Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.

Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism.

Ultrasound findings in EHEC-associated hemolytic-uremic syndrome and their clinical relevance.

PURPOSE: Hemolytic-uremic syndrome (HUS) and acute kidney injury (AKI) after infection with Shiga toxin-producing E. coli (EHEC) are clinically important complications. We present a retrospective analysis of abdominal ultrasound findings in patients with HUS caused by EHEC O104:H4 (n = 41). METHODS: We assessed intrarenal resistance indices and quantitated kidney parenchymal density by the kidney/liver intensity ratio using computer-based image analysis. Findings in EHEC-HUS were compared to those in AKI due to other reasons (n = 60) and 19 healthy volunteers. RESULTS: Kidneys in EHEC-HUS patients showed severe morphologic changes with striking parenchymal echogenicity. Renal resistance index was increased in HUS (0.80 ± 0.08) compared to patients with AKI due to glomerulopathy (0.69 ± 0.08, p < 0.001) or patients with other causes of AKI (0.74 ± 0.10, p < 0.01). Parenchymal density was increased in EHEC-HUS (1.39 ± 0.35) compared to AKI due to glomerulopathy (1.18 ± 0.20, p < 0.05), other causes of AKI (1.12 ± 0.21, p < 0.001) and healthy controls (0.86 ± 0.16, p < 0.001). Patients with atypical HUS showed increased parenchymal density (1.43 ± 0.37), similar to those with EHEC-HUS. EHEC-HUS patients who required dialysis treatment had higher parenchymal density (1.58 ± 0.08) compared to those without dialysis (1.14 ± 0.05, p = 0.0004). Extrarenal findings in EHEC-HUS included hepatomegaly (45%), splenomegaly (39%), ascites (84%) and pleural effusions (84%). CONCLUSIONS: Patients with EHEC-HUS had a characteristic constellation of morphologic abnormalities on ultrasound examination, indicating that the effects of HUS are not limited to the kidney but include multiple organs, possibly mediated through systemic capillary leakage. Assessment of parenchymal echogenicity contributes to the differential diagnosis of AKI. Parameters reflecting renal perfusion correlated with severity of disease and thus may have prognostic value in future patient evaluation.

Imaging in anatomy: a comparison of imaging techniques in embalmed human cadavers.

BACKGROUND: A large variety of imaging techniques is an integral part of modern medicine. Introducing radiological imaging techniques into the dissection course serves as a basis for improved learning of anatomy and multidisciplinary learning in pre-clinical medical education. METHODS: Four different imaging techniques (ultrasound, radiography, computed tomography, and magnetic resonance imaging) were performed in embalmed human body donors to analyse possibilities and limitations of the respective techniques in this peculiar setting. RESULTS: The quality of ultrasound and radiography images was poor, images of computed tomography and magnetic resonance imaging were of good quality. CONCLUSION: Computed tomography and magnetic resonance imaging have a superior image quality in comparison to ultrasound and radiography and offer suitable methods for imaging embalmed human cadavers as a valuable addition to the dissection course.

Effect of isovolemic, isothermic hemodialysis on cerebral perfusion and vascular stiffness using contrast computed tomography and pulse wave velocity.

BACKGROUND: Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness. METHODS: Chronic hemodialysis patients (7 male/3 female, mean age 58 years) were recruited. Cerebral blood flow and arterial pulse wave velocity were measured before and immediately after a hemodialysis session. To exclude effects of volume changes we kept ultrafiltration to a minimum, allowing no change in body weight. Isothermic conditions were maintained by using the GENIUS single-pass batch-dialysis system with a high-flux polysulfone dialyser. Cerebral blood flow was measured by contrast-enhanced computed tomography. Pulse wave velocity was measured using the SphygmoCor (AtCor Medical, USA) device by a single operator. RESULTS: This study shows for the first time that isovolemic, isothermic hemodialysis neither affected blood pressure or heart rate, nor total or regional cerebral perfusion. There was also no change in pulse wave velocity. CONCLUSIONS: Mechanisms other than the dialysis procedure itself might be causative for the high incidence of ischemic strokes in this patient population. Moreover, the sole removal of uremic toxins does not lead to short-term effects on vascular stiffness, underlying the importance of volume control in this patient population.

Renal function and survival in 200 patients undergoing ECMO therapy.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in the intensive care unit (ICU) setting to improve gas exchange in patients with acute respiratory distress syndrome as well as in patients pre- and post-heart and lung transplantation. In this clinical setting, acute kidney injury (AKI) is frequently observed. So far, it is unknown how AKI affects the survival of critically ill patients receiving ECMO support and whether veno-veno and veno-arterial ECMO have different effects on kidney function. METHODS: This is a retrospective analysis of patients undergoing ECMO treatment in medical and surgical ICUs in a tertiary care centre. We evaluated all patients undergoing ECMO treatment at our centre between 1 January 2005 and 31 December 2010. Data from all 200 patients (83F/117M), median age 45 (17-83) years, were obtained by chart review. Follow-up data were obtained for up to 3 months. RESULTS: Three-month survival of all patients was 31%. Of the 200 patients undergoing ECMO treatment, 60% (120/200) required renal replacement therapy (RRT) for AKI. While patients without RRT showed a 3-month survival of 53%, the survival of patients with AKI requiring RRT was 17% (P = 0.001). Longer duration of RRT was associated with a higher mortality. CONCLUSIONS: AKI requiring RRT therapy in patients undergoing ECMO treatment increases mortality in ICU patients. Future studies have to clarify whether it is possible to identify patients who benefit from the combination of ECMO and RRT.

Evaluation of sound speed for detection of liver fibrosis: prospective comparison with transient dynamic elastography and histology.

OBJECTIVE: The degree of liver fibrosis determines the prognosis and treatment of patients with chronic viral hepatitis. Transient elastography (TE) has been accepted as a noninvasive method for assessment of liver fibrosis. Sound velocity (SV) changes are also dependent on elastic properties of tissue. The aim of this pilot study was to evaluate whether SV estimation of liver tissue allows the determination of fibrosis stages in patients with chronic viral hepatitis. METHODS: Prospectively, 50 healthy volunteers and 149 patients received stiffness (TE, 50-Hz vibrator, 5-MHz array) and SV (conventional ultrasound, C5-2-MHz transducer) measurements. Eighty-four patients received representative liver biopsies. The estimated SV and stiffness were compared using liver biopsy as a reference (METAVIR fibrosis stage [F] scoring system [Hepatology 1996; 24:289-293]). Descriptive statistics, analysis of variance, receiver operating characteristic curve analysis, and box plot analysis as well as intra-operator and interoperator reproducibility analyses were performed. RESULTS: The SV ranged from 1540 to 1650 m/s. The mean SV ± SD was significantly different between healthy volunteers (1559 ± 11 m/s) and patients with F0-F3 (1575 ± 21 mm/s) and F4 (1594 ± 18 m/s) disease (P < .001). For detection of liver cirrhosis, the area under the receiver operating characteristic curve for SV was 0.80 (95% confidence interval, 0.69-0.89). With a cutoff value of 1589 m/s, the sensitivity, specificity, and positive and negative predictive values of SV for detection of liver cirrhosis were 82%, 76%, 70%, and 86%, respectively. Sound velocity measurements were reproducible (15%) and had acceptable operator independence (19%). CONCLUSIONS: The SV of liver tissue depends on the fibrosis stage. An SV of 1589 m/s or higher detects cirrhosis with high sensitivity. Therefore, SV measurement appears to be a promising new method for noninvasive quantification of liver fibrosis.

Plasma exchange therapy in steroid-unresponsive relapses in patients with multiple sclerosis.

BACKGROUND: Plasma exchange (PE) is well established for conditions such as rapid progressive vasculitis associated with autoantibodies against neutrophil cytoplasmic antigens (ANCA), anti-glomerular basement membrane (GBM) antibody disease, or thrombotic thrombocytopenic purpura (TTP). Also, several neurological disorders, such as acute worsening in myasthenia gravis, Guillan-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), can successfully be treated with PE. Only small case series have previously shown that PE is also effective in relapses in patients with multiple sclerosis (MS). METHODS: We report our experiences of PE therapy in a series of 20 patients with 21 steroid unresponsive MS relapses. RESULTS: A marked-to-moderate clinical response with clear gain of function in 76% of patients with uni- or bilateral optic neuritis and in 87.5% of patients with relapses other than optic neuritis was observed. CONCLUSIONS: PE is an effective and well tolerated therapeutic option for steroid-unresponsive MS relapses.