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Biomedical subjects

R J Stephens

Publications and source records attributed to R J Stephens.

At least 19 recordsLinked to original sources
PubMed1992

Quantitative determination of hydroxy fatty acids as an indicator of in vivo lipid peroxidation: oxidation products of arachidonic and docosapentaenoic acids in rat liver after exposure to carbon tetrachloride.

An improved gas chromatography-mass spectrometry method has been applied to the quantitation of both in vitro and in vivo products of lipid peroxidation in rat liver stimulated with carbon tetrachloride. The method avoids problems of autoxidation of unsaturated fatty acids during sample preparation, and the sensitivity permits assays on as little as 1 mg of tissue. This permits small samples of tissue to be obtained by biopsy from the same organ, thus making it possible to perform in vivo time studies on a single animal. Lipids from whole tissue or cell preparations are simultaneously extracted and reduced by catalytic hydrogenation and then saponified and derivatized to their pentafluorobenzyl esters and trimethylsilyl ethers. Quantitation is accomplished by negative ion chemical ionization gas chromatography-mass spectrometry, using either deuterated compounds or naturally occurring fatty acid metabolites as internal standards. Hydroxy fatty acids which result from reduction of the hydroperoxides of arachidonic and docosapentaenoic acids are found to increase within 20 min after exposure of liver or hepatocyte suspensions to carbon tetrachloride.

Animals↗
PubMed1991

Quantitative determination of hydroxy fatty acids as an indicator of in vivo lipid peroxidation: gas chromatography-mass spectrometry methods.

A new method has been developed for the quantitation of lipid peroxidation products by gas chromatography-mass spectrometry. An important advantage over existing gas chromatography-mass spectrometry methods is the elimination of autoxidation during sample preparation. The sensitivity is sufficient to permit measurement of lipid peroxidation products under normal physiological conditions on as little as 1 mg of tissue. Lipids from whole tissue samples or cell preparations are reduced by catalytic hydrogenation during extraction. The hydrogenation stabilizes the compounds by saturating the double bonds and reducing the hydroperoxides to hydroxy derivatives. The saturated lipids are then saponified and the resulting fatty acids are converted to pentafluorobenzyl esters. Hydroxy fatty acids are further converted to trimethylsilyl ether derivatives. Quantitation is accomplished by negative ion chemical ionization gas chromatography-mass spectrometry, using deuterated internal standards. Specific products from polyunsaturated fatty acids can be quantitated, and the method differentiates between products produced by free-radical and photooxidation mechanisms. Increased levels of lipid peroxidation products, above normal physiological levels, that result from prooxidant conditions, such as exposure of animals to carbon tetrachloride, can be measured.

Animals↗
PubMed1991

Assessment of quality of life in small-cell lung cancer using a Daily Diary Card developed by the Medical Research Council Lung Cancer Working Party.

Three hundred and sixty-nine patients in an MRC study of combination chemotherapy and radiotherapy for small-cell lung cancer of limited extent were asked to complete a Daily Diary Card which enabled an assessment of their quality of life to be made during and after treatment. The information derived from the card suggests that although cytotoxic chemotherapy has an adverse effect upon quality of life, this impairment only affects the first 2 or 3 days following each course of treatment, although there is also a small deterioration which may be associated with the 'nadir' effect of the blood counts about 10 days after each course. These results should assist physicians in counselling patients about the likely effects of treatment. Just over half of the patients (196) were subsequently randomised to either a further six courses of maintenance chemotherapy or no further chemotherapy, and it is also shown that the patients allocated to no maintenance chemotherapy experienced a gradually deteriorating quality of life, as opposed to the brief but more severe adverse effects which occurred following each course in the maintenance chemotherapy group; this supports the hypothesis of a palliative effect in this latter group. The findings demonstrate that the Daily Diary Card is a sensitive instrument capable of yielding useful information.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A Medical Research Council phase II trial of alternating chemotherapy and radiotherapy in small-cell lung cancer. The Medical Research Council Lung Cancer Working Party.

In a non-randomised study in six centres in the UK, 24 patients with previously untreated small-cell lung cancer of limited extent were treated with a regimen of alternating chemotherapy and radiotherapy to assess response, toxicity, and the feasibility of applying such a regimen on a multicentre basis in the UK. The intention was to give six courses of chemotherapy on five consecutive days at 4-week intervals: etoposide 75 mg m-2 on days 1, 2, and 3; doxorubicin 40 mg m-2 on day 1; cisplatin 100 mg m-2 on day 2; and cyclophosphamide 300 mg m-2 on days 2, 3, 4 and 5. A dose of 20 Gy thoracic radiotherapy was to be given following the 2nd and the 3rd courses, and one of 15 Gy following the 4th course. After 12 patients had been admitted, the cisplatin dosage was reduced to 80 mg m-2 because of unacceptable toxicity. Two patients were withdrawn during treatment on review of their histology because their diagnosis was found to be incorrect. Only one patient of the 12 treated with cisplatin 100 mg m-2 was able to complete treatment, compared with five of the eligible ten given the lower dosage. Among the 22 patients with confirmed small-cell disease, a complete response was reported in 14 (64%) and a partial response in a further three (total response rate 77%). Myelosuppression was the commonest serious adverse effect. It occurred in 19 of the 24 patients and gave rise to septicaemia in five, four of whom were receiving the higher cisplatin dose. Sixteen patients required blood transfusion and ten platelet transfusion. Vomiting, oesophagitis, and peripheral neuropathy occurred in 12, four and four patients, respectively, and radiation pneumonitis developed in two. Treatment was considered a contributory cause of death in four. The working party concluded that the alternating regimen was feasible in only a small proportion of centres in the UK, and decided not to embark on a multicentre randomised trial comparing alternating with conventional scheduling.

Activities of Daily Living↗
PubMed1978

Cytologic responses of postnatal rat lungs to O3 or NO2 exposure.

At the level of exposure employed (approximately 14.0 ppm NO2 or 0.85 ppm O3) epithelial cells at the juncture of the terminal airways and proximal alveoli have previously been shown to be seriously injured or destroyed in maturing (35 days of age or older) and adult lungs. Subsequent repair results in the formation of a tissue nodule at this location. In contrast, postnatal rats between birth and weaning have been shown to be highly resistant to the cytotoxic effects of both NO2 and O3. Prior to wearning, exposure to O3 resulted in little or no injury when examined with either the light or electron microscope, and only minor injury and loss of cilia from epithelial cells lining the terminal airways was noted after NO2 exposure. Subsequent to weaning at 20 days of age, however, there was a progressive increase in the cellular response in both the terminal airways and proximal alveoli after exposure to either oxidant gas. A plateau in the response is reached at approximately 35 days of age and continues until the animals are approximately 1 year old. The data are discussed in terms of current theories on endogenous antioxidant mechanisms.

Animals↗
PubMed1977

Acute leukaemia after busulphan.

During a double-blind study of two years' cytotoxic chemotherapy with busulphan or cyclophosphamide in patients who had had resection of carcinoma of the bronchus the long-term effects of these two drugs were also studied. Four of the 243 patients treated with busulphan developed leukaemia compared with none of the 234 treated with cyclophosphamide and none of the 249 on placebo. None of these four patients received radiotherapy or other cytotoxic chemotherapy before leukaemia was diagnosed, and all four were among the 19 patients who developed pancytopenia while taking busulphan, five to eight years before leukaemia became clinically apparent. These findings suggest that busulphan is leukaemogenic, though its mode of action is uncertain.

Acute Disease↗
PubMed1977

An improved method for the histochemical localization of glucose-6-phoshate dehydrogenase in animal and plant tissues.

An improved procedure is reported for the histochemical localization of glucose-6-phosphate dehydrogenase in fresh-frozen sections of animal and plant tissues. Used in this procedure are an incubation medium and an inert high-molecular-weight polyvinyl alcohol as a stabilizer to check enzyme diffusion. The incubation medium consists of 10 mg each of nicotinamide adenine dinucleotide phosphate and nitroblue tetrazolium chloride and 60 mg of glucose-6-phosphate per 20 ml of 22% polyvinyl alcohol solution in 0.2 M Tris-maleate buffer, pH 7.2. Use of this medium has given consistent results with the tissues tested. Because the use of an electron-transfer agent in the incubation medium often resulted in enzyme diffusion, its use in glucose-6-phosphate dehydrogenase localization is considered undersirable. Incubation time of 15 to 30 min for animal tissue and 20 to 45 min for plant tissue of 37degreesC was found to be optimal for producing the characteristic blue formazan at the reaction sites.

Adrenal Cortex↗
PubMed1976

Erythropoiesis in the yolk sac of the bat Tadarida brasiliensis cynocephala.

The process of erythropoiesis and vasculogenesis in the yolk sac of the bat (Tadarida brasiliensis cynocephala) has been studied through the use of both light and electron microscopy. Stem cells arise from the leading edge of the migrating splanchnic mesoderm and transform into primitive erythroblasts. Differentiation involves either contact or association with the endodermal cells, since all erythropoietic activity occurs on the endodermal side of the expanding vascular bed, and many of the cells are in close apposition to the lateral or basal plasma membranes of the endodermal cells. Endodermal cells also phagocytize developing primitive erythroblasts during the later stage of the process when erythropoiesis is subsiding in the yolk sac. Cells destined to become the endothelium of the expanding vascular bed also arise from the leading edge of the migrating splanchnic mesoderm. Their process of differentiation involves the development of cytoplasmic extensions that may surround a group of differentiating erythroblasts, enclosing them in the newly formed lumen of the blood vessel. The cytoplasmic extensions make contact and develop junctional complexes with similar processes from other cells to complete the lumen of the lengthening vascular bed. Cells of the granulocyte series or megakaryocytes are not observed in the yolk sac of the bat as has been described in certain other species.

Animals↗
PubMed1976

5-year follow-up of cytotoxic chemotherapy as an adjuvant to surgery in carcinoma of the bronchus.

This report gives the 5-year findings of a double-blind study of long-term cytotoxic chemotherapy as an adjuvant to surgery in patients receiving busulphan or cyclophosphamide for carcinoma of the bronchus compared with a group receiving a placebo. Of 243 patients initially allocated busulphan, 234 cyclophosphamide and 249 placebo, 28%, 27% and 34% respectively were alive at 5 years. There were significant associations between mortality from bronchial carcinoma and histological involvement of the resected intrathoracic nodes and the histology of the tumour. Haematological toxicity, especially thrombocytopenia, was frequent and severe in the busulphan series, and low platelet counts continued long after chemotherapy was stopped.

Bronchial Neoplasms↗
PubMed1976

Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3.

Rats were exposed to either NO2 or O3 to determine whether nonciliated cells (Clara cells) could divide and differentiate into ciliated cells in the terminal bronchioles. Dividing cells were labeled with tritiated thymidine, visualized in the light and electron microscopes using autoradiographic techniques, and studied for up to 15 days after labeling. Electron microscopic autoradiography 1 hour after injection of tritiated thymidine showed that all labeled cells in the terminal bronchioles were nonciliated. However, 4 days after injection of tritiated thymidine, 67.8 per cent of the labeled cells were nonciliated and 32.2 per cent were ciliated. Light microscopic autoradiography showed that the new labeled ciliated cell population was stable for up to 15 days. These results indicate that nonciliated cells divide and the sister cells may form new ciliated and nonciliated cells. Thus, nonciliated cells can act as progenitor cells for the terminal bronchiolar epithelium.

Animals↗
PubMed1975

Construction and implantation of a cannula system for repeated injections into localized regions of the rat brain.

The construction and method of implantation of a brain cannula for chronic use in rats is described. All the components of the cannula system are easily made from stainless steel tubing and no machined parts are required. The use of a metal key eliminates the need for tapped holes during implantation. Although little time is required to prepare each animal the system remains firmly fixed to the skull and allows injections to be made accurately into selected brain areas.

Animals↗
PubMed1975

Survey of the sputum cytology service in England and Wales.

Of the 231 laboratories carrying out sputum cytology in England and Wales, information on the staffing, laboratory procedures, workload, records, and results for the year 1971 was obtained from 228 (98.7%) by means of a questionnaire, which was completed in 1973 in 81% of the laboratories and at the end of 1972 in the remainder. At the time the questionnaire was completed, the number of laboratories per region offering a service ranged from 6 to 25. Most of the processing of specimens was done by technicians and non-medical screeners (technicians without recognized qualifications) and most of the microscopy by pathologists and technicians. Papanicolaou and/or haematoxylin and eosin stains were used in 97% of the laboratories. During 1971, the number of specimens tested per laboratory ranged from 9 to 6000. A median of 381 specimens and 165 patients were tested per laboratory. Almost all specimens were submitted by hospitals and chest clinics and only 1% by general practitioners. An estimated median of 6.5% of all cytological specimens were sputum, most of the remainder being cervical smears. Laboratories varied greatly in their positive (0%-24%) and doubtful positive (0%-27%) rates. An estimated 63 000 patients had their sputum tested in 1971, and about 6300 had positive reports, rather less than one-quarter of all patients diagnosed as having lung cancer in England and Wales in 1971. The cost of the service was estimated to be of the order of pound375 000 at 1974 prices; that is, pound2.50 per specimen or pound6.00 per patient tested. An improved service might best be provided by district general hospital laboratories testing at least 1000 specimens per year so that a high level of accuracy in reporting could be assurred. A large proportion of the microscopy might be done by non-medical graduates and technicians under the supervision of pathologists.

Cervix Uteri↗