Investigating chronic rejection processes after experimental liver/small bowel transplantation.
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Biomedical subjects
Publications and source records attributed to A Thiede.
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BACKGROUND: Graft infection after vascular prosthetic reconstruction for the treatment of peripheral arterial occlusive disease (PAOD) is a rare but severe complication with poor outcome. The options for surgical treatment are not uniformly accepted and remain controversial. PATIENTS AND METHODS: We retrospectively analyzed the histories of 30 patients treated for prosthetic graft infection (Szilagyi grade III) in our hospital between 1994 and 1999 to determine which forms of treatment were best suited for which types of patient. In the majority of cases the initial treatment was lower-extremity bypass surgery. The most frequent location of infection was the groin (73%). Staphylococci (13% of which were methicillin resistant) were the most common type of bacteria. The overall incidence of prosthetic infection was 2.3%. RESULTS: After confirmation of the infection by computed tomography (CT) or white blood cell scintigraphy, one of the following 5 forms of surgical treatment was performed: 1. Removal of the infected prosthesis and its simultaneous replacement by an autologous vein bypass. 2. Bypass removal and secondary replacement by an autologous vein. 3. Extra-anatomical replacement. 4. Graft removal and primary amputation. 5. Local therapy with debridement and secondary wound healing. In some patients primary amputation after graft infection was necessary to prevent further deterioration with fulminant sepsis. The overall mortality was 17%, the amputation rate was 60%. CONCLUSIONS: The best results were achieved by early complete removal of the alloplastic material and one-step replacement by either an autologous vein or extra-anatomic bypass. This resulted in a limb salvage rate of 54% and 40% and mortality rates of 9% and 0%, respectively.
BACKGROUND: Functional results after rectal resection with straight coloanal anastomosis are poor. While most functional aspects are improved with coloanal J pouch anastomosis, it is still unclear whether this translates into better quality of life. The aim of this trial was to investigate health-related quality of life as a primary endpoint in patients undergoing sphincter-saving rectal resection. METHODS: Sixty-four patients were randomized to either straight (n = 32) or coloanal J pouch (n = 32) anastomosis. Patients were studied before operation, at the time of stoma reversal and at 3-month intervals for 1 year thereafter. Quality of life was measured using two generic (Gastrointestinal Quality of Life Index and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30) and one disease-specific (EORTC QLQ-CR38) instruments. Functional results using a standardized score as well as manometric variables were recorded. RESULTS: Thirty-nine patients (19 with a pouch and 20 with a straight anastomosis) completed the trial. There was a marked difference between the two groups with regard to quality of life profile. Patients with a pouch reconstruction had a significantly better quality of life, particularly in the early postoperative period. CONCLUSION: Patients undergoing low anterior rectal resection and coloanal J pouch reconstruction may expect not only better functional results but also an improved quality of life in the early months after surgery compared with patients who receive a straight coloanal anastomosis.
INTRODUCTION: In a prospective trial we analysed the results and the management of complications following a combined endovascular and vascular surgical therapy of peripheral occlusive arterial disease (POAD). PATIENTS AND METHODS: From November 1998 until January 2001 a total number of 61 patients with 64 extremities were included in this study. By preoperative angiography 19 patients had stenoses at three levels, 42 patients suffered from stenoses at two levels. The iliac axis was recanalized by intraluminal angioplasty (ITA) plus stent placement under general anesthesia. Simultaneously an infrainguinal bypass reconstruction and a local thrombendarterectomy (TEA) rsp. were performed. Intra- and postoperative complications and the patency rates as assessed by colour doppler ultrasound and angiography were analysed. RESULTS: The rate of conversion from endovascular to conventional surgery was 12.5 %. In 56 cases the endovascular therapy of the iliac axis was successful. In 28 patients a distal bypass was implanted, in 25 patients a local TEA was performed. Intraoperatively 6 dissections (10.7 %) were noted, dislocation of stents were seen in 4 patients (7.1 %), perforations occurred in 2 patients (3.6 %). Both perforations and 5/6 dissections were detected intraoperatively and were treated by endovascular means without complications. The early postoperative patency rate was 98.2 %, the secondary patency rate was 100 % and the cumulative patency rate after two years was 98.2 %. DISCUSSION: ITA and stent placement in the iliac axis can be established quickly and safely by the vascular surgeon. Intraoperative complications can be managed by endovascular means in most cases. Stent dislocation is avoidable in most cases. The complication rate after such combined endovascular therapy and conventional vascular surgery is determined by the surgical but not the endovascular part. Excellent early results and low complication rates lead to the conclusion that endovascular therapy in combination with conventional vascular surgery seems to be a reasonable supplement to the therapeutic options for the treatment of POAD.
Sigmoid diverticulitis is in case of complications like perforation, abscess and peritonitis a life-threatening disease. A diagnostic work up with high sensitivity is mandatory. In a prospective study upon 247 patients with the possible diagnosis of acute diverticulitis ultrasound is a screening method with a high specificity (97 %) and leads in combination with the hydrocolonsonography and the colour flow doppler to a high sensitivity (76 %). Without any typical findings in ultrasound, helical CT scan is the best method in the evaluation of the acute diverticulitis (sensitivity and specificity 100 %), because contrast enema is inferior to CT in the evaluation of abscesses (6 %) and perforation (53 %). CT has in case of perforation and of abscesses a sensitivity of 90 % and 100 %, while ultrasound has a sensitivity of 12 % to perforation and of 39 % to abscesses.
Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery can cause serious consequences for patients who depend on control of pitch and a clear and forceful voice, like singers or professional speakers. We used the Neurosign 100(R) nerve monitor to identify 157 nerves in 108 patients undergoing thyroid surgery. The EBSLN was successfully identified in 98.7 % of cases. The recording electrode could be placed either into the cricothyroid muscle or the vocal cord. The latter position proved superior if the recurrent laryngeal nerve had to be identified as well. 16 percent of the nerves crossed the branches of the superior thyroid artery at or below the upper pole of the gland, posing a "high risk" for intraoperative lesions. Our data confirm the results of smaller studies reporting this type of nerve course in 12 % to 14 % of patients. The present findings show a significant number of EBSLN to be in danger of injury when the superior thyroid artery is ligated during thyroid surgery. Neuromonitoring proofed to be a reliable method to identify the nerve, which is an important element in concepts to prevent its injury.
In 56 postoperative patients with primary hyperparathyroidism we analysed retrospectively whether a single-sided or minimal invasive operative procedure could have been utilized. Additionally the sensitivity of (99m)TC-Sestamibiscintiscanning and ultrasound of the neck region was assessed. Single gland disease was found in 49 patients, 6 patients had primary multiglandular disease and one patient revealed a double adenoma. The overall sensitivity of (99m)TC-Sestamibiscintiscanning and ultrasound was found to be 78 % and 53 % respectively. In 46 patients the operation would have been started minimal invasive, in 7 of these patients a conversion to bilateral exploration would have been necessary because of four gland hyperplasia, double adenoma or misleading preoperative localisation. In 39 patients a successful minimal invasive procedure would have been possible. A primary bilateral exploration would have been necessary in 10 patients because of either coexisting goiter or questionable localisation of the pathological altered gland. Since sensitivity of localisation diagnostics is low with regard to multiglandular disease, parathyroid hormone should be monitored intraoperatively whenever minimal invasive operative procedures are performed.
Two different aspects of the influence of neuromonitoring on the possible reduction of post-operative recurrent laryngeal nerve palsies require critical examination: the nerve identification and the monitoring of it's functions. Due to the additional information from the EMG signals, neuromonitoring is the best method for identifying the nerves as compared to visual identification alone. There are still no randomized studies available that compare the visual and electrophysiological recurrent laryngeal nerve detection in thyroid operations with respect to the postoperative nerve palsies. Nevertheless, comparisons with historical collectives show that a constant low nerve-palsy-rate was achieved with electrophysiological detection in comparison to visual detection. The rate of nerve identification is normally very high and amounts to 99 % in our own patients. The data obtained during the "Quality assurance of benign and malignant Goiter" study show that in hemithyreoidectomy and subtotal resection, lower nerve-palsy-rates are achieved with neuromonitoring as compared to solely visual detection. Following subtotal resection, this discrepancy becomes even statistically significant. While monitoring the nerve functions with the presently used neuromonitoring technique, it is possible to observe the EMG-signal remaining constant or decreasing in volume. Assuming that a constant neuromonitoring signal represents a normal vocal cord, our evaluation shows that there is a small percentage of false negative and positive results. Looking at the permanent recurrent nerve palsy rates, this method has a specificity of 98 %, a sensitivity of 100 %, a positive prognostic value of 10 %, and a negative prognostic value of 100 %. Although an altered neuromonitoring signal can be taken as a clear indication of eventual nerve damage, an absolutely reliable statement about the postoperative vocal cord function is presently not possible with intraoperative neuromonitoring.
BACKGROUND & AIM: Duodeno-gastro-esophageal reflux (DGER) as measured with bilirubin monitoring is observed in many patients with reflux disease especially in Barrett's esophagus. As acid suppression is an effective therapy of reflux disease, DGER is frequently just considered as a bystander of acid reflux. To define the importance of DGER, reflux of duodenal contents was evaluated by bilirubin monitoring in the stomach. METHODS: 100 patients with reflux disease were evaluated (62 m, 38 f, 50 (12) years). 26 patients had Barrett's esophagus, 57 had esophagitis and 17 non- erosive reflux disease (pH pos.). All patients were evaluated with simultaneous 24-hour bilirubin monitoring in the esophagus and stomach. Results were compared to 35 measurements of healthy volunteers in the esophagus and 41 measurements in the stomach. RESULTS: Normal values: DGER - Exposure time esophagus > 11.8 % using an absorbance value > 0.14, duodenogastric reflux (DGR) - Exposure time stomach >24.8 % using an absorbance value > 0.25. 56 % of the patients had DGER, 41 % had DGR. 29 of the 41 patients with DGR had DGER (71 %), while 27 of the 56 patients with DGER had physiologic duodenogastric reflux (48 %). DISCUSSION: About 30 % of the patients with reflux disease show DGER combined with excessive DGR. Therefore, DGER is not just a bystander of acid reflux. The excessive DGR in some patients adds additional potentially dangerous substances to the esophageal reflux.
Glomus organs are small arteriovenous anastomoses chiefly responsible for thermoregulation of the distal portion of the extremities. Glomangiomas are benign tumors of these bodies. They occur preferentially in the fingers and toes, but some case reports describe primary glomangiomas in the respiratory or gastrointestinal tract and genitals. To date, no glomangiomas of the liver have been reported. We report on a 61-year-old patient in whom routine ultrasound disclosed a subcapsular well-defined mass in the liver. Further imaging showed that the mass did not correspond to any of the usual liver tumors. Biopsy finally revealed it to be a primary glomangioma of the liver. Clinically, there was lack of appetite and weight loss over a period of several months. Owing to the possibility of malignant transformation of glomangiomas, as described in the literature, the tumor was excised under existing clinical symptoms and continued slow growth. Further histological evaluation of the tumor did not reveal malignancy. Primary glomangioma of the liver is a new differential diagnosis for benign liver neoplasms. Because there is a potential for malignant transformation, the existence of clinical symptoms and continuing growth are indications for resection.
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The surgical suture should be chosen in dependence of the tissue being operated upon and be oriented on the main properties of its chemical composition. Synthetic absorbable suture materials are the first choice in the majority of the procedures, to prevent the formation of foreign body reaction--excepting sites subjected to continuous mechanical stress, for example hernias, orthopedic and vascular surgery. By causing lesser tissue damage and interfilament bacterial transport, monofilament sutures are preferable than multifilament ones. However, knotting monofilament sutures requires additional skills in comparison to multifilament strains, due to their special handling an knotting properties.
The antibody SC-1 is a human IGM molecule, which binds to a tumor specific receptor. This SC-1 receptor is detectable on biopsies, it is present in about 50% of gastric cancers. After binding of the antibody to the receptor the tumor cells go into apoptosis. 50 patients expressing the SC-1 receptor on their tumors have been treated with SC-1 prior to gastrectomy. In 80% of cases apoptosis induction could be demonstrated in the tumors. The only side effect of the SC-1 therapy was a reversible episode of fever during antibody infusion in 8% of our patients.
BACKGROUND AND AIMS: We investigated the influence of donor MHC antigen expression on graft survival after parathyroid transplantation in three different strain combinations. METHODS: MHC class I and II expression on parathyroid tissue of Lewis (LEW), Dark Agouti (DA), and Wistar-Furth (WF) rats was first analysed semiquantitatively by immunohistochemistry. Additionally, five groups were transplanted: (1) LEW to LEW, (2) DA to DA, (3) LEW to DA, (4) WF to LEW, and (5) DA to LEW. METHODS: MHC class I expression was strong in DA, moderate in WF, and weak in LEW rats; MHC class II expression was negative in all three strains. In the interstitium of all investigated tissue specimens, the proportion of MHC class II-expressing cells was low. RESULTS: After syngeneic transplantation, graft survival could be documented over the whole observation period. A mean graft survival of 20 (+/-2) days was observed following transplantation from LEW to DA, grafts in the group WF to LEW were rejected after 13 (+/-1) days, and graft function lasted 8 (+/-2) days in the group DA to LEW. The number of intragraft leukocytes expressing MHC class II molecules was equal in all groups, whereas increased levels of MHC class I on rat parathyroid tissue before transplantation resulted in a more rapid rejection. CONCLUSION: These results demonstrate that immunogenicity of rat parathyroid tissue seems to be determined by the amount of MHC class I expressed on donor parenchymal cells.
BACKGROUND: Drug-induced tolerance of rat liver allografts is well documented. We analyzed cellular events during immunosuppressive therapy on day (d) 10 and in the late phase (d 100) after transplantation to assess for characteristics in the intrahepatic leukocyte (IHL) population in the phase of tolerance. METHODS: Lewis rats served as recipients of Dark Agouti rat livers. Temporary immunosuppression with either cyclosporine (CsA) monotherapy (3 mg/kg/d) or triple therapy that consisted of a subtherapeutic CsA dosage (0.25 mg/kg/d) and monoclonal antibodies directed against the interleukin-2 receptor (IL-2R, CD25) and the intercellular adhesion molecule-1 (ICAM-1, CD54) was administered from postoperative d 0 to d 13. Cell migration and cell activation within liver grafts was assessed by standard histology and flow cytometry. IHL apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL). RESULTS: Both CsA monotherapy and triple therapy prolonged liver allograft survival to more than 100 d and led to the induction of donor-specific tolerance. Untreated recipients rejected their allografts within 14 d. In both groups, donor-specific IHLs initially dropped to 18% to 25% on d 10, but they rebounded to as much as 40% on d 100 as a common characteristic of both groups. Within this population, donor-specific T cells were dominant. In both groups, increased numbers of activated (IL-2R+) CD8+ T lymphocytes were present on d 100. No accumulation of apoptotic IHL was observed on d 100. Their proportion was unchanged in the triple therapy group and slightly decreased in the CsA group compared to the syngeneic controls. CONCLUSIONS: The present study reveals that tolerant liver allografts are repopulated by donor-specific T lymphocytes. This phenomenon is independent of the type of applied immunosuppression. The persistence of activated CD8+ T cells in the phase of proven donor-specific tolerance on d 100 indicates that liver tolerance is associated with the state of a permanent intragraft immune activation. It seems that the coexistence of donor cells with infiltrating recipient cells within liver grafts, termed intrahepatic cell chimerism, is characteristic for tolerated liver allografts.
Liver cirrhosis in patients with short bowel syndrome is successfully treated in humans by simultaneous liver/small bowel transplantation. However, until now, a clinically relevant experimental rat model for this procedure has not existed. We therefore established a protocol that, for the first time in rats, allows the simultaneous transplantation of arterialized liver and small bowel into an orthotopic position. Short-term immunosuppression induced not only allograft acceptance but tolerance (as demonstrated by indicator heart/skin transplantation). The immunosuppressive dose required to achieve this result was dramatically less than that of protocols for successful small bowel transplantation alone. Immunohistochemistry detected a transient rejection crisis before tolerance. During this crisis, apoptotic recipient-type T lymphocytes, mainly CD8+ cells, accumulated in the liver but not in the small bowel allograft. The initiation of T-cell apoptosis is one possible explanation for the specific immunosuppressive effect of the liver allograft, which also supports the simultaneously transplanted small bowel allograft in our model.
MHC antigen expression in parathyroid tissue and its influence on graft survival after allogeneic transplantation were investigated using a heterotopic rat transplantation model. MHC class I and II expression in parathyroid tissue of Lewis (LEW), Dark Agouti (DA), and Wistar-Furth (WF) rats was analysed semi-quantitatively by using immunohistochemistry. MHC class I expression was strong in DA, moderate in WF, and weak in LEW rats parenchyma, whereas MHC class II expression was negative. In the interstitium of all investigated tissue specimens, the proportion of MHC class II-expressing cells was low. Additionally, four groups were transplanted: 1) LEW to LEW, 2) DA to DA, 3) LEW to DA, and 4) WF to LEW. After syngeneic transplantation, graft survival could be documented over the whole observation period. A median graft survival of 20 (+/-2) days was observed after transplantation from LEW to DA, whereas grafts in the group WF to LEW were rejected after 13 (+/-1) days. The number of intra-graft leucocytes expressing MHC class II molecules was the same in all groups, whereas increased levels of MHC class I in parathyroid tissue before transplantation resulted in a more rapid rejection. These results indicate that immunogenicity of rat parathyroid tissue might be determined by the amount of MHC class I expressed in donor parenchymal cells. Further experiments are necessary to validate this observation.