E-cadherin mutation-associated diffuse gastric adenocarcinoma: penetrance and non-penetrance

According to the published medical literature to date, prophylactic gastrectomy undertaken in the context of carriage of a germline truncating E-cadherin mutation and an appropriate positive family history will lead to the discovery of occult foci of adenocarcinoma in all gastrectomy specimens. We describe the first published case of a patient whose prophylactic gastrectomy in this setting failed to reveal any dysplastic or malignant foci. Furthermore the patient's nephew, who was found to carry an identical E-cadherin mutation on family screening and also underwent prophylactic gastrectomy, was shown to have multi-focal diffuse adenocarcinoma after analysis of the gastrectomy specimen. Both patients were also found to have penetrant genetic haemochromatosis. Within this case, we discuss the clinical manifestations and penetrance of germline E-cadherin mutations and the difficult decisions facing both clinicians and families with this mutation. We also speculate on how these patients' undiagnosed genetic haemochromatosis may have influenced the pathology encountered.     

Dracunculiasis eradication: the final inch

This report summarizes the status of the Dracunculiasis Eradication Program as of early 2005. Nine of the 20 countries that were endemic for this disease when the program began have already interrupted transmission, Asia is free of Guinea worm, and five of the remaining disease-endemic countries reported less than 50 cases each in 2004. Ghana and Sudan each reported 45% of the 16,026 cases in 2004. Except for Sudan, whose reports are delayed, cases in the remaining disease-endemic countries were reduced by 61% during the first quarter of 2005 compared with the same period of 2004. With accelerating momentum towards zero cases in all countries, the recent settlement of Sudan's north-south civil war, and a new challenge grant from the Bill & Melinda Gates Foundation, the way now seems clear to finish eradicating dracunculiasis by 2009 in Sudan and earlier elsewhere. "The rule of the final inch... The work has been almost completed, the goal almost attained... In that moment of fatigue and self-satisfaction it is especially tempting to leave the work without having attained the apex of quality... In fact, the rule of the Final Inch consists in this: not to shirk this crucial work. Not to postpone it... And not to mind the time spent on it, knowing that one's purpose lies... in the attainment of perfection."--Alexander Solzhenitzyn, The First Circle.     

Student extra

A recent survey found that up to 70 per cent of students felt their supernumerary status was not always respected on clinical placements. The most common reasons were staff shortages on ward and mentors being too busy to spend time with students.     

Characterization of the T-cell response in a patient with phenindione hypersensitivity

The oral anticoagulant phenindione [2-phenyl-1H-indene-1,3(2H)-dione] is associated with hypersensitivity reactions in 1.5 to 3% of patients, the pathogenesis of which is unclear. We describe a patient who developed a severe hypersensitivity reaction that involved both the skin and lungs. A lymphocyte transformation test showed proliferation of T-cells from the hypersensitive patient, but not from four controls on exposure to phenindione in vitro. Drug-specific T-cell clones were generated and characterized in terms of their phenotype, functionality, and mechanism of antigen presentation. Forty-three human leukocyte antigen class II restricted CD4(+) alphabeta T-cell clones were identified. T-cell activation resulted in the secretion of interferon-gamma and interleukin-5. Five of seven clones proliferated with phenindione alone, whereas two clones also proliferated with 2-phenylindene. Certain T-cell clones were also stimulated by R- and S-warfarin; computer modeling revealed that warfarin can adopt a phenindione-like structure. Phenindione was presented to T-cells via two pathways: first, bound directly to major histocompatibility complex and second, bound to a processed peptide. Our data show that CD4(+) T-cells are involved in the pathophysiology of phenindione hypersensitivity. There may be cross-sensitivity with warfarin in some phenindione hypersensitive patients.     

Multiple joint tuberculosis presenting as HLA-B27 disease

A case of multifocal osteoarticular tuberculosis in a young Caucasian male is presented. The diagnostic difficulty, compounded by slow progression of the disorder and the presence of the tissue antigen HLA-B27, is discussed.