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Biomedical subjects

H M Dodds

Publications and source records attributed to H M Dodds.

22 records · Page 2Linked to original sources

Tuberculous peritonitis in patients undergoing chronic home peritoneal dialysis.

Peritonitis is a well-recognized complication of chronic peritoneal dialysis. However, in many instances the etiology of the peritonitis remains obscure despite intensive evaluation. Recent reports have suggested that pulmonary and extrapulmonary tuberculosis occurs with increased incidence in chronic hemodialysis patients. We report the first three cases of tuberculous peritonitis occurring in patients being treated with chronic intermittent peritoneal dialysis. The lack of active tuberculosis elsewhere and the predominance of polymorphonuclear leukocytes in peritoneal fluid made the diagnosis particularly difficult in this setting. The characteristics of the peritoneal fluid are quite similar to that seen in bacterial peritonitis, and unlike that found in peritonitis due to tuberculosis in nondialyzed patients. Tuberculous peritonitis should be suspected in peritoneal dialysis patients with chronic or relapsing peritonitis in whom the diagnosis of bacterial or fungal peritonitis cannot be confirmed.

Ascitic Fluid↗

Primary actinomycoma of the third ventricle--the colloid cyst. A histochemical and ultrastructural study.

Primary actinomycoma of the third ventricle has been reported to be a very rare form of central nervous system actinomycosis. Others have demonstrated actinomycotic-like colonies in colloid cysts of the third ventricle. We have confirmed these structures (HLS) in five colloid cysts and have demonstrated by various histochemical stains that they consist of desoxyribose nucleic acid, base protein and phospholipid. Ultrastructurally, they consist of amorphous to granular electron dense material, probably deposited on a lamellar substructure. On the basis of the available information, we believe that the lesions, previously reported as primary actinomycomas, are actually colloid cysts containing degenerative HLS. The possible origin of the hyphal-like structures is discussed.

Actinomyces↗

The inhibition of acetylcholinesterase by irinotecan and related camptothecins: key structural properties and experimental variables.

Irinotecan (CPT-11), a water-soluble and semi-synthetic topoisomerase I poison of the camptothecin family, has activity against both adult and paediatric malignancies. Recently, we demonstrated that CPT-11 (lactone) is also a potent inhibitor of human acetylcholinesterase (AChE) at clinically relevant concentrations. Attachment of heterocyclic and branched amino groups onto the camptothecin back-bone continues to be a strategy for the synthesis of water-soluble analogues, but this may lead to undesirable inhibition of AChE. In this study, we screened a range of camptothecin analogues, degradation products and metabolites for their ability to inhibit AChE. Those compounds possessing N-substitutions at C-10 were all found to inhibit AChE in a similar kinetic manner to CPT-11, but with a broad range of potencies. It is recognized that the charge-state is important for ligands that bind to the peripheral anionic site and we postulated that the protonated distal piperidine of CPT-11 would be important. To address this question, an N-methyl piperidinium iodide analogue was synthesized and tested. This derivative inhibited electric eel AChE with an inhibition constant (Ki) of 1 nM. Kinetic and deacylation experiments demonstrated that it acted relatively less as an inhibitor of deacylation than CPT-11. Overall, our experiments reveal that nitrogenous substitutions at the permissive C-10 of the camptothecin backbone may lead to AchE inhibition, particularly if they involve a quaternary nitrogen.

Acetylcholinesterase↗