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Biomedical subjects

U Hofmann

Publications and source records attributed to U Hofmann.

117 records · Page 7Linked to original sources

[Clinical aspects and problems in thoracic dystrophy].

We report about a child with Jeune-syndrome in whom surgical enlargement of the thorax at the age of 4 months was performed. In the beginning there was a significant improvement of the respiratory situation. Due to resorption of the interposed ribs there was again a shrinking of the thorax and a deterioration in the child's condition. A reoperation at the age of 8 months couldn't improve the situation anymore, because at that time the child had already additional problems such as pulmonary hypertension and broncho-pulmonary dysplasia. We overview the literature and line out our opinion about the indication for surgical enlargement of the thorax in children with Jeune syndrome.

Asphyxia Neonatorum↗

Extracranial non-testicular teratoma in childhood and adolescence: introduction of a risk score for stratification of therapy.

PATIENTS AND METHODS: According to previous literature incomplete tumor resection, coccygeal or ovarian primary site and immaturity are known risk factors for relapse in teratoma. To establish a risk score points are allocated for resection, primary site and histology in the following manner and added: incomplete resection 4 points, primary site coccyx 3 points, ovary 2 points, other site 1 point, histological grading 0-3 points. This score system is evaluated on 270 extracranial non-testicular teratoma cases collected between 1982 and 1995 in the MAKEI cooperative treatment protocols of the German Society of Pediatric Oncology and Hematology. Treatment was resection alone (230 patients) or resection followed by postoperative adjuvant chemotherapy (40 patients). RESULTS: Patients treated with surgery alone: 28/230 (12%) patients relapsed, 14/230 (6%) patients showed highly malignant histology (mostly yolk sac tumor) in relapse. Mortality in case of relapse was 6/28 (21%). Patients scoring > or = 6 points (n = 45) had a relapse rate of 21/45 (47%) resulting in a 23%-mortality (5/21). Patients scoring < 6 points (n = 185) had a 4%-relapse risk (8/185) resulting in 13%-mortality (1/8) (p < 0.01). Patients treated with surgery and adjuvant chemotherapy: 7/40 patients (18%) suffered a relapse, none of them showing malignant histology. Mortality rate in case of relapse was 3/7 (43%). Patients scoring > or = 6 points initially treated with adjuvant chemotherapy (n = 18) had a relapse rate of 7/18 (39%), compared to patients scoring < 6 points (n = 22), in whom no relapses occurred (p < 0.01). There were no highly malignant relapses in the group treated with adjuvant chemotherapy. Regardless of the scored points the difference in highly malignant relapse histology comparing the group treated with surgery and adjuvant chemotherapy to the group treated with surgery was statistically significant (p = 0.02). CONCLUSION: The risk score system marks a high risk group including 63/270 (23%) of all evaluated extracranial non-testicular teratoma cases (scoring > or = 6 points). In this group 28/35 (80%) of relapses and 8/9 (89%) of tumor deaths occurred. For this high risk group a randomized trial will be suggested to evaluate the effect of adjuvant chemotherapy on the rate of malignant relapses. It should also be investigated, if adjuvant chemotherapy will influence relapse rate and mortality.

Child↗

Phase 2 trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma.

This phase II study was performed to determine the induction of a specific T-cell response, the clinical response rate, and toxicity of vaccination with different HLA class I-binding peptide epitopes derived from the melanocyte differentiation antigen tyrosinase in patients with stage IV melanoma. The study population consisted of 16 patients with metastatic disease and two patients who were macroscopically free of disease at study entry after resection of recurrent skin lesions. Patients received intradermal injections of 200 microgram [corrected] peptide corresponding to their HLA type on day 3, and 75 or 150 microg granulocyte-macrophage colony-stimulating factor on days 1 to 4. Vaccinations were repeated at weeks 2, 4, 6, 10, and 14. Monitoring of peptide-specific T-cell frequencies in the peripheral blood was performed using an interferon gamma ELISPOT assay. Eleven of the 16 patients with metastatic disease went off the protocol within the first 10 weeks because of tumor progression. Of the five patients with metastatic disease who received all six vaccinations, one patient showed a mixed response with regression of some lung metastases; two patients with progressive disease before vaccination had stable disease for 6 and 18+ months; and two patients had progression of their disease. The two patients who had all their metastases resected before vaccination did not have relapses for 6 and 12+ months after vaccination. Induction of tyrosinase-reactive T cells was found in these two patients and in two others with metastatic disease, including the one who achieved a mixed response and one with stable disease. This study shows limited clinical and immunologic activity of HLA class 1-peptide vaccination in combination with granulocyte-macrophage colony-stimulating factor in stage IV melanoma patients.

Bone Neoplasms↗

MR imaging in pediatric airway obstruction.

Magnetic resonance (MR) imaging of the trachea was performed in 27 children with congenital tracheal narrowing. The diagnoses included aortic arch anomalies (n = 7), innominate artery compression (n = 13), pulmonary artery compression (n = 5), and tracheomalacia (n = 2). Demonstration of the trachea and the surrounding tissue and vessels on MR images allowed the evaluation of the cause of tracheal compression and the degree and location of collapse. Patients were examined with MR imaging if the cause of airway obstruction was still unclear after bronchoscopy. It is concluded that MR imaging is a well suited modality for characterizing tracheal narrowing without using ionizing radiation or intravenous contrast medium.

Airway Obstruction↗

Comparison of S100 protein and MIA protein as serum marker for malignant melanoma.

BACKGROUND: Detection of S100 beta in serum has been shown to be a significant prognostic marker for malignant melanoma in earlier studies. Melanoma inhibiting activity (MIA) has recently been detected as a new serum marker for malignant melanoma. MATERIALS AND METHODS: In the present study, serum levels of S100 beta protein and MIA were measured over a time period of up to 18 months in 271 serum samples from 65 melanoma patients at different stages of disease, during chemotherapy and/or immunotherapy. In addition, 46 sera of control patients were analysed. The aim of this study was to compare both potential markers. S100 beta was measured using the immunoluminometric assay LIA-mat Sangtec (Byk Sangtec Diagnostica) with a cut-off level of 0.12 microgram/l. MIA was determined by the MIA ELISA kit (Roche) using a cut-off level of 6.5 ng/ml. RESULTS: In 53 patients a direct correlation of S-100 values and clinical course could be observed (81.5%), whereas in 48 patients MIA-values and clinical course (73.8%) showed an association. S100 beta levels were incorrectly elevated in 5 out of 25 sera, "false positive" (20%)) and were in 8 out of 40 sera not elevated despite the detection of metastases "false negative" (20%)). Assessing the MIA levels, 2 out of 25 probes were false positive (8%) and 13 out of 40 probes false negative(32.5%). CONCLUSION: Our data strongly suggest that S100 and MIA represent serum tumor markers that are valuable both in therapy-monitoring and in detection of tumour progression.

Antineoplastic Combined Chemotherapy Protocols↗

Identification of thiodiglycolic acid, thiodiglycolic acid sulfoxide, and (3-carboxymethylthio)lactic acid as major human biotransformation products of S-carboxymethyl-L-cysteine.

S-Carboxymethyl-L-cysteine (CMC) is used both as an orally administered mucolytic agent and as a probe drug for uncovering polymorphic sulfoxidation of other sulfur-containing drugs in humans. However, several recent studies could not confirm the formation of significant amounts of urinary sulfoxides of CMC or its decarboxylation product S-methyl-L-cysteine. The metabolism of CMC and a 13C-labeled isotopomer was therefore reinvestigated in 11 and 14 humans, respectively, and emphasis was laid on monitoring of potential alternative metabolic pathways. Combined capillary gas chromatography/electron impact or negative-ion chemical ionization mass spectrometry employing stable isotope-labeled analogues as internal standards were used for identification and quantification of CMC metabolites in human urine. Three nitrogen-free metabolites that were identified as thiodiglycolic acid (TDGA, mean: 19.8% of the dose/24 hr), thiodiglycolic acid sulfoxide (TDGA-SO, mean: 13.3% of the dose/24 hr), and (3-carboxymethylthio)lactic acid (TLA, mean: 2.1% of the dose/8 hr), cumulatively account for about one-third of the dose during a urinary collection period of 24 hr. In addition, trace amounts of both TDGA and TLA exist as endogenous components in urine from persons not administered exogenous CMC at levels of about 5 and 1 nmol/ml, respectively. Both major metabolites TDGA and TDGA-SO, that were not considered in previous sulfoxidation phenotyping, are predominantly excreted after 8 hr. These results demonstrate the existence of a pyruvate-like metabolic pathway and suggest the necessity of a revision of the hitherto accepted biotransformation route of CMC in humans.

Biotransformation↗

Cellular requirements of IgE-antibody regulation.

The low affinity receptor for IgE (Fc epsilon RII), which is identical to CD 23 has been recently implicated in a variety of functions. It appears as an early stage specific marker in the ontogeny of the IgM-bearing B cell. In humans the CD 23 is also exposed on T-cells in patients with elevated IgE, while in rodents Fc epsilon RII seems to be mainly present on T-lymphocytes. Fc epsilon RII can also be detected on macrophages, eosinophils and platelets. Activation of these cells induces an amplification of the inflammatory response. It is currently suggested that IgE-binding molecules, which are related to CD 23, modulate IgE synthesis according to their degree of glycosylation. Evidence has been provided recently that interleukin 4 induces the expression of Fc epsilon RII (CD23). The action of interleukins, IgE binding factors and cytokines on the complex events of IgE-induction and synthesis are currently studied.

Animals↗