deficient for ATP6V0A2 revealed a delay, which was absent in cells deficient for the ARCL-associated proteins GORAB or PYCR1. Furthermore, fibroblasts from patients with ATP6V0A2 mutations displayed elevated TGF-ß signalling and increased TGF-ß1 levels in the supernatant. Our current findings expand the genetic and phenotypic spectrum and suggest that, besides the known glycosylation defect, alterations in trafficking and signalling processes are potential key events in the pathogenesis of ATP6V0A2-related ARCL.

Follow-up of gastro-intestinal stromal tumours (GIST) during treatment with imatinib mesylate by abdominal MRI.

Typical MRI findings for gastro-intestinal stromal tumours (GIST) under treatment with imatinib were evaluated. MRI was performed in 45 patients (25 responders, 20 non-responders) with metastatic or locally advanced, unresectable GIST. Target lesions were selected and re-evaluated after 2, 4, and 6 months of therapy with imatinib. The target tumour response (TTR) was classified according to RECIST criteria. TTR, signal intensity in the centre and border of the lesion and the presence and the extension of a hypervascular rim were analysed. The mean diameter of the marker lesions decreased significantly (P<0.001) from 7.1+/-2.6 cm to 5.9+/-2.3 cm after 6 months. Accuracy of RECIST criteria was 51%, 69% and 73% on MRI 2, 4 and 6 months for response assessment. In addition, responders had higher signal-to-noise ratios on T2-w images after 2 months (P<0.05) and a decrease of vascularised areas in the lesion 4 and 6 months after treatment (each P<0.01), when compared with non-responders. Beyond the size measurement for response assessment, MRI provides additional information of tumour response using SI of T2-w images and quantification of vascularised areas of GIST manifestations.

Emergency donor heart protection: application of the port access catheter technique using a pig heart transplantation model.

BACKGROUND: Organ shortage limits the number of transplantations, and donor deterioration may precede and often prevent conventional organ preservation. This study evaluates in situ perfusion as a bedside method for cardiac allograft procurement in a large animal model. METHODS: Thirty Landrace pigs (42 +/- 7 kg) were studied. The hearts in the conventional group underwent cardioplegic arrest with University of Wisconsin solution and sodium-hydrogen exchange inhibitor cariporide as an additive; they were explanted and stored on ice before transplantation. In the in situ group, one catheter was placed in the ascending aorta and another in the right atrium. After disconnection from the ventilator, hypoxia caused circulatory arrest. The aorta was endoclamped, and in situ perfusion of the aortic root was maintained with University of Wisconsin solution and cariporide. After explantation, hearts were stored on ice for 120 min. All hearts were implanted according to the Shumway technique. Ventricular pressure and cardiac output were monitored online, and troponin-I was measured intermittently. Two hours after weaning from extracorporal circulation, the animals were killed and histology was performed. RESULTS: Catheters were placed through introducers within 5 min. Functional recovery and histology were comparable between the two techniques. Troponin-I increased in both groups during reperfusion but at a faster rate in the in situ technique (P <0.01). CONCLUSION: In situ perfusion may be suitable for cardiac transplants when donor deterioration requires urgent organ preservation. Catheters can be placed at bedside and modified to achieve multi-organ protection through additional perfusion of the abdominal aorta.

[Differential diagnosis of intra- and perilienal tumors by use of a RES-specific MRI contrast agent]. / Differenzialdiagnose von Intra- und Perilienalen Tumoren mit Hilfe eines RES-spezifischen MRT-Kontrastmittels.

PURPOSE: To describe the additional benefit in detection and differential diagnosis of peri- and intrasplenic tumors by use of an superparamagnetic iron oxide contrast agent (SPIO). MATERIALS AND METHODS: We represent 7 patients with known malignant tumors. Aim of the examination was the detection and characterisation of intra- or perisplenic tumors. We performed T2w TSE breath triggered sequences before and 10 min after application of SPIO and T1w Flash 2D GRE sequences before and after SPIO and Gadopentetate dimeglumin application. All images were presented to two radiologists, who were asked to asses the presence and characterisation of tumors by using a five-point confidence scale. RESULTS: In two patient intrasplenic hemangiomas were detected, intrasplenic lymphoma, metastasis was excluded, respectively. In two patients perisplenic tumors were diagnosed as gastrointestinal stroma tumors, confirmed by biopsy. In two patients accessory spleens were identified and lymph node metastasis excluded. In one patient an intrasplenic cyst was diagnosed. SPIO enhanced T2w images and Gadopentetate dimeglumin enhanced T1w sequences were evaluated as superior. CONCLUSION: The examination of the spleen by use of superparamagnetic iron oxides offers additional abilities in depiction and charaterisation of intra- and perisplenic tumors in first experiences. First clinical observations indicate that a combination of SPIO enhanced T2w sequences and Gadopentetate dimeglumin enhanced T1w dynamic sequences might be superior to other sequences in detection and characterisation of splenic tumors.

Sodium-hydrogen inhibitor cariporide (HOE 642) improves in situ protection of hearts from non-heart-beating donors.

BACKGROUND: Reperfusion injury is a vital problem in non-heart-beating donor (NHBD) organs. The sodium-hydrogen inhibitor cariporide is thought to improve cellular integrity after ischemia and reperfusion. Recently, we demonstrated the possibility of preserving hearts with in situ perfusion after circulatory death. The purpose of this study was to determine whether cariporide improves in situ heart protection. METHODS: We studied 20 pigs (18 +/- 2 kg). Hearts in the conventional group (CON, n = 6) underwent cardioplegic arrest with University of Wisconsin solution and then were explanted and stored for 150 minutes on ice. In the other groups, a catheter was placed in each ascending aorta and right atrium. After disconnecting the ventilator, hypoxia caused circulatory arrest within 7 +/- 2 minutes. The aorta was endoclamped, and continuous in situ perfusion of the aortic root was maintained for 60 minutes with University of Wisconsin solution (UW, n = 7) or with UW solution and cariporide (CAR, n = 7). After explantation, the hearts were stored on ice for 90 minutes. In all groups, hearts were reperfused with homologous, whole pig blood in an isolated working heart model for 45 minutes. We monitored stroke-work index on-line, intermittently measured troponin I and malondialdehyde, and compared light microscopic examinations among the groups. RESULTS: Stroke-work index was higher in the CAR group compared with the UW group during the last 20 minutes of reperfusion (10(3)dynes x cm x beats(-1)x gm(-1), 6.6 +/- 1.4 vs 4.5 +/- 2.0, p < 0.05), troponin I was lower in the CAR group compared with the UW group (161 +/- 32 ng/ml vs 277 +/- 35 ng/ml, p < 0.05). Results of malondialdehyde and light microscopic examinations were slightly better in the CAR group, without reaching statistical significance. CONCLUSION: Cariporide as an additive to UW solution improves functional recovery and decreases myocardial damage in hearts from NHBDs protected with an in situ perfusion technique.

[Diagnosis of tumors of the small intestine with the aid of CT contrast enema. Sellink CT technique evaluated in 63 patients]. / Diagnostik von Dünndarmtumoren mit Hilfe des CT-Enteroklysma. Die CT--Sellink ausgewertet bei 63 Patienten.

PURPOSE: Aim of the study was to compare the visualisation of small bowel tumours particularly lymphoma of the small bowel by enteroclysma, computed tomography (CT) and computed tomography following enteroclysma. METHODS: We examined 97 examinations in 63 patients. Non Hodgkin's Lymphoma was the primary malignancy in 44 patients, metastasis of different malignancies in 8 patients, primary malignancies of the small intestine in 5 patients, mesenteric tumours in 4 patients and postoperative stricture in another 2 patients. CT following enteroclysma (CT Sellink) was performed as helical CT in 55 patients and as incremental CT in 42 patients. Examinations were evaluated by two radiologists. Evaluation criteria were small bowel distension, perceptibility of details and topographic correlation. RESULTS: Manifestations of lymphoma were found in 32 patients, infiltration of bowel wall in 12 patients. In three patients metastases of melanoma were found. In three patients the suspicion for small bowel tumours was not verified in CT Sellink. The perceptibility of details was evaluated as ameliorated in 45.5% of examinations over all. CONCLUSIONS: CT Sellink offers remarkable advantages in the diagnosis of small bowel tumours compared with enteroclysma and "conventional" computed tomography under intra-venous and oral contrast media. CT Sellink was feasible over a time of 7 years now in clinical praxis. This examination represents an optimized standard in small intestine examination.

[BALTOMA--long-term follow-up]. / BALTOMe--ein Langzeitverlauf.

PURPOSE: The purpose of this work was to describe the findings and the long term follow up of pathologically confirmed bronchus-associated lymphoid tissue lymphoma (BALTOMA) in 6 patients. METHODS: CT examinations and conventional radiological examinations were reviewed and compared to describe typical radiological findings and patterns of pulmonary manifestations. It were described the number of lesions and characteristics like presence of airspace consolidation, ground-glass attenuation, bubble-like radiolucencies, air bronchogram, bronchial dilatation, Infiltration and the long term behaviour of the manifestations. RESULTS: Lesions with a positive air bronchogram, no infiltration of extrapulmonary tissue or extrapulmonary manifestations were revealed as typical findings. Only a slow or no progression of disease was shown in most patients over a term of up to twelve years. CONCLUSIONS: The lymphoma of the bronchus-associated lymphoid tissue of the lung is a rare tumor. A positive air bronchogram, a multiplicity of disease, bilateral lesions, a fibrotic transformation of the lung tissue and no growth or only a slow groth over al long term of observation are typical radiological findings.