Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.

OBJECTIVE: Tacrolimus has been shown to provide superior immunosuppression in various solid organ transplant settings. The purpose of our study was to compare the survival of porcine lung allografts after induction with either cyclosporine A (CsA) or tacrolimus. METHODS: Single lung transplantation from MHC mismatched donors was performed in 10 minipigs. Immunosuppression included 1.5 mg/kg per day methylprednisolone and 1.0 mg/kg per day azathioprine. CsA (n=5) was adjusted to trough levels of 300-500 ng/ml, tacrolimus (n=5) was adjusted to 16-26 ng/ml. All immunosuppressive drugs were discontinued on postoperative day (POD) 28. Allograft survival was monitored by sequential chest radiographs, bronchoscopy and transbronchial biopsy histology. Peripheral blood leukocytes were scanned for donor chimerism and CD3, CD4, CD8 and CD25 expression. RESULTS: The animals survived a 4-week course of immunosuppression without radiological or histological signs of rejection on POD 28. Median allograft survival in CsA-treated animals was 55+/-15 days and all animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrolimus-treated animals, median survival was 152+/-65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). The degree of donor leukocyte chimerism and the frequency of CD4+CD25+ T-cells were higher in the tacrolimus group, however, these differences were not statistically significant. CONCLUSION: The results of our study show that primary immunosuppression with tacrolimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model.     

Liver transplantation for severe Amanita phalloides mushroom poisoning

Amanita phalloides mushroom poisoning is an increasingly common and potentially lethal problem for which liver transplantation offers definitive therapy in selected patients. When significant liver dysfunction appears, early transfer to a liver transplant center is important to identify appropriate candidates and to begin the search for a donor organ. The clinical course of five severely poisoned patients, four of whom underwent liver transplantation, is reviewed. Indications for transplantation included primarily a markedly prolonged prothrombin time that was only partially correctable and a constellation of findings including metabolic acidosis, hypoglycemia, hypofibrinogenemia, and increased serum ammonia, following a marked elevation in serum aminotransferase levels. Unlike viral fulminant hepatic failure, grade III or IV hepatic encephalopathy, marked elevation of the serum bilirubin level, and azotemia were not indications for transplantation. Resected livers demonstrated hepatocyte viability of 0% to 30%. Manifestations of Amanita poisoning complicating preoperative and/or postoperative care included severe diarrhea, gastrointestinal hemorrhage, hypophosphatemia, bowel edema, and marrow suppression with lymphopenia, thrombocytopenia, and neutropenia. All five patients are well 1 year later. This largest experience with liver transplantation for Amanita poisoning further defines the early clinical and laboratory indications for, and the unique complicating features of, transplantation in this setting.     

Comparison of photocoagulation with the argon, krypton, and diode laser indirect ophthalmoscopes in rabbit eyes.

PURPOSE: The purpose of this study is to compare photocoagulation with the argon green, krypton red, and diode infrared laser indirect ophthalmoscopes in an experimental setting. METHODS: Photocoagulation was performed with each of the laser indirect ophthalmoscopes in a grid pattern within one sector of the same eye of 14 Dutch-belted rabbits. Treatment was performed either with or without scleral depression. Measurements of the retinal burn diameters were performed after hemisecting the globes, and the burns were examined with light microscopy. RESULTS: Variation in burn intensity and diameter (10% to 28%) was common with all 3 laser indirect ophthalmoscopes. Five times more output energy was required to make equivalent burns with the diode laser indirect ophthalmoscope than with the argon or krypton laser indirect ophthalmoscopes. Choriovitreal hemorrhages only occurred during scleral depression. Histopathologically, the argon green laser indirect ophthalmoscope burns spared the choroid and inner sclera, while the intense krypton and diode burns had full-thickness choroidal involvement and even thermal injury to the inner sclera. Scleral depression reduced the mean energy required to create equivalent burns with all three laser indirect ophthalmoscopes. There was a 10% to 40% reduction in the mean retinal burn diameter with scleral depression (argon green, P < 0.0005; krypton red, P < 0.0005; and diode, P < 0.025). CONCLUSION: Photocoagulation with the argon green, krypton red, or diode infrared laser indirect ophthalmoscopes is a safe and effective method of retinal ablation. Decreasing the posterior nodal distance of the eye with scleral depression will produce a smaller spot on the retina with the laser indirect ophthalmoscope.     

Korrektureingriffe am Fuß nach posttraumatischen ischämischen Kontrakturen

Operationsprinzip Korrektur eines Pes equinus adductus durch keilf?rmige Resektion des Chopart-Gelenkes mit Keilbasis dorsolateral. Bei gleichzeitigem Pes varus keilf?rmige Resektion des subtalaren Gelenkes mit Keilbasis lateral (Lange 1962 [7], Myerson et al. 1986 [8], Witt et al. 1985 [13]) (Abbildungen 1a bis 1f). Bei gleichzeitigem Tarsaltunnelsyndrom Dekompression des Nervus tibialis durch Spaltung des Retinaculum musculi flexorum. Zur Korrektur von Krallenzehen Resektion der jeweiligen distalen Grundphalangen nach Hohmann; bei flektierten Endgelenken Resektion der distalen Mittelphalangen. (Auf diese Techniken wird hier nicht eingegangen).      

Myocardial perfusion and function in dogs with moderate coronary stenosis

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl=1.077 ± 0.15 versus ANT:POS StD=0.477 ± 0.11, P<0.03) and was confirmed with radio-labeled microspheres measurements (ANT:POS Cntl=1.18 ± 0.2 ml/min/g versus ANT:POS StD=0.44 ± 0.1 ml/min/g; P<0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P<0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P=NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl=0.964 ± 0.02 versus StD=0.884 ± 0.03; P<0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.     

Blood transfusion-induced suppression of delayed-type hypersensitivity to allogeneic histocompatibility antigens

In this study delayed-type hypersensitivity against histocompatibility antigens in mice was suppressed by a single donor-specific blood transfusion. Whole blood as well as purified white blood cells and purified red blood cells were capable of inducing suppression. White cells appeared more potent in inducing suppression than red cells. Suppression was dose-dependent, still detectable after administration of as little as 0.001 ml of whole blood and maximal at a dose of 0.1 ml. The suppression was already present a few hours after transfusion and proved to be long-lasting. The suppressive effect could be transferred to naive recipients by Thy-1+, L3T4-, Lyt-2+ spleen cells. This suppressor T cell population was of recipient origin--which excludes the possible involvement of "veto cells" and suppresses the afferent phase as well as the efferent phase of the DTH response.     

Interaction of PSD-95 with potassium channels visualized by fluorescence lifetime-based resonance energy transfer imaging

Resonance energy transfer (RET) has been extensively used to estimate the distance between two different fluorophores. This study demonstrates how protein-protein interactions can be visualized and quantified in living cells by time-correlated single-photon counting (TCSPC) imaging techniques that exploit the RET between appropriate fluorescent labels. We used this method to investigate the association of the potassium inward rectifier channel Kir2.1 and the neuronal PDZ protein PSD-95, which has been implicated in subcellular targeting and clustering of ion channels. Our data show that the two proteins not only colocalize within clusters but also interact with each other. Moreover, the data allow a spatially resolved quantification of this protein-protein interaction with respect to the relative number and the proximity between interacting molecules. Depending on the subcellular localization, a fraction of 20 to 60% of PSD-95 molecules interacted with Kir2.1 channels, approximating their fluorescent labels by less than 5 nm.     

Changes in anti-Müllerian hormone serum concentrations over time suggest delayed ovarian ageing in normogonadotrophic anovulatory infertility

BACKGROUND: Anti-Müllerian hormone (AMH), produced by growing pre-antral and early antral ovarian follicles, has been shown to be a useful marker for ovarian ageing. Serum AMH concentrations are elevated during reproductive life in anovulatory women, especially in those patients exhibiting polycystic ovaries (PCO). The current study was designed to investigate whether the decrease in AMH serum concentrations over time is different comparing women with normogonadotrophic anovulation [World Health Organization (WHO) group 2 (including polycystic ovary syndrome (PCOS)] and normo-ovulatory controls. METHODS AND RESULTS: AMH serum levels were assessed on two occasions in 98 patients suffering from WHO 2 anovulatory infertility as well as in 41 normo-ovulatory premenopausal women. Median time interval between both visits was 2.6 years (range 0.3-9.0) for WHO 2 patients compared with 1.6 years (range 1.0-7.3) in controls. Serum AMH concentrations were significantly (P < 0.0001) elevated on both occasions in WHO 2 patients (AMH1, median = 7.5 microg/l, range 0.1-35.8; and AMH2, median = 6.7 microg/l, range 0.0-30.6) compared with controls (AMH1, median = 2.1 microg/l, range 0.1-7.4; and AMH2, median = 1.3 microg/l, range 0.0-5.0). Regression analysis, corrected for age, indicated a significant relative decrease in serum AMH concentrations over time for both groups (P < 0.001). However, the decline in serum AMH in WHO 2 patients was significantly less compared with controls (P = 0.03). CONCLUSION: The present longitudinal study shows that serum AMH concentrations decrease over time both in women presenting with WHO 2 anovulatory infertility and in normo-ovulatory controls. The decrease in WHO 2 patients is less pronounced despite distinctly elevated concentrations. This observation may suggest retarded ovarian ageing and hence a sustained reproductive life span in these patients.