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Biomedical subjects

M Schäffer

Publications and source records attributed to M Schäffer.

At least 19 recordsLinked to original sources

[Pancreas removal by external teams].

Combined pancreas and kidney transplantation is an established procedure for terminal or preterminal, uremic, type 1 diabetics. The current procurement technique allows simultaneous recovery of liver and pancreas. One problem is the assessment of organ quality. It remains unclear how many pancreas organs must be withdrawn during back-table preparation. Between June 1994 and December 2003, 271 pancreas transplantations were performed at our transplant centre. Two hundred sixty-two (89.7%) pancreas grafts were harvested by teams which were not part of the transplant team. Twenty-one (8.0%) grafts were discharged for transplantation at the time of back-table preparation. Liposis of the graft and critical vessel situations were the main reasons for withdrawal. Two kidney grafts were not usable for transplantation, and 92% of the pancreas grafts were. This demonstrates the high standard of pancreas procurement in the Eurotransplant region.

Adipose Tissue↗

[Combined pancreas kidney transplantation after isolated kidney transplantation].

Simultaneous pancreas kidney transplantation (SPK) is an established therapy for type 1 diabetics with end stage or preterminal renal disease. SPK is superior to isolated kidney transplantation (KTX) in diabetic patients. Even pancreas-re-transplantations are more common in these patients now, mostly after SPK. But Experience with SPK after KTX is rare. Between 1994 and 2003 six Re-SPK 4.5 to 8.5 years after KTX were performed in our department. Average age of the recipients was 40.5 years. They had been suffering from diabetes for an average of 29.3 years. Four recipients were on dialysis again, whereas two had preterminal renal insufficiency. Pancreas transplants were drained through the bladder (n = 1) or into the small intestine (n = 5) with systemic venous anastomosis. After a median observation period of 28 months (8 to 99 months) all six recipients are insulin free. One patient lost his kidney graft due to severe acute rejection. Therefore kidney graft survival is 83 %. Four acute rejections (66 %) were observed in 4 patients. Only one rejection was treated successfully by steroids. Two rejections could be stopped with antibodies. 3 patients had infections in the early postoperative period (sinusitis, urinary tract infection, wound infection). Even after KTX with graft failure, diabetic patients suffering from renal disease can be re-transplanted successfully with SPK.

Adult↗

[Gene therapy in diabetic foot].

In gene therapy nucleic acids are used for therapy. There are three different concepts in gene therapy for chronic wounds. (1) Synthesis of human recombinant growth factors by gene therapy techniques, (2) Ex-vivo transfection of cell cultures (fibroblasts, keratinocytes) with growth factor DNA and subsequent transplantation of transfected cells on chronic wounds. (3) In-vivo transfection with growth factor DNA, e.g., gene gun, liposomes, viral vector. Clinical studies on gene therapy for diabetic foot ulcers are only available for the local application of human recombinant PDGF-BB growth factor. Meta-analysis shows there is a low but significant effect of PDGF-BB on neuropathic diabetic ulcers, leading to an increase of healing by 10-15% within 20 weeks of treatment.

Animals↗

[Treatment strategies in wound healing disorders].

Wound healing problems are caused by traumatic influence, due to iatrogenic effects as well as special circumstances of the patient and a combination of all these. The special difficulties of disturbed wound healing in trauma surgery are the possible involvement of the fractured bone and the danger of osteitis. Acute wound healing problems like infected hematoma, necrosis of the wound margins or dehiscense require early or emergency revision surgery with debridement and necrectomy. The sanitation of soft tissue problems encloses secondary sutures, meshgraft as well as local or free flaps. The goal of treatment in wound healing problems must be the avoidance of acute or chronic osteitis.

Fracture Fixation, Internal↗

goosecoid expression represses Brachyury in embryonic stem cells and affects craniofacial development in chimeric mice.

The homeobox gene goosecoid, originally identified in Xenopus, is expressed in the organizer or its equivalent during gastrulation in the frog, chick, zebrafish and mouse. To investigate the role of goosecoid in mouse development, we have generated embryonic stem cells that stably overexpress the murine homolog of goosecoid. These cells show a repression of the gastrulation-associated gene Brachyury. Interestingly, repression of Brachyury is conserved between Xenopus and mouse despite the lack of conservation of the Brachyury promoter. Further characterization of the goosecoid-overexpressing ES cells revealed that they maintain the expression of stage-specific embryonic antigen-1, and teratomas derived from goosecoid-overexpressing cells show the presence of cell types derived from all three germ layers. Some highly chimeric mice derived from goosecoid-overexpressing cells displayed skull defects. These observations suggest that goosecoid may play a role in specification of anterior mesendodermal fates and specifically in mouse craniofacial development.

Animals↗

[Diagnosis and therapy of tumor of Vater's ampulla].

BACKGROUND AND OBJECTIVE: Complete removal of tumours of the ampulla (papilla) of Vater is generally recommended, because of the known adenoma-carcinoma sequence yet the uncertainty regarding diagnosis of dignity of such tumours. The aim of this study was tho analyse different treatment concepts on the basis of data from a personal series of cases. PATIENTS AND METHODS: Clinical, laboratory and histological data as well as treatment and course in nine patients (three women, six men; mean age 62 [46-82] years) with ampulla of Vater adenoma, treated at one hospital, were analysed retrospectively. The patients had been followed for 6-36 months. RESULTS: All tumours had been removed endoscopically. Partial duodenopancreatectomy had subsequently been performed in two patients because of severe dysplasia. One tumour with moderately severe dysplasia had recurred locally within two months of endoscopic removal and was resected transduodenally. There had been no further recurrences 3 to 36 months later. CONCLUSION: If there is no evidence of malignity and frequent follow-up can be ensured, endoscopic removal of a tumour of the ampulla of Vater is justified. Otherwise transduodenal excision of the ampulla or partial duodenopancreatectomy should be undertaken.

Adenoma↗

[The wound care center in surgery: an interdisciplinary concept for diagnostic and treatment of chronic wounds].

In Germany there is no standardized wound care for patients with chronic wounds in specialized centers. We have established a wound care unit for the past 6 years. The principal concept of therapy was characterized by standardized local surgery, moist wound dressings and concomitant treatment of the underlying disease. We performed local therapy, coordinated the interdisciplinary treatment and developed a new wound documentation system for quality control. We established a close network, integrating general practitioners and home care organizations to realize a mainly outpatient treatment supported by short hospital therapy. Exclusive outpatient treatment was performed in 42% of all patients. According to our prospective data, we achieved an improvement in wound care: 69% of the wounds resistant to therapy for a mean of 30 months healed within 12 months after therapy according to our protocol. Our data strongly supported the importance of local surgery: neither wound depth nor wound infection had any influence on the healing rate, presumably due to radical excisional debridement of necrotic tissue. The presented data justify on medical and economic grounds the establishment of such wound care centers in Germany.

Ambulatory Care↗

[Immune regulation of wound healing].

Wound healing is a complex cascade of biochemical and cellular events designed to achieve restoration of tissue integrity following injury. Immune cells are critical for the outcome of healing. Much has been learned about the individual events that are involved in this process. Knowledge is scant, however, about the spatial and temporal interweaving of these events and how one step sets the stage for subsequent observed phenomena. Imbalance of stimulating and inhibiting factors causes failure of healing. Immunosuppressive states interfere with a normal immune response and impair wound repair. Clinically, new therapeutic approaches to modulate impaired healing are based on a knowledge of immune regulation of wound healing.

Animals↗

[Temporary expression pattern in wound secretions and peripheral wound biopsies].

The local availability of growth factors and oxygen plays an important role in the healing of cutaneous lesions. We were able to quantify the ischemia in a standardized ischemic full-wall flap by measuring the ptiO2, and investigate the healing of defined wounds. The analysis of the immune histochemical section showed a significantly reduced expression of IGF-I in the wound edge of ischemic wounds. Simultaneously the rate of proliferation was reduced here. Probably the local chronic hypoxia leads to reduced IGF-I synthesis and thus to reduced proliferation and delayed wound healing. Further investigation is necessary to confirm this hypothesis. In a clinical study of wounds which had been treated with vacuum sealing we could establish no difference in the concentration of IGF-I in the wound fluid of seriously contaminated wounds in comparison to primary fasciotomy wounds. We therefore postulate a primary endocrinal secretion for IGF-I in cases of cutaneous wound healing; higher local consumption or reduced serum levels could stimulate the autocrinal local secretion of IGF-I. Further investigation is, however, needed in order to confirm this hypothesis.

Animals↗

Korundamine A, a novel HIV-inhibitory and antimalarial "hybrid" naphthylisoquinoline alkaloid heterodimer from Ancistrocladus korupensis.

A unique heterodimeric naphthylisoquinoline alkaloid, korundamine A (2), comprised of two different monomeric biaryl halves, has been isolated from the Cameroonian tropical liana Ancistrocladus korupensis. Korundamine A is the first "hybrid" dimer found in the Ancistrocladaceae; in vitro, it demonstrated anticytopathic activity against HIV-1 and antimalarial activity against Plasmodium falciparum.

Animals↗

Ancistroguineines A and B as well as ancistrotectorine-naphthylisoquinoline alkaloids from Ancistrocladus guineënsis.

The isolation of three naphthylisoquinoline alkaloids from the leaves of Ancistrocladus guineënsis is described. Their complete structures were established by spectroscopic, chiroptical and degradative methods. Thus, two hitherto unknown 5,8'-coupled naphthylisoquinoline, named ancistroguineines A and B, were isolated, constituting the first example of a pair of 3-epimeric naphthylisoquinoline alkaloids. Moreover, ancistrotectorine, a 7,3'-coupled alkaloid previously known only from the South-East Asian species Ancistrocladus tectorius, was isolated. Its absolute stereostructure was confirmed by oxidative degradation and by comparison of experimental and calculated CD spectra.

Alkaloids↗

Ancistrobertsonine A and related naphthylisoquinoline alkaloids from Ancistrocladus robertsoniorum.

From the as yet unexplored East African Liana, Ancistrocladus robertsoniorum, several naphthylisoquinoline alkaloids have been isolated, based mainly on High Speed Countercurrent Chromatography (HSCCC). The structure of the new compound, ancistrobertsonine A, was elucidated by chemical and spectroscopic methods. Furthermore, the known alkaloids ancistrocladine, its atropo-diastereomer, hamatine, and its regioisomer, ancistrobrevine B, were isolated.

Alkaloids↗

Effects of neurotoxins and hindpaw inflammation on opioid receptor immunoreactivities in dorsal root ganglia.

Three types of opioid receptors mediate peripheral opioid antinociception in inflammation. Recently, antisera that recognize unique epitopes of the cloned mu-, delta-, and kappa-opioid receptors have been developed. Using these antisera we examined the regulation of opioid receptors in rat dorsal root ganglia after hindpaw inflammation and the influence of neurotoxins for primary afferent neurons and sympathetic neurons thereon. Peripheral tissue inflammation was produced by injection of complete Freund's adjuvant into the right hindpaw. Capsaicin was injected subcutaneously once a day for three days using a total dose of 150 mg/kg. 6-hydroxydopamine was injected intraperitoneally 75 mg/kg/day for three days. Freund's adjuvant induced a marked increase in the percentage of mu-, but a decrease in delta- and kappa-opioid receptor-positive neurons. Capsaicin significantly decreased mu-, delta- and kappa-opioid receptor immunoreactivity in both Freund's adjuvant treated and non-treated rats. No significant changes on the mu-, delta- and kappa-opioid receptor immunoreactivities were observed after 6-hydroxydopamine treatment in either Freund's adjuvant-treated or non-treated rats. Our studies indicate: (1) Peripheral inflammation can differentially regulate the expression of the three opioid receptors in dorsal root ganglia neurons with an up-regulation of mu- and down-regulation of delta- and kappa-opioid receptors. 2) A significant portion of mu-, delta- and kappa-opioid receptors are located on capsaicin-sensitive neurons in dorsal root ganglia of both non-inflamed and inflamed hindlimbs. 3) The expression of opioid receptors in dorsal root ganglia of either inflamed or non-inflamed hindlimbs is not influenced by sympathetic postganglionic neurons.

Animals↗

Lymphocyte function in wound healing and following injury.

BACKGROUND: Injury activates a cascade of local and systemic immune responses. METHODS: A literature review was undertaken of lymphocyte function in wound healing and following injury. RESULTS: Lymphocytes are not required for the initiation of wound healing, but an intact cellular immune response is essential for a normal outcome of tissue repair. Injury affects lymphocyte immune mechanisms leading to generalized immunosuppression which, in turn, increases host susceptibility to infection and sepsis. Although the exact origin of post-traumatic immunosuppression remains unknown, stress hormones and immunosuppressive factors, such as inflammatory cytokines, prostaglandin E2 and nitric oxide, affect lymphocyte function adversely. Post-traumatic impairment of T lymphocyte immune function is reflected in decreased lymphocyte numbers, as well as altered T cell phenotype and activity. Antibody-producing B lymphocytes are variably affected by injury, probably secondary to alterations of T lymphocyte function, as a result of their close interaction with helper T cells. Therapeutic modulation of the host immune response may include non-specific and specific interventions to improve overall defence mechanisms. CONCLUSION: Early resuscitation to restore lymphocyte function after injury is important for tissue repair and the prevention of immunosuppression.

Animals↗

[Interdisciplinary treatment concepts in chronic wounds].

Interdisciplinary concepts for the treatment of chronic wounds are mandatory because of the multifactorial reasons causing ulceration. This is a report on 6 years' experience at the wound care unit in Tübingen. Patients with chronic wounds (mainly diabetic, venous, and ischemic ulcers) were treated primarily as outpatients according to a standardised and interdisciplinary wound care protocol. Quality control was guaranteed by a standardised wound documentation system. The evaluation of this data demonstrates an overall healing rate of 69% within 52 weeks (mean). Before patients were referred to Tübingen, unsuccessful therapy was characterised by a mean wound duration of 35 weeks. The results presented justify this interdisciplinary wound care unit.

Chronic Disease↗