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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 55 records · Page 3Linked to original sources

Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma.

Pancreatic cancer can seldom be resected, and chemotherapy has only a limited effect on survival or tumour load. We did a phase I/II trial in 14 patients with pancreatic cancer to assess the safety of local activation of low-dose ifosfamide. We encapsulated genetically modified allogeneic cells, which expressed a cytochrome P450 enzyme, in cellulose sulphate and delivered them by supraselective angiography to the tumour vasculature. These cells locally activated systemically administered ifosfamide. The tumours of four patients regressed after treatment, and those of the other ten individuals who completed the study remained stable. Median survival was doubled in the treatment group by comparison with historic controls, and 1-year survival rate was three times better. Further studies of this cell-therapy-based treatment combined with chemotherapy for inoperable pancreatic cancer are warranted.

Adenocarcinoma↗

[Costs of type 2 diabetes in Germany. Results of the CODE-2 study].

BACKGROUND AND OBJECTIVE: Diabetes is an increasing and widespread chronic disease causing considerable costs for the health care system. In the CODE-2 Study (Costs of Diabetes in Europe-Type 2) the total expenses for type 2 diabetics in Germany were evaluated and analyzed for the first time. PATIENTS AND METHODS: The CODE-2-study has been performed in eight European countries. In the German arm of the study, medical, demographic, and economic data of 809 patients were obtained retrospectively for a one year period, using face-to-face interviews with 135 physicians. These results were projected for the overall population of type 2 diabetes patients in Germany. RESULTS: The annual costs caused by type 2 diabetes patients in Germany in 1998 amount to 31.4 billion DM. The majority of these costs (61%) were covered by statuatory and private health insurance. The annual expenses of the statuatory Health Insurance (SHI) for these patients amounted to 18.5 billion DM. These costs divided in 50% spent for inpatient treatment, 13% for ambulatory care, and 27% for medication. Diabetes medication (insulin, oral antidiabetic drugs) accounted for only 7% of total SHI costs. Only 26% of all diabetic patients were adjusted to HbA1c values < 6.5% according to the therapeutic targets of the European Diabetes policy group. 50% of the type 2 diabetic patients exhibited severe macro- and/or microvascular complications. The costs per patient--compared to the average expenses for SHI insured patients--increased with complication state from the 1.3-fold (no complications) up to the 4.1-fold (macro- and microvascular complications). CONCLUSIONS: The overall costs for patients with type 2 diabetes are higher than expected from previous estimates. Diabetes related complications and concomitant diseases are the predominant reasons for these high costs. Control of blood glucose is inadequate for the majority of diabetic patients. To prevent long-term complications, an optimized treatment of type 2 diabetes is imperative not only from a medical but also from a health economics point of view.

Adult↗

In vivo laser-induced interstitial thermotherapy of pig liver with a temperature-controlled diode laser and MRI correlation.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of a new temperature-controlled Diode laser to generate in vivo tissue coagulations with laser-induced interstitial thermotherapy (LITT) in pig liver and MRI-correlation of these necroses. STUDY DESIGN/MATERIALS AND METHODS: Each of four animal subjects received eight treatments at four different constant temperatures (70, 80, 90, and 100 degrees C) and at two out of three different intervals (3, 6, 9 minutes), resulting in a total of 32 lesions. After sacrificing, the liver was examined in an open MRI (0.35T). Tissue necrosis was measured macroscopically and compared with the size measured by MRI. RESULTS: The size of the necrosis was energy dependent with the largest extent at 100 degrees C at 9 minutes (2.1 cm). The correlation between macroscopic lesion size and MRI findings was significant (P > 0.036). Histological workup excluded carbonization in every case. CONCLUSIONS: LITT carried out with the Diode laser provides reproducible necroses of pig liver in vivo. MR-imaging results compared favorably with those obtained by pathologic specimens.

Animals↗

Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel's thyroiditis) caused by an occlusive vasculitis.

Riedel's thyroiditis is a rare disease determined by an invasive fibrosclerotic transformation of the thyroid gland. It may be one manifestation of multifocal fibrosis with still unknown etiology. Because it mimics carcinoma, a biopsy must be performed to get the correct diagnosis. The condition is self-limiting when confined to the neck. Prognosis depends on the extent of extracervical fibrosclerosis. We present a patient with a huge cervical and mediastinal, unilateral thyroid mass expanding to the aortic curve, which led to tracheal deviation and compression with symptoms of stridor and dyspnea. These symptoms continued under a course of high-dose steroids; thus an operation was necessary to relieve the airway obstruction and limit inflammation. Intraoperative and pathological findings showed an inflammatory infiltration of the adjacent neck muscles and a sterile abscess caused by an occlusive vasculitis. Therefore, hemithyroidectomy had to be performed instead of a local limited resection.

Abscess↗

[Primary renal hemangiosarcoma. Case report and review of the literature].

Primary hemangiosarcoma of the kidney is a very rare tumor for which only 23 case reports appear in the literature worldwide. An additional case of renal angiosarcoma in an adult is reported. The patient developed local tumor recurrence with multiple metastases within 4 weeks and died although there was no evidence of metastases at the time of nephrectomy.

Adult↗

Percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas.

The objective of this study was to evaluate the sensitivity and specificity of percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas. In a 1-year period 158 image-guided percutaneous core-needle biopsies of enlarged lymph nodes were performed on 149 consecutive patients using a Tru-cut needle fired by a biopsy gun. In 135 cases the biopsy findings could be confirmed by histologic examination of additional tissue samples (n = 59) or by correlation with the patient's clinical and radiologic course (n = 76). The final diagnoses were malignant lymphoma in 65 cases, leukemic nodal infiltration in 2, nodal metastases from a solid tumor in 37 and benign changes or no evidence of malignancy in 31 cases. The core-needle biopsies correctly diagnosed 58 of 65 malignant lymphomas, corresponding to a sensitivity of 89% and a specificity of 97%. Fifty-five of the 58 (95%) correctly diagnosed malignant lymphomas could be subclassified on the basis of the core-needle biopsy. Image-guided core-needle biopsy of enlarged lymph nodes with a Tru-cut needle is a useful method for the diagnosis and subclassification of malignant lymphomas.

Adolescent↗

Oxidative pentose phosphate pathway and pyridine nucleotides in relation to heartwood formation in Robinia pseudoacacia L.

Most tree species show in the inner parts of their woody axes often a dark colored zone, the heartwood. Its formation is a genetically determined, programmed cell death which is characterized by the activation of metabolic pathways which lead to the formation of phenolic heartwood extractives. In the present paper we report on the key position of the oxidative pentose phosphate pathway (OPP) for this process. The OPP plays a crucial role in anabolic processes and is involved in the interconversion and rearrangements of sugar-phosphates with the net production of NADPH. In tissues of Robinia pseudoacacia L. which are transferred to heartwood, enhanced activities of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) are present. A consequence of these increased enzyme activities is a shift in the pyridine nucleotide pool towards NADP+NADPH at the expense of NAD+NADH. These alterations in the metabolism and the redox status probably provide precursors and reduction equivalents being required for the synthesis of heartwood phenolics. The non heartwood forming species Acer pseudoplatanus L. shows neither a radial gradient nor seasonal changes in the amounts of pyridine nucleotides across the trunkwood. The results are discussed in connection with programmed cell death, mitochondrial activity, and heartwood formation.

Catalysis↗

Gravity sensing in moss protonemata.

Moss protonemata are a valuable system for studying gravitropism because both sensing and upward curvature (oriented tip growth) take place in the same cell. We review existing evidence, especially for Ceratodon purpureus, that addresses whether the mass that functions in sensing is that of amyloplasts that sediment. Recent experiments show that gravitropism can take place in media that are denser than the apical cell. This indicates that gravity sensing relies on an intracellular mass rather than that of the entire cell and provides further support for the starch-statolith hypothesis of sensing. Possible mechanisms for how amyloplast mass functions in sensing and transduction are discussed.

Bryopsida↗

Activation of the dopaminergic system of medial prefrontal cortex of gerbils during formation of relevant associations for the avoidance strategy in the shuttle-box.

1. A detailed analysis of behavior is a prerequisite for identification of components of information processing during learning. 2. Components of shuttle-box learning like the signal detection and signal evaluation can be differentiated using behavioral events such as the attention response and the orienting response. 3. Chiefly during evaluation of signal meaning in the acquisition phase of the avoidance strategy the extracellular DA is increased in mPFC. 4. The kinetics of prefrontal dopaminergic activation from trial to trial depends on the stage of avoidance learning. 5. The increase of DA in mPFC can be an indicator for the involvement of working memory principles in signal evaluation stages of conditioning.

Animals↗

A novel HLA-DRB1 sequence, DRB1*11272.

We describe the complete exon 2 sequence of a novel HLA-DRB1 allele, DRB1*11272. This allele differs from the DRB1*11271 allele by a synonymous mutation in codon 77 where an AAT is replaced with AAC, both encode for the amino acid asparagine. The same motif at codon 77 has also been found in DRB1*1107, DRB1*1333, DRB1*0422 and in most DRB1*03 alleles. A partial exon 2 sequence of this allele has previously been deposited in the EMBL Sequence Database under the accession number AF186407.

Alleles↗

Long-term combination of interferon alfa-2b and ribavirin for hepatitis C recurrence in liver transplant patients.

The purpose of this study was to evaluate the feasibility, tolerability and efficacy of long-term combination therapy with interferon-alfa 2b (IFNalpha-2b) and ribavirin (Rb) for recurrent hepatitis C after liver transplantation. Fifteen patients with histologically confirmed hepatitis C after liver transplantation were treated. After a basic course of 12 months (IFNalpha-2b 3 MU/3 times a week; Rb 3 x 200 mg/day), patients achieving clearance of viremia underwent maintenance therapy with ribavirin (3 x 200 mg/day). Patients without virological response continuously received combination therapy. Levels of HCV RNA, aminotransferases and bilirubin were followed. Therapy led to a significant decline of transaminases and bilirubin in all patients (p < 0.05). Sixty-four per cent of patients had clearance of viremia after 12 months. Sustained virolo gical response was 88%. In patients without virological response, continuation of combination therapy prevented another biochemical relapse of hepatitis. Treatment was accompanied by severe hematological side-effects, requiring medical support in a majority of patients. In two patients (13.5%), therapy finally had to be withdrawn because of major hematological disorders. These results indicate that long-term combination therapy with IFNalpha-2b and Rb is effective in the treatment of recurrent hepatitis C and in preventing further relapse of disease after liver transplantation, but side-effects may require cessation of therapy.

Adult↗

Immune reconstitution and production of intracellular cytokines in T lymphocyte populations following autologous peripheral blood stem cell transplantation.

For the better understanding of engraftment properties after autologous peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery, immune reconstitution and functional capacity of cytokine production in different lymphocyte populations were examined. In a prospective study, we examined 24 patients suffering from different malignancies after autologous PBSCT. The examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells and NK cells were analyzed using flow cytometry. The expression and kinetics of cytokines in T lymphocytes were evaluated in 10 patients by intracellular staining of cytokines after PMA/ionomycin stimulation. We observed rapid hematopoietic engraftment proceeding to stable long-term reconstitution. For CD3(+) lymphocytes, a consistent reconstitution associated with an increase in CD3(+)CD8(+) cytotoxic T cells was observed, whereas the CD3(+)CD4(+) helper/inducer T cells remained low (< 200/microl). Impaired B lymphopoiesis with severe depression (<1%) was detected 1 month after PBSCT but recovered thereafter (12.8% after 3 months). The percentages of cytokine-producing T cells and the mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for producing IFNgamma, in particular for CD3(+)CD4(+) T cells, compared to healthy volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired immune reconstitution, especially regarding the regeneration of B lymphocytes and T helper cells, was observed. The CD4(+) subpopulation remained low throughout the period of examination, whereas the B cells showed a delayed recovery after 3 months. Cytokine production proved to be sufficient after in vitro stimulation in T cell populations with the exception of IFNgamma synthesis.

Adult↗

Kinetics of CFU-Mk after automated plateletpheresis.

BACKGROUND AND OBJECTIVES: Platelet count, thrombopoetin (TPO) level and the compartment of megakaryocyte progenitor cells (CFU-Mk) are major determinants in the regulation of thrombopoiesis. The aim of this study was to investigate the potential changes in the compartment of CFU-Mk and their correlation with serum TPO levels and platelet count after plateletpheresis. MATERIALS AND METHODS: Twelve healthy individuals were randomly assigned to undergo single-donor plateletpheresis. A collagen-based in vitro culture system was used to determine the number of peripheral blood (PB) CFU-Mk before and after donation and on days 1, 4 and 7 thereafter. TPO levels were measured by a specific enzyme-linked immunosorbent assay and whole blood counts were performed using an automated cell counter. RESULTS: The pre-apheresis platelet count (mean +/- SEM: 276 +/- 13 x 10(9)/l) decreased after plateletpheresis to a nadir of 194 +/- 8 x 10(9)/l (P < 0.001), showed a gradual increase on days 1 and 4, and reached pre-apheresis values by day 7 (280 +/- 11). The serum TPO levels were found to be significantly increased on days 1 and 7 as compared to baseline levels (baseline value 103.3 +/- 18.5 pg/ml versus day-1 value 135.8 +/- 25.8 pg/ml and day-7 value 132 +/- 30.19 pg/ml; P < 0.03 and P < 0.03, respectively). The numbers of CFU-Mk in PB were significantly elevated on day 4 only (125 +/- 21 colonies/ml of PB versus pre-apheresis values of 68 +/- 18 colonies/ml of PB, P < 0.005). CONCLUSIONS: These findings suggest that platelet loss during plateletpheresis affects thrombopoiesis at the progenitor cell level, probably through alterations in TPO plasma concentrations.

Blood Cell Count↗

Miniaturized tests for computer-assisted identification of motile Aeromonas species with an improved probability matrix.

AIMS: To develop miniaturized tests for the phenotypic identification of motile Aeromonas species using an improved probability matrix. METHODS AND RESULTS: Conventional tests were miniaturized for use in 96-well plates, and their performance assessed using 60 aeromonads comprising type and reference strains as well as clinical, fish and water isolates. A revised probability matrix for Aeromonas hybridization groups 1-14, including A. allosaccharophila, A. bestiarum, A. encheleia and A. popoffii, was developed. Using 26 tests, all the reference strains were correctly identified with the revised probability matrix, and 80% of the isolates were correctly identified at a Willcox probability level of 95%. CONCLUSION: The compact test format, coupled with a robust identification matrix, provides a convenient basis for identifying motile aeromonads. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification system for identifying aeromonads will be of use to medical and veterinary laboratories undertaking disease diagnosis.

Aeromonas↗

RHD sequencing: a new tool for decision making on transfusion therapy and provision of Rh prophylaxis.

The serological differentiation of weak D from partial D, D-negative and D-positive is not always unequivocal. Therefore, sequencing of the RHD gene is required in some cases. Very recently, several new differences between RHD and RHCE have been identified which permitted us to design primers close to the exon/intron boundaries of the RHD-exons. We evaluated these primers in 83 D-positive and 18 D-negative blood donors and applied the new method for the characterization of the RHD gene in six individuals with weak D phenotype. The amplification reactions were concordant with serological findings in 100 of 101 donors (99.0%). In one D-positive donor the PCR for exons 2 and 5 gave a negative result, while the sequence of the remaining eight exons was unchanged. By sequencing samples with very weak D serological reactions, we identified weak D type 4.2.2 and weak D type 15, both previously reported to be associated with anti-D-alloimmunization. Consequently, we recommended the selection of D-negative blood in the weak D type 4.2.2 patient, and the provision of Rh prophylaxis for pregnant women with weak D type 15. In summary, a new RHD sequencing method was developed which can be applied if serological reactions are inconclusive.

Blood Donors↗

Transdermal fentanyl: little absorption in two patients with systemic sclerosis?

Two patients suffering from systemic sclerosis (SSc) were treated with the 25 micro/hr transdermal fentanyl patch for pain from either deltoid muscle tendinitis of the left arm or from ischemia of the left-hand thumb. When the medication was changed to either oral morphine or oral methadone, the effects did not correspond to the drug conversion table. These findings suggest that patients with SSc and other systemic skin diseases may be at risk for limited absorption of transdermal fentanyl. In contrast, no restriction of the absorption of transdermal testosterone was observed.

Journal Article↗