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Background/AimsMast cells, when activated, secrete a large number of fibrogenic factors and have been implicated in the development of fibrotic conditions of the liver, lung, and skin. There is evidence that renal fibrosis is closely linked with a chronic inflammatory cell infiltrate within the interstitium, but a potential role for mast cells in this process has yet to be defined. Therefore, the numbers of mast cells in normal and fibrotic kidneys with various pathologies were investigated.MethodsMast cells were quantified in renal transplants showing acute and chronic rejection and cyclosporin toxicity, kidneys removed for chronic pyelonephritis, and renal biopsies from patients with IgA nephropathy, membranous nephropathy, and diabetic nephropathy. Mast cells were stained using two methods: acid toluidine blue detected less than 30% of the mast cells revealed by immunohistochemistry for mast cell tryptase.ResultsMast cells were scarce or absent in normal kidney (median, 1.6 mast cells/mm²) but numerous throughout the cortex and medulla in all specimens that showed fibrosis. They were almost entirely confined to the renal interstitium. Mast cells were present in large numbers in biopsies from patients with membranous nephropathy (median, 21.7 mast cells/mm²) and diabetic nephropathy (median, 29.2 mast cells/mm²), which were selected on the basis of showing chronic injury. In 24 unselected IgA nephropathy biopsies there was a close correlation between numbers of mast cells and the extent of interstitial fibrosis (r = 0.771; p < 0.0001). In renal transplant biopsies, mast cells were associated with allograft fibrosis in chronic rejection (median, 27.1 mast cells/mm²) and chronic cyclosporin toxicity (median, 10.6 mast cells/mm²) but not acute rejection (median, 2.7 mast cells/mm²) or acute cyclosporin toxicity (median, 2.0 mast cells/mm²). There was no detectable increase in mast cell numbers during acute rejection in those transplants that subsequently progressed to chronic rejection. In some biopsies the mast cells were largely intact, but in most cases some or all were degranulated.ConclusionsAn increased number of mast cells is a consistent feature of renal fibrosis, whatever the underlying pathology, and the number of mast cells correlates with the extent of interstitial fibrosis. This suggests that mast cells might play a pathogenetic role in the fibrotic process.

AimMany deaths fall in the "grey" area between those that are clearly natural and those that are unnatural. There are no guidelines to help doctors in dealing with such cases and death certification is often arbitrary and inconsistent. In an attempt to initiate debate on these difficult areas, and with the ultimate aim of achieving national consensus, the views of coroners in England and Wales were sought.MethodsSixteen clinical scenarios, with causes of death, were circulated to all coroners in England and Wales. For each case they were asked to provide a verdict, with explanation. The deaths fell into three groups: (1) postoperative, (2) a combination of trauma and natural disease, and (3) infectious disease.ResultsSixty four questionnaires were returned. There was near consensus (> 80% concordance) in only two of the 16 cases. In five, there was no significant agreement between coroners in the verdicts returned ("natural causes" versus "misadventure/accidental"). These included all three cases in which death resulted from a combination of trauma and natural disease (a fall after a grand mal fit; falls resulting in fractures of bones affected by metastatic carcinoma and osteoporosis), bronchopneumonia after hip replacement for osteoarthritis, and new variant Creutzfeldt-Jakob disease. The comments made for each case indicate that the variation between coroners in whether or not to hold an inquest, and the verdict arrived at, reflect the lack of a definition for natural causes, together with differences in the personal attitudes of each coroner.ConclusionsThere is considerable variation in the way in which coroners approach these borderline cases, many of which are common in clinical practice. This study indicates a need for discussion, working towards a national consensus on such issues. It highlights the importance of good communication between coroners and medical staff at a local level.

AimsTo determine the frequency at which classic manifestations of anaphylaxis are present at necropsy after fatal anaphylactic reactions.MethodsA register has been established of fatal anaphylactic reactions in the UK since 1992, traced from the certified cause of death and other sources. Details of the previous medical history and the reaction suggest anaphylaxis as the cause of death for 130 cases; a postmortem report was available for 56.ResultsThe 56 deaths studied included 19 reactions to bee or wasp venom, 16 to foods, and 21 to drugs or contrast media. Death occurred within one hour of anaphylaxis in 39 cases. Macroscopic findings included signs of asthma (mucous plugging and/or hyperinflated lungs) (15 of 56), petechial haemorrhages (10 of 56), pharyngeal/laryngeal oedema (23 of 56), but for 23 of 56 there was nothing indicative of an allergic death. Mast cell tryptase was raised in 14 of 16 cases tested; three of three tested had detectable IgE specific for the suspected allergen.ConclusionsIn many cases of fatal anaphylaxis no specific macroscopic findings are present at postmortem examination. This reflects the rapidity and mode of death, which is often the result of shock rather than asphyxia. Investigations that might help determine whether anaphylaxis was the cause of death had rarely been performed. In the presence of a typical clinical history, absence of postmortem findings does not exclude the diagnosis of anaphylaxis.

Primary hyperoxaluria is a rare genetic disorder characterised by calcium oxalate nephrolithiasis and nephrocalcinosis leading to renal failure, often with extrarenal oxalate deposition (systemic oxalosis). Although ischaemic complications of crystal deposition in vessel walls are well recognised clinically, these usually take the form of peripheral limb or cutaneous ischaemia. This paper documents the first reported case of fatal intestinal infarction in a 49 year old woman with systemic oxalosis and advocates its consideration in the differential diagnosis of an acute abdomen in such patients.