Biomedical subjects
Publications and source records attributed to S Wilhelm.
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Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI) after allogeneic hematopoietic stem cell transplantation is associated with a high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we evaluated the efficacy of replacing CI by daclizumab in patients with graft-versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five patients with RI were treated with daclizumab 1 mg/kg intravenous (i.v.)/week, discontinuation of the CI and continuation of the remaining GVHD treatment. All patients had acute GVHD (steroid-sensitive (n=4), steroid-refractory (n=10)) or chronic GVHD (n=4) and were treated with CI before the start of daclizumab. Nine of 13 patients with TAM treated with daclizumab and discontinuation of CI achieved complete remission of TAM, two had stable disease, and one patient did not respond. Patients receiving daclizumab for RI without TAM showed stabilization (2/5) or improvement (3/5) of renal function. Four of 14 patients with acute GVHD achieved CR, two partial remission, eight patients did not respond and 11/14 died at a median of 39 days after start of the daclizumab. Our data demonstrate that replacement of CI by daclizumab can improve TAM and RI. However, mortality remains high in patients with acute GVHD.
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Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine. Due to genetic variation between the European and the US genotype as well as within both genotypes detection of PRRSV is a diagnostic challenge. This paper reports on a ring test to compare different established reverse transcriptase polymerase chain reaction methods applied routinely in 16 different laboratories in Germany. Three different sets of samples were sent to the laboratories which were to be analysed as follows: (i) basis package: detection of PRRS (yes/no); (ii) differentiation package I: differentiation of EU and US genotypes; and (iii) differentiation package II: differentiation of EU field isolates and EU vaccine strain. A total of 80% of the samples of the basic package were analysed correctly, the analysis of the differentiation package I revealed 61.82% correctly tested samples and the two laboratories that analysed the differentiation package II showed only one correct result. The ring test showed that the majority of incorrect diagnoses were false-negative results.
This study aims to provide information on the occurrence of spotted fever rickettsiae in Ixodes ricinus ticks in southern Germany. A total of 2,141 I. ricinus ticks was collected in Bavaria. Pools of 5-10 ticks were studied by a PCR targeting the rickettsial citrate synthase gene gltA. The average prevalence rate was 12% (257 of 2,141). Sequencing data exclusively identified Rickettsia helvetica DNA. Results and other data demonstrate the possible role of R. helvetica in I. ricinus as a source of human infections in southern Germany.
BACKGROUND AND OBJECTIVE: Allogeneic transplantation can not be offered to many patients due to potential side-effects of conventional conditioning. Dose-reduced conditioning approaches improve tolerability, however, treatment efficacy may be reduced as well. We have, therefore, developed a dose intense but toxicity reduced conditioning regimen based on treosulfan and fludarabine and report first results. PATIENTS AND METHODS: 65 patients with a median age of 50 years were transplanted from related (n = 21) or unrelated donors (n = 44) after conditioning with treosulfan (3 x 10, 3 x 12 or 3 x 14 g/m(2) i. v.) and fludarabine (5 x 30 mg/m(2) i. v.). 21 patients were in complete remission (CR) and 44 patients had not reached a CR at the time of transplantation. 59 of 65 patients were considered unfit for a conventional conditioning regimen. RESULTS: The actuarial overall survival after 3 years is 59.2 %, the event-free survival 40.1 %. Patients with a related donor or transplantation in CR had a better overall (85.4 resp. 74.2 %) and event-free survival (52.2 % resp. 61.9 %). The cumulative incidence of relapse at 3 years was 26.2 %. Non-relapse mortality at day 100 is 17.4 % (cumulative incidence). In stepwise Cox regression analyses for overall survival, event-free survival and non-relapse mortality the covariables transplantation in CR vs. not in CR and the donor status were shown to be influential. CONCLUSIONS: These results with a conditioning therapy of treosulfan and fludarabine indicate that patients despite higher age, concomitant disease or after intensive pretreatment can be successfully transplanted without increased treatment-related mortality.
Dogs with food hypersensitivity usually develop chronic pruritic dermatoses virtually indistinguishable from atopic dermatitis. These reactions are often called food allergy but the pathogenesis is poorly characterized. Several studies have addressed the incidence of canine adverse reactions to food but the outcomes were conflicting. The gold standard for the diagnosis of such a condition is the restricted dietary trial and the subsequent provocation challenge. Some attempts have been made to develop serological tests but none of these tests accurately predicted canine food sensitivity. The aim of the present study was to determine the incidence of food hypersensitivity dermatitis and to evaluate a newly developed serological test for the diagnosis of food allergy in dogs. Only 9% of 55 dogs with dermatological signs compatible with food hypersensitivity or atopic dermatitis have been diagnosed as food hypersensitive dogs. The repeatability of the serological test has shown to be insufficient.
High dose busulfan is widely used in preparative regimens for bone marrow transplantation. We describe three cases of accidental busulfan overdosing. Two adults received a single dose of 8 and 18 mg/kg busulfan, respectively. Doses of 9 x 4 mg/kg were ingested by a 14-year-old girl, who experienced seizures. In all cases, no severe liver toxicity including veno-occlusive disease was observed. Plasma samples were obtained from two patients. Busulfan plasma concentrations were far above published values after high-dose busulfan treatment. Busulfan was eliminated by a first-order process. All patients survived these high doses of busulfan and successful transplantation was possible. Two patients died from refractory GvHD on days 91 and 80 after transplantation. One patient is alive in remission after an observation time of 18 months. These cases show that busulfan overdosing may occur and pharmacokinetic evaluation is warranted to estimate risk of early and late toxicity.
Steroid-resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be associated with a high mortality. We report the results of a phase II study of treatment of steroid-resistant aGVHD with the IL-2 receptor antibody daclizumab combined with the TNF-receptor fusion protein etanercept. Treatment consisted of daclizumab 1 mg/kg given i.v. on days 1, 4, 8, 15, 22 and etanercept 16 mg/m(2) s.c. on days 1, 5, 9, 13, 17. A total of 21 patients (age 15-61 years) with steroid-resistant aGVHD after alloHSCT were included in the study. Donor types were HLA-matched related (n=6), HLA-matched unrelated (n=14), and HLA-mismatched unrelated (n=1). Eight patients achieved complete, and six showed partial remission of aGVHD. Seven patients did not respond. Four of 21 patients are currently alive with a median follow-up of 586 (185-1155) days. Three patients died due to relapsed malignancy. Treatment-related mortality was due to infectious complications (n=11) or organ failure due to aGVHD (n=3). In total, 12 patients developed subsequent chronic GVHD. In conclusion, the data demonstrate an acceptable response rate of the combination of daclizumab and etanercept in the treatment of steroid-resistant aGVHD. Nevertheless, long-term mortality due to infectious complications and chronic GVHD remains high.
High-level synthesis of complex enzymes like bacterial [NiFe] hydrogenases, in general, requires an expression system that allows concerted expression of a large number of genes. So far, it has not been possible to overproduce a hydrogenase in a stable and active form by using a customary expression system. Therefore we started to establish a new, T(7)-based expression system in the phototrophic bacterium Rhodobacter capsulatus. The beneficial properties of this bacterial host in combination with the unique capacity of T(7) RNA polymerase to synthesize long transcripts will allow the high-level synthesis and assembly of active hydrogenase as well as other complex enzymes in the near future.
Two cases of feline leukaemia virus (FeLV)-associated dermatosis are described. The first cat was affected by an ulcerative dermatitis identified as a giant-cell dermatosis. The second case was a cutaneous lymphoma. In both cases, FeLV antigens and FeLV genome were demonstrated in the affected skin immunologically and with polymerase chain reaction, respectively. The first case suggests that, like other retroviruses, at least some strains of FeLV can induce syncytium formation. As FeLV antigens and genome were demonstrated in a serologically negative cat, the second case suggests that focal skin FeLV replication may occur. FeLV-associated dermatoses are rare skin conditions that may be under-diagnosed.
Porcine circovirus type 2 (PCV2) seems to cause reproductive failure in sows not only in experimental studies. A retrospective study was made with a total of 252 aborted fetuses, mummified fetuses, stillborn and nonviable neonatal piglets to determine the presence of PCV2, porcine parvovirus (PPV) and porcine respiratory and reproductive syndrome virus (PRRSV) by PCR. PCV2 was found in all stages of gestation in 27.1 percent of samples examined. A statistically significant association could be shown between the detection of PCV2 and PRRSV. However, no significant association was seen between the detection of PCV2 and PPV and between PPV and PRRSV.
In the last few years, the mass media and also scientists have been showing an increasing interest in poxviruses. What kind of infections can be found in animals and men today? The following review gives an overview on current taxonomy, properties, epidemiology, and diagnosis of zoonotic poxviruses.
The graft vs. leukemia (GVL) effect is one of the most important factors of anti-tumor activity after allogeneic hematopoetic stem cell transplants (alloSCT). Its effectiveness depends mainly on the tumor biology as well as the tumor burden. Patients with a high tumor burden may not respond to GVL-effect despite otherwise sensitive biology. Campath-1H is known as an effective treatment of chronic lymphocytic leukemia (CLL). Due to its ability to induce profound immunosuppression, it has also been used as part of conditioning regimens before alloSCT. We report a patient, who received campath-1H in combination with docetaxel for treatment of chemotherapy and donor lymphocyte infusion resistant CLL after alloSCT, who developed shortly after discontinuation of treatment with campath-1H severe eosinophilia of the peripheral blood and typical clinical as well as histological signs of cutaneous chronic graft vs. host disease followed by complete clearance of CLL. The clinical course demonstrates the impact of the tumor burden on the GVL-effect, as well as the effectiveness of campath-1H in the presence chemo-resistance in a patient with CLL. Furthermore, the GVL effect was not abrogated by the use of campath-1H.
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BACKGROUND: Increasing need for and potential shortage of blood products have intensified the search for alternative oxygen carriers. A solution to this problem could be use of the bovine hemoglobin-based oxygen carrier HBOC-201. While hemodynamic reactions to cell-free hemoglobin have been studied, little knowledge exists about tissue oxygenation properties of hemoglobin solutions, especially in comparison with red blood cells (RBCs). STUDY DESIGN AND METHODS: Tissue oxygenation in skeletal muscle of 12 anesthetized dogs was examined after decrease of hemoglobin concentrations by means of hemodilution to hematocrit 10% and subsequent transfusion with either HBOC-201 or autologous banked RBCs. In addition to hemodynamic parameters, blood gas concentrations and oxygen content in arterial and muscular venous blood, tissue oxygen tension (tPO(2)) were measured in the gastrocnemius muscle with a polarographic needle probe. RESULTS: Hemodilution increased muscular blood flow and oxygen extraction and decreased tPO(2). Transfusion decreased muscular oxygen extraction in the RBC group but not in the HBOC-201 group (P <.01). The 10th percentile of tPO(2) increased by 400% after the first dose of HBOC-201 (P <.001 vs posthemodilution) but only by 33% after equivalent RBC transfusion (P <.01 vs HBOC-201). Increases in the 50th (120%, P <.05) and 90th (31%) percentiles and all percentiles of tPO(2) after the second and third HBOC-201 dose were less pronounced but higher than in the RBC group. CONCLUSION: Compared with RBC transfusion, infusion of low doses of HBOC-201 maintain enhanced oxygen extraction after extended hemodilution and provide faster and higher increase in muscular tissue PO(2).
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