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Biomedical subjects

A Parry

Publications and source records attributed to A Parry.

47 records · Page 3Linked to original sources
PubMed1988

Lack of detectable DNA alkylation for bromhexine in man.

It is known that in vitro incubation of the expectorant drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) with nitrite yields methylcyclohexyl nitrosamine (NMCA). NMCA is capable of methylating DNA when administered to rats. In vivo tests with bromhexine have also demonstrated that the drug methylates DNA when it is orally administered in the presence of sodium nitrite, presumably due to the intragastric formation of NMCA. In this study the potential of bromhexine to methylate nucleic acids in man, under physiological conditions, has been investigated. 20 volunteers were orally administered on each of three successive days 48 mg of bromhexine hydrochloride, labelled with three deuterium atoms in the N-methyl group. Urine was collected before treatment and subsequent to the last dose, and analysed by GC-MS for d0- and d3-7-methylguanine. 7-Methylguanine is naturally occurring in urine owing to the turnover of t-RNA of which it is a minor constituent. It is also a repair product from nucleic acids methylated by carcinogens, which is known to be excreted unmetabolised largely within 24 h of the methylation process. Unlabelled 7-methylguanine was present at levels of 7.36 +/- 2.43 mg/d in control urine and 6.12 +/- 2.36 mg/d in treated urine, in accord with previously published values. The excretion of isotopically labelled 7-methylguanine averaged 0.43 +/- 0.077% of the unlabelled concentration for control urines and 0.44 +/- 0.066% for treated urines, i.e. no d3-7-methylguanine could be detected following the drug treatment. The observed signals were largely accounted for by the naturally occurring isotopes 13C and 15N.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

The determination of urinary 3-methyladenine in humans as a potential monitor of exposure to methylating agents.

The determination of urinary 3-methyladenine has been explored as a potential monitor of exposure to methylating carcinogens. A method based on the use of high resolution gas chromatography--mass spectrometry has been developed for measuring this methylated base in human urine. Urine is extracted by XAD-2 column chromatography and the extract purified by reverse phase C18 h.p.l.c. Derivatization with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide yields the mono-tert-butyldimethylsilyl derivative of 3-methyladenine which has good gas chromatographic properties and is stable towards hydrolysis. The gas chromatographic separation was carried out using an SE-52 capillary column and quantitation made by electron impact selective ion monitoring mass spectrometry employing deuterium-labelled 3-methyladenine added initially to the urine as internal standard. Measurable levels (4.50-16.07 micrograms/24 h) of the methylated base have been found in control (i.e. nominally unexposed) human urines.

Adenine↗
PubMed1987

Modulation of CD4 antigen expression on human gingival Langerhans cells by gamma interferon.

Human gingival organ culture was used to test the hypothesis that gamma interferon (gamma-IFN), which induces HLA-DR and HLA-DQ antigens on Langerhans cells, modulates CD4 antigen expression on these same cells. Before culture, the density of CD4+ cells in the gingival epithelium was 12.7% +/- 3.8% of the density of CD1+ cells. gamma-IFN (200 IU/ml) enhanced CD4 expression such that at 24 h, all CD1+ cells also expressed CD4. Prostaglandin E2, which in isolation had no effect, partially abrogated the stimulatory effect of gamma-IFN on CD4 expression. These results imply that gamma-IFN and prostaglandin E2 are two signals which regulate CD4 expression on gingival Langerhans cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMedDate not supplied

Airway stenoses after lung transplantation: management with expanding metal stents.

Success in lung transplantation has been hindered by airway complications, usually as a result of anastomotic ischemia and stenosis. We report our experience with expanding metal stents in managing airway stenoses after lung transplantation. From April 1984 through November 1993, 46 single lung, 5 double lung, and 154 heart-lung transplantations were performed at Papworth Hospital. All patients received immunosuppression with azathioprine, cyclosporine, methylprednisolone, and induction antithymocyte globulin. Fourteen patients (nine single lung, two double lung, and three heart-lung) had an airway stenosis requiring a stent. The most common features were shortness of breath, wheezing or stridor, and a fall in pulmonary function tests (11 patients). Three patients had pneumonia. Airway stenosis was diagnosed on bronchoscopy an average of 61 days after transplantation (range 3 to 245 days). Stent placement occurred an average of 18 days after the diagnosis (range 2 to 84 days). One heart-lung transplant recipient received a silicone rubber stent. All other patients received expanding metal stents. Six patients required multiple stent placements. After stent placement the average increase in the forced expiratory volume in 1 second was 117%. Infection complicated the stenoses in 12 patients. Pseudomonas aeruginosa and Aspergillus fumigatus were the most common pathogens, each occurring in six cases. Multiple pathogens were isolated in seven cases. Three patients died as a direct consequence of their airway problems. Two died of pneumonia despite stenting, and a third died of acute occlusion of the silicone rubber stent. Expanding metal stents are an effective treatment of airway stenoses in lung transplant recipients. Patients with suspected airway problems should be referred for early bronchoscopy with the potential for stent placement.

Adult↗