Characterization of hepatic microcirculatory impairment induced during portal-venous infusion of endothelin-1 by thermal diffusion technology.
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Biomedical subjects
Publications and source records attributed to T Kraus.
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By means of thermodiffusion, monitoring of hepatic microcirculation was performed in 43 patients during the first week after liver transplantation. A significant decrease of liver perfusion was registered in 15 patients with early rejection. The disturbance of hepatic microcirculation preceded the increase of transaminases by 36 hours and the subsequent biopsy by 60 hours. Already 12 hours after the beginning of corticoid therapy liver perfusion started to recover. The quantification of hepatic microcirculation may facilitate faster diagnosis and treatment of early rejection following liver transplantation.
Gadolinium-DTPA enhanced dynamic MR imaging is a new method for the quantification of portal bloodflow and liver perfusion. In this study we evaluated the validity of this method comparing it with thermodiffusion and dopplerflowmetry in pigs. We found a significant correlation of tissue perfusion between dMRI and thermodiffusion and of portal bloodflow between dMRI and dopplerflowmetry. Partial occlusion of the portal vene was accurately detected by dMRI. Dynamic MRI could become a valuable diagnostic method for the quantification of liver perfusion.
Hernias of the obturator foramen are rare. They are described mostly in elderly female patients in poor health. Often the correct diagnosis is stumbled upon as a result of surprising intraoperative findings. Surgical therapy is indicated often by the clinical symptoms of an incarcerated hernia. Herniation of the entire urinary bladder with hemorrhagic infarction has never been described before. For an anatomical reduction of the hernia it was necessary to resect the superior pubic ramus. For plastic reconstruction a marlex mesh was used.
The ILO classification of pneumoconiotic changes in the lungs and pleura has become a standardized and widely accepted method of documentation in occupational medicine. Recently a classification system for computed tomography/high-resolution computed tomography (CT/HRCT) findings in the lung has been proposed as well. For both classification systems, computed-assisted programs have been developed that allow the storage and archiving of the results as well as further statistical processing. The programs are compatible with usual hardware configurations, have a comprehensible and transparent structure, and are easy to learn and adaptable to individual needs. The use of the computer-assisted classification systems is presented in the example of an insulator exposed to asbestos. The system of data documentation and processing has proved to be very practicable in the more than 2000 patients studied thus far.
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There is evidence that endothelin (ET) is involved in disturbances of the hepatic microcirculation after warm ischemia. In this study we investigated the influence of a mixed ETA-, ETB-receptor antagonist (Bosentan) on ischemia-reperfusion damage of the liver by means of intravital fluorescence microscopy (IVM). Clamping of the left liver lobe (= warm ischemia) was performed in 16 male Wistar rats for 70 min. The treatment group (N = 8) received 15 mg/kg Bosentan (Ro-47-0203) 1 min prior to reperfusion. Controls (N = 8) received an equivalent amount of Ringer's solution. Between 20 and 90 min after reperfusion, leukocyte-endothelial cell interactions in sinusoids and postsinusoidal venules as well as perfusion of hepatic acini were studied. Application of Bosentan improved sinusoidal blood flow, attenuated manifestations of microvascular perfusion failure, and decreased the number of rolling leukocytes in postsinusoidal venules. Our results provide further evidence that ET is involved in postischemic impairment of hepatic microhemodynamics during reperfusion.
The recent identification of coreceptors that mediate efficient entry of human immunodeficiency virus type 1 (HIV-1) suggests new therapeutic and preventive strategies. We analyzed simian immunodeficiency virus (SIV) entry cofactors to investigate whether the macaque SIV model can be used as an experimental model to evaluate these strategies. Similar to primary HIV-1 isolates, a well-characterized molecular clone, SIVmac239, which replicates poorly but efficiently enters into rhesus alveolar macrophages and an envelope variant, SIVmac239/316Env, with an approximately 1,000-fold-higher replicative capacity in macrophages used the beta-chemokine receptor CCR5 for efficient entry. The transmembrane portion of 316Env allowed low-level entry into cells expressing CCR1, CCR2B, and CCR3. A single amino acid substitution in the V3 loop of SIVmac239/316Env, 321P-->S, impaired the ability to enter into the T-B hybrid cell line CEMx174 but had relatively little effect on entry into primary cells and HOS.CD4 cells expressing CCR5. Although CEMx174 cells do not express CCR5, most SIVmac variants entered this hybrid cell line efficiently but did not enter the parental T-cell line CEM. It seems likely that CEMx174 cells express an as-yet-unidentified, perhaps B-cell-derived cofactor which allows efficient entry of SIVmac.
OBJECTIVE: Clozapine increases the levels of cytokines and soluble cytokine receptors. The authors investigated whether haloperidol has similar effects. METHOD: Rectal temperature, white blood cell counts, and plasma levels of cytokines and soluble cytokine receptors were assessed before and during 6 weeks of haloperidol treatment in 10 psychiatric patients. RESULTS: Haloperidol at mean doses of 7.0 mg/day (SD = 3.4), 6.9 mg/day (SD = 3.4), and 5.0 mg/day (SD = 3.1) at the end of the 1st, 2nd, and 6th weeks of treatment, respectively, did not affect rectal temperature, white blood cell counts, or plasma level of interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor p55 or p75, or soluble interleukin-2 receptor. CONCLUSIONS: Haloperidol is unlikely to confound the results of studies investigating disease-related alterations in the levels of a broad range of cytokines and soluble cytokine receptors in schizophrenia.
We investigated cytokine production and accessory cell function in human macrophage hybridoma cell lines and primary monocytes after infection with HIV-1. HIV-1 infection induced IL-10 production in the macrophage hybridoma cell line with loss of IL-12 1 wk after infection. There were also significant increases in production of IL-10 (537 +/- 521 vs 687 +/- 625 pg/ml) while there was a reduction in IL-12 (6.3 +/- 3.1 vs 1.2 +/- 1.0 pg/ml, p = 0.021) in the primary monocytes 5 days after HIV-1 infection. In addition, the hybridoma cell lines and primary monocytes failed to support PHA, Con A, PWM, or anti-CD3- induced T cell proliferation 1 wk after infection. The viability of the T cells cocultured with the HIV-1-infected macrophage cell lines or the primary monocytes as determined by propidium iodide staining was unaltered and there was no increase in apoptosis-specific DNA strand breaks or increased expression of Bcl-2 in the T cells. No soluble suppressor factor was present, since UV-inactivated supernatants from the hybridoma cell line and primary monocytes failed to inhibit mitogen- and anti-CD3-induced T cell proliferation. Early events in T cell activation, including calcium flux and phosphotyrosine kinase activity, were intact in the T cells cocultured with the HIV-1- infected hybridomas and monocytes but there was reduced IL-2 production. Addition of exogenous IL-2 restored the proliferative responses. Taken together, these data suggest that alteration of cytokine production and accessory cell function for mitogens and anti-CD3-induced T cell proliferation independent of induction of apoptosis, suppressor factor production, or inhibition of T cell signaling occurs very early after HIV-1 infection and may contribute to the global immunosuppression observed in AIDS.
Continuous monitoring of renal cortical blood flow (RCBF) in the perioperative setting of aortic or renal vascular surgery could facilitate the early detection of vascular complications, possibly resulting in a reduction of postoperative renal failure. A new prototype system for measurement of parenchymous organ perfusion based on the principle of thermal diffusion ("TD"-Thermal Diffusion Electrode, Thermal Technologies Inc., Cambridge, MA, USA) was used for RCBF measurements in the outer cortex of the porcine kidney. We validated the sensitivity of the device to detect renal blood flow impairment, comparing TD flow data with renal artery blood flow values (RABF), measured by ultrasonic flow probes. The hypothesis was tested that acute disturbances of RCBF, induced by a variable degree of renal artery stenosis, can be immediately detected and continuously monitored by TD measurements in the porcine renal cortex. Mean baseline RCBF measured by TD electrodes was 68.1 +/- 25.0 ml/100 g/min. Mean baseline RABF was 102.1 +/- 26.6 ml/min. Controlled induction of a variable degree of renal arterial occlusion by implanted vascular balloon occluders was always followed by an immediate and proportional decline of RCBF, as measured by TD. Flow data obtained with both methods were significantly correlated by linear regression (r=.82, r2=.68; P < 0.0001). Dynamic changes of RABF in the time course of renal artery partial/total occlusion and arterial flow release could be continuously followed by detection of corresponding flow changes of RCBF. We conclude that the TD system investigated in the current study allows a continuous and sensitive determination of porcine renal cortex perfusion. A clinical evaluation of the method, e.g., in the perioperative setting of aortic or renal transplantation surgery, now appears to be justified.
High endothelin (ET) concentrations were recently detected in human bile after orthotopic liver transplantation (OLT). In the present study we compared biliary ET/big-ET levels measured by radioimmunoassay (RIA) in liver graft recipients (n = 37) with levels measured in non-transplant patients during cholecystectomy (n = 38) to clarify the influence of transplantation on the levels of biliary ET peptides. HPLC elution profiles of biliary ET were analyzed for characterization of ET peptide composition and validation of RIA analysis in bile extracts. Mean ET/big-ET levels in the common bile duct after OLT were significantly elevated (ET, 20.9 +/- 15; big-ET, 39.2 +/- 19 fmol/ml) compared to levels in non-transplant patients (ET, 5.7 +/- 4.9; big-ET, 12 +/- 8 fmol/ml). Highest ET/big-ET levels were measured in the gall bladder during cholecystectomy (ET, 61.7 +/- 41; big-ET, 75 +/- 28 fmol/ml). ET and big-ET levels were correlated by linear regression. HPLC analysis reveals the presence of high levels of ET/big-ET in human bile. Biliary ET mostly represents ET-1. High biliary ET levels after OLT appear to be derived from active endothelial secretion and probably reflect hepatic endothelial stress after preservation/ reperfusion. High biliary ET levels could be involved in the mediation of functional cholestatic syndromes after OLT.
To date, no method is available for the continuous long-term monitoring of liver microcirculation in patients. Experimentally, thermodiffusion has been validated in the quantification of hepatic perfusion. In an attempt to investigate the practicability of thermodiffusion technology in patients after liver transplantation thermodiffusion probes were inserted into the graft in seven patients during liver transplantation. Continuous monitoring started intraoperatively and was performed until day 7, when the probes were extracted transcutaneously. No probe-related complications (i.e., hemorrhage, infection) were observed. In four patients with normal graft function, liver perfusion recovered within 12 h from the intraoperative reduction to a range between 85 and 93 ml/100 g per min. In contrast, primary graft failure (n = 1) was characterized by a constant decrease of hepatic perfusion (< 50 ml/100 g per min). In prolonged reperfusion injury (n = 1), a second peak of transaminases was paralleled by an impairment of liver microcirculation. In one patient, R2 rejection on day 7 was preceded by a drop in hepatic perfusion 48 h earlier. Thus, thermodiffusion is a safe and reliable method for the continuous quantification of liver microcirculation after transplantation in patients. Measurements are reproducible for at least 7 days. Changes in hepatic perfusion during postoperative complications can be detected. The characteristics of microcirculatory disorders will have to be defined in a larger number of patients.
The standard ILO classification for pneumoconiotic changes using conventional X-ray films has become well established. In recent years computed tomography has played an increasing role in occupational medicine and above all in the assessment of pneumoconiosis. Therefore a standardised method of classification for CT also seems necessary. A system of classification developed by occupational hygienists and radiologists allows a detailed description of parenchymal and pleural changes and the use of 28 additional symbols. Furthermore, special diagnoses relevant to occupational medicine and additional comments can be made. The classification system was tested in practice in the research project "Early diagnosis of asbestos-related diseases" (Frühdiagnostik asbestverursachter Erkrankungen). It was shown to be both practicable and easily reproducible, intra-individually and interindividually.
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