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Biomedical subjects

H Bier

Publications and source records attributed to H Bier.

At least 19 recordsLinked to original sources
PubMed2006

[The subclavicular route for the pectoralis major myocutaneous flap].

BACKGROUND: The pectoralis major myocutaneous flap (PMMF) is an important reconstructive tool for lesions in the head and neck region. Using the supraclavicular route, the PMMF reliably transfers large amounts of well-vascularized skin and muscle into defects of the upper aerodigestive tract. However, limited length and arc of rotation as well as excessive bulk can be problematic. PATIENTS AND METHODS: In the current study, these problems have been addressed by passing the pedicle deeply to the clavicle. Following flap harvest, the pedicle was passed in the subclavicular plane in 15 head and neck cancer patients for primary and secondary reconstruction. RESULTS: Using this route it was possible to increase the medium length of PMMF to 3 cm compared to the supraclavicular route. No total flap necrosis occurred, however, temporary complications were observed in three of 15 cases (20%)--partial flap necrosis occurred in two cases and fistula formation was observed in one case. This rate is in accordance with complication rates described for the supraclavicular route. However, in long-term follow-ups we observed a fracture of the clavicle in two patients in whom, in contrast to the others, the periostium was not only prepared posteriorly but over the whole circumference. CONCLUSIONS: The subclavicular route for PMMF increases the length and arc of rotation available for reconstruction without compromising vascular supply to a higher degree than with the conventional supraclavicular route. Furthermore, this concept decreases the bulk of the PMMF pedicle which is functionally and cosmetically favourable. Thus, the subclavicular route of PMMF is safe and allows an extension of the reconstructive possibilities.

Clavicle↗
PubMed2006

[Collagen injection for augmentation of periprosthetic leakage after tracheo-esophageal voice restoration].

After laryngectomy the majority of patients receive a vocal rehabilitation by tracheo-esophageal puncture and insertion of voice prosthesis. Periprosthetic leakage causing aspiration represents a well known complication and is frequently treated by temporary removal of the prosthesis with shrinkage of the shunt. Here we describe 10 patients with such a leakage treated by collagen injection for periprosthetic tissue augmentation. A mean of 1,6 injections were necessary for complete control of the leakage. The injection was well tolerated and was found effective for median period of 9,3 months. In our hands the periprosthetic collagen injection represents an effective and well tolerated procedure for temporary augmentation of tracheo-esophageal leakage in post-laryngectomy patients. However, alternative fillers without pre-testing necessity and longer augmentation intervals should be considered.

Collagen↗
PubMed2005

[Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report].

A 34-year-old female patient with a three year history of generalized granuloma annulare was treated systemically with dapsone (DADPS). Six weeks after the onset of treatment, the patient developed an extensive tonsillitis of the base of the tongue with fever and malaise. Routine laboratory work showed a leukocytopenia with agranulocytosis. Further investigation revealed a marked decrease of the enzyme activity of N-acetyltransferase 2, which plays an important role in dapsone metabolism. Treatment included the cessation of dapsone, antibiotic coverage, and G-CSF leading to the rapid improvement of symptoms and normalization of leukocyte counts. Dapsone-induced angina agranulocytotica is a rare event and is interpreted as an idiosyncratic reaction. Depending on genetic polymorphisms of various enzymes, dapsone can be metabolized to immunologically or toxicologically relevant intermediates. Because of the risk of severe hematologic reactions, dapsone should only be employed for solid indications and with appropriate monitoring.

Adult↗
PubMed2005

[Squamous cell carcinoma of the head and neck. Principles and current concepts of immunotherapy].

Biologic therapies able to induce or up-regulate anti-tumor immune responses could represent a complementary approach to improve the conventional treatment of squamous cell carcinomas of the head and neck (SCCHN). Patients with SCCHN are frequently immunocompromised due to the elimination and dysfunction of critical immune effector cells. Therefore, it might be necessary to restore these immune functions to allow for the generation of effective anti-tumor host responses. Simultaneously, to prevent tumor escape from immunological recognition and destruction, it might also be necessary to alter antigenic and immunogenic attributes of the malignant cells. The present overview summarizes general aspects, historical data, and recent advances in the field of immunotherapy of SCCHN, including non-specific immune stimulation, transfer of immunocompetent cells, gene therapy, use of monoclonal antibodies, and anti-cancer vaccines.

Cancer Vaccines↗
PubMed2005

Increased C-reactive protein in ACE-inhibitor-induced angioedema.

AIMS: This study was designed to identify new factors which may contribute to angiotensin-converting-enzyme-inhibitor (ACEI)-induced angioedema. METHODS: In a retrospective cohort study we examined 25 patients who used an ACEI and presented at our emergency room with acute angioedema as well as 18 patients with unknown cause of angioedema and a total of 21 patients on ACEI-therapy without previous angioedema. We measured markers of inflammation such as acute-phase proteins (C-reactive protein, fibrinogen), leukocyte count and body temperature. RESULTS: The mean interval between initiation of ACEI treatment and first manifestation of angioedema was 35.8 +/- 5.3 months. During symptomatic angioedema, mean plasma levels of C-reactive protein and fibrinogen were significantly increased by 7.3-fold and 1.5-fold, respectively, while leukocyte count and body temperature were normal. These changes disappeared after successful treatment of angioedema and were not found in patients with angioedema of unknown cause and those receiving ACEI without having experienced angioedema. CONCLUSION: Our findings demonstrate for the first time that ACEI-induced angioedema is associated with strongly increased plasma levels of CRP. We suggest that CRP is involved in the pathophysiology of ACEI-induced angioedema.

Aged↗
PubMed2004

[ACE inhibitor-induced angioedema in the head and neck region. A matter of time?].

BACKGROUND: Angioedema in the head and neck region is potentially life-threatening and may occur as a side effect of inhibitors of the angiotensin-converting-enzyme (ACEI). So far, little is known about the time between the first application of ACEI and the occurrence of angioedema, or of possible cofactors and laboratory changes. MATERIAL AND METHODS: A total of 21 patients with angioedema during the course of ACEI treatment were compared to 11 patients with angioedema of unknown cause. These were retrospectively analysed for the following criteria: (1) duration of ACEI medication, (2) leading and concomitant diseases, (3) history of allergies, (4) co-medication, (5) laboratory changes, (6) treatment success, and (7) manifestation of recurrent episodes. RESULTS: The mean interval between the initiation of ACEI therapy and the first occurrence of angioedema exceeded 2 years. Values for the acute phase proteins C-reactive protein (CRP) and fibrinogen were significantly increased in the ACEI group compared to the control group. CONCLUSIONS: In any case of angioedema in the head and neck region, a side effect of ACEI must be taken into consideration even if the medication has been taken for months or years.

Adult↗
PubMed2003

[Argon plasma coagulation (APC) for palliative treatment of tracheostomal recurrences].

INTRODUCTION: To reduce tumor recurrences in the tracheostomal region mostly surgical measures come to the fore. PATIENTS AND METHODS: In six incurable patients with peristomal tumor recurrence, we performed nine palliative tumor reductions using argon plasma coagulation (APC). This electrosurgical non-contact technique has been described to produce effective hemostasis and favorable wound surfaces. RESULTS: In all nine procedures APC led to rapid and reliable hemostasis. Postoperative bleedings did not occur, and dry wound surfaces adjusted to the level of surrounding body contours considerably facilitated the wound aftercare. After eight of nine APC operations the immediate insertion of conventional cannulas was feasible instead of the tracheostomy tubes needed in the interim, and the patients were again able to change the cannula themselves. Two laryngectomized individuals could resume use of their voice prosthesis. CONCLUSION: APC is particularly suitable for the palliative surgical treatment of tumor recurrences in the tracheostomal region, because it helps to circumvent typical problems of conventional surgery.

Aged↗
PubMed2001

Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx.

In this open uncontrolled phase I study, nine patients with stage III and IV squamous cell carcinoma of the head and neck (SCCHN) were treated with five administrations of the humanized antiepidermal growth factor receptor monoclonal antibody EMD 72000 in three consecutive ascending dose groups. Loading doses of 100 mg (group I), 200 mg (group II), and 400 mg (group III) were followed by four weekly maintenance doses of half the loading doses, i.e. 50, 100, and 200 mg, respectively. Two EMD 72000 administrations were scheduled before and three after surgery. The objectives of this trial were (a) to investigate the safety and toxicity of multiple EMD 72000 doses, (b) to determine the cumulative maximum tolerated dose of EMD 72000 at dosages between 300 mg and 1,200 mg, and (c) to determine the serum pharmacokinetics of EMD 72000. In total, 102 adverse events (AEs) were reported: five of toxicity grade 3, 18 of toxicity grade 2, 66 of toxicity grade 1, and 38 of toxicity grade 0. All AEs of toxicity grade 3 were considered to be not or remotely related to EMD 72000. The most frequent study drug-related AEs were fever and a transient elevation of liver enzymes. In all patients, the time to reach peak serum concentrations (tmax) was within 1-3 h of the start of each EMD 72000 infusion. Average peak serum concentrations (Cmax) after correction for dosage appeared to be dose-independent, whereas the half-life (t1/2) showed dose dependency. In conclusion, EMD 72000 was very well tolerated in patients with advanced stage SCCHN. The pharmacokinetic data from this trial suggest the feasibility of conducting future studies with weekly doses of 200 mg EMD 72000.

Aged↗
PubMed2001

Serum level and tissue expression of c-erbB-1 and c-erbB-2 proto-oncogene products in patients with squamous cell carcinoma of the head and neck.

The proto-oncogene products erbB-l (EGF-Receptor) and erbB-2 (HER-2/neu), distinct members of the epidermal growth factor receptor family, are frequently overexpressed in squamous cell carcinoma of the head and neck (SCCHN). The accumulation of these transmembrane proteins may lead to significant amounts of the respective extracellular receptor domains (ECD) that are shed from the tumour cell surface and enter blood circulation, thus representing potential serum tumour markers. For erbB-l and erbB-2, we determined the ECD serum levels with enzyme-linked immunosorbent assays and evaluated the protein expression in tumour tissue by immunohistochemistry. The present study included 49 patients (37 untreated, 12 recurrences) and the same number of age- and sex-matched healthy controls. In 24 patients ECD serum levels were determined before and 6 weeks after surgery. Mean ECD serum levels for erbB-1 and erbB-2 were 54.8+/-1.6 and 153.7+/-6.1 fmol/ml in cancer patients, and 54+/-1.5 and 147.9+/-4.5 fmol/ml in healthy controls, respectively. There was no significant difference between untreated and recurrent disease. Serum ECD follow-ups 6 weeks after surgery revealed a significant 12.3% decline of erbB-1 but no change of erbB-2 values. Immunohistochemistry showed strong staining for erbB-1 in 78% and erbB-2 in 47% of the SCCHN specimens. No correlation was detectable between receptor ECD serum levels and receptor tissue expression, tumour stage, and tumour differentiation. Hence, ECD serum levels of erbB-1 and erbB-2 are not considered to be valuable tumour markers in SCCHN.

Adult↗
PubMed2000

Relapsing polychondritis in childhood--case report and short review.

Relapsing polychondritis (RP) is a disease of unknown etiology and it is characterized by inflammation of the cartilage. While the clinical picture of RP in adults is well described, RP in childhood is poorly documented. We describe a young girl presenting with acute dyspnea, stridor and polyarthritis. The diagnosis of RP was made 2 years after first presentation, when auricular chondritis occurred. Based on a MEDLINE search, reports on RP in childhood were reviewed. The frequency of chondritis and systemic manifestations of RP in children was compared to data in adults and found to be very similar. RP in childhood can be a life-threatening and debilitating disease.

Adult↗
PubMed1998

Anti-(epidermal growth factor) receptor monoclonal antibodies for the induction of antibody-dependent cell-mediated cytotoxicity against squamous cell carcinoma lines of the head and neck.

Squamous cell carcinomas of the head and neck (SCCHN) frequently display high levels of the epidermal growth factor receptor (EGFR). Since EGFR is expressed on the cell surface it may form a suitable target for anticancer therapy with anti-receptor monoclonal antibodies (mAb). Besides the interference with receptor/ligand interactions, binding of mAb to EGFR leads to immunoglobulin-coated tumour cells that may induce or enhance non-specific immune effector mechanisms like antibody-dependent cell-mediated cytotoxicity (ADCC). In established cell lines of SCCHN (UM-SCC 11B, 14C, 22B, and 8029 NA) we investigated the antitumour activity of allogeneic peripheral blood mononuclear cells (PBMC) in combination with rat (ICR 62), mouse (EMD 55900), and humanized (EMD 72000) anti-EGFR mAb. In addition, autologous PBMC were available for tumour line UD-SCC 4. The EGFR protein content of the tumour cell lines ranged between 170 fmol/mg protein and 8100 fmol/mg protein, and MCF-7 cells served as receptor-negative controls. PBMC activity against SCCHN targets was determined in 96-well microtitre-plate monolayer cultures by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after coincubation for 4 h, 24 h and 72 h at effector target ratios of 1:1, 5:1, 10:1 and 20:1. PBMC subpopulations were obtained by macrophage depletion (plastic adherence) or natural killer (NK) cell enrichment (magnetic bead negative selection). Prolonged time of exposure and increased effector:target ratios revealed marked antitumour activity of PBMC alone. This non-specific immune destruction was enhanced considerably by humanized and rat, but not mouse anti-EGFR mAb. Increased EGFR protein in tumour cells partly correlated with an intensification of ADCC but was accompanied by decreased primary PBMC cytotoxicity. The utilization of PBMC subpopulations suggested a mainly NK-cell-mediated ADCC, which appeared to benefit directly or indirectly, e.g. via the secretion of cytokines, from other PBMC components. In conclusion, humanized (EMD 72000) and rat (ICR 62) anti-EGFR mAb were able to generate strong antitumour ADCC in target monolayers of SCCHN.

Antibodies, Monoclonal↗
PubMed1996

Chemosensitivity of head and neck squamous carcinoma cell lines is not primarily correlated with glutathione level but is modified by glutathione depletion.

Glutathione has a variety of important physiological functions in cellular metabolism and defense, including protection from radicals, oxidative stress, and electrophilic compounds. On the basis of this interaction with both endogenous and synthetic substances, glutathione and the key enzyme for its conjugation, glutathione S-transferase, appear to be critical determinants in tumor cell resistance to several antineoplastic drugs, e.g. platinum analogs. In ten established head and neck cancer cell lines (UM-SCC 10A, 10B, 11B, 14A, 14B, 14C, and 22B, HLac79, 8029NA, and 8029DDP4) chemosensitivity to cisplatin, carboplatin, 5-fluorouracil, and bleomycin, as well as cellular glutathione content and activity of glutathione S-transferase were determined. The results revealed no correlation between the sensitivity of tumor cells to any of the drugs tested and the level of glutathione or the activity of glutathione S-transferase. However, the cisplatin-resistant subpopulation 8029DDP4 showed the highest glutathione level and marked cross-resistance to bleomycin. Glutathione depletion with buthionine sulfoximine led to moderately increased sensitivity towards cisplatin and carboplatin in all cell lines, but did not affect their response to 5-fluorouracil or bleomycin. These results suggest that the level of glutathione or the activity of glutathione S-transferase is not a suitable parameter for the assessment of chemosensitivity in head and neck squamous-cell carcinoma lines. However, response to platinum analogs is influenced by alterations of the initial intracellular glutathione concentration.

Carboplatin↗
PubMed1995

Dose-dependent access of murine anti-epidermal growth factor receptor monoclonal antibody to tumor cells in patients with advanced laryngeal and hypopharyngeal carcinoma.

The murine IgG2a monoclonal antibody (mAb) EMD 55900 was produced against the human epidermoid carcinoma cell line A431, with binding occurring to the polypeptide chain of the external domain of human epidermal growth factor receptor (EGF-R). In the present clinical study, 12 patients with advanced squamous cell carcinoma of the larynx or hypopharynx received a single dose of either 20, 100 or 400 mg EMD 55900 3 days prior to laryngectomy and neck dissection. Clinical signs and laboratory parameters of toxicity, development of human anti-mouse antibodies, and mAb plasma concentrations were monitored. In tumor specimens studied from primary tumors and lymph node metastases, expression of EGF-R, distribution of EMD 55900, and occupation of EGF-R by EMD 55900 (double staining) were determined by immunohistochemistry. Single-dose administration of EMD 55900 was very well tolerated in all patients, and good (100 mg) to excellent (400 mg) homogeneous binding of mAb to EGF-R was obtained in the advanced laryngeal and hypopharyngeal carcinomas studied.

Adult↗
PubMed1995

Immunohistochemical examination of 11 cell lines derived from human head and neck squamous cell carcinomas, their recurrences or metastases.

Since in vitro derived tumor cell lines usually correspond to their tumors of origin, a potential biological difference between a primary tumor and its derivative metastases and recurrent tumors should be reflected in established tumor cell lines. The aim of this study was to determine useful cellular markers in permanent tumor cell lines of head and neck squamous cell carcinomas (SCC) and to evaluate a possible relationship between these markers and the origin of selected cell lines. The cell lines, established in the laboratory of T. Carey at the University of Michigan (UM) (Ann Arbor, Mich., USA), were derived from primary tumor and its metastases (UM-SCC 10A, 10B), primary tumor and its recurrent tumors (UM-SCC 14A, 14B, 14C) and single tumors (UM-SCC 11B, 17A, 22B). An additional tumor cell line (HLac 79) was isolated by H.-P. Zenner (Tubingen, Germany) and a clone (8029 NA) with its cisplatin-resistant subline (8029 DDP4) was established in our laboratory. As markers we chose three groups known to be related to growth behavior and/or tumor differentiation: cytoskeletal proteins, oncogene products and membrane-associated antigens. These markers were detected by immunohistochemical methods using commercially available monoclonal antibodies. The "metastatic" and "recurrent" cell lines showed changes in comparison to the corresponding "parental" lines, which could be associated with a higher degree of de-differentiation, such as the occurrence of vimentin and neuroectodermal proteins, loss of HLA-ABC or HLA-DR and increased expression of epidermal growth factor receptor. The expression of cytokeratins was more stable and dissociation of the classical cytokeratin pairs was observed only in a few cases. Oncogene products were practically identical in cell lines from parental and recurrent or metastatic tumors. These data serve not only as a basis for further experiments with these cell lines but also provide information about the biological significance of various markers in newly established cell lines from primary tumors.

Antibodies, Monoclonal↗
PubMed1995

[Morphologic and immunohistochemical studies of organ cultures of human tracheal biopsies].

Most likely the transformation of epithelial cells to carcinoma cells takes place during the process of differentiation. In order to study in vitro carcinogenesis, an experimental system for organ cultures was developed in which human respiratory epithelial from tracheal biopsies differentiate within six weeks. The mucosal and submucosal layer of small tracheal biopsies was cut into pieces measuring 3 x 3 and 5 x 5 mm2, respectively, and placed on Gelita cubes (Braun-Melsungen, Germany) measuring 10 x 10 x 10 mm3 with the epithelium facing up. The culture medium (RPMI 1640 supplemented with 10% fetal calf serum, 200 mM L-glutamine, 100 IU/ml penicillin, and 100 micrograms/ml streptomycin) was added in a way that the tissue lay between the medium and air. Gelita deteriorates in about two to three weeks. However, the cultures are easily transferred to fresh Gelita cubes using the rest of the old Gelita. These organ cultures were fixed at regular intervals, and histological sections were stained with hematoxylin eosin or monoclonal antibodies against cytoskeletal intermediate filament proteins. These morphological and histological studies revealed that the epithelial cells differentiated under these conditions in at least 39 days. The mesenchymal elements remained viable without showing strong proliferation. The implication of these techniques for studying carcinogenesis in vitro is discussed.

Antibodies, Monoclonal↗