Malignant fibrous histiocytoma in the area of the head and neck]

Although malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life, it is fairly rare in the head and neck region (3-6%). Between 1983 and 1991 8 patients with MFH in the head and neck region have been observed and treated at the ENT-department of the University of Tübingen. 5 patients have been operated (laryngopharyngeal localization), 2 patients underwent irradiation (unresectable fast growing T4-tumors of the pharynx and thyroid) and one female patient refused further therapy after two resections elsewhere. Operated patients showed no evidence of disease 2-8 years after resection (all margins have been controlled histologically). Both irradiated patients died 4 respectively 2 months after full (70 Gy) and incomplete (17 Gy) radiotherapy without visible positive effects. Both patients developed pulmonary metastasis. Since MFH can grow in thin layers along musculaoponeurotic structures the exact size is not always demonstrable by ultrasound, CT or MR scans. Metastasis occur in up to 40%, preferentially in regionary lymph nodes, in lung, liver and skeletal system. These phenomenon requires a full pretherapeutic staging. Histologically MFH is sometimes hard to distinguish from other tumors as for example various sarcomas and pleomorphic carcinoma. Therefore, immunohistochemical (mesenchymal markers) and electron microscopical investigations are advised. Resection with exact histological controll of all margins is the therapy of choice. We experienced that laryngeal MFH (n = 3) can be resected without laryngectomy under certain circumstances. Although unsuccessfull in our two cases, according to the literature, radiotherapy should be administered in unresectable cases. Depending on localization and size of MFH long survival, in single cases healing, of this disease is possible by surgical treatment.     

Distribution of cholinergic neurons in the chick spinal cord during embryonic development. Comparison of ChAT immunocytochemistry with AChE histochemistry.

The location of cholinergic neurons was studied during the development of the chick embryo spinal cord. A comparison between choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry was performed. ChAT-positive neurons could be detected only from embryonic day 9 (E9) onwards by the FITC technique and from E12 onwards by the PAP technique. These neurons were located mainly in the medial and lateral motor columns in the ventral horn of the gray matter and some of them were observed in the intermediate region of the spinal cord. AChE-containing cell bodies were much more numerous than the ChAT immunoreactive ones and were distributed in the ventral horn of the gray matter, the intermediate gray region and mostly off the apical part of the dorsal horn. ChAT should provide a reliable and specific marker for cholinergic neurons.     

Semliki Forest virus-induced polykaryocyte formation is an ATP-dependent event

Summary Infection of Aedes albopictus cells with Semliki Forest virus (SFV) leads to polykaryocyte formation below pH 6.2. This syncytium formation is accompanied by a decrease of the cellular ATP level. Addition of inhibitors of oxidative phosphorylation leads to a rapid, total depletion of ATP in infected cells at pH 6 and results in an inhibition of polykaryocyte formation. However, when cells were exposed for only a few minutes to pH 6 in the presence of the inhibitors and then kept at pH 7.2, the ATP level partially recovered to values sufficient for syncytium formation. Similar results were obtained after ATP depletion induced by 2-deoxyglucose. Thus, it can be concluded that SFV-induced syncytium formation is an ATP-dependent event.With 6 Figures     

Active-specific immunotherapy for melanoma

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.     

CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

Preservation of the non-rectangular cuticular plate/cell axis angle of outer hair cells

Motile properties of outer hair cells (OHCs) may contribute to sharp tuning and amplification in the mammalian cochlea. Shape changes of isolated OHCs in response to various physical and chemical influences have been investigated intensively. However, determinations of shape may have been influenced by unanticipated effects of preparation and preservation of the OHCs investigated. Thus, in a first step, lengths of freshly isolated OHCs from the guinea pig cochlea were determined using a video-enhancing magnification system. The cuticular plate/cell axis angle (CP/CA angle) was then measured in native cells and under the influence of potassium chloride and potassium gluconate incubation. To show the influence of glutaraldehyde (GA) fixation on the isolated OHCs, fixative dependent changes on cell length and CP/CA angle were recorded in native and preincubated OHCs. In these experiments, the cell length of vital isolated OHCs was between 41.5 m, in the basal turn, and 103.7 m, in the apical turn. The average CP/CA angle was 106° ± 4.2° (n = 324 cells, turns 1–4) with no statistically significant differences for the four turns. Under the influence of potassium chloride, cell length was reduced by 8.1%. Potassium gluconate incubation led to a shortening of cell length, followed by a 5.3% increase after 5 min. The CP/CA angle under potassium chloride was decreased (97.0°) and was then increased under the influence of potassium gluconate (110.7°) as a result of cuticular plate tilting. Cell shrinkage after fixation depended on the fixative's osmolarity and on the GA concentration. Increased GA levels amplified cell shrinkage from 34% for hypo-osmolar solutions to 15% in iso-osmolar and 29% in hyperosmolar solutions. The CP/CA angle of native and incubated OHCs was not different from those fixed with GA. The present data provide a rational basis for isolated OHC shape parameters. Moreover, functionally induced changes can be better interpreted when OHCs are influenced by fixatives, as shown in the GA experiments.