Primary duodenal adenocarcinoma: a ten-year experience with 79 patients

The comet assay is frequently used to measure DNA damage in individual cells. In order to better understand the mechanisms behind the technique, we have studied the behaviour of DNA under different electrophoresis conditions in mammalian cells exposed to gamma radiation. The comet tails obtained after neutral electrophoresis seem to consist of DNA loops which are attached to structures in the nucleus, since the DNA cannot move in the second direction after two-dimensional electrophoresis. When the DNA is labelled by a short pulse, microautoradiography reveals that all label appear in the head of the comets when neutral electrophoresis is applied. After chase incubation, the label moves out into the tails. This gives further support to the view that the DNA loops are fixed to some structure in the nucleus where also the DNA synthesis takes place. Under alkaline electrophoresis conditions, however, the entire comet tails move in the new electrophoresis direction. Thus, it appears that the alkaline comet tails consist of free DNA fragments. Further, the effects of alkaline concentration and sodium chloride during unwinding and electrophoresis are discussed. Throughout the study, a protocol for drying and fixation of the comets has been used.     

MDA-MB-453, an androgen-responsive human breast carcinoma cell line with high level androgen receptor expression

The role of androgens and the androgen receptor (AR) in the development and progression of breast cancer is poorly understood. To further define a potential model for androgen action in breast cancer, MDA-MB-453 cells, which express AR in the absence of oestrogen receptors and progesterone receptors, were further characterised in terms of AR expression and androgen responsiveness. High level expression of AR was confirmed by northern blot analysis, radioligand binding and immunocytochemistry, and could not be accounted for by AR gene amplification. Three endogenous androgen-responsive genes (fatty acid synthetase, gross cystic disease fluid protein of 15 kDa and prolactin receptor) and a transfected reporter gene, containing an androgen-responsive element, were induced following androgen administration. A synthetic androgen, mibolerone, induced moderate (27% above control) stimulation of MDA-MB-453 cell proliferation, which was abrogated by the simultaneous administration of the synthetic androgen antagonist, anandron, demonstrating that the effect was AR-mediated. In summary, MDA-MB-453 cells express high levels of functional AR, and thus provide a valuable in vitro model for further studies on androgen regulation of gene expression, and perhaps cell proliferation in breast cancer.     

Cytotoxic activity of platelets and peripheral blood mononuclear cells from oncology patients and healthy donors

Testicular germ cell tumour is said to be a model for curable neoplasm. However, the prognosis of primary extragonadal germ cell tumour does not appear to be as promising. Though similar in histology, the biology of primary extragonadal germ cell tumour is different as exemplified by the patients in this review. Eight patients with primary mediastinal germ cell tumours were treated with intensive cisplatin-based chemotherapy. All, except one, had non-seminomatous components. The poor prognosis of mediastinal germ cell tumour is due to a combination of poor treatment results with the cisplatin-based regimen and the development of non-germ cell and haematological malignancies.     

Some practical improvements in the continual reassessment method for phase I studies

The Continual Reassessment Method (CRM) is a Bayesian phase I design whose purpose is to estimate the maximum tolerated dose of a drug that will be used in subsequent phase II and III studies. Its acceptance has been hindered by the greater duration of CRM designs compared to standard methods, as well as by concerns with excessive experimentation at high dosage levels, and with more frequent and severe toxicity. This paper presents the results of a simulation study in which one assigns more than one subject at a time to each dose level, and each dose increase is limited to one level. We show that these modifications address all of the most serious criticisms of the CRM, reducing the duration of the trial by 50-67 per cent, reducing toxicity incidence by 20-35 per cent, and lowering toxicity severity. These are achieved with minimal effects on accuracy. Most important, based on our experience at our institution, such modifications make the CRM acceptable to clinical investigators.     

Lumbosacral lipomas with spinal bifida

Spinal dysraphism is usually accompanied with lumbosacral lipoma. The neurological deficits such as lower extremities sensorimotor disturbances, bowel and bladder dysfunction are produced by tethering, compression of lipoma and direct transmission of external force on the spinal cord during growth period. 25 patients treated surgically at our hospital between May, 1985, and January, 1993, were reviewed. Surgical approach was designed for debulking the lipomatous mass, untethering and decompressing the cord, repairing the dural defect and paraspinal muscle cleft. 2-59 months (mean 37.5 mons) after operation the 2 patients whose neurological system were normal before operation remained intact. In other 23 patients, bowel function recovered in 75%, active urination restored and improved in 66.2%. Motor dysfunction and paresthesia of the lower extremities alleviated in 78.3%. A case of mild uremia returned to normal and another moderate case improved. None was deteriorated by the operative procedure except one case in which a posterior nerve root was injured.     

Progression of chronic obstructive pulmonary disease after multiple episodes of an occupational inhalation fever

A carding machine operator in a synthetic fabric plant experienced marked symptomatic deterioration of obstructive pulmonary disease after multiple episodes of an occupational inhalation fever. Polytetrafluoroethylene was used in the industrial process and polymer fume fever is suspected as a cause of his febrile illnesses. A state industrial hygiene inspection revealed that major repairs had been performed on an air scrubber system in close proximity to the patient's work area after he had left the plant because of disability. We believe that this case provides further evidence that polymer fume fever is not always a benign, self-limited illness, especially when workers suffer multiple episodes and/or have underlying pulmonary disease.     

Formalin-induced chemiluminescence in model protein-lipid systems

Mechanisms of formalin--induced luminescence of protein-lipid complexes have been studied. Free radical reactions of lipid oxidation were shown to be necessary for generating luminescence quanta. The luminescence intensity was mostly promoted by fluorescing products formed in the reoxidized system protein-lipid. Formalin-induced flash of luminescence in these systems may evidently serve as an express-method for analysing protein sample contamination with unsaturated lipids.