Popliteal entrapment syndrome: non-invasive diagnosis and complete recovery after surgery in an 11-year-old boy.

We present an unusual case of popliteal entrapment syndrome type I in an 11-year-old boy. Presenting symptoms were exercise-related pain and pallor in his left lower leg. The diagnosis of popliteal entrapment syndrome was established by acral plethysmography, colour-coded Doppler sonography and MRI. After myotomy of the gastrocnemius muscle the symptoms resolved completely. Post-operative duplex scan showed normal blood flow, even in plantar flexion of the foot.

Fluence and mutagenic side effects of excimer laser radiation applied in ophthalmology in human lymphocytes in vitro.

PURPOSE: To investigate the influence of different fluences in 193 and 248 nm excimer laser radiation on the yields of chromatid and chromosome aberrations induced in human lymphocytes in vitro. METHOD: Heparinized human blood was exposed to 193 or 248 nm excimer laser radiation. The fluence was gradually increased from 21 to 400 mJ/cm2 in 193 nm (constant total energy of 250 J) and from 150 to 377 mJ/cm2 in 248 nm radiation (constant total energy of 500 J). Chromatid and chromosome aberrations were then analysed microscopically. RESULTS: The yields of chromatid breaks and achromatic lesions depend on the fluence per pulse. This dependence contains a linear component, indicating a threshold of about 70 mJ/cm2 fluence in 193 nm and of about 250 mJ/cm2 fluence in 248 nm laser radiation. An increase of the yield of dicentric chromosomes could only be observed at the highest fluence tested (377 mJ/cm2) in the 248 nm series. Over 126 mJ/cm2 in 193 nm radiation no lymphocytes could be cultured and therefore no aberrations could be found. CONCLUSIONS: Our findings show that the fluence of 193 nm and of 248 nm excimer laser radiation has an effect on the yields of chromatid breaks and achromatic lesions in human lymphocytes under in vitro conditions.

Biological dosimetry after extensive diagnostic x-ray exposure.

The yield of chromosome aberrations (dicentric and ring chromosomes) was determined for five patients who had been extensively exposed to diagnostic x rays. Remarkably high aberration yields were obtained for each of them leading to correspondingly high equivalent whole body doses ("biological dosimetry"). The contribution of iodized contrast media and computing tomography to the biologically estimated doses is discussed.

Chromosome aberrations in human lymphocytes apparently induced by Chernobyl fallout.

Sixteen people (15 from Byelorussia, one from Kiev) possibly exposed to radioactivity released by the Chernobyl accident were investigated for chromosome aberrations induced in lymphocytes. Statistically significant increases of the yield of dicentric chromosomes were observed in five people.

[Calcium antagonists as amplifiers of the mutagenicity of cytostatic drugs]. / Kalziumantagonisten als Wirkverstärker der Mutagenität von Zytostatika.

Some calcium antagonists enhance synergistically the mutagenic efficiency of cytostatics. The results so far obtained concerning this phenomenon are described and discussed: (1) chromosome aberrations induced (in vitro) in human lymphocytes (cytostatics; bleomycin and peplomycin; calcium antagonists: verapamil and fendiline), (2) chromosome and chromatid aberrations induced (in vitro) in Chinese hamster ovary (CHO) cells (cytostatic: mitomycin C; calcium antagonist: verapamil), (3) gene mutations induced in the bacterium Salmonella typhimurium (cytostatics: mainly various anilinoacridine drugs; calcium antagonist: verapamil). In all 3 studies neither verapamil nor fendiline proved to be mutagenic when applied alone. The "comutagenicity" of calcium antagonists is compared with the enhancement of the cytotoxic (cell killing) efficiency of cytostatics by calcium antagonists. Both phenomena--potentiation of mutagenicity and of cytotoxicity--are interpreted on the basis of the "accumulation hypothesis". According to this hypothesis those calcium antagonists would enhance the mutagenic and cytotoxic efficiency of the cytostatics by inhibiting their extrusion from the cell. Consequently, the cytostatics would be accumulated in the cell and this would increase their mutagenic and cytotoxic efficiency. Since not all calcium antagonists investigated so far enhance the mutagenicity and cytotoxicity of cytostatics, this potentiation seems not to be caused by their calcium antagonistic action per se. Molecular, evolutionary, and medical aspects of the "accumulation hypothesis" are shortly discussed.

Time-saving in biological dosimetry by using the automatic metaphase finder Metafer2.

The amount of time-saving by using the Metafer2 metaphase finder for routine analysis of radiation-induced chromosome aberrations (biological dosimetry) was determined. Metaphases were prepared by standard methods from cultures of human peripheral blood lymphocytes and stained either with Giemsa or with the FPG method. The metaphase finder was used for detecting metaphases on the microscope slides and for automatically processing the evaluation data. In our laboratory, standardized analysis of 1000 metaphases requires at least 3 working days for cell culturing and slide preparation and 51.5 working hours for cytogenetic analysis. When using the metaphase finder the time required for cytogenetic analysis is reduced to 17.3 working hours (time-saving factor: 51.5/17.3 h = 3.0). In our prolonged method, including more than one scoring of each slide and karyotyping of metaphases with chromosome aberrations, the analysis times for 1000 cells are 132 and 70 working hours, respectively (time saving factor: 132/70 h = 1.9).

Significance testing in mutagen screening: the dependence of statistical power on the control sample size.

The continuous accumulation of control data in multicellular mutagen screening systems prompted us to study the dependence of the statistical power on the size of the control sample (for fixed control values). Two widely used screening systems were chosen: dicentric chromosomes in human lymphocytes and recessive sex-linked lethals in Drosophila melanogaster. The power increases rapidly at first as the control sample size increases, then levels off at a few tens of thousands of control units tested and thereafter remains almost constant up to the historical control. The practical implications from our study are discussed.

Enhancement of the mutagenicity of anticancer drugs by the calcium antagonists verapamil and fendiline.

The enhancement of the mutagenicity of anticancer drugs by the calcium antagonists verapamil (CAS 52-53-9) and fendiline (CAS 13042-18-7) is reviewed. Both calcium antagonists enhance synergistically the induction of chromosome aberrations (dicentric and ring chromosomes) in cultured human lymphocytes by the antitumor agent bleomycin. Since two other calcium antagonists, nifedipine and diltiazem, when tested with the same system, did not show this effect, the comutagenicity of verapamil and fendiline does not seem to be related with calcium antagonism per se. Verapamil furthermore potentiates the induction of various chromosome and chromatid aberrations in Chinese hamster ovary (CHO) cells in vitro by the antitumor agent mitomycin C. In bacteria (Salmonella typhimurium) verapamil enhances synergistically the induction of gene mutations (frameshifts) by several anticancer drugs, including various anilinoacridine derivatives. When applied alone, neither verapamil which was tested in each of the three studies (human lymphocytes, CHO-cells, and bacteria) nor fendiline, which was tested only in human lymphocytes, proved to be mutagenic. To explain the comutagenicity of verapamil and fendiline, it is assumed that they prevent the mutagen (e.g., bleomycin) to be extruded from the cell. Consequently, the mutagen would be accumulated intracellularly and this would enhance its efficiency.

A model for testing the mutagenicity of excimer laser radiation in ophthalmology.

Because excimer laser radiation is applied more and more in therapeutic and refractive corneal surgery, the possibility of mutagenic side effects of this treatment should be considered. A mutagenicity model is presented approximating closely the ophthalmological conditions when mutagenic effects are studied: Heparinized human blood is filled into the anterior chamber of an enucleated cow eye. After irradiation of the cornea with the excimer laser, the blood is removed and whole blood cultures are set up. Lymphocytes are stimulated, fixed during metaphase, and scored for chromatid and chromosome aberrations. First results obtained with this model after 248 nm laser irradiation (500 J, 277 mJ/cm2, 10 or 20 Hz) revealed no mutagenic effects. However, when the blood was exposed under the same physical conditions in a quartz chamber (positive control), statistically highly significant increases of the yields of chromatid aberrations were observed.

[Induction of chromosome aberrations in human lymphocytes as a model for evaluating the mutagenic effect of excimer laser irradiation in ophthalmology]. / Die Induktion chromosomaler Aberrationen in menschlichen Lymphozyten als Modell zur Prüfung der mutagenen Wirkung von Excimerlaserstrahlung in der Ophthalmologie.

A model for testing the mutagenicity of excimer laser radiation in ophthalmology is presented. In contrast to other studies using cell monolayers, in our study with this model human peripheral lymphocytes (heparinized whole blood) are exposed to laser irradiation at different conditions. The possible mutagenicity of secondary radiation after exposure of the cornea is also considered. The heparinized blood is either injected into the anterior chamber of an enucleated bovine eye or filled into a quartz chamber (positive control). After irradiation the lymphocytes are stimulated and fixed during metaphase, after which the metaphases are scored for chromatid and chromosome aberrations. In the positive control group, exposure to 248 nm excimer laser radiation (500 J, 277 mJ/cm2, 10 and 20 Hz) was followed by a highly significant increase in the yield of chromatid aberrations (chromatid breaks and achromatic lesions).

Enhancement of bleomycin-induced DNA damage by exposing isolated DNA to high concentrations of the calcium antagonist verapamil.

The calcium antagonist verapamil was found to enhance synergistically the DNA (desoxyribonucleic acid) strand breakage activity of the radiomimetic antitumor agent bleomycin in vitro. The induction of single and double strand breaks in isolated DNA was investigated by agarose gel electrophoresis. Three types of DNA (two plasmids and one native eukaryotic DNA) were used as target molecules. The effect of verapamil was concentration dependent (concentration range tested: 0.75-3.0 mmol/l). However, at those low concentrations, as they were used in cytotoxicity assays and cytogenetic experiments, no potentiating effect of verapamil on bleomycin action could be observed. The significance of these findings is discussed with respect to various hypothesis concerning the potentiation of tumor drug efficiency by verapamil and other calcium antagonists.

[The effective dose equivalent: clarification and comments on the new dosage concept]. / Die effektive Aquivalentdosis: Erläuterungen und Anmerkungen zu einem neuen Dosiskonzept.

The concept of the effective dose, based on stochastic radiation effects (genetic damage and cancer), is explained and discussed. Reasons are given why this concept should consider the cancerogenic action of radiation only and not, in addition, the hereditary radiation effects. This view does not contradict our knowledge that the gonads have to be protected especially carefully from the mutagenic action of ionising radiation.

Chromosome aberrations induced in human lymphocytes by an X-radiation accident: results of a 4-year postirradiation analysis.

After occupational and medical radiation exposures structural chromosome aberrations may be induced in the lymphocytes of the irradiated persons. Many authors have estimated the radiation dose from the yields of dicentric aberrations. We analysed the influence on the dicentric yield of increasing time intervals between irradiation and blood sampling from a person involved in an X-radiation accident (radiography). During a 4-year follow-up we observed an approximately 7-fold decline of the dicentric yield up to the 25th month and thereafter an almost constant value. Since the decline did not commence until around the 10th month after the exposure, an exponential decrease of dicentric yield with time should be considered with reservation in this study, although it cannot be entirely ruled out. We conclude that in 'biological dosimetry' blood should be sampled as early as possible after the exposure. Furthermore, computation of 'half-times' of lymphocytes to allow for a delay in blood sampling seems uncertain after partial body exposures to high doses. Therefore in such cases dose estimates obtained 1 or more years after irradiation should be considered as minimum values.

[New results on the linearity of the dose-response relationship of radiation-induced mutation]. / Neue Ergebnisse zur Linearität der Dosis/Wirkung-Beziehung strahlen-induzierter Mutationen. Untersuchungen an menschlichen Zellen im Niedrigdosisbereich.

Mutations induced by ionizing radiation in germ cells may affect future generations; mutations induced in somatic cells may damage the irradiated persons themselves, because radiation carcinogenesis is assumed to result from genetic damage induced in somatic cells. Since we are exposed mainly to low doses of ionizing radiation, both from natural and artificial sources, especially the dose dependence of radiation-induced mutations in the low-dose range is of interest. A review of recent studies on the induction of mutations by X-rays in human cells (in vitro) favors the hypothesis that in the low-dose range the dose dependence is linear, without a "threshold."

Enhancement of the cytogenetic efficacy of the antitumor agent bleomycin by the calcium and calmodulin antagonist fendiline.

The induction of chromosome aberrations (dicentric and ring chromosomes) in human lymphocytes by the antitumor agent bleomycin is synergistically enhanced when bleomycin is applied together with the calcium antagonist fendiline (Sensit).

Synergistic enhancement of the bleomycin and peplomycin induced mitotic index reduction by verapamil.

The cytostatics bleomycin and peplomycin are known to reduce the mitotic index. It is shown that in cultured human lymphocytes the heart drug verapamil (Isoptin) increases this effect synergistically. This seems to be for the first time that synergism in the reduction of the mitotic index by chemical agents has been demonstrated.

The cytogenetic efficiency of the antitumor agents bleomycin and peplomycin is enhanced by the heart drug verapamil (isoptin).

The induction of 2-break chromosome aberrations (dicentrics and ring chromosomes) in human lymphocytes by the antitumor agents bleomycin and peplomycin is strongly enhanced when those agents are applied together with the heart drug verapamil (isoptin).