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Biomedical subjects

W Land

Publications and source records attributed to W Land.

At least 37 records · Page 2Linked to original sources

Computer-assisted ex vivo, normothermic small bowel perfusion.

BACKGROUND: In the present study, a technique for computer-assisted, normothermic, oxygenated, ex vivo, recirculating small bowel perfusion was established as a tool to investigate organ pretreatment protocols and ischemia/reperfusion phenomena. A prerequisite for the desired setup was an organ chamber for ex vivo perfusion and the use of syngeneic whole blood as perfusate. METHODS: The entire small bowel was harvested from Lewis rats and perfused in an organ chamber ex vivo for at least 2 h. The temperature was kept at 37 degrees C in a water bath. Three experimental groups were explored, characterized by different perfusion solutions. The basic perfusate consisted of syngeneic whole blood diluted with either NaCl, Krebs' solution or Krebs' solution and norepinephrine to a hematocrit of 30%. In addition, in each group l-glutamine was administered intraluminally. The desired perfusion pressure was 100 mm Hg which was kept constant with a computer-assisted data acquisition software, which measured on-line pressure, oxygenation, flow, temperature and pH and adjusted the pressure by changing the flow via a peristaltic pump. The viability of the preparation was tested by measuring oxygen consumption and maltose absorption, which requires intact enzymes of the mucosal brush border to break down maltose into glucose. RESULTS: Organ perfusion in group 1 (dilution with NaCl) revealed problems such as hypersecretion into the bowel lumen, low vascular resistance and no maltose uptake. In contrast a viable organ could be demonstrated using Krebs' solution as dilution solution. The addition of norepinephrine led to an improved perfusion over the entire perfusion period. Maltose absorption was comparable to tests conducted with native small bowel. Oxygen consumption was stable during the 2-hour perfusion period. CONCLUSIONS: The ex vivo perfusion system established enables small bowel perfusion for at least 2 h. The viability of the graft could be demonstrated. The perfusion time achieved is sufficient to study leukocyte/lymphocyte interaction with the endothelium of the graft vessels. In addition, a viable small bowel, after 2 h of ex vivo perfusion, facilitates testing of pretreatment protocols for the reduction of the immunogenicity of small bowel allografts.

Absorption↗

Ethics regarding living-donor organ transplantation.

During the last two decades, an intensive discussion has taken place in the field of medical ethics, which has lead to a reawakening of interest in the subject of living-donor organ transplantation and a re-evaluation of the moral problems related to it. In this process, traditional professional ethics have, to a large extent, been replaced by more complex modes of moral reasoning. The ethical principle of respect for the autonomy of persons has proven to be of prime importance in this field.

Ethics, Medical↗

Mycophenolate mofetil-based, cyclosporine-free induction and maintenance immunosuppression: first-3-months analysis of efficacy and safety in two cohorts of renal allograft recipients.

BACKGROUND: The currently used macrolide immunosuppressants, i.e., cyclosporine and tacrolimus, exert considerable nephrotoxicity. We aimed to avoid the nephrotoxic effects by applying a cyclosporine-free regimen for the induction as well as for the maintenance treatment of renal allograft recipients using mycophenolate mofetil (MMF) as the primary immunosuppressant. METHODS: Thirteen patients were converted from cyclosporine (CsA) to MMF monotherapy. For 4 weeks, MMF (2 g/day) was added to the CsA treatment, before CsA was tapered by weekly steps of 25 mg/day and without "safeguard treatment" with additional immunosuppressants. In a second approach, 12 patients older than 50 years, and receiving a renal graft from a donor older than 50 years, were treated primarily with MMF combined with steroids and an induction therapy using antithymocyte globulin, and without the addition of CsA. RESULTS: Thirteen long-term renal transplant patients could be converted from CsA to MMF monotherapy. Conversion resulted in an immediate and long-lasting improvement of their median creatinine values by 20%. No serious adverse events occurred. In the second cohort of 12 patients, MMF was used as the primary immunosuppressant. All patients are alive and no grafts were lost after 4 months (n= 12) and after 6 months (n=7). The median creatinine values achieved after 4 and 6 months were 1.16+/-0.25 and 1.30+/-0.21 mg/dl, respectively. One patient was converted to CsA because of a reversible rejection episode (8.3%), and another patient was converted because of cytomegalovirus disease. Major complications consisted of wound-healing disturbances (16.6%) and cytomegalovirus infections (41.6%). CONCLUSION: MMF monotherapy can be safely applied as long-term maintenance immunosuppression with improvement of renal function. Steroids are not required as an adjunct to MMF. MMF monotherapy, in the absence of drug-related nephrotoxicity, is particularly beneficial for grafts derived from marginal donors, such as donors of advanced age.

Acute Disease↗

Early loss of renal transplants in patients with thrombophilia.

BACKGROUND: We considered the possibility that thrombophilia may propagate graft thrombosis and therefore we evaluated the protein C system, which is a natural anticoagulant. Potential alterations in this system include protein C or protein S deficiency, inhibition through a lupus anticoagulant (LA), or a resistance to activated protein C due to the factor V Leiden (FVL) mutation. METHODS: One hundred thirty-two consecutive renal transplant patients, not known to have abnormal thrombostasis, in whom 1-year graft survival could be assessed, underwent laboratory testing for protein C or S activity, LA, and FVL. Transplant survival and demographic data were extracted from the hospital record. RESULTS: We identified 18 patients with thrombophilia (FVL, 10; LA, 6; protein S, 2) who had received a total of 28 renal transplants. Of these 28 transplant recipients, 11 transplants were lost within the first year, compared with 21 of 155 transplants to 114 patients without thrombophilia (P=0.0003). Median graft survival for patients with thrombophilia was 30 months (range: 0 to 166), compared with 86 months (range: 0 to 212) for patients without thrombophilia (P<0.01). The presence of thrombophilia represented a 3.5-fold (95% confidence interval, 2.3-5.3-fold) risk for 1-year graft loss. CONCLUSION: In this retrospective study, patients with thrombophilia had a significantly higher risk of early transplant failure. These data point toward a potential contribution of thrombophilia to transplant loss, a hypothesis that needs further study.

Adult↗

Allogenic grafting of vascularized bone segments under immunosuppression. Clinical results in the transplantation of femoral diaphyses.

Trauma surgery lack, substitute, for the reconstruction of large defects of the long bones. Encouraged by the promising results of bone allotransplantation in animal models, we successfully performed vascularized bone transplantation in humans. Vascularized femoral diaphyses were allogenically transplanted into three patients suffering from chondrosarcoma or post-traumatic osteomyelitis with postoperative immunosuppression. The bone segments were harvested from multi-organ donors and perfused with UW solution. After back-table preparation, the grafts were transplanted into the defect zone. Interlocking devices were used in these operations. Vascular anastomoses were performed in end-to-side technique. The early clinical course of the patients was not free of anatomical, technical, or immunological complications. However, all patients are currently free of malignancy and infection. They are also free of pain and full weight bearing. We conclude that allogenic grafting of vascularized bone segments has the potential to become an alternative for the replacement of large bone defects.

Adult↗

Aggressive treatment of the first acute rejection episode using first-line anti-lymphocytic preparation reduces further acute rejection episodes after human kidney transplantation.

The detrimental effect of acute rejection episodes on long-term outcome of renal allografts in cyclosporin-treated patients is well established, although has not been seen by all investigators. To analyse the possibility that aggressive treatment of the first episode may ameliorate this detrimental effect, we performed an open label, randomised prospective trial in cyclosporin-based, immunosuppressed recipients of postmortem renal allografts in order to compare two different treatment protocols during primary acute rejection episodes: (1) group 1 of 25 patients received 3 x 250 mg methylprednisolone (MP) i.v.; (2) group 2 of 25 patients received 7 x anti-thymocyte globulin (ATG)-Fresenius i.v. (4 mg/kg body weight). During a period of 4 years, the following clinical observations were made: (1) The incidence of an acute re-rejection episode was significantly reduced in the ATG-treated study group (16%) compared to the MP-treated study group (72%); (2) The severity of the first acute rejection episode (intensity of renal dysfunction measured in terms of 10-day creatinine area under curve) showed no significant difference between the groups (37 mg x 10-d/dl to 58 mg x 10-d/dl); and (3) The half-lives of allografts in both groups have not shown any significant differences so far. In conclusion, aggressive treatment of the first rejection episode of renal allografts with the use of ATG reduced the incidence of re-rejection episodes which, however, are not reflected so far by improvement of the 4-year survival rate of these allografts. Since it could be observed that re-rejection is an even worse predictor for chronic transplant failure, a better long-term outcome of renal allografts in ATG-treated patients may be expected during a longer observation period. The incidence of a third episode was also reduced in the ATG-treated group (0%) compared to the MP-treated group (12%).

Adult↗

Vascularized knee joint transplantation in man: a report on the first cases.

Four transplantations of an allogeneic vascularized human knee joint were performed at the Trauma Center Murnau between April 1996 and July 1997. The indication for the procedure was the total loss of the knee joint including the extensor apparatus due to severe trauma. These were the first transplants of this type. Management of patients started with closure of soft-tissue defects. After successful completion, stabilization was achieved with femoral and tibial nails plus a temporary arthroplasty. AB0 compatibility and a negative cross-match were the main criteria for selecting patients for transplantation. Interlocking compression nails were used for osteosynthesis. Vascular anastomoses between graft and recipient vessels were established by the end-to-side technique. Immunosuppression was started as a quadruple induction therapy for 3 days, then reduced to a two-drug maintenance therapy with cyclosporine and azathioprine. Six months posttrans-plantation the osteotomies were bridged by callus and the patients became completely mobile. Radiographic and histological examinations revealed vital graft tissue.

Adolescent↗