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Biomedical subjects

I Brown

Publications and source records attributed to I Brown.

At least 109 records · Page 6Linked to original sources

Hyporeninemic hypoaldosteronism. New associations.

Hyporeninemic hypoaldosteronism occurred in a 49-year-old man with chronic endocrine and exocrine pancreatic insufficiency secondary to pancreatectomy and in a 64-year-old man with recurrent pancreatitis, exocrine pancreatic insufficiency, and prolonged magnesium deficiency. Hyporeninemic hypoaldosteronism has never, to our knowledge, been reported in these clinical settings before and may be masked by the malabsorption of pancreatic insufficiency.

Aldosterone↗

Biodistribution of 6-[211At]astato-2-methyl-1,4-naphthoquinol bis(diphosphate salt) and 211At- in mice with a transplanted rectal adenocarcinoma.

6-[211At]astato-MNDP is currently being investigated as a potential high LET endoradiotherapeutic drug. Biodistribution and whole-body radiation retention studies have been carried out with 6-[211At]astato-MNDP and 211At- in a murine rectal tumour model; results indicate that the 211At-C bond in the compound is metabolically stable for at least 6 h. The Mean Biological Concentration of 6-[211At]astato-MNDP in tumour tissue ranged from 170-253% over an initial 12 h period; this was higher than that observed for the [211At]astatide anion. Conversely, the uptake of compound into radiobiologically critical organs was significantly lower.

Adenocarcinoma↗

Radioactive derivatives of 2-methyl-1, 4-naphthoquinol bis (diphosphate salt) as anti-cancer drugs with high LET radiations.

From the results of the alpha-particle track autoradiography, the alkaline phosphatase studies, the biodistribution investigations and the therapeutic experiments with the transplanted Franks and Hemmings (1978) adenocarcinoma of the rectum in mice, an important finding is the striking selectivity of the uptake of the compound 6-211 At-astato-2-methyl-1, 4-naphthoquinol bis (diphosphate salt), after intraperitoneal injection into the tumour cell nuclei and in many cases into the nuclei of tumour stem cells, together with negligible uptake into normal colon and narrow. The compound, 6-211 At-astato-2-methyl-1, 4-naphthoquinol bis (diphosphate salt) has been found to cure about two-thirds of the transplanted adenocarcinoma of the rectum in mice after a single intra-peritoneal injection of 3-4 microCi. This approach can be regarded as a form of metabolically-directed drug targetting on to a tumour product which is an enzyme, an alkaline phosphatase isozyme, present in the cells of some tumours. The compound is being studied further from the point of view of possible human therapeutic applications.

Alkaline Phosphatase↗

alpha-Particle track autoradiography for localization of a 211At-astatinated drug.

A potential endoradiotherapeutic drug, 6-211At-astato-2-methyl-1,4-naphthoquinol bis (diphosphate salt), incorporating the alpha-emitting radio-halogen astatine-211 of half-life 7.2 h, is shown to be valuable for localization studies by means of alpha-particle track autoradiography in malignant and normal cells and tissues in the mouse with transplanted adenocarcinoma of the rectum.

Adenocarcinoma↗

Experimental epithelioid cell granulomas, tubercle formation and immunological competence: an ultrastructural analysis.

An ultrastructural study of the cells comprising tubercles in experimental mycobacterial granulomas in rats is presented. Tubercle formation was compared in: (1) primary infections due to BCG at 49 days, (2) reinfection with BCG at 7 days, 8 months after primary infection and (3) lesions due to preformed BCG/anti-BCG complexes in antibody excess in unprimed animals at 10 days. The most rapid elimination of antigen with resolution of the lesion in the reinfection lesions, was effected by the early recruitment of cells morphologically characteristic of activated macrophages and immature epithelioid cells. The next best performance was in the immune complex lesion which at its height was maintained by a roughly constant size due to promonocytes, monocytes, macrophages, activated macrophages and immature epithelioid cells accumulated at the site. True epithelioid cells were rare. The slowest rate of healing in the primary 49 day granulomas, was associated with the whole spectrum of mononuclear phagocyte series of cells. All granulomas were surrounded by a cuff of mixed lymphocytes, interdigitating cells and fibroblasts. The rapid resolution of the reinfection lesions appeared as a loosely compacted infiltration of cells which allowed intimate contact of lymphocytes and macrophages. This was distinct from the tightly compared and compartmentalised zones of lymphocytes and macrophages which inhibited contact in the most slowly resolving lesions. An intermediate arrangement was seen in the immune complex granuloma. Another factor which predisposed to rapid resolution was the high vascularity of the central region of the granulomas. In the slow resolving group vascularity was diminished and peripherally situated.

Animals↗

The roles of lactose and Clostridium difficile in the pathogenesis of enteral feeding associated diarrhoea.

This study investigated the influence of the disaccharide lactose on the incidence of clinically significant enteral feeding associated diarrhoea. In this double blind study both groups each of 25 patients were randomised to receive either a lactose containing diet Clinifeed 400 in 25 patients or a lactose free diet Ensure in 25 patients. Diarrhoea occurred with equal frequency in both treatment groups, even in those patients with symptomatic and biochemical evidence of impaired lactose handling. Although the onset of diarrhoea was significantly associated with antibiotic administration (p<0.01), Cl. difficile was not isolated from the stools of any patient with diarrhoea.

Journal Article↗

The in vitro selective concentration of an 125I-iodinated compound in human tumor cells.

Uptake studies of the potential endoradiotherapeutic agent, 6-125I-iodo-2-methyl-1,4-naphthoquinol bis(diammonium phosphate) have been carried out in vitro on a wide range of normal and malignant human cells. In general, for a standardized dose of 0.1 microCi/ml, the uptake of the compound into normal cells was 0.0015-0.135 pCi/cell. Uptake into malignant cells was significantly higher than normal cells; uptakes of 0.89-11.3 pCi/cell were noted for melanoma, teratoma of testis, osteosarcoma and adenocarcinoma of colon and pancreas. Comparative uptake ratios for melanoma: Chang liver cells and testicular teratoma:normal testis were 29 23, respectively. Larger uptake ratios are usually observed with higher doses.

Absorption↗

Invited review. Nervous system antigens.

Some of the better characterized proteins (markers) of the nervous system are described. The availability of specific antibodies to these markers has allowed the localization and assay of the proteins in tissue and biological fluids. There is some evidence that autosensitization may occur. Clinical application of these markers includes the evaluation and prognostic significance after stroke and head injury. The diagnostic histopathological use of the markers in the investigation of various tumours is summarized.

Antigens↗

6-125I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) as a potential radio-halogenated anti-cancer agent: in vitro investigations and possible clinical implications.

6-125-I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) (6-125I-iodo-MNDP) has been synthesised and studied as the prototype of a class of potential radio-halogenated anti-cancer agents. The incorporated 125I provides Auger electron radiations which behave like high LET radiations in the treatment of tumours, though the accompanying X- and gamma-radiations make an undesirable contribution to the total body dose. The in vitro experiments reported show that 6-125I-iodo-MNDP is selectively concentrated in the cells of some human malignant tumours by factor of about 15 to 20 or more in relation to the cells of normal origin studied. On the basis of dosimetric considerations and comparison with clinical treatment with tritiated methylnaphthoquinol diphosphate, practical dosage of 6-125I-iodo-MNDP is suggested and clinical indications and safety of use are discussed. The types of tumour of particular interest are inoperable cases of carcinoma of the colon, carcinoma of the pancreas, malignant melanoma and osteosarcoma. Further investigations are in progress.

Animals↗

Intraosseous ganglia.

A case report of a fifty eight year old lady with symmetrical cystic lesions in the bases of the metacarpal bones of both thumbs. The histology showed an intraosseous ganglion which has not previously been reported in this location.

Female↗