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H J Gassel

Publications and source records attributed to H J Gassel.

At least 37 records · Page 2Linked to original sources
PubMed2000

Long-term small bowel allograft function induced by short-term FK 506 application is associated with split tolerance.

Functional long-term allograft survival after experimental small bowel transplantation (SBT) is limited by chronic rejection. Initial application of high-dose FK 506 has been shown to induce stable long-term graft function. In order to examine whether this long-term function is associated with donor-specific tolerance, we analyzed the functional status of recipient T cells in vivo and in vitro. One-step orthotopic SBT was performed in the allogeneic Brown Norway (BN)-to-Lewis rat strain combination. FK 506 was given daily at a dose of 2 mg/kg from days 0-5 in the rejection model and from days 0-9 in the long-term functional model. Mean survival time in the rejection model was 98 +/- 2.8 days. Histological examination of these small bowel allografts disclosed signs of chronic rejection. In contrast, all animals of the long-term functional model survived long term (> 250 days) without clinical signs of chronic rejection. The latter model, furthermore, produced evidence of donor-specific tolerance. Whereas heterotopic Dark Agouti (DA) hearts were rejected regularly within 7 days, BN hearts survived indefinitely (> 70 days). In vitro, mixed leukocyte reactivity of CD4+ T cells was similarly strong against donor (BN) antigens as against third-party (DA) antigens. The split tolerance revealed by our in vivo and in vitro results enabled acceptance of both the small bowel allograft without signs of chronic rejection and of donor-specific heart allografts.

Animals↗
PubMed2000

Asymptomatic aneurysm of the proximal right subclavian artery: a rare ultrasound diagnosis.

True aneurysms of otherwise normal subclavian arteries are uncommon peripheral vascular anomalies. Most patients with subclavian artery aneurysms are symptomatic by presenting neurologic signs. We report a young woman who had an asymptomatic true aneurysm of the right subclavian artery assumed to be of congenital origin. This case is unique in that the aneurysm was in the extremely rare anatomic location of the right supraclavicular fossa between the origins of the right subclavian artery and the vertebral artery. Aneurysms of the right subclavian artery may represent a potential pitfall in conventional gray-scale ultrasound of the neck particularly the supraclavicular fossa. Differential diagnosis includes cervical cyst, pharyngo-esophageal diverticulum, vascular anomalies, struma, enlarged lymph node, as well benign or malignant neoplasms. Color duplex ultrasound should be performed as the method of choice for further analysis of suspected aneurysms. In this report the role of B-mode ultrasound and color duplex ultrasound is discussed in relation to digital subtraction- and MR angiography in confirmation of the diagnosis.

Adult↗
PubMed2000

Different kinetics of donor cell populations after isolated liver and combined liver/small bowel transplantation.

Spontaneous tolerance induction after liver transplantation also supports additional transplants, e.g. a small bowel graft, from the same donor (tolerogenic effect). Chimerism serves as a possible explanation of this phenomenon. Isolated liver (LTx) and combined liver/small bowel transplantation (LSBTx) are compared. LSBTx and LTx were performed in the BN --> LEW rat strain combination without immunosuppression. Parenchymal damage during rejection was monitored by sequential standard histology. Donor/recipient populations were identified and further differentiated for immunohistochemical single and double staining. A small number of donor specific leukocytes can be detected on all days in host organs (microchimerism). A significantly larger donor leukocyte population survives long-term in the sinusoids of liver (graft chimerism). Sinusoidal donor leukocytes survive rejection and recover in number after tolerance induction. Rejection of liver allografts and infiltration by host leukocytes are more pronounced after LSBTx than after LTx. Accordingly, during rejection a steeper decline of sinusoidal donor leukocytes is observed after LSBTx and recovery after tolerance induction is not as marked. Microchimerism apparently plays no significant role in either transplantation model. The number of sinusoidal donor leukocytes, however, mirrors closely host immune responses.

Animals↗
PubMed2000

Sonography for selecting candidates for laparoscopic cholecystectomy: a prospective study.

OBJECTIVE: We assessed the value of sonography in predicting intraoperative difficulties for patients undergoing laparoscopic cholecystectomy and in identifying indicators for conversion to conventional cholecystectomy. SUBJECTS AND METHODS: Upper abdominal sonography was performed (according to a checklist) in 75 consecutive patients before laparoscopic cholecystectomy. Sonographic findings were verified by the surgeon in the operating room. RESULTS: Conversion from laparoscopic surgery to laparotomy was performed in five patients (6.7%). Of 75 patients, 19 had sonograms revealing gallbladder wall thickening (>4 mm); surgical preparation difficulties in 16 of these patients led to laparotomy in four patients. Sensitivity, specificity, positive predictive value, and accuracy of wall thickening as an indicator of technical difficulties were 66.7%, 94.1%, 84.2%, and 85.3%, respectively. Sensitivity, specificity, positive predictive value, and accuracy of wall thickening as an indicator of surgical conversion were 80.0%, 78.6%, 21.1%, and 78.7%, respectively. Technical difficulties at laparoscopy occurred in all five patients with pericholecystic fluid on sonography (sensitivity, 20.8%; specificity, 100%; positive predictive value, 100%; accuracy, 74.7%) and led to laparotomy in three patients (sensitivity 60.0%, specificity 97.1%, positive predictive value 60%, accuracy 94.7%). The accuracy of sonography for cholecystolithiasis was 100%. CONCLUSION: On sonography, gallbladder wall thickening is the most sensitive indicator and pericholecystic fluid is the most specific indicator of technical difficulties during laparoscopic cholecystectomy. Such difficulties may require conversion to laparotomy.

Abdomen↗
PubMed1999

Videomicroscopic imaging of graft mucosa for monitoring immunosuppressive therapy after small intestinal transplantation in rats.

BACKGROUND: Early diagnosis of rejection and effective immunosuppressive treatment are essential after small intestinal transplantation. To date little is known about microscopic alterations of the intestinal mucosa of the graft during rejection. We attempted to determine whether videomicroscopic imaging of the graft mucosa is a suitable method for monitoring immunosuppressive therapy. METHODS: Real-time videomicroscopic imaging of an ileostoma was performed daily after allogeneic heterotopic small bowel transplantation in the rat (BN to LEW) with and without FK506 immunosuppression. Subsequently, the videomicroscopic findings were compared with the histologically determined grade of rejection. RESULTS: A semiquantitative staging system was established for the intravital mucosal changes during graft rejection. The earliest changes related to rejection appeared on POD 6 in the untreated allogeneic group. The mucosa developed patchy paleness and the mucosal architecture was interrupted in places. The crypts were slightly widened and their color turned dark red (stage I). These alterations spread progressively over the mucosa on POD 7 (stage II). On POD 9 the mucosa appeared pale, the villi were shortened, and the crypts appeared wide and rounded (stage III). In the animals treated with FK506 similar changes were observed, but with a delayed onset. When FK506 was administered as antirejection therapy at the onset of rejection, a temporary improvement of mucosal alterations was observed (stage II --> stage I). The video-microscopic stages correlated with the histological grade of rejection. CONCLUSIONS: The introduction of videomicroscopy has made computer-based high resolution imaging of mucosal microarchitecture possible. With videomi-croscopy beginning rejection can be detected, although it can still be reversed with antirejection therapy. This is a new noninvasive technique that might be of high clinical relevance.

Acute Disease↗
PubMed1999

Helical CT cholangiography for the detection and localization of bile duct leakage.

OBJECTIVE: We describe the use of helical CT cholangiography or helical CT after administration of biliary i.v. contrast material to verify and localize bile duct leakage. CONCLUSION: Helical CT cholangiography revealed bile leaks in seven patients after penetrating trauma or liver or gallbladder surgery and excluded bile leaks in two patients with blunt liver trauma. Endoscopic retrograde cholangiography was performed in only one of seven patients with bile leakage and was avoided in an additional two patients in whom CT cholangiography excluded leakage. The method is a feasible, noninvasive tool for the detection and localization of bile leaks and may help avoid endoscopic retrograde cholangiography.

Adult↗
PubMed1998

Apoptosis of T lymphocytes in liver and/or small bowel allografts during tolerance induction.

BACKGROUND: Apoptosis of parenchymal cells has been described during allograft rejection. Immunologically privileged tissue in the mouse has been found to prevent rejection by initiating apoptosis of infiltrating lymphocytes. The aim of this study was to investigate whether apoptosis may play a role in T-cell regulation during rejection and subsequent tolerance induction after liver transplantation (LTx) and combined liver/small bowel transplantation (LSBTx). METHODS: LTx and LSBTx (Brown Norway-->Lewis) were performed without immunosuppression. Cell migration, activation, and apoptosis were investigated by means of sequential histology, immunohistochemistry, and the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling assay. Donor (Brown Norway) and third-party (Dark Agouti) cardiac allografts were transplanted into LSBTx recipients to determine specific tolerance. RESULTS: Transient acute cellular rejection occurred after LTx and LSBTx and was followed by specific tolerance. The kinetics of apoptosis were similar in liver allografts after LTx and LSBTx, but differed from the processes in small bowel allografts after LSBTx. Apoptosis of parenchymal cells in the grafted livers correlated directly with interleukin-2 receptor expression of the infiltrating T cells. During the late phase of rejection, a peak of apoptosis in the lymphocyte infiltrate was demonstrated, characterized as predominantly apoptotic CD8+ T lymphocytes. CONCLUSIONS: These results demonstrate that specific tolerance is achieved in both LTx and LSBTx after a transient rejection crisis. Apoptosis is involved in graft rejection and tolerance induction. Activation of T lymphocytes correlates with parenchymal cell apoptosis in the allograft. T-cell inactivation seems to result in apoptosis of cytotoxic T cells and tolerance, which appears to be unique to the liver allograft.

Animals↗
PubMed1998

Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen)

OBJECTIVE: To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases. METHODS: Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only. RESULTS: The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients. CONCLUSION: According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was therefore terminated.

Adult↗
PubMed1998

[Role of apoptosis in induction of tolerance after liver and liver/small intestine transplantation].

Liver induced tolerance and the protecting effect towards a co-transplanted organ are well known effects after liver transplantation in rats. Isolated liver transplantation and combined liver/small bowel transplantation are used to investigate the cellular mechanisms of those two phenomenons. In both transplantation models a transient rejection process can be observed. During this response recipient derived graft infiltrating T-cells are subsequently inactivated. The initial peak of apoptotic cell death in the liver lobuli decreases and is followed by an increase in apoptosis of the infiltrating T-cells during the end of the rejection response. Donor specific tolerance occurs after LTx and LDDTx respectively, proofed by indicator heart transplantation.

Animals↗
PubMed1998

[Interim analysis of a prospective, randomized multi-center study by the "Liver Metastases" Study Group: adjuvant intra-arterial chemotherapy after curative liver resection of colorectal metastases].

Recurrence after resection of colorectal liver metastases occurs after 9-12 months in up to 80% of patients. Half of the relapses is isolated to the liver. An intraarterial chemotherapy with 5-FU and folinic acid was compared to only resection. Main objective of the trial was survival. Within 14 days after resection followed the 6-month therapy with 5-FU 1000 mg/m2 continuously over 5d/28d and Folinic Acid 200 mg/m2 over 15 minutes 5d/28d. The first interim-analysis with 226 randomised patients showed in the intention-to-treat-analysis a median survival of 34.5 months (m.) with therapy versus 40.8 months (p = 0.1519 with a negative trend. (95%-Confidence interval for hazard ratio: [0.5; 1.15]) and time to progression of 14.2 m. with therapy versus 13.7 m. Severe toxicities (WHO grade III/IV) occurred in 25.6% of cycles and 62.9% of patients. Mainly registered were stomatitis (57.6%) and nausea (55.4%). The recruitment of patients for study was terminated, because in best case the risk to die could be lowered only by 15% and therefore clinical relevant prolongation of survival is not to achieve with this type of adjuvant therapy.

Adult↗
PubMed1998

[Selective immunosuppression with monoclonal antibodies against ICAM-1 and LFA-1 with FK 506 after experimental small intestine transplantation in the rat].

Prevention of allograft rejection remains a major problem after small bowel transplantation (SBT) and requires potent immunosuppressive regimens. In a variety of transplant models, e.g. liver or heart transplantation, the supplementary application of monoclonal antibodies (mabs) against adhesion molecules is effective in both prolonging graft survival and inducing long-term graft acceptance or tolerance in some cases. In this study anti ICAM-1 (1A29) and anti LFA-1 (WT1) mabs were used in combination with a subtherapeutic dose of FK 506 for 13 days after allogeneic SBT in the rat. The results of this study indicate that in contrast to the induction of allospecific tolerance after liver transplantation, the addition of anti ICAM-1 and/or of anti LFA-1 mabs after SBT reverses the FK 506 effect and results in early graft rejection. It has been shown that higher dosages of these mabs, given alone or in combination with CsA or FK 506, result in long-term survival of cardiac allografts in both, rats and mice [4-8]. Graft survival after pancreas transplantation is prolonged [6]. However, these negative therapeutic effects of the mabs 1A29 and WT1 after SBT have to be critically reevaluated and further analysed.

Animals↗
PubMed1998

[Intra-arterial (5-FU/FA and FUDR) versus systemic chemotherapy (5-FU/FA) of non-resectable colorectal liver metastases].

The relative efficacy of HAI FUDR, HAI 5-FU/FA, and i.v. 5-FU/FA chemotherapy for the treatment of unresectable colorectal liver metastases was compared in a prospective randomized clinical trial. The response rate after HAI treatment was significantly higher as compared to i.v. treatment with no statistical benefit regarding survival and time to progression. HAI FUDR treatment was inferior as compared to HAI or i.v. 5-FU/FA. i.v. 5-FU/FA-therapy is therefore the method of choice outside clinical trials.

Adult↗