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Biomedical subjects

W Hamelmann

Publications and source records attributed to W Hamelmann.

At least 19 recordsLinked to original sources

The advantages and disadvantages of nerve monitoring during thyroid surgery in childhood.

BACKGROUND: Intraoperative damage of the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (EBSLN) are common and cause complications in thyroid surgery. The method of intraoperative electrophysiological neuromonitoring (IONM) of the RLN and the EBSLN has been used in adults for several years. The question is whether IONM can be used in paediatric surgery for the identification and functional control of the RLN and the EBSLN, and what the advantages and disadvantages of using it are. METHODS: Surgical treatment of benign (n = 9) and malign (n = 2) thyroid diseases was carried out in eleven children (median age: 13 years) with a total of 18 nerves at risk (NAR). The function of the vocal cord was monitored in all children before and after surgery. Intraoperative identification and functional control of RLN and EBSLN was performed using the Neurosign 100. All results before and after resection of the thyroid gland were documented. RESULTS: A clear and reliable identification of the RLN and the EBSLN was possible in all cases. All NAR showed a constant physiological nerve signal before and after surgical resection of the thyroid gland. However, in one young patient the postoperative examination of the vocal cord revealed a partial paralysis on the left side after thyroidectomy, despite the constant intraoperative signal of the RLN. After a period of six months, normal functioning had resumed. CONCLUSION: The IONM of both RLN and EBSLN in adult surgery could be used successfully in paediatric surgery. In this study a clear and positive identification of both nerves was possible in all patients. Therefore the IONM of the RLN and EBSLN could develop into a successful and easy method for the prevention of intraoperative nerve damage during thyroid surgery in childhood and young adolescence. Assuming that a constant IONM signal represents a normal vocal cord, our evaluation showed that there is a small percentage of false negative and positive results.

Adolescent↗

Immunogenicity of parathyroid allografts in the rat: immunosuppressive dosages effective in passenger leukocyte-rich small bowel transplants are not effective in parathyroid gland transplants with few passenger leukocytes.

BACKGROUND AND AIMS: The passenger leukocytes harboured within an allograft induce a massive allo-immune response that leads to allograft rejection if not countered by immunosuppression. We compared the response to short-term immunosuppression of parathyroid gland transplants possessing few passenger leukocytes with that of passenger leukocyte-rich small bowel transplants. METHODS: Heterotopic parathyroid and orthotopic small bowel transplantation was performed in a Wistar Furth-to-Lewis rat strain combination. Immunosuppression with cyclosporine A (CsA) was administered in different dosages for 14 days. Dysfunctional allografts were examined immunohistologically. RESULTS: CsA more effectively suppressed the immune response provoked by immunogenic small bowel grafts than that induced by less-immunogenic parathyroid grafts. Immunosuppression with 20 mg/kg per day induced long-term survival in the small bowel (165+/-21 days) but not in the parathyroid (28+/-3 days). All rejected grafts featured massive cellular infiltration by activated T cells as a sign of immune rejection. CONCLUSION: Immunosuppressive dosages effective in passenger leukocyte-rich small bowel transplants were not as effective in parathyroid gland transplants harbouring few passenger leukocytes. In spite of the paucity of passenger leukocytes in parathyroid grafts it is more difficult to control by immunosuppression the immune response to them than that to the passenger leukocyte-rich small bowel.

Animals↗

Combined surgical and antifungal treatment of a subcutaneous infection due to Paecilomyces lilacinus.

Paecilomyces lilacinus was the causal agent of a case of subcutaneous infection in a patient with liver cirrhosis. Surgical treatment in combination with systemic amphotericin B therapy led to complete recovery. Retrospectively performed microdilution testing revealed dose dependent in vitro susceptibility of the isolate to voriconazole (MIC = 2 g/ml) and terbinafine (MIC = 1 microg/ml).

Abscess↗

Surgical management of prosthetic vascular graft infection: comparative retrospective analysis of 30 consecutive cases.

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.

Aged↗

[Patient selection criteria for single-sided or minimal invasive operative procedures in primary hyperparathyroidism (pHPT)].

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.

Adenoma↗

[Does intraoperative nerve monitoring reduce the rate of recurrent nerve palsies during thyroid surgery?].

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.

Electromyography↗

Influence of donor MHC class I antigen expression on graft survival after rat parathyroid allotransplantation.

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.

Animals↗

Rat parathyroid allotransplantation: Influence of MHC antigen expression on graft survival.

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.

Animals↗

[Transplantation of porcine Langerhans islets for therapy of type I diabetes. The way to clinical application].

Transplantation of isolated pancreatic islets provides an interesting alternative to the present cure for diabetes: insulin injections and pumps. These are characterized by an insufficient glucose haemostasis and in the long run can induce kidney failure, blindness, heart failure, and amputations. Up to now more than 293 allogeneic islet transplantations have been performed in diabetics with chronical kidney failure. Despite some success, no real breakthrough has been yet achieved, though great efforts are being made to improve the various methodological steps on the way to clinical transplantation. The use of animal (xenogeneic) organs could be a solution to overcome the shortage of allogeneic donors. The current experimental and clinical research focuses on the use of pigs as organ donors, which have a number of advantages over the immunologically more compatible primates. This article reports on success and open questions concerning the efforts to isolate porcine islets for future clinical transplantation: the search for a suitable pig breed, the various isolation steps, purification and in vitro culture, transplantation models using-small and large animals, first clinical trials, and immunological reactions against the xenogeneic tissue. In addition, strategies to circumvent tissue rejection and future perspectives are discussed.

Alginates↗

[Cellular immune reactivity in xenogenic "human-anti-pig" transplant combination].

The worldwide lack of human organ donors puts the pig as potential xenogeneic donor species into the prime of interest. Aim of the present in vitro study is the analysis of T-cell activation in the clinically attractive combination "pig-to-human". Peripheral human blood leukocytes (hPBL) and peripheral porcine blood leukocytes (pPBL) were co-cultured for 4-8 days in the xenogeneic mixed lymphocyte reaction (xMLR) and cell proliferation was measured by 3H-thymidine uptake. Both cell populations were separated into T-cells and antigen presenting cells (APC) to analyze direct and indirect antigen recognition. The results show that (a) activation of human T-cells occurs, (b) the strength of activation depends e.g. on the human responder ("high" and "low" responders), (c) the strength of activation is independent of the responder's HLA-DR status, and (d) direct T-cell activation dominates over indirect activation. Thus, T-cell activation is another immunological barrier that has to be overcome before xenotransplantation can be clinically approached.

Adult↗

Expression pattern of extracellular matrix proteins in the pancreas of various domestic pig breeds, the Goettingen Minipig and the Wild Boar.

UNLABELLED: In spite of progress in biotechnology, isolation of porcine pancreatic islets remains a difficult task with unpredictable results. One reason could be the lack of knowledge as to the expression of extracellular matrix proteins in porcine exocrine and endocrine tissues, particularly in "islet capsules". Such proteins are subject to digestion by proteases, yet they might have a protective function for the fragile islets. OBJECTIVE: Of our study was a detailed histological analysis of the extracellular matrix proteins in various pig breeds. A broad panel of commercial, human-specific antibodies were used, since antibodies against porcine tissue were not available. METHODS: Frozen pancreatic tissue section of 7 domestic pig breeds, the Goettingen Minipig and the Wild Boar were stained with antibodies against collagen types I, II, III, IV, V, VI, VII, IX, laminin, fibronectin, vitronectin and elastin. Binding of antibodies was detected by immunoperoxidase and evaluated microscopically. Human and rat tissue was treated in the same way. RESULTS: (1) With the exception of anti-collagen type II, type VII and vitronectin, all antibodies revealed distinct binding patterns in the pancreas of the different pig breeds. However these antibodies bound on human cartilage and skin. (2) Collagen types I, III, IV, laminin and fibronectin are expressed on porcine pancreatic "islet capsules". (3) Expression levels of these proteins on "islet capsules" vary in the different pig breeds. However, no significant differences could be found in the expression pattern of collagen types I, III, IV, laminin and fibronectin, comparing domestic, experimental and wild type pigs. (4) Older individuals (Goettingen Minipig) appear to express higher levels of proteins on "islet capsules" than younger ones. CONCLUSIONS: Antibodies with specificity for human extracellular matrix proteins can be used successfully in the porcine pancreas. Thus, analysis of the structure and composition of porcine pancreatic tissue can be performed even without pig-specific antibodies. Particularly, the effects of various proteases and collagenases on the pancreatic tissue can now be monitored by immunohistochemical analysis allowing a rational design of protease mixtures for the isolation of pancreatic islets.

Animals↗

[The risk of needle-stick-injuries during abdominal closure].

A randomized study is being presented, which compares closure of laparotomy with 2 different needles (sharp: HR48, blunt: HR48PP = protect point). Handling and glove perforation rate is to be compared. 400 gloves in 100 laparotomies have been tested. Slightly more effort was reported from the surgeon to perforate the fascia with the blunt needle, but there was also a significantly lower perforation rate in the glove of his non-dominant hand. To avoid a contamination during operation the use of blunt needles has to be recommended.

Abdomen↗

Immediate destruction of xenogeneic islets in a primate model.

Transplantation of pancreatic islets from other species to man has the potential to cure diabetes, but whether such islet grafts will be subject to damage due to natural antibody-mediated hyperacute rejection is unknown. We have examined the fate of islet xenografts in a recipient with direct relevance to man, the cynomolgus monkey. Rabbit islets were prepared by an intraductal collagenase technique and incubated in neat rabbit, human, or cynomolgus serum, with and without heat inactivation, for up to 6 days. Islets were analyzed by flow cytometry for IGG and IGM binding, and scored for viability by supravital staining. For in vivo studies, isolated islets were prepared from 4 New Zealand White rabbits (15-34 x 10(3) islets 70-85% purity) and transplanted beneath the kidney capsule of normal cynomolgus monkeys after aggregation in either a rabbit or monkey blood clot. The tissue was retrieved at various times up to 4 days after transplantation and processed for light and electron microscopy. The results showed that rabbit islets bind heterophile antibody of both IGG and IGM subtypes. There was slow loss of islet viability in vitro over 3 days of culture in neat human or cynomolgus serum. Destruction of islets in vivo was more rapid with visible damage within 6 hr associated with neutrophil infiltration. Subsequently, there was heavy mononuclear cell infiltration leading to total destruction within 4 days. The results suggest that immediate mechanisms of graft rejection, possibly compliment and neutrophil mediated, represent a major barrier to islet xenotransplantation in humans.

Animals↗