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R Hagen

Publications and source records attributed to R Hagen.

At least 19 recordsLinked to original sources
PubMed2000

Aflatoxin B1-induced mitotic recombination in L5178Y mouse lymphoma cells.

Aflatoxin B1 is a human hepatocarcinogen. It is also a known point mutagen in bacteria and mammalian cells. This mutagenic activity may be at least partly responsible for its carcinogenic activity. However, recent studies show that aflatoxin B1 induces mitotic recombination in the yeast Saccharomyces cerevisiae. Because numerous reports have implicated mitotic recombination in mechanisms leading to carcinogenesis and because no one has shown that aflatoxin B1 induces recombination in mammalian cells, we decided to examine the ability of aflatoxin B1 to induce recombination in a mammalian cell line. We used a combination of methods, analysis for loss of heterozygosity and whole chromosome in situ hybridization, to identify mechanisms of chromosome mutation, including mitotic recombination in the mammalian L5178Y mouse lymphoma cell system. Our experiments revealed that mitotic recombination caused approximately 60% or more of the aflatoxin B1-induced mutagenic lesions in this cell system. Thus, mitotic recombination plays an important role in aflatoxin B1-induced mutagenesis in mammalian cells and possibly in chemically induced mutagenesis and carcinogenesis. This work suggests that multiple genetic lesions may be involved in aflatoxin B1-induced pathology.

Aflatoxin B1↗
PubMed1999

Free-flap reconstruction for laryngeal preservation after partial laryngectomy in patients with extended tumors of the oropharynx and hypopharynx.

Partial laryngeal resection often results in major aspiration problems, making larynx preservation during surgical removal of tumors of the oropharynx and hypopharynx impossible. However, free flaps can be used to reconstruct perilaryngeal tissue, thus preserving the larynx and ensuring a better quality of life for patients. We present the results of forearm free-flap reconstruction of the supraglottis in 22 patients who underwent resections of extended squamous cell carcinomas of the oropharynx and hypopharynx. A total of 9 patients had T3 lesions and 13 had T4 lesions. All patients were additionally treated with radiation therapy alone (to 70 Gy) or in combination with chemotherapy (Cisplatin; 5-fluorouracil). The mean follow-up was 2.4 years. In four patients, tracheostomy could be closed. Five patients suffered from severe aspiration, one of whom had to undergo a laryngectomy. Six patients had mild aspiration and 7 patients had no aspiration, but extensive edema made decanulation impossible. A total of 13 patients were free of disease, 4 patients died of disease, 1 patient died as the result of a second primary cancer and 1 patient died of other causes. Three patients are alive with persistent tumor. Although the majority of patients experienced a better quality of life as a result of larynx preservation, aspiration has remained a problem following treatment.

Adult↗
PubMed1999

[Outcome after resection of extensive oropharyngeal carcinomas and defect coverage by microvascular anastomosis of a radialis flap].

BACKGROUND: Extensive tumors of the oropharynx require an open approach and plastic reconstruction for good oncologic and functional results. PATIENTS AND METHODS: From January 1988 through December 1996 at the Department of Otolaryngology, Head and Neck Surgery, of the University of Würzburg, 62 patients with extensive tumors of the oropharynx underwent surgical treatment (T2 = 6, T3 = 24, T4 = 32). In 40 patients, the resection was performed via a median mandibulotomy approach, in 22 patients using a lateral pharyngotomy. All patients underwent postoperative radiotherapy up to 70 Gy. RESULTS: Using the Kaplan-Meier method, the five-year survival was 80% for T2, 52% for T3, and 22% for T4. Four patients (7%) presented with a second primary carcinoma, and one also had a third carcinoma. Seven patients who died of T3- and T4-tumors had distant metastases, among them 5 patients who were free of local disease. A regular oral diet was possible on average 14 days postoperatively. All patients underwent tracheostomy. Ninety percent of them were decanulated one year postoperatively. CONCLUSIONS: Resection of extensive carcinomas of the oropharynx and microvascular reconstruction produces good oncological and functional results. The best access to extensive tumors is provided by a mandibulotomy. The advantage of this excellent approach outweighs an increasing morbidity in occasional cases.

Combined Modality Therapy↗
PubMed1998

[Indications and risks of manual lymph drainage in head-neck tumors].

BACKGROUND: Secondary lymphedema of the head and neck can develop as a result of obstruction of lymphatic channels following the surgical removal of lymph nodes and fibrosis due to irradiation. This can be treated with manual lymphatic drainage. An increase of tumor recurrence due to this therapy is at controversial discussion. PATIENTS: In a retrospective study 191 patients treated for head and neck cancer were questioned on occurrence of lymphedema and therapy with manual lymphatic drainage. RESULTS: 100 patients had received lymphatic drainage, whereas 91 patients belonged to the group without lymphatic drainage therapy. In 37 cases a tumor recurrence or local metastases were reported, 18 of whom had received lymphatic drainage and 19 belonged to the control group. Among these 37 patients neither the group with lymphatic drainage nor the control group differed significantly concerning stage of cancer, histopathological grading, the in sano/non in sano resection of the primary tumor and a lymphangiosis carcinomatosa. An increased recurrence rate among patients who underwent a lymphatic drainage therapy could not be found. CONCLUSION: A lymphatic drainage therapy for patients presenting with lymphedema after the oncological therapy does not increase the rate of local recurrencies. Moreover it improves the quality of life after the cancer therapy. As only few data are available for cases with non in sano surgery and tumors with lymphangiosis carcinomatosa these cases should be excluded from a lymphatic drainage therapy. A spreading of occult tumor cells in these patients might be possible.

Carcinoma, Squamous Cell↗
PubMed1998

[Voice prostheses with sound-producing metal reed element--an experimental study and initial clinical results].

BACKGROUND: Following total laryngectomy the voice is produced by esophageal speech as well as with voice prostheses by vibrations of pharyngeal mucosal folds. This pharyngeal sound normally has a significantly lower fundamental frequency than the healthy voice (men about 120 Hz, women about 240 Hz, pharyngeal voice about 70 Hz), which is a handicap especially for female laryngectomy patients. In order to improve the postlaryngectomy voice, a new type of voice prostheses containing an integrated sound-producing metallic reed element was developed (ADEVA Company, Lübeck, Germany). METHODS/PATIENTS: Thirty-five of these new sound-producing voice prostheses were tested in vitro for different prosthesis-specific physical parameters (pressure, flow, sound pressure, flow resistance, frequency range). In 15 voice prosthesis speakers, a sound-producing prosthesis was introduced during a routine outpatient visit. Besides measurement of the above mentioned physical parameters in patients with conventional and sound-producing prostheses, the resulting voice as also evaluated by means of a video recording. RESULTS: In vitro all prostheses with the metallic reed element produced a clear sound. Flow resistance of the prostheses was slightly elevated by the reed element. Insertion of the prostheses was hindered by the reed element. Period of uninterrupted sound production was prolonged after insertion of a sound-producing prosthesis and patients could speak on a lower pressure level, but the sound of the reed element was permanently distinguishable only in 6 of 15 patients. CONCLUSIONS: In principle a variation of the pharyngeal voice by means of a sound producing element, which is integrated into a voice prosthesis, is possible. The current design of the metallic reed element tested is not yet suitable for routine clinical use: 1. The reed element is too sensitive and is easily damaged during insertion, so the insertion device has to be improved. 2. The sound producing element is blocked by small amounts of tracheal secretions, so that this element should be replaceable separately without requiring removal of the silicone value (if possible by the patient himself). Prior to insertion of the sound producing voice prosthesis the maximum air flow through the shunt should be measured to determine if the patient can produce the necessary air flow for activation of the reed element. A further improvement for these special types of voice prostheses would be a sound producing element, which generates a variable frequency of sound. Limiting the patient to only one fundamental frequency creates a monotone, which does not sound naturally. Initial progress toward a sound-producing voice prostheses has been made. This should be followed by the necessary improvements in order to improve the feasibility of this design for routine clinical use.

Equipment Failure Analysis↗
PubMed1998

Cytotoxic and genotoxic effects of paclitaxel (Taxol) and radiation in a squamous cell carcinoma cell line of the larynx.

Paclitaxel (Taxol) is an antimicrotubular agent which blocks the cells in the G2/M phase of the cell cycle. Because of this mechanism it is presumed that this drug could function as a radiation sensitizer. The cytotoxic and genotoxic effects of paclitaxel and a combination of paclitaxel and radiation were studied in the human laryngeal carcinoma cell line HLac 79. The growth of the cells was significantly reduced at concentrations of paclitaxel as low as 10 nM. Flow cytometry data showed a G2/M block after exposure to paclitaxel. Radiation at 12 and 24 h after drug treatment exerted an additive but no radiation sensitizing effect. As genotoxic effect paclitaxel induced multinucleated cells, possibly in a synergistic manner, at low concentrations (10 nM) and radiation doses up to 3 Gy.

Antineoplastic Agents, Phytogenic↗
PubMed1997

[Laryngeal cancer treatment concept in metastases].

The prognosis of laryngeal carcinoma worsens dramatically with the discovery of primary or secondary lymph node metastases. Thus consistent prophylaxis and therapy of metastases is indispensable. The standard therapy of manifest cervical lymph node metastases is surgery, if possible using the approach of conservative neck dissection. In cases of a lymph node stage N3, i.e. fixated metastases with a diameter greater than 6 cm, individually adapted therapy in necessary because of the extremely poor prognosis. Elective treatment of the N0 neck is surgical, too; however, the site of the primary tumour, possibly infiltrated compartments and, accordingly, invasion of deep lymphatic vessels have to be considered. Special care is necessary if the so-called primitive glottis is invaded (arytenoid region, aryepiglottidian fold, epiglottis). In the case of distant metastases a temporary remission can be obtained with chemotherapy in most cases, but this chemotherapy should not be forced, because there exists no real chance of cure. The trend is towards less aggressive, outpatient schedules of chemotherapy.

Chemotherapy, Adjuvant↗
PubMed1997

[Extramedullary plasmacytoma--manifestation in petrous bone].

BACKGROUND: Extramedullary plasmocytoma of the temporal bone is a rare neoplastic disorder. Only a very few cases are described in the world literature. CASE: We report on a patient who presented with the clinical signs of a glomus jugular tumor. Postoperative histological evaluation revealed an extramedullary plasmocytoma of the temporal bone. CONCLUSION: If a glomus tumor is suspected, histological investigation appears necessary if surgery is not possible or is contraindicated.

Angiography↗
PubMed1997

Cranial vault moulding by the transcutaneous activation of implanted magnets.

The technique of distraction osteogenesis has not been widely used in the treatment of injuries of the head and face because of the need for external fixators. By using magnetic, rather than mechanical, forces to drive bone movement we hope to expand the applications of the technique to include the treatment of cranial vault deformities. Fifteen immature rabbits were studied. When they were 6 weeks old each had a magnet fixed to their left parietal bone. A head frame was attached and a magnet of either the opposite polarity to, (group 1), or the same polarity as, (group 2), the implanted magnet was mounted on the frame. Five weeks later the rabbits were sacrificed. There were significant differences in parietal skull width and in several measures of skull length between the animals in group 1 and those in group 2. These results demonstrate that, in this model, magnetic forces can be used to modify skull growth.

Animals↗
PubMed1996

[Magnesium seeding in therapy of pediatric hemangioma of the temporal region, lower eyelid and orbit].

BACKGROUND: Magnesium seeding of haemangiomas is a form of treatment already successfully used in 1900. PATIENT: We report about a male infant with a haemangioma of the left temporal region, underlid and orbit. Maximum depth at the time of indication for magnesium seeding was 28 mm with an intraorbital extension of 7 mm. COURSE OF THERAPY: Magnesium seeding of the haemangioma first lead to a standstill and within 8 weeks to a significant remission. After this period, maximum depth was 6.7 mm without any intraorbital extension. CONCLUSION: Magnesium seeding is a hopeful and low-risked alternative in the therapy of infantile haemangiomas.

Eyelid Neoplasms↗
PubMed1995

Nasotracheal airway-oropharyngeal alimentary canal: a microvascular technique for reconstruction of the upper airway after total laryngectomy.

Every patient who has to be laryngectomized because of a carcinoma is concerned with the loss of his or her voice and the presence of a permanent tracheostoma in his or her neck. While various methods for producing a substitute voice are available (esophageal voice, voice devices, voice-shunt operations with or without voice prosthesis), it is usually impossible after laryngectomy to reconstruct a complete upper airway so that the tracheostoma can be closed. One potential method for reconstruction of the airway is its division into a nasotracheal airway and an oropharyngeal alimentary canal. Ten Alsatian dogs were laryngectomized, and a microvascularly anastomosed jejunal autograft was inserted as a junction between the tracheal stump and the circularly exposed nasopharynx, while the pharynx was reconstructed separately. One week postoperatively, oral feeding could be started again; at the same time breathing was possible via the reconstructed nasotracheal airway, which was kept open by insertion of a silicone tube. By means of this microvascular technique, a complete nasal airway could be reconstructed surgically after laryngectomy.

Anastomosis, Surgical↗
PubMed1994

Juvenile nasopharyngeal fibroma: androgen receptors and their significance for tumor growth.

Since the publications of Martin, et al. (1948) and Schiff (1959), who were the first to report on the administration of sex hormones to juvenile nasopharyngeal fibroma (JNF) patients, several authors have described the different clinical effects and histologic changes after androgen and estrogen application. Since the mechanism of action of sex steroids in juvenile nasopharyngeal fibroma is almost unknown, the authors have studied androgen receptor binding in cultured tumor fibroblasts from three patients with JNF. Maximum androgen binding (Bmax) of the tumor fibroblasts approximated to that of genital skin fibroblasts, which served as a control androgen target tissue with high receptor density. Furthermore, in vitro experiments showed that the growth rate of tumor fibroblasts increased when testosterone was added to the culture medium, while the addition of two antiandrogens, cyproterone and flutamide, caused a reduction in growth rate. It is concluded from these results that JNF is a hormone-dependent tumor stimulated by testosterone whose growth rate may, at least in vitro, be reduced by antiandrogens such as cyproterone and flutamide.

Cell Division↗
PubMed1991

[Hormone dependence of juvenile nasopharyngeal fibroma].

Since Martin (1948) and Schiff (1959) first reported the use of sex hormones in JNF patients, many authors have described the various clinical effects and histological changes found after administration of androgens or estrogens. In 1980, Johns attempted unsuccessfully to detect estrogen receptors in the tissue of tumors from JNF patients. In 1987, however, Farag et al. succeeded in the demonstration of androgen receptors in homogenates of such tumor tissue.--In 1989, the authors were able to determine the uptake and receptor-binding of radioactively labelled dihydrotestosterone in cultured fibroblasts from a tumor from a 16-year-old JNF patient, and to confirm this result in two other cases. The maximum levels of hormone binding to the fibroblasts was much the same as is found with genital skin fibroblasts, included in the study as a control androgenic target-tissue with high receptor-density. At the same time it was demonstrated that it was possible to stimulate the tumor fibroblasts in vitro by adding testosterone to the culture medium. The attempt to block cell growth with the antiandrogen cyproterone acetate, was not successful, however. This can possibly be put down to the high progestogenic activity of this antiandrogen. Further in vitro studies with substances which are purely androgenic (e.g., flutamide) or with the acetate-free form of cyproterone (which has no progestogenic activity) will possibly be of help in the search for a substance capable of blocking tumor growth.

Adolescent↗
PubMed1991

[Fibrinolytic therapy in sudden deafness with recombinant tissue-type plasminogen activator. Hemorheologic and therapeutic effects].

In the course of a pilot study, the effects of fibrinolysis treatment with rt-PA (Actilyse, Thomae, Biberach; 100 mg) on the recovery of hearing and hemorheologic parameters were investigated in 12 patients suffering from sudden hearing loss. The authors' approach was based on two considerations, (1) the possibility that, in cases of sudden hearing loss, the oxygen supply to the cochlea is totally or partially blocked by a microthrombus which could be dissolved by rt-PA and (2) the fact that lysis markedly improves the flow characteristics of the blood (as has been demonstrated in studies with streptokinase and urokinase). This human-plasminogen activator, produced by genetic engineering, is superior (also in terms of possible side-effects) to other lysin enzyme preparations (streptokinase, urokinase) because of its highly selective effects on thrombi (low activation of plasma plasminogen) and its short half-life (approx. 4 min). In nine of 12 patients, the treatment brought about a marked improvement in hearing or its complete restitution (three of the patients has initially been deaf in the affected ear). In the three nonresponders there was serologic evidence of an inner-ear infection (neuroborreliosis, cytomegaly, influenza B). The most interesting rheologic effect was the reduction of plasma viscosity (average decrease about 18%), since such a reduction cannot be attained with other, comparable rheologic measures (isovolemic or hypervolemic hemodilution). In spite of the convincing hemorheologic effects, fibrinolysis cannot yet be recommended as treatment for sudden hearing loss. Further studies have still to be done on spontaneous healing, the effects of hemorheologic measures on the blood circulation of the inner ear, and on the oxygen requirements of the ear affected by hearing loss.

Adult↗
PubMed1991

[Functional nasopharyngeal fiberoptic endoscopy for pre-therapeutic diagnosis of sleep apnea syndrome in infants. A case report].

We report a 2-year-old infant with severe obstructive sleep apnoea. The symptoms had deteriorated for several months, and indicated complete obstruction shortly after the child fell asleep, with reduction of the oxygen saturation to under 30%. Since the obstruction could only be interrupted by waking the child, a tracheostomy was proposed. Endoscopy under general anaesthesia revealed no pathological findings. The stenosis could only be seen using transnasal fibre-optic endoscopy when the obstruction occurred during sleep: the oropharyngeal wall collapsed at the level of the velopharyngeal sphincter. A tube passed through the nose and through the collapsing section of the pharynx to the entrance of the larynx prevented the apnoea. The parents were taught to introduce and fix the tube. After an observation period of 1 year the larynx had stabilized spontaneously, and the tube has to be introduced only rarely.

Child, Preschool↗