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U Schulz

Publications and source records attributed to U Schulz.

At least 19 recordsLinked to original sources
PubMed2006

["Asleep-awake-asleep"-anaesthetic technique for awake craniotomy].

Awake craniotomy in tumor and epilepsy surgery or for the implantation of electrodes for deep brain stimulation requires specific anesthesiological strategies. Propofol allows for quick emergence and has little effect on the respiratory function of the usually spontaneously breathing patient. Pain control may be instituted by hemiscalp block for trepanation or local infiltration for deep brain electrode implantation. In addition, low dose remifentanil is recommended for trepanation (i.e. tumor or epilepsy surgery). The airway may be secured by an ordinary Magill tube placed transnasally with its tip underneath the epiglottis. To protect the patient against vomiting an adequate antiemetic prophylaxis is required.

Anesthesia↗
PubMed2006

Unusual case of an 18-year-old heart transplant recipient with endocardial fibroelastosis.

An 18-year-old female Japanese patient who suffered from heart failure and severe pulmonary hypertension was referred to our clinic. The etiology of her cardiomyopathy was unclear. Inhaled prostacyclin therapy resulted in an improvement of pulmonary arterial pressure and allowed us to avoid lung transplantation. Heart transplantation resulted in a complete remission of her respiratory function. Autopsies of the explanted heart revealed massive endomyocardial fibroelastosis. We concluded that endomyocardial fibroelastosis has to be considered a cause of heart failure in young adults with unclear cardiomyopathy.

Adolescent↗
PubMed2006

[Stereotactic body radiotherapy (SBRT) -- an overview under special consideration of SBRT and LITT in the therapy of liver metastases].

Stereotactic body radiotherapy (SBRT) is a high dose radiotherapy, the radiation dose is applicated one-time or in a few fractions exactly to the tumor or metastases under maximal separation from the normal tissue. Because of this a major expenditure of medical and technical efforts are necessary, a detailed description of the proceedings is following in the methodic part of this article. Indications of SBRT are especially medical irresectable lung tumors of early stages, primary liver/biliary tumors and pulmonary or liver metastases if there is an oncological benefit for the patients. The side effects are moderate, the local tumor control rate is between 78 to 100 %. Depending on the primary tumor the overall survival is prolonged statistically significant. In the Klinikum Krefeld indications of SBRT vs chemotherapy, LITT or resection are discussed by an interdisciplinary conference of gastroenterologists/oncologists, radiologists, radiooncologists and surgeons. An example of LITT will be shown also.

Female↗
PubMed2006

The controversy of donor serum sodium levels in heart transplantation--a multicenter experience.

BACKGROUND: Elevated donor serum sodium is a phenomenon often encountered in the management of brain dead donors. The clinical relevance on recipient outcome is less examined. We investigated the impact of elevated donor serum sodium levels (DSL) on outcome after heart transplantation in 1800 heart transplantations. METHODS: Data was conducted in a retrospective analysis from 1989 until 2005. The transplantations were performed at three German heart transplant centers. The joined database included DSL at the time of organ procurement, recipient and donor age, ischemia time, primary graft failure and survival data. RESULTS: Mean DSL was 147.7 +/- 10.3 l/l (range 111 - 208 l/l). Recipients were divided into 4 groups with percentiles of 141, 147, and 154 l/l resulting in DSL of A: 135.8 +/- 4.4, B: 143.6 +/- 1.7, C: 149.7 +/- 1.9, and D: 161.3 +/- 7.7 l/l for the four quartiles. Primary graft failure occurred in 2.6 % of the patients with A: 2.8 %, B: 2.8 %, C: 3.7% and D: 1.4 % ( P = n.s.). Mean 5- and 10-year-survival rates were 70.9 % (57.6 %) with A: 71.1 % (53.86 %), B: 69.3 % (53.9 %), C: 72.7 % (61.0 %), D: 71.2 % (62.4 %), respectively ( P = n. s.). In a multivariate analysis a significant impact on postoperative results could be revealed for recipient age ( P = 0.002), ischemia time ( P = 0.002) and donor age ( P = 0.009). DSL were no individual risk factor in the multivariate analysis. CONCLUSION: There was no impact of donor serum sodium levels neither on early postoperative results, nor on long-term outcome indicating that cardiac allografts from donors with elevated sodium levels might be transplanted successfully, achieving favourable results.

Adolescent↗
PubMed2005

Interferon (IFN)-gamma is a main mediator of keratinocyte (HaCaT) apoptosis and contributes to autocrine IFN-gamma and tumour necrosis factor-alpha production.

BACKGROUND: Apoptosis of keratinocytes or intestinal epithelial cells is an important pathophysiological mechanism of organ damage during acute graft-versus-host disease. OBJECTIVES: To analyse in detail the mediators and their mutual interaction leading to keratinocyte apoptosis. METHODS: Experiments were performed using a keratinocyte cell line (HaCaT) and human skin explant cultures. RESULTS: Supernatants (SN) of major histocompatibility complex nonmatched mixed lymphocyte cultures (MLCs) induced apoptosis in HaCaT cells and also in keratinocytes from skin biopsies. Although both interferon (IFN)-gamma and Fas ligand (FasL) were detected in MLC-SN by enzyme-linked immunosorbent assay, the apoptosis-inducing capacity could be fully abrogated by neutralization of IFN-gamma, but not by neutralization of FasL. Recombinant (r) IFN-gamma induced HaCaT keratinocyte apoptosis in a dose- and time-dependent manner. Induction of HaCaT apoptosis by rFasL alone was induced only at higher doses than present in MLC-SN, but apoptosis was dramatically enhanced in the presence of rIFN-gamma. Further synergistic effects with IFN-gamma in the induction of apoptosis were also observed with agonistic antitumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 antibody, soluble TRAIL and TNF-alpha. However, in contrast to FasL and TRAIL, TNF-alpha alone did not induce HaCaT apoptosis. Interleukin-1beta and lipopolysaccharide did not enhance the apoptosis-inducing effect of IFN-gamma. Beside its apoptosis-inducing capacity in HaCaT cells, rIFN-gamma also induced autocrine IFN-gamma production, and combined treatment with IFN-gamma and TNF-alpha induced autocrine TNF-alpha production. Neutralization of autocrine IFN-gamma protected HaCaT cells from apoptosis. CONCLUSIONS: Taken together, our data suggest a central role for IFN-gamma in HaCaT keratinocyte apoptosis but also show the importance of co-acting mediators such as TNF-alpha, TRAIL and FasL, which potentiate the effect of paracrine and autocrine IFN-gamma and TNF-alpha release.

Apoptosis↗
PubMed2004

[Long-term changes in peripheral blood leukocyte and lymphocyte populations in ENT-carcinoma patients. A flow cytometric study in 346 ENT-carcinoma patients and 31 healthy controls].

BACKGROUND AND AIM: The aim of this investigation was the quantification of leukocyte/lymphocyte populations in the peripheral blood of ENT-carcinoma patients before and long after therapy. PROBANDS AND METHOD: PBL T-lymphocytes and NK-cells were examined in 346 patients and 31 controls using flow cytometry. In 248 participants additional populations of leukocytes, monocytes, granulocytes, lymphocytes in toto, CD4+- and CD8+-lymphocytes, CD4+8+-lymphocytes, B-lymphocytes, activated T-lymphocytes, NK-cells and CD3+56+-T-lymphocytes were studied. RESULTS: We demonstrated a long-term reduction in T-lymphocytes (CD4+-lymphocytes) in patients more than 10 years after receiving therapy, caused mainly, but not solely, by radio/chemotherapy. We also showed a long-term, significant increase in NK-cells after more than 10 years in patients following therapy without renewed carcinoma in comparison to controls, patients prior to therapy or patients with a recurrence of carcinoma. CONCLUSIONS: Due to long-term deficits in CD4+-lymphocytes, and considering the possible protective effect of NK-cells in treated patients, an immune-supportive therapy is recommended.

Acute Disease↗
PubMed2002

The detection of apoptosis in a human in vitro skin explant assay for graft versus host reactions.

AIMS: Keratinocyte apoptosis is a major pathogenic mechanism in dermal complications, such as graft versus host disease (GVHD), after allogeneic bone marrow transplantation. However, the mechanisms by which recipient target cells undergo apoptosis in GVHD are still unclear, but may result from DNA damage caused by chemotherapeutic agents and/or by direct cytokine action. The basis of this investigation was to correlate keratinocyte apoptosis with (1) the severity of graft versus host reactions (GVHR) in vitro and (2) the clinical grade (0--III) of GVHD. METHODS: Skin sections generated from an in vitro skin explant model for detecting experimental or clinically relevant GVHR were investigated for the detection of apoptotic nuclei using the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) technique. This investigation also aimed to establish whether the TUNEL assay could be used as an additional, predictive method for the severity of GVHD before transplantation in potential patient/donor pairs given standard GVHD prophylaxis (cyclosporin A and methotrexate). RESULTS: By comparing mean values of apoptosis for each GVHR grade in a cohort of 83 retrospective skin sections it was shown that as the severity of GVHR increased there was a parallel increase in the percentage of apoptotic cells (p < 0.0001). However, the correlation between clinical GVHD grade II--III and overall keratinocyte apoptosis (> 2.6%) did not reach this degree of significance (chi(2): 4.2; degrees of freedom, 1; p = 0.04; Fisher's exact test: p = 0.06). CONCLUSIONS: The detection of apoptosis correlated with degree of GVHR using an in vitro assay and a higher degree of apoptosis tended to correlate with more severe GVHD. Further studies in a larger cohort of patients, using other methods to detect apoptosis in conjunction with the TUNEL assay, may give additional insight into the complex immunopathophysiology of GVHD.

Apoptosis↗
PubMed2001

The B-chain of mistletoe lectin I efficiently stimulates calcium signaling in human Jurkat T-cells.

Mistletoe lectin I (ML I), a heterodimeric disulfide-linked type II ribosome inactivating protein, exhibits immunomodulatory potency in stimulating the cytokine release in vitro and in vivo. However, data concerning early activation events in T-cells induced by ML I and its A and B chain preceding cytokine secretion and the receptors involved are of limited availability. Here we show by flow cytometric measurements that human T-lymphoblastoid Jurkat cells express surface glycoprotein receptors for ML I. One of which is shown to be the CD2 antigen involved in a variety of T-cell signaling events. The lectin induces in Jurkat T-cells an increase of the cytosolic calcium concentration ([Ca(2+)](i)) consisting of both, the transient release of Ca(2+) from internal stores and a sustained influx of extracellular Ca(2+). Studies with isolated A- and B-chains provided evidence that the lectin-induced increase in [Ca(2+)](i) is mediated by ML IB. The ML I and ML IB stimulated cellular calcium responses are inhibited by saccharidic competitors. In transiently transfected E6.1 cells ML IB stimulated the expression of the luciferase reporter construct pNFAT-TA-Luc that is activated through the nuclear factor of activated T-cells (NFAT). The ML IB stimulated expression of the reporter luciferase (Luc) is completely inhibited by cyclosporin A (0.2 microM) and by FK 506 at 0.05 microM. Pretreatment of Jurkat E6.1 cells with 1-deoxymannojirimycin (dMJ), an inhibitor of cis-Golgi alpha-mannosidase I, strongly reduced cell binding of ML IB-FITC and the ML IB induced calcium response. Benzyl-alpha-GalNAc, an inhibitor of O-linked glycosylation, has slightly decreasing effects in ML IB-FITC binding and was without effects on the lectin stimulated increase in [Ca(2+)](i). Inhibition of the lectin induced calcium responses by cholera toxin and by inhibitors of protein kinases as well as the absence of calcium responses in CD3- and CD45- Jurkat T-cell clones suggest that ML IB has the potency to induce early T-cell activation events.

Adjuvants, Immunologic↗
PubMed2001

Different types of human leukemias express the message for TNF-alpha and interleukin-10.

Leukemic cells proliferate under the influence of cytokines. In particular, the colony-stimulating factors stimulate the growth and proliferation of myeloid leukemia cells. Under normal conditions, tumor necrosis factor-alpha (TNF-alpha) is produced by activated monocytes, whereas interleukin- 10 (IL-10) is produced by several cell types like monocytes and lymphocytes. The autocrine production of cytokines by leukemic cells may have a pathogenic role in the progression of leukemia or may be an epiphenomenon. In this study, we investigated the expression of TNF-alpha and IL-10 in human leukemic cells by RT-PCR and by a cytoplasmic protein assay. Most cases of acute myelogenous leukemia (AML) (7/8 cases) and all cases of acute lymphoblastic leukemia (ALL) (n = 2), chronic myelogenous leukemia (CML) (n = 5), both in chronic phase and during blast crisis, expressed the mRNA for TNF-alpha and IL-10. A patient whose blasts were positive for IL-10 and negative for TNF-alpha, had high circulating levels of IL-10 and failed to respond to donor lymphocyte infusions. Using a cytoplasmic protein assay, generally low levels of cytoplasmic TNF-alpha and IL-10 were found which increased in case of TNF-alpha following stimulation with lipopolysaccharide. Taken together, our data show that most leukemic cells express the mRNA for a proinflammatory cytokine (TNF-alpha) and an immunosuppressive cytokine (IL-10). More work is necessary to determine under which conditions these cytokines actually paralyze the immune system and thereby permit the progression of leukemia.

Gene Expression Profiling↗
PubMed2001

Successful use of cardiac allograft from serotonin antagonist intoxication.

BACKGROUND: Compromised organ donors are generally not accepted for heart transplantation (HT) despite the increasing number of critically ill patients on the waiting lists. By extending the donor criteria to include certain cases of intoxication, the organ shortage may be reduced. METHODS: The case of a successful orthotopic HT with an allograft from a donor poisoned by antidepressant overdose is presented. RESULTS: Early graft function was satisfactory with anteroseptal dyskinesis and an ejection fraction of 75% on echocardiography. The cardiac allograft recipient suffered some postoperative complications including gastrointestinal problems. The following period was up to now uneventful. Discharge from the intensive care unit was after 4 days. In-hospital stay was prolonged at 26 days. CONCLUSIONS: Because of limited myocardial toxicity, donor hearts from certain victims of antidepressant intoxication may be safely used for HT. Existing cardiac organ donor criteria must be reevaluated to maximise the available organ pool.

Adult↗
PubMed2001

Spinal AVM, epidermal nevus, and rhabdomyosarcoma: A rare neurocutaneous syndrome?

A 26-year-old man with a history of an embryonal rhabdomyosarcoma arising from the urachus and a large, right-sided, epidermal nevus presented with a rapidly evolving tetraparesis. Investigations confirmed an intramedullary hemorrhage of the cervical spinal cord and an extensive arteriovenous malformation (AVM). An association between his nevus, rhabdomyosarcoma, and spinal AVM is hypothesized.

Adult↗
PubMed2001

Histological correlation between different centers using the skin explant model to predict graft-versus-host disease following bone marrow transplantation.

Acute graft-versus-host disease (GVHD) remains the major complication of allogeneic stem cell transplantation (SCT) with an incidence of 40-60% and a mortality of up to 50%. Several assays have been developed to try to predict the development of GVHD including the mixed lymphocyte culture reaction, cytotoxic and helper T lymphocyte precursor frequency assays. In the Northern region of England we have used an in vitro skin explant model for predicting GVHD in MHC compatible bone marrow transplant recipients since 1988. The aims of the present study was to test the reproducibility of the model in two other bone marrow transplant centers in Europe. The assay consists of incubating patient skin explants with effector cells from mixed donor versus recipient lymphocyte cultures and the subsequent detection of graft-versus-host reactions by histopathological grading (0-IV) of the skin explants. 503 slides from 134 patients were evaluated. All were graded for negative GVHR grade 0-I or positive grade II-IV. Results from control and test slides significantly correlated between centers to the p value of 0.0001 by Fisher's exact probability test. These results show that the skin explant assay is reproducible between centers and supports the continued use of the assay to predict GVHD in allogeneic stem cell transplant recipients.

Biopsy↗
PubMed2001

Outcome of heart transplantation in patients previously infected with hepatitis C virus.

The lack of knowledge about the course of hepatitis C virus infection (HCV) before heart transplantation (HTx) prompted us to describe our experience with 4 such patients who presented with positive HCV serology before surgery. Two experienced non-liver related deaths at 3.5 and 5 years after HTx, and none of the patients developed signs of hepatic insufficiency during the follow-up (mean 3.8 years). Tests for HCV antibodies were frequently negative, whereas viral RNA was detected in 81% of the measurements, showing that virus detection techniques seem to be more sensitive than serology techniques in detecting HCV infection in this group of patients. Although immunosuppression promotes active HCV replication, it does not seem to change the chronic features of HCV infection during the first years in patients with good liver function.

Adult↗
PubMed2000

High concentration of soluble HLA-DR in the synovial fluid: generation and significance in "rheumatoid-like" inflammatory joint diseases.

In the search for its role in inflammatory joint diseases, soluble HLA-DR (sHLA-DR) was quantitated in 72 synovial fluids (SF) by a newly established immunoenzyme assay. Unlike other soluble receptors which accumulated only moderately (sCD25, sCD4) or negligibly (sHLA class I, sCD8) in the SF, SF sHLA-DR levels exceeded serum levels by up to 3 orders of magnitude and varied disease dependently from "control" values (traumatic synovitis and osteoarthritis: 9.9 +/- 6.1 ng/ml). Clear-cut different SF sHLA-DR values in HLA-DR-associated "rheumatoid-like" (136.5 +/- 130.0 ng/ml) vs HLA-B27-associated "spondylarthropathy-like" arthritic forms (28.4 +/- 29.1 ng/ml) were most significant comparing oligoarticular juvenile chronic arthritis type I (147.6 +/- 112.6 ng/ml) and type II (3.3 +/- 1.1 ng/ml), thus offering a new classification marker. Also ex vivo, large amounts of sHLA-DR were released spontaneously by SF mononuclear cells and found to be related to the T-cell activation state. SF sHLA-DR may be shed in large complexes or micelles, as it eluted mainly at >450 kDa on gel filtration. Western blotting revealed that the majority of SF sHLA-DR consisted of full-length alpha- and beta-chains. Minor fractions of smaller sized antigens seemed to be generated by proteolytic cleavage rather than by alternative splicing, since only minute amounts of HLA-DRB mRNA lacking the transmembrane exon could be amplified by RT-PCR. Distinct forms of high-dose sHLA-DR, able to provoke rather than to suppress T-cell responses, are discussed as contributing to some HLA-DR disease association.

Adolescent↗
PubMed2000

Human GRB10 is imprinted and expressed from the paternal and maternal allele in a highly tissue- and isoform-specific fashion.

As part of a systematic screen for novel imprinted genes of human chromosome 7 we have investigated GRB10, which belongs to a small family of adapter proteins, known to interact with a number of receptor tyrosine kinases and signalling molecules. Upon allele-specific transcription analysis involving multiple distinct splice variants in various fetal tissues, we found that human GRB10 is imprinted in a highly isoform- and tissue-specific manner. In fetal brains, most variants are transcribed exclusively from the paternal allele. Imprinted expression in this tissue is not accompanied by allele-specific methylation of the most 5' CpG island. In skeletal muscle, one GRB10 isoform, gamma1, is expressed from the maternal allele alone, whereas in numerous other fetal tissues, all GRB10 splice variants are transcribed from both parental alleles. A remarkable finding is paternal-specific expression of GRB10 in the human fetal brain, since, in the mouse, this gene is transcribed exclusively from the maternal allele. To our knowledge, this is the first example of a gene that is oppositely imprinted in mouse and human.

Abnormalities, Multiple↗