Magnetresonanztomographische Diagnostik der peripheren Durchblutung*

PURPOSE: This article describes the potential of dynamic contrast- enhanced magnetic resonance tomography (DCE-MRT) for the visualization and quantification of blood flow of lower leg muscles at rest and after individually adjusted muscular exercise. PATIENTS AND METHODS: Five cases were chosen to exemplify the qualitative and semi-quantitative blood flow evaluation in the lower leg muscles. The crural muscle state was determined with an isometric maximal strength measurement from a female patient with peripheral arterial occlusive disease (pAVK), a male patient with coronary heart disease (KHK) without clinical signs of a pAVK, a volunteer with sufficient physical activity in accordance with the Freiburg Questionnaire of Physical Activity and two professional athletes. After calibration of the plantarflexion ergometer MR-PEDALO (Figures 2a and 2b) for the execution of auxotonic muscle work a 1- minute alternating foot extension and flexion exercise on MRPEDALO was performed in the MR machine. Instead of the lower leg splint shown in Figures 2a and 2b the MR coil fits exactly in MR-PEDALO used for DCE-MRT. Mechanical work performed during the 1-minute exercise ranged from 52 watt seconds (Ws) to 244 Ws (0.65 W to 4.07 W), indicating similar interindividual work loads in relation to the individual maximum isometric strength. DCE-MRT was performed at rest and immediately after auxotonic exercise test (T1w 2DFLASH- GE sequence with TR/TE/alpha: 100 ms/6 ms/70 degrees; field of view: 400; matrix: 81 x 256; slice thickness: 10 mm; acquisitions: 73 at 8.3 s each; total examination time: 9.24 min; bolus application of Magnevist, Schering, 0.02 ml/kg kg, 20 ml bolus NaCl, flow 2 ml/s, 22G cannula in a cubital vein). Signal intensity (SI) curves were analyzed with DynaVision (MeVis gGmbH, Bremen, Germany). RESULTS: Measuring peripheral blood flow needs appropriate muscular stress tests. The SI-curves of the region of interest (ROI) representing the peroneus, tibialis anterior and gastrocnemius muscle run almost parallel at rest. Workloads between 52 Ws and 244 Ws (0.65 W and 4.07 W), similar in relation to the individual maximum isometric strength, induce distinctive changes of the upslope, wash-in, peak and washout of SI-curves preferably for the peroneus muscle and less predominant also for the tibialis anterior muscle and gastrocnemius muscle respectively. The first case, a 55-year-old female patient with peripheral arterial occlusive disease (pAVK) stage Fontaine IIb before (Figure 3a) and after (Figure 3b) percutaneous transluminal angioplasty (PTA) of a right femoral artery stenosis shows after interventional treatment a rapid post-exercise SI-increase in the peroneus muscle. The steeper SI-curve indicates a better contrast medium inflow due to an improved perfusion. The second case, a 65-year-old man suffering from coronary heart disease without clinical signs of pAVK (Figure 4) exercised with a workload of 92 Ws. After stress test the ROI for the peroneus muscle shows a clear intensity increase. After exercise the SI-curve for the tibialis anterior muscle shows a similar, but less predominant change while the shape of the SI-curve of the gastrocnemius muscle remains mainly identical. A 23-year-old male person with average physical activity (Figure 5) performed DCE-MRT of the left lower leg after stress test with 172 Ws demonstrating a rapid signal increase in the peroneus muscle while the synergistic tibialis anterior muscle and antagonistic gastrocnemius muscle show a comparatively slow contrast-medium wash-in. A 26-year-old male athlete (Figure 6) exercised with 196 Ws showing a rapid contrast medium inflow in the peroneus muscle and initially also in the synergistic tibialis anterior muscle. A contrast-medium wash-out appears in both muscles, while the shape of the gastrocnemius muscle SI-curve remains substantially unchanged. A 26-year-old female athlete (Figure 7) exercised with 244 Ws. Post exercise SI-curves show a distinctive and rapid increase of contrast medium wash-in with a sharp peak particularly in the peroneus muscle and similarly in the tibialis anterior and gastrocnemius muscle. After exercise all SI-curves show a wash-out phase. CONCLUSION: SI-curves show relative increase in correlation with Time-to-Peak (TTP) decrease and Mean-Intensity to Time Ratio (MITR) increase indicating blood flow reserve mobilization after exercise. Individual muscle state seems to be linked to muscle recruitment and muscle coordination reflected by post-exercise SI-curves. The gastrocnemius muscle shows comparatively low SI-curve changes after muscular load test. Further methodological standardization and optimization of the stress test is mandatory to assure intra- and interindividual comparisons. Due to direct visualization and quantitative evaluation of the peripheral microcirculation DCE-MRT has a diagnostic potential for monitoring therapeutic response in peripheral circulation disorders and sports medicine.     

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.     

“It feels like home”: Transgender youth in the Midwest and conceptualizations of community climate

Community climate toward sexual and gender minority (SGM) youth is associated with higher rates of victimization and poorer health and wellbeing-related outcomes such as depression and suicidal ideation. However, this field of research has underemphasized the experiences of transgender youth, particularly within the Midwestern context which is marked by vast rurality and characterized as sociopolitically conservative. Using qualitative and community-based methods, this study identified factors that impact community climate from the perspective of transgender youth (n = 19) in the Midwest and situated them within the Ecological Systems Theory (EST). Thematic analysis of interviews revealed four themes: resources, visibility, policies, and ideologies. Themes often crossed levels within the EST, indicating the complexity and interrelated nature of climate across local, regional, and national contexts. Implications for theory, research, and practice are discussed.     

Clinical and Immunologic Predictors of Death After an Acute Opportunistic Infection: Results from ACTG A5164

Background: In the pre–antiretroviral therapy (ART) era, markers of increased disease severity during an acute opportunistic infection (OI) were associated with mortality. Even with ART, mortality remains high during the first year after an OI in persons with advanced HIV infection, but it is unclear whether previous predictors of mortality remain valid in the current era. Objective: To determine clinical and immunological predictors of death after an OI. Methods: We used clinical data and stored plasma from ACTG A5164, a multicenter study evaluating the optimal timing of ART during a nontuberculous OI. We developed Cox models evaluating associations between clinical parameters and plasma marker levels at entry and time to death over the first 48 weeks after the diagnosis of OI. We developed multivariable models incorporating only clinical parameters, only plasma marker levels, or both. Results: The median CD4+ T-cell count in study participants at baseline was 29 cells/µL. Sixty-four percent of subjects had Pneumocystis jirovecii pneumonia (PCP). Twenty-three of 282 (8.2%) subjects died. In univariate analyses, entry mycobacterial infection, OI number, hospitalization, low albumin, low hemoglobin, lower CD4, and higher IL-8 and sTNFrII levels and lower IL-17 levels were associated with mortality. In the combined model using both clinical and immunologic parameters, the presence of an entry mycobacterial infection and higher sTNFrII levels were significantly associated with death. Conclusions: In the ART era, clinical risk factors for death previously identified in the pre-ART era remain predictive. Additionally, activation of the innate immune system is associated with an increased risk of death following an acute OI.     

Surgical treatment of cholangiocellular carcinoma and proximal bile duct tumors

According to its different location, clinical features, treatment modalities and prognosis, intrahepatic cholangiocarcinoma should be well differentiated from proximal bile duct carcinoma. There is no therapeutic measure with curative potential apart from surgical treatment. Partial or extended hepatectomy is the treatment of choice in cholangiocarcinoma. Thereby, hilar resection in combination with hepatectomy is increasingly performed in proximal bile duct carcinomas. In most centers liver transplantation is not considered as a therapeutic option for irresectable cholangiocarcinomas.     

Electron microscopic and time lapse studies of mitosis in cultured rat hepatocytes

Primary cultures of adult rat hepatocytes in a serum-free medium were observed by time lapse cinematography to proceed through mitotis and cytokinesis. An ultrastructural study of these cultures is presented with electron micrographs of each stage of mitosis and cytokinesis. The cultured hepatocytes begin to enter prophase about 48 hr after plating and proceed through mitosis in approximately 70 min not including cytokinesis. During this time, they remain somewhat flattened and joined to neighboring cells rather than rounding up. Both mononucleate and binucleate hepatocytes proceed through mitosis. Some mononucleate cells do not undergo cytokinesis, resulting in the formation of binucleate cells. In binucleate hepatocytes, both nuclei proceed through prophase simultaneously. Usually a single mitotic spindle with a large metaphase plate containing chromosomes from both nuclei is observed. Cytokinesis frequently occurs in binucleate hepatocytes which have a single mitotic spindle. Some binucleate cells form tripolar or 4-polar metaphase plates. In tripolar metaphases, some cells do not divide, resulting in multinucleate cells, whereas others undergo cytokinesis yielding three mononucleate cells or one binucleate and one mononucleate cell. Two mitotic spindles located perpendicularly to each other with microtubules intertwining have been observed in 4-polar metaphases. In this latter case, no cytokinesis has been observed. This study shows that both mononucleate and binucleate adult rat hepatocytes cultured in a serum-free medium in the presence of epidermal growth factor not only synthesize DNA, but progress through mitosis and often cytokinesis.