Correlation of apoptotic potential of simple oxiranes with cytotoxicity.

The measurement of primary DNA damage caused by oxirane chemicals can be confounded by apoptotic-generated DNA autolysis. The apoptogenic potential of oxiranes requires knowledge of the relationship between the apoptotic threshold dose and cytotoxic dose for interpretation of DNA damage assays. This research determined the relationship between cytotoxic and apoptotic doses for seven simple oxiranes of varying structure. This relationship between cytotoxic and apoptotic thresholds was determined simultaneously in in vitro cell culture. L929 cells in log-phase growth were exposed to the oxiranes for 24 h in 25 cm(2) and then assayed fluorometrically in 96-well plates for Caspase 3. Viability was assessed using Trypan Blue exclusion and loss of Caspase 3 activity. Ranked apoptotic potency was: diepoxybutane (DEB)>styrene oxide (SO)>phenyl glycidyl ether (PGE)>epichlorhydrin (EPI)>glycidol (GLY)>epoxybutane (EB)>epoxycyclohexane (ECH). Relative cytotoxicity was significantly correlated (r(s)=0.86, p=0.02) with potencies: DEB>EPI>PGE>SO>GLY>EB>ECH. These structurally-diverse, simple oxiranes were all capable of inducing apoptosis at doses several-fold below their cytotoxic concentrations. Difunctionality and aromaticity were key predictors of potency for both. Caspase 3 activity was an accurate indicator of necrosis which correlated with Trypan Blue results.

[Mobile autonomous robots-Possibilities and limits]. / Intelligente autonome Roboter - Möglichkeiten und Grenzen.

Besides industrial robots, which today are firmly established in production processes, service robots are becoming more and more important. They shall provide services for humans in different areas of their professional and everyday environment including medicine. Most of these service robots are mobile which requires an intelligent autonomous behaviour. After characterising the different kinds of robots the relevant paradigms of intelligent autonomous behaviour for mobile robots are critically discussed in this paper and illustrated by three concrete examples of robots realized in Lübeck. In addition a short survey of actual kinds of surgical robots as well as an outlook to future developments is given.

Quantum mechanical quantitative structure activity relationships to avoid mutagenicity in dental monomers.

The objective of this study was to identify through quantum mechanical quantitative structure activity relationships (Q-QSARs) chemical structures in dental monomers that influence their mutagenicity. AMPAC, a semiempirical computer program that provides quantum mechanical information for chemical structures, was applied to three series of reference chemicals: a set of methacrylates, a set of aromatic and a set of aliphatic epoxy compounds. QSAR models were developed using this chemical information together with mutagenicity data (Salmonella TA 100, Ames Test). CODESSA, a QSAR program that calculates quantum chemical descriptors from information generated by AMPAC and statistically matches these descriptors with observed biological properties was used. QSARs were developed which had r2 values exceeding 0.90 for each study series. These QSARs were used to accurately predict the mutagenicity of BISGMA. a monomer commonly used in dentistry, and two epoxy monomers with developing use in dentistry, GY-281 and UVR-6105. The Q-QSAR quantum mechanical descriptors correctly predicted the level of mutagenicity for all three compounds. The descriptors in the correlation equation pointed to components of structure that may contribute to mutagenesis. The QSARs also provided 'dose windows' for testing mutagenicity, circumventing the need for extensive dose exploration in the laboratory. The Q-QSAR method promises an approach for biomaterials scientists to predict and avoid mutagenicity from the chemicals used in new biomaterial designs.

Single-case experimental designs in medical education: an innovative research method.

This paper presents an argument for more extensive use of single-case experimental research designs in medical education research. Single-case experimental designs consist of a group of experimental techniques that are widely used in the social sciences but are just beginning to be utilized by medical researchers. The method emphasizes reliable observations of behavior, repeated measurements of outcome, and individualized tailoring of objectives for each subject; all of these occur within a system that allows an experimental analysis to be conducted. Single-case designs are particularly useful when only small numbers of participants are available for a relatively long period of time. Trends in medical education toward individualized instruction, adult-centered learning, and fine-grained analyses of medical skills and knowledge make this field especially amenable to single-case experimental designs. Issues of internal and external validity, generality, practicality, and ethics are discussed, and several typical designs are illustrated. While the emergence of qualitative research methods in medical education may prove useful, single-case designs can maintain experimental science's emphasis on methodologic rigor, while allowing the flexibility often needed to conduct research in applied settings.

[The layers of the gallbladder wall: an ultrasound-anatomic comparative study]. / Die Schichten der Gallenblasenwand: Eine sonographisch-anatomische Vergleichsuntersuchung.

In a sonographic-histological comparative test, operatively withdrawn gallbladders in native and formol-fixed states were examined. The thickness of the gallbladder wall and of its layers was measured sonographically. Afterwards the gallbladders were reexamined microscopically in the sonographic sectional plane and the measurement was repeated. By removal of the single layers of the wall and by repeated sonographic measuring, sonographic and microscopic measurements of the parietal layers could be correlated. Both gallbladder wall thickness and thickness of the single anatomic layers can be evaluated sonographically. The correlation between sonographic and histological measurements is fairly to highly significant. The sonographically measurable layers can be related to the following anatomical layers (when measuring from outwards to inwards): 1. echogenic layer = initial echo and subserosa; 2. echo-poor layer = muscularis; 3. echogenic layer = lamina propria; 4. echo-poor layer = mucosal epithelium; 5. echogenic layer = exit echo.

[The chemoradiotherapy of advanced colorectal carcinoma--the results and toxicity in a pilot study with 44 patients]. / Chemoradiotherapie des fortgeschrittenen kolorektalen Karzinoms--Ergebnisse und Toxizität einer Pilotstudie mit 44 Patienten.

Forty-four evaluable patients with advanced colorectal cancer were treated with simultaneous chemoradiotherapy to the small pelvis. In 34 patients locally recurrent disease and in ten patients primary tumors had been resected. 34 patients had gross and ten patients had microscopic residual tumor after surgical resection, seven of the latter with distant metastases. Radiotherapy was given to a dose of 50 Gy in five weeks. During the first two weeks of treatment simultaneous chemotherapy was applied, using continuous 24 hour intravenous infusion of 5-fluorouracil at 500 mg/m2 on days 1 to 5 and 8 to 12 and bolus injection of mitomycin C at 5 mg/m2 on days 5 and 12. Two-year local control rates in patients with microscopic residual were 76% compared to 36% in patients with gross residual disease. Two-year survival rates were 5/7 patients for microscopical residual tumor and 13/30 patients (44%) with gross residual tumor. Considerable rates of acute and late toxicity were observed, however, these rates were not higher than results reported by others. In view of the increasing interest in chemoradiotherapy for residual and recurrent colorectal cancers, a randomized multicenter study has been opened (ARO I/91). Aim of this clinical trial is to find out, whether patients with advanced colorectal cancer benefit from simultaneous chemoradiotherapy.

[Dose-finding study for hyperfractionated, accelerated radiotherapy plus simultaneous carboplatin administration in patients with locoregionally advanced head and neck cancer]. / Dosisfindungsstudie zur hyperfraktionierten, akzelerierten Strahlentherapie plus simultaner Carboplatin-Gabe bei Patienten mit lokoregionär fortgeschrittenen Kopf-Hals-Karzinomen.

Therapy of large inoperable squamous cell-carcinomas of the head and neck is considerably problemful. Combined simultaneous radio-chemotherapy with carboplatin and radiotherapy with hyperfractionated accelerated radiation is small effective than conventional monofractionated radiotherapy alone and may reduce side effects. Aim of the following study was dosage optimisation of the applicated carboplatin.

[An atypical site of a solitary eosinophilic granuloma in the distal humerus]. / Atypische Lage eines solitären eosinophilen Granuloms am distalen Humerus.

The case of a ten-year old girl, presenting with pain and restricted movement of the left arm is reviewed. X-rays and bone scan suggested an Ewing's sarcoma of the left humerus, so that the child was referred to surgery. Surprisingly, the histological examination of the surgical specimen revealed a solitary eosinophilic granuloma of the bone.

[The therapeutic results and early and late toxicities of the treatment of anal canal carcinoma by radiotherapy or chemoradiotherapy]. / Therapieergebnisse, Früh- und Spättoxizität der Behandlung des Analkanalkarzinoms durch Strahlentherapie oder Chemoradiotherapie.

From 1975 to 1989 114 patients with anal canal carcinoma were treated, 81 of these with radiotherapy (RT) alone and 33 with chemoradiotherapy (CRT), 80% respectively 82% of the patients were colostomy-free at the onset of therapy. RT was given to a total dose of 60 Gy in six weeks, for CRT additional simultaneous 5-fluorouracil (500 mg/m2 days 1 to 5 and 8 to 12) and mitomycin C (5 mg/m2 days 5 and 12) was administered. 67% respectively 82% of the patients had UICC stage II to IIIB disease predominantly with G2 and G3 squamous cell carcinomas. Local control after three years was 79% for the RT group vs. 82% for the CRT group. Three-year survival rate was 68% and 71%, respectively. These differences were not significant. Only for G1- compared to G3-tumors there is a significantly higher survival rate. Acute and late damage was slightly lower for the RT treatment group (77% and 25%) compared to the CRT group (79% and 30%). In both treatment groups there was one patient needing a permanent colostomy due to radiation induced proctitis. In conclusion, RT or CRT should be the primary form of treatment in patients with and canal carcinoma and abdominoperineal resection should only be performed in case of local recurrence or tumor persistence. The final decision about the indications for RT or CRT can only be made with the results of a prospective randomized trial.

Tumors of the urinary bladder in painters: a case-control study.

In a case-control study, 403 male patients with a diagnosis of "bladder tumor" and (as controls) 426 patients suffering from prostate disease were investigated. The results of this study indicate that past employment as a painter was associated with an excess risk of bladder tumor. The relative risk of bladder tumor estimated for painters was 2.76. The possible role of benzidine-based azodyes (or azodyes based on substituted benzidines) as a carcinogenic risk factor for painters is discussed.

Treatment results and acute and late toxicity of radiation therapy for testicular seminoma.

From 1977 to 1988, 215 patients with a diagnosis of testicular seminoma were referred to the University Hospital, Hamburg, West Germany, for radiation therapy (RT). In 15 patients a careful review of the histologic condition showed signs of embryonal cell carcinoma. Three patients refused completion of therapy. No patient was lost to follow-up. On this basis, a retrospective review of 197 patients was carried out. One hundred thirty-three patients were classified as Stage I (67%), 39 as Stage II (20%), 8 as Stage III (4%), and 17 as Stage IV (9%). One hundred eighty patients had classic seminoma and 17 had anaplastic seminoma. All patients underwent high inguinal orchiectomy before treatment. Seven patients with Stages III and IV received chemotherapy before RT. Patients with Stages I and II were treated with 40-Gy photons to paraaortic and parailiac fields. Ten patients with Stage III and IV seminoma received 30-Gy photons to mediastinal and supraclavicular fields as well. Sixty patients received additional inguinal RT. The overall 5-year survival rate (corrected for intercurrent death, except for treatment toxicity) was 100% for Stage I, 100% for Stage II, 87% for Stage III, and 87% for Stage IV. The mean follow-up time was 6.3 years (range, 0.6 to 11.9 years). An evaluation of all patients showed no difference according to histologic condition or prior chemotherapy. Mediastinal and supraclavicular irradiation showed no improvement in treatment results. Acute toxicity consisted of mild to moderate emesis, increased bowel frequency, erythema, and, in four cases leucopenia and thrombopenia (all World Health Organization [WHO] Grades I to II). However, one patient died of a pulmonary fibrosis 1 month after mediastinal irradiation and 2 months after polychemotherapy, and a gastroduodenal ulcer developed in another patient 1.5 months after paraaortic RT and prior polychemotherapy. Overall, the data suggest that to avoid overtreatment and consecutive treatment morbidity reduced doses of 30 Gy and a restrictive treatment planning adapted to the individual risk are sufficient for RT for testicular seminoma. An alternative to postoperative RT in Stage I (and possibly Stage II) seminoma could be no RT, but close follow-up instead.

Results of fast neutron therapy of adenoidcystic carcinomas of the head and neck at the neutron facility Hamburg-Eppendorf.

Between July 1977 and March 1988, 31 patients with an adenoidcystic carcinoma were treated with fast neutrons of a 14 MeV-DT-generator at our department. Primary locations were: parotid gland eight cases, paranasal sinus five cases, submandibular gland five cases, trachea four cases and other locations nine cases. The median follow-up of our patients was 16 months. Most of the patients had advanced tumors. The calculated local control rate is 65% at two years.

Results of fast neutron therapy of adenoid-cystic carcinomas of the head and neck at the neutron therapy facility Hamburg-Eppendorf.

Between 1977 and 1987, 30 patients with adenoid-cystic carcinomas of the head and neck region were treated, at the Hamburg-Eppendorf neutron therapy facility, with a 14 MeV-DT-generator. The present review deals with 15 patients treated before October 1986 e.g. with follow up longer than one year. These results, although preliminary, tend to confirm that fast neutrons is the best irradiation modality of adenoid-cystic carcinomas of the head and neck region, especially when surgery is not possible, or cannot be radical.

The effects of stereotyped behaviour on orienting and tonic cardiac activity.

The relationship of cardiac activity to stereotyped behaviour was studied in profoundly mentally retarded persons, using both inter-group comparisons. The first intra-group comparison involved examining the relative magnitude of an orienting response to an auditory stimulus during the occurrence or nonoccurrence of stereotyped body rocking. While no differences were found between periods of rocking and non-rocking when behavioural measures of orienting were used, smaller changes in post-tone heart rate were observed during periods of stereotyped rocking. A second intra-group comparison found that stereotyped behaviour was associated with a significant increase in heart rate but no change in heart rate variability when compared to periods of no stereotyped activity. Finally, using an inter-group comparison, individuals who displayed stereotyped body rocking exhibited higher tonic heart rates and lower heart rate variability during periods of no stereotyped behaviour than was observed in matched control subjects. This result suggests that stereotyped behaviour may be correlated with reduced vagal tone.

[Clinical studies of the quantitative changes in mineral salt content of irradiated vertebral body metastases with 2-energy computerized tomography]. / Klinische Untersuchungen über die quantitative Veränderung des Mineralsalzgehaltes in bestrahlten Wirbelkörpermetastasen mit der 2-Energie-Computertomographie.

Results are represented a clinical experimental series of examinations in 19 patients having osteolytic and osteoplastic metastases in the region of the vertebral column. An attempt was made to quantify the changes in mineral salt content after high-voltage therapy, via two-energy computed tomography. The vertebral bodies with osteolytic affection showed directly after completion of the irradiation an individually highly differentiated increase in mineral salt content. This was due both to recalcification of the osteolysis and an increase in mineral salt content of the still intact spongiosa. Likewise, an increase in mineral salt content was seen in patients with osteoplastic metastases, in the tumour-free bony substance. The methodical approach is described and the different reactive behaviour of the vertebral body metastases in response to radiotherapy is discussed.