Biomedical subjects

C Teschendorf

Publications and source records attributed to C Teschendorf.

10 recordsLinked to original sources

PubMed2005

[Colorectal carcinoma in elderly patients].

The median age of patients with newly diagnosed colorectal carcinoma is about 70 years. Due to a steady rise of the life expectancy in the Western world the group of patients being older than 70 to 75 years will grow substantially. This will result in increased numbers of colorectal cancers. Patients in this age group are underrepresented in controlled clinical trials if not excluded to begin with. This is particularly true for trials conducted for adjuvant or palliative chemotherapy for colorectal cancer. Partly due to this lack of data leading to uncertainty chemotherapy is offered tients. However, the present data for patients >70 years show equall effectivity with regard to tumor response. This is true for all standard chemotherapy agents, such as 5-FU, folinic acid, capecitabine, irinotecan and oxaliplatin. With respect to toxicity some trials show an increased risk in toxic side effects for 5-FU-based combination therapies. There are no age-specific differences for the other drugs. Therefore, patients who are older than 70 years should be offered state-of-the-art chemotherapy in the adjuvant as well as palliative setting. For a balanced treatment decision one has to take into account the overall performance and organfunction alongside the mental and social capacity of the elderly patient.

Aged↗

PubMed2004

5-Fluorouracil induces arterial vasocontractions.

BACKGROUND: From 2% to 10% of cancer patients treated with 5-fluorouracil (5-FU) will develop symptomatic cardiotoxicity. Nevertheless, the underlying pathophysiology is mostly unknown. PATIENTS AND METHODS: We investigated the influence of intravenous chemotherapy (CTX) on the diameter of the brachial artery using high resolution ultrasound in patients with malignant tumors, mostly gastrointestinal cancer. Cytostatic drugs included 30 cases with 5-FU and 30 cases with non-5-FU CTX (cis/carboplatin, anthracycline and cyclophosphamide). In addition, plasma levels of big endothelin were assessed prior to and after CTX. RESULTS: Fifteen of 30 patients (50%) showed a contraction of the brachial artery after the end of 5-FU application (median 11%, range 4.3-18.5), whereas no single contraction was noticed in 30 patients following non-5-FU-based CTX. Vessel tonus generally normalized within 30 min after stopping 5-FU. Five patients positive for 5-FU associated vessel contraction were repeatedly exposed to 5-FU. Vessel contractions reoccurred in 86% (18/21) of these administrations. When patients with 5-FU bolus application were pre-treated with glyceroltrinitrate no contraction of the brachial artery was detected in five out of five occasions. There was a trend towards increased big endothelin plasma levels after 5-FU application (median 1.52 versus 1.99 fmol/ml; P = 0.07), whereas big endothelin levels remained unchanged after non-5-FU CTX (1.83 versus 1.83 fmol/ml; P = 0.99). CONCLUSIONS: Application of 5-FU is commonly accompanied by arterial vessel contractions, which is likely to represent the first step in 5-FU-induced cardiotoxicity. 5-FU-associated vessel contractions were highly reproducible on re-exposure and were in the case of bolus application completely preventable by glyceroltrinitrate.

Adult↗

PubMed1998

Developing VDEPT for DT-diaphorase (NQO1) using an AAV vector plasmid.

PURPOSE: One enzyme/prodrug combination that has the potential to be used in virally directed enzyme/prodrug therapy (VDEPT) is the obligate 2-electron reducing enzyme, DT-diaphorase (NQO1), with bioreductive agents such as EO9. The present studies were undertaken to determine if this enzyme, as well as the reporter molecule, green fluorescent protein (GFP), could be expressed from a single dicistronic unit under control of the CMV promoter in an adeno-associated virus (AAV) background. METHODS: The human ovarian tumor cell line, SAU, and the mouse sarcoma cell line, KHT/iv, were studied due to their low level of NQO1 expression. These cells were transfected with pTRUF3-NQO1 using a liposome-mediated protocol. RESULTS: The results indicate that this construct has the ability to increase the total protein level of NQO1 by 66-fold in SAU and 102-fold in KHT/iv after 24 h. Furthermore, the level of NQO1 activity in SAU increased from undetectable levels to approximately 200 nmol/min/mg, and the NQO1 activity in KHT/iv increased approximately 10-fold following transfection. Expression of the GFP reporter was readily detectable in both cell types using FACS analysis. CONCLUSIONS: Taken together, these results indicate that this proviral AAV vector plasmid will allow for the production of a recombinant AAV, which can coordinately express the enzyme NQO1 and the GFP reporter for use in vivo in VDEPT studies with various bioreductive agents which are substrates for NQO1.

Animals↗

PubMed1998

c-kit mutation and osteopetrosis-like osteopathy in a patient with systemic mast cell disease.

We describe the case of a 69-year-old man with systemic mastocytosis and severe osteopetrosis who carries a somatic activating mutation in the c-kit proto-oncogene. The patient initially presented with urticaria pigmentosa, progressing to systemic mast cell disease with severe anemia due to bone marrow involvement, chronic diarrhea, and hepatosplenomegaly. Direct sequencing using amplimers from reverse transcriptase-polymerase chain reactions (RT-PCR) from skin mast cell-derived RNA revealed a point mutation in the c-kit proto-oncogene at position 2468, introducing a new recognition site for the restriction endonuclease HinfI. Treatment with interferon-alpha 2a, prednisone, and erythropoietin was initiated. Subsequently, clinical symptoms improved significantly and hemoglobin levels are now stable at 13 g/dl.

Aged↗

PubMed1998

A fluid-filled condom causing intestinal obstruction: nonsurgical therapy of an ileus by ultrasound-guided transabdominal tapping.

Ingested foreign bodies are rare causes of intestinal obstruction in the adult. Condoms, if swallowed, are usually filled with drugs and found in body packers as a vehicle for drug smuggling. We report the case of 31-year-old male who presented with symptoms and signs of intestinal obstruction. He had swallowed a fluid-filled condom the day before. Ultrasonography of the abdomen revealed a fluid-filled foreign body within the small bowel. Due to radiological signs of an ileus and due to the fact that the patient's symptoms did not resolve after spasmolytic therapy the condom was tapped transcutaneously under ultrasonographical guidance. This procedure immediately relieved his symptoms. The further course was uneventful.

Abdominal Pain↗

PubMed1996

Differential effect of the activation of protein kinase A on the protein synthesis and secretion in the T-helper 2 cell line D10.G4.1.

The authors analysed the effect of protein kinase A (PKA) activation on the protein synthesis and secretion in the T-helper 2 cell line D10.G4.1 (D10) using an assay that allows the detection of almost all secreted proteins of a cell. IL-4 and IL-10 were quantified. Three groups of secretory products could be defined. The T-cell receptor (TCR)-induced production of the first group (A) of proteins including IL-4 was enhanced by low concentrations of PKA activators. At higher concentrations the enhancement was less marked. The synthesis and secretion of a second group (B) of proteins including IL-10 remained unaffected. The production of a third group (C) of proteins was inhibited in a concentration-dependent manner. Biochemical analysis revealed a block of phospholipase C gamma (PLC gamma) activity by PKA activators. When D10 cells were stimulated by a phorbol ester plus calcium ionophore the production of group A proteins was enhanced almost fourfold, whereas production of group B proteins was unaffected by PKA activation. This effect was observed at all concentrations of various PKA activators tested. The secretion of group C proteins was no longer inhibited. The same results were obtained when analysing IL-4 and IL-10 m-RNA by Northern blotting. The data demonstrate a lymphokine specific mode of action on a single cell basis. Furthermore, it suggests that the inhibitory action of PKA in D10 cells is due partly to blocking of PLC gamma activity.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Primary non-Hodgkin's lymphoma of the vagina. Case report and review of the literature.

The genital tract as primary site of malignant non-Hodgkin's lymphoma in women is extremely rare, whereas secondary involvement in advanced disease is found in about 40% of cases. In this report a patient is presented who had a primary vaginal non-Hodgkin's lymphoma of the centroblastic type according to the Kiel classification, with an excellent response to cytotoxic chemotherapy (CHOP) and event-free disease for 3 years. A review of the literature shows that favorable prognosis of localized disease seems to be a common experience. Primary involvement of the vagina can be successfully treated by pelvic irradiation, but in young women cytotoxic chemotherapy should be considered to preserve fertility.

Adult↗

PubMed1995

Recovery by splenectomy in patients with relapsed thrombotic thrombocytopenic purpura and treatment failure to plasma exchange.

Thrombotic thrombocytopenic purpura is a serious, potentially fatal disease, and conventional plasma exchange appears to be the best initial therapy. Following this approach, survival in 90% of patients is available. In patients with relapse and treatment failure to plasma exchange, splenectomy is recommended. The rationale for splenectomy and the relevant pathomechanisms involved are obscure. In the present paper two patients with TTP are reported who first responded to conventional treatment strategies but later relapsed. Resumption of previous therapy was not able to continuously maintain normal platelet levels. Thus, splenectomy was considered to be indicated. In contrast to former reports, repeated cycles of conventional plasma exchanges were performed until a transient steady state (12 hrs) of the platelet counts occurred. Then splenectomy was performed immediately and, in contrast to former reports, no reinstitution of treatment was necessary after splenectomy. In addition no postoperative complications (bleeding, neurologic impairment) have been observed. This favorable outcome might be due to the strategy of repeated conventional plasma exchange procedures. The follow-up shows now event free disease for 2 years.

Adrenal Cortex Hormones↗

PubMed1995

Hyperviscosity syndrome: efficacy and comparison of plasma exchange by plasma separation and cascade filtration in patients with immunocytoma of Waldenström's type.

The hyperviscosity syndrome is a common problem in patients suffering from IgM paraproteinemia. In this situation cytotoxic chemotherapy alone is insufficient and additional plasma therapy is required. Until recently, conventional plasma exchange was the only plasma therapy available. While this method has proven its efficacy, it eliminates proteins unselectively. Cascade filtration, on the other hand, has been established to remove proteins as a function of their size offering the prospect of a highly selective withdrawal of macromolecules. In the work presented, the efficacy of conventional plasma exchange and cascade filtration was evaluated performing both techniques at random in cases of hyperviscosity syndrome due to immunocytoma of Waldenström's type (n = 11/group). In these patients, conventional plasma exchange decreased plasma viscosity by 48%; cascade filtration was less effective (26%), correlating with a smaller decrease of IgM (conventional plasma exchange 42% vs cascade filtration 27%). The profile of other plasma proteins studied did not change significantly with either treatment. Furthermore, we observed no differences regarding serious side-effects. In conclusion, we could not demonstrate a superior effect of cascade filtration as compared to conventional plasma exchange in the treatment of hyperviscosity syndrome.

Aged↗

PubMed1993

Detection of distinct sets of newly synthesized polypeptides in supernatants of TCR-triggered T cell clones. Implication for the search for new lymphokines.

Using metabolic radiolabelling of proteins, which are newly synthesized during TCR-triggered T cell activation we were able to visualize distinct patterns of secreted polypeptides (with molecular weights ranging from 6 to 44 kDa) in supernatants of different T helper-1, T helper-2 and cytotoxic T cell clones. Most of these detected proteins are secreted in response to TCR-crosslinking (or to combined action of PMA and A231287), in an extracellular Ca(2+)-dependent manner and their appearance in supernatants was completely blocked by the addition of RNA synthesis or protein synthesis inhibitors or EGTA. Cyclosporin A (CsA) blocks secretion of several detected polypeptides, but does not affect TCR-triggered synthesis and secretion of others reflecting the existence of TCR-triggered, CsA-insensitive protein synthesis and secretion pathway. The insensitivity of secretion of several easily detectable polypeptides to inhibition by CsA offers a promising approach to further define the CsA-resistant and calcineurin-independent molecular pathways of TCR-triggered T cell activation. Several lymphokines (e.g., interferon-gamma, tumor necrosis factor, interleukin-4 and interleukin-10) are identified among the visualized set of secreted polypeptides. Since other, yet unidentified, secreted polypeptides in the same set of secreted proteins share important properties with known lymphokines it seems promising to use described approach in search for new lymphokines.

Animals↗