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D Jäger

Publications and source records attributed to D Jäger.

At least 73 records · Page 4Linked to original sources

[Penetrating duodenal ulcer as a complication of a hepatic artery port catheter in hepatic metastasis of sigmoid carcinoma].

CASE REPORT: We report a typical complication of hepatic artery infusion therapy (HAI) in a patient with colon cancer metastatic to the liver. One year after the last HAI-therapy the patient presented with upper gastrointestinal bleeding. Endoscopy showed a large duodenic ulcer penetrating into an adjacent hepatic colon cancer metastasis. The hepatic artery catheter was visible at the ground of the duodenic ulcer. CONCLUSION: Thirty-five percent of patients under HAI-therapy develop gastric/duodenic ulcers. The severity of the HAI complication presented here, however, is quite uncommon.

Adenocarcinoma↗

Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma.

Peptides derived from melanocyte differentiation antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma Regression of antigen-expressing tumors as well as selection of antigen-loss variants in the presence of antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte differentiation antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing antigen-positive tumors in the presence of antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated antigens need to be considered in attempts at making vaccination more effective.

Adult↗

Reproducibility and validity of electric source localisation with high-resolution electroencephalography.

The present study investigates the reproducibility and validity of the EEG source localisation of somatosensory evoked potentials (SEPs) using high-resolution EEG (61 scalp electrodes) and a source reconstruction on the basis of the individual brain morphology as obtained from magnetic resonance images (MRIs). The somatosensory evoked potentials (SEPs) to electrical stimulation of the right median nerve were repeatedly collected from the scalp of one healthy subject in 9 replications run on 9 different days. The source reconstruction for the 19 ms SEP component was performed by using a single moving dipole model as a source model. Two different head models were used: a spherical 3 shell model and a more realistically shaped 3 compartment model computed using the boundary element method (BEM). The source locations of the 19 ms SEP component were found to be highly reproducible using both head models: the mean standard deviation of the dipole locations was found to be 2.6 mm for the 3 shell model and 4 mm for the more realistically shaped head model. By projection into the individual MRI, the dipoles resulting from either head models were found to be located within the postcentral gyrus. The electric source locations were consistent with the maximum of the task-specific changes seen in a functional magnetic resonance imaging (fMRI) experiment when using the same somatosensory stimulation protocol.

Brain Mapping↗

The effect of hypericum extract on cardiac conduction as seen in the electrocardiogram compared to that of imipramine.

The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a randomized, double-blind, multicenter treatment study of 209 patients suffering from depression. ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine. At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings. In the first ECG analysis comparing high dose hypericum extract with imipramine, a prolongation of the conduction intervals PR, QRS and QTc was found for imipramine. In contrast, a small acceleration of conduction was seen for the high-dose hypericum extract. The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract. It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract. The reduction in pathological ECG features after treatment with hypericum extract may have resulted mainly from the change of medication, probably tricyclics, to hypericum extract. Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients, high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants.

Adult↗

Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo.

Peptide epitopes derived from differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for MHC-restricted cytotoxic T lymphocytes (CTL). The characterization of multiple CTL-defined antigenic determinants has opened possibilities of development of antigen-targeted vaccines. In the present study, we determined CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase, and gp100/Pmel17 in 3 HLA-A2+ melanoma patients. Then, we assessed the immune responses to synthetic melanoma-associated peptides injected intradermally. After 3 cycles of immunization with peptide alone, we used systemic GM-CSF as an adjuvant during the fourth cycle of immunization. Enhanced DTH reactions and CD8+ CTL responses were observed after treatment with systemic GM-CSF. Immunohistochemical characterization of DTH-constituting elements revealed infiltrates of CD4+ and CD8+ T lymphocytes and strong expression of IL-2 and gammaIFN, suggesting the activation of CD4+ ThI and CD8+ CTL by peptides presented by MHC-class-I molecules of dermal APC. Objective tumor regression was documented in all patients. We conclude that systemic GM-CSF enhances immune responses to melanoma-associated peptides and supports CTL-mediated tumor rejection in vivo.

Adjuvants, Immunologic↗

Cytolytic T cell reactivity against melanoma-associated differentiation antigens in peripheral blood of melanoma patients and healthy individuals.

Antigenic peptides derived from several differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs). To examine their potential role in tumour-directed immune responses in vivo, we determined CTL reactivity against seven antigenic peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens in the peripheral blood of 10 HLA-A2+ healthy controls and 26 HLA-A2+ melanoma patients. The influenza matrix peptide (GILGFVFTL) presented by HLA-A2.1 was used as a control peptide. CTL reactivity was assessed in a mixed lymphocyte 'peptide' culture assay. Reactivity against Melan A/MART-1-derived peptide antigens was readily detectable in both melanoma patients and controls. Reactivity directed against tyrosinase-derived peptide antigens was also detected in both melanoma patients and healthy individuals, but less frequently. A measurable response against gp100/Pmel17-derived antigens was found in 1/10 controls and in 1/26 of the melanoma patients. Reactivity against the influenza matrix peptide was common in both melanoma patients and controls. Our findings show that precursor CTLs against melanocyte differentiation antigens can be detected in peripheral blood of melanoma patients and healthy individuals. The pattern of CTL reactivity directed against melanoma-associated antigens does not seem to be altered in melanoma patients. Despite antigen-specific CTL reactivity, tumour growth was not prevented in melanoma patients and autoimmune phenomena were not detected in healthy individuals. It remains to be determined whether precursor CTLs recognizing melanocyte differentiation antigens can be activated by immunization and lead to effective tumour rejection in vivo.

Amino Acid Sequence↗

Temporal and spatial distribution of V-ATPase and its mRNA in the midgut of moulting Manduca sexta.

The spatial and temporal distribution of the plasma membrane V-ATPase and its encoding mRNA in the midgut of Manduca sexta were investigated during the moult from the fourth to the fifth larval instar. Digoxigenin-labelled RNA probes were used for in situ hybridization of V-ATPase mRNA of both peripheral and integrated subunits; monoclonal antibodies to subunits of the peripheral sector of the purified plasma membrane V-ATPase were used for immunocytochemistry. Extensive mRNA labelling was found in both mature columnar and goblet cells of intermoult and moulting larvae. Hybridization screening in several tissues suggested that only cells with increased V-ATPase biosynthesis were labelled by our hybridization method. Mature goblet cells contain a large amount of V-ATPase in the apical plasma membrane and were therefore expected to contain V-ATPase mRNA. The intense mRNA signal found in mature columnar cells was unexpected. However, after refining the techniques of tissue preparation, immunolabelling in apical blebs of columnar cells was demonstrated. Since this immunoreactivity did not appear to be membrane-associated, it suggested a cytosolic localization of peripheral V1 subunits. The mRNA encoding subunit A of the peripheral V1 sector was distributed unevenly in columnar cells with a strong apical preference, whereas the mRNA for the proteolipid of the integral V0 sector was evenly distributed in the cytosol. This spatial pattern reflected the distribution of free ribosomes and rough endoplasmic reticulum in the cell, supporting the view that V1 subunits are synthesized at free ribosomes, whereas the V0 subunits are synthesized at the rough endoplasmic reticulum. All undifferentiated cells exhibited intense mRNA signals for V-ATPase subunits of both holoenzyme sectors from the start of proliferation and thus precursors of columnar and goblet cells could not be distinguished.

Animals↗

[Signs of right heart stress in diurnal normoxemic patients with chronic obstructive lung disease and nocturnal hypoxemia].

Nocturnal hypoxemia in daytime normoxemic patients with COPD may lead to an increased right ventricular afterload due to pulmonary hypertension. We investigated the frequency of clinical, electrocardiographical, and radiological signs of right cardiac insufficiency (SRCI) in 178 consecutive COPD-patients [71 bronchitis, 25 emphysema, 82 bronchitis plus emphysema; PaO2 = 60 mm Hg]. Patients with asthma, left ventricular impairment, obstructive sleep apnea syndrome, primary pulmonary hypertension, and neuromuscular diseases were excluded. Polysomnography was performed in all patients. They were divided into 3 groups concerning SRCI: missing, doubtful, and secure SRCI. Parameters of nocturnal pulse oximetry were analyzed within the three groups (Student's t-Test. Chi2-Test. p < 0.05). 25.8% of the patients had secure SRCI without a significant frequency difference between patients with bronchitis and/or emphysema. Patients with secure SRCI had a significant lower mean nocturnal SaO2 than those with missing SRCI (92.7 +/- 2.5 vs. 90.3 +/- 3.5%). With regard to the high prevalence of SRCI in association with nocturnal hypoxemia routine control of nocturnal oxygenation is recommended in daytime normoxemic COPD-patients for the early decision for nocturnal oxygen therapy.

Adult↗

Regulation of plasma membrane V-ATPase activity by dissociation of peripheral subunits.

The plasma membrane V-ATPase of Manduca sexta larval midgut is an electrogenic proton pump located in goblet cell apical membranes (GCAM); it energizes, by the voltage component of its proton motive force, an electrophoretic K+/nH+ antiport and thus K+ secretion (Wieczorek, H., Putzenlechner, M., Zeiske, W., and Klein, U. (1991) J. Biol Chem. 266, 15340-15347). Midgut transepithelial voltage, indicating net active K+ transport, was found to be more than 100 mV during intermoult stages but was abolished during moulting. Simultaneously, ATP hydrolysis and ATP-dependent proton transport in GCAM vesicles were found to be reduced to 10-15% of the intermoult level. Immunocytochemistry of midgut cryosections as well as SDS-polyacrylamide gel electrophoresis and immunoblots of GCAM demonstrated that loss of ATPase activity paralleled the disappearance of specific subunits. The subunits missing were those considered to compose the peripheral V1 sector, whereas the membrane integral V0 subunits remained in the GCAM of moulting larvae. The results provide, for the first time, evidence that a V-ATPase activity can be controlled in vivo by the loss of the peripheral V1 domain.

Adenosine Triphosphate↗

[Effect of the degree of revascularization on left ventricular function after aortocoronary bypass operation].

BACKGROUND: The extent of myocardial revascularisation by aortocoronary bypass surgery can only be quantitatively evaluated by using precise criteria. In this retrospective study the effect of coronary surgery on left ventricular function was analyzed. PATIENTS AND METHODS: In 161 patients, 148 male and 13 female, aged 52.5 +/- 7.0 years (33 to 69 years) with 1 (7%), 2 (38%) or 3 vessel disease (55%) the left ventricular function was analyzed by Swan-Ganz catheterization at rest and on exercise, five months before and after coronary bypass operation. Coronary artery and bypass lesions were quantified according to a new detailed score including diseased main or side branches, segment 1 to 3, type of irrigation and area reduction of the artery cross-section. Pulmonary capillary wedge pressure and cardiac index were measured and related to the grade of revascularisation (RG) and pre-operative ejection fraction (EF), classified in the groups RG1 < 50%, n = 54; RG2 50 to 74%, n = 52; RG3 > or = 75%, n = 55, EF1 < 60%, n = 30 and EF2 > or = 60%, n = 129. RESULTS: The change in pulmonary capillary wedge pressure on exercise was in RG1, RG2 and RG3 -26.2%, -29.0% and -40.9%, respectively (p < 0.001). It was significantly higher in RG2 and RG3 than in RG1. The increase in cardiac index on exercise was significant only in groups RG2, RG3 and EF2 (p < 0.005). CONCLUSION: Adequate improvement of left ventricular function can be expected when a grade of revascularisation of 50% and more is achieved.

Adult↗

Immunogenetic studies on HLA-DR in German coal miners with and without coal worker's pneumoconiosis.

Coal worker's pneumoconiosis is caused by the pulmonary deposition of coal dust, including silica particles. Several factors such as chemical composition and physical properties of silica-containing dust, particle size distribution, intensity, and duration of exposure influence the disease development. Genetic factors may also be involved. To define whether HLA-DRB may function as a genetic factor for predisposition to coal worker's pneumoconiosis, we determined DRB1, 3, 4, 5 alleles. For this purpose, DRB typing with sequence-specific oligonucleotide probes in 204 German miners with pneumoconiosis and in 52 German miners without pneumoconiosis was used. The miners had worked under comparable conditions. The frequency of DR8 (1*0801-0804) was increased in patients developing pneumoconiosis during the first 15 years of mining (p = 0.047). The frequency of DR1 (1*0101-0103) was elevated (p = 0.022) and that of DR52 (3*0101, 3*0201, 3*0202, and 3*0301) was reduced (p = 0.026) in miners without pneumoconiosis. Our data show that the presence of DR1 and the absence of DR52 support the resistance to coal worker's pneumoconiosis. Furthermore, DR8 may be involved in the rapid development of coal worker's pneumoconiosis.

Adult↗

Two-dimensional echocardiographic assessment of right cardiac pressure overload in patients with chronic obstructive airway disease.

Two-dimensional echocardiography was used to estimate right cardiac pressure overload in patients with chronic obstructive airway disease. Area measurements of the four heart chambers were carried out from the apical four-chamber view. Additionally, the respiratory behaviour of the inferior vena cava was examined from the subcostal view. A good apical imaging of the four-chamber view for area measurement was obtained in 44 out of 48 patients with chronic obstructive airway disease. The respiratory behaviour of the inferior vena cava was investigated from the subcostal view in 38 patients. Within 8 days after echocardiography, right cardiac catheterization was carried out in order to measure pulmonary artery and right atrial mean pressures and to determine pulmonary vascular resistance. A good correlation was found between pulmonary artery mean pressure and the following echocardiographic parameters: area index (area/body surface) of the two right heart cavities (r = 0.83), right-to-left ventricular area ratio (r = 0.82) and right-to-left cardiac area ratio (ratio between the added areas of both right heart cavities on the one side and the added areas of both left heart cavities on the other; r = 0.82). Correlation between these parameters and pulmonary vascular resistance (r = 0.71, 0.66 and 0.71, respectively) and between the right atrial mean pressure and the right atrial area index was less close (r = 0.64). On the other hand, the respiratory behaviour of the inferior vena cava proved to be highly specific but not very sensitive in predicting a pathological right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Function, Right↗

[The long-term effect of molsidomine on frequency of hemorrhage, portal and cardiac hemodynamics in patients with liver cirrhosis--a pilot study].

The aim of the study was to examine the effects of maintenance molsidomine therapy on portal and cardiac haemodynamics in patients with confirmed alcoholic or nonalcoholic liver cirrhosis and portal hypertension. Molsidomine is a selective reducer of preload without development of tolerance. 16 patients with portally decompensated cirrhosis of the liver following an initial or recurrent episode of bleeding form oesophageal/fundal varices were on long-term treatment (4-24 months) with 2 or 3 x 8 mg molsidomine/day (Corvaton retard). They were followed up after 3-6 months. 6 of the 16 had been treated previously with propranolol for haemorrhage prophylaxis over 11 +/- 15 months. In a total of 70 treatment months with propranolol, 10 recurrent bleeds had occurred. During 166 treatment months with propranolol, 10 recurrent bleeds had occurrences of bleeding. This long-term treatment showed reductions in hepatic venous pressure gradient of 24.8% (n = 8) (p < 0.05), variceal pressure of 28.7% (n = 7) (p < 0.05) and size of varices of 17% (n = 8). This occurred without any clinically relevant impairment of systemic cardiovascular regulation. Therefore long-term therapy with molsidomine may be suitable for prophylaxis of haemorrhage of oesophageal varices.

Adult↗

[Stepwise diagnosis of respiratory latex allergy].

Latex proteins bound to the powder of latex gloves are potent aeroallergens which can cause severe immediate-type allergic reactions of the upper and lower respiratory tract. To evaluate the clinical relevance of positive skin prick tests or IgE antibodies to latex we developed a sequence of provocation tests for the diagnosis of latex induced rhinitis or asthma. 14 patients are presented, 11 working in the medical field. All had positive skin prick test to latex milk and specific IgE-antibodies to a latex glove extract, six were atopic. 14 reported symptoms of the upper respiratory tract, 11 dyspnea related to latex contact. Nasal provocation with a suspension of powder from latex gloves or a glove extract could prove latex rhinitis in all cases by rhinomanometry. Bronchial obstruction was seen in four cases with one severe asthma attack in this test. The workplace-related provocation test with latex gloves was less sensitive for latex-asthma (3/9 positive) than the direct bronchial provocation test with a latex glove extract (6/7 positive), the three latex allergic patients without a history of dyspnea remaining negative in both. Provocation tests are highly sensitive for latex allergy of the respiratory tract and therefore of special importance in the diagnostic procedure.

Adult↗