Biomedical subjects
Publications and source records attributed to I J Simpson.
Endovascular infection due to salmonellae is an uncommon condition with an extremely poor prognosis. We describe a patient with endovascular infection due to Salmonella hadar who was cured by prolonged medical treatment with third generation cephalosporin and fluoroquinolone antibiotics.
A 28-year-old male presented with profound hypokalemia and was found to have a variant of Bartter's syndrome with nephrocalcinosis, hypercalciuria, normal distal fractional reabsorption of chloride and normal sodium delivery to the distal tubule.
Explore the source record for details and available documents.
Surreptitious diuretic use was found in a patient with longstanding hypokalaemia thought to be due to Bartter's syndrome. Measurement of urinary chloride excretion and repeated qualitative testing for diuretics in the urine were necessary to make a diagnosis.
Explore the source record for details and available documents.
From 1978 to 1983 a total of 328 patients was admitted to Royal Newcastle Hospital Intensive Care Unit with chest injuries; 255 had other injuries as well. Of the 328, 171 developed acute respiratory failure, 174 received mechanical ventilation (159 for acute respiratory failure) and 46 died. The commonest causes of death were head injury (19), sepsis (10) and uncontrollable haemorrhage (10). Associated head (131) and/or abdominal (89) injuries tripled mortality. Those without respiratory, cardiac, renal or hepatic failure (155) had a mortality rate of 5.8% while the remainder had mortality rates of 21.6%, 12.5%, 37.5% and 100%, for respiratory (171), cardiac (8), renal (8) and hepatic (5) failures, respectively. Shock was present on admission in 55, of whom 19 died. Sepsis developed in 59 and 14 with this complication died. Sepsis remains a potentially avoidable late cause of death and attention needs to be directed towards limiting invasive techniques of management to those which are necessary, and towards early diagnosis of abdominal injuries with early exploratory surgery. The best chance of survival in the initial phase of injury may lie in the establishment of an integrated regional trauma centre system together with improved pre-hospital and retrieval systems.
Because antibody responses to the alternative complement pathway activator, cobra venom factor, are T-dependent and B mice therefore do not develop resistance to its action, it was possible to examine whether renal injury occurs under circumstances of protracted third-phase alternative pathway activation. After periods of up to three months, no evidence from measurements of blood urea or proteinuria or from examinations with light microscopy immunofluorescence or electron microscopy was obtained to indicate a directly nephrotoxic effect of this type of complement activation.
The pathologic features of 29 cases of Goodpasture's syndrome occurring during a 13-yr period in Auckland have been reviewed and correlated with clinical findings. There were 20 males and nine females in the series; two of the males and three of the females were Maoris. Age at the time of onset of symptoms ranged from 17 to 75 yr, with about 76% of the patients being from 17 to 27 yr of age. Sixteen (55%) of the patients died from less than a week up to about two years following the onset of symptoms, and the remaining 13 are live from 30 weeks to 14 yr after initial presentation. Underlying renal disease varied from mild focal glomerulitis to end-stage glomerulonephritis by light microscopy, but characteristic glomerular changes were seen in all specimens examined by electron and immunofluorescent microscopy. The lungs of 13 of the patients examined at autopsy showed typical abnormalities. The syndrome pursues a notably variable clinical course, affects a considerable proportion of females, occurs over a wide age range, and appears to be disporportionately common among Maoris.
Animals were depleted of complement using cobra venom factor and the influence of complement depletion on the course of renal infection was studied. Complement depletion markedly increased the susceptibility of renal tissue to a challenge with an E. coli strain sensitive to the bactericidal activity of normal serum, but did not influence the outcome of a challenge with a serum-resistant strain of E. coli. These observations are consistent with the hypothesis that complement-mediated host immune mechanisms do play a role in the biology of renal infection and are an important component of the host's immune response in pyelonephritis.
In the autologous phase of nephrotoxic induced by sheep antibody to glomerular basement membrane (GBM) in Dunkin-Hartley and C4 deficient strain guinea-pigs, less than 50% of animals developed proteinuria at the height of the autologous antibody response despite high anti-sheep immunolglobulin tetres and fixation of guinea-pig IgG and complement in the kidney. tonly two of thirty-sdven animals (5-4%) developed progressive. In a passive model of autologous phase injury using high titres rabbit antibody to sheep IgG, proteinuria failed to occur despite fixation of up to 95 microng rabbit antibody per kidney. Repeated injection of sheep nephrotoxic antibody (NTab) caused a persisting nephrotic syndrome but not the characteristic proliferative lesion of anti GBM diseases in other species.
Defibrination with ancrod in nephrotoxic nephritis in rabbits. In rabbits with nephrotoxic nephritis, defibrination with ancrod provided protection when administered during the autologous phase, after extensive glomerular fibrin deposition had occurred and crescents and renal failure were developing. When further glomerular fibrin deposition was prevented by defibrination, deposited fibrin was rapidly removed, indicating that glomerular fibrin-clearing mechanisms are retained in crescentic nephritis. Defibrination had no effect on the extent of glomerular C3 deposition or on the amount of proteinuria.
The role of complement has been studied in the autologous phase of nephrotoxic nephritis (NTN) in rabbits. No reduction in glomerular fibrin deposition, crescent formation or protection from renal failure was observed in either the standard model of NTN when decomplementing doses of cobra venom factor (CVF) were given before the autologous phase or in a telescoped model when CVF was administered before the nephrotoxic antibody. In the latter situation glomerular fibrin deposition and crescent formation were found in the absence of detectable deposition of C3. However, substantial protection was observed when circulating polymorphonuclear leucocytes (PMN) were depleted by antipolymorph serum. These observations establish the existence of a system of allergic glomerular injury mediated by PMN but independent of C3. It is postulated that this system may account for the glomerular injury seen in patients with Goodpasture's syndrome in whom glomerular C3 deposition is not found.
A patient with Goodpasture's syndrome has recovered after treatment with immunosuppressive drugs (cyclophosphamide and prednisolone) and removal of circulating antibodies by plasma exchange. This was performed on seven occasions and seems to have hastened the decline in circulating antibody levels. Undertaken early in the course of the disease plasmapheresis could prove a useful addition to its therapy.
In guinea-pig nephrotoxic nephritis induced by a sheep antibody there was minimal glomerular capillary deposition of C3 and accumulation of polymorphonuclear leucocytes (PMN) in the heterologous phase. The C4-deficient strain developed the same injury as normal Duncan-Hartley animals. Complement depletion with cobra venom factor, polymorph depletion with nitrogen mustard or anti-PMN serum and treatment with antihistamines provided no protection. The relationship between the dose of nephrotoxic antibody and the proteinuria was similar for gamma1 and gamma2 subclasses and the F(ab')2 fragment of gamma1 antibody. However, the F(ab') and F(ab) antibody fragments, though fixing on the glomerular basement membrane, did not cause proteinuria. It is concluded that the development of proteinuria in this system: is largely independent of the complement-polymorph system; is due to the fixation of the F(ab')2 fragment of the antibody molecule; and does not depend on an intact Fc piece.
The protective effects of anticoagulants in nephrotoxic nephritis in rabbits have been studied, using various doses of heparin and defibrination with ancrod. Massive doses of heparin (2000 units/kg/day) were required before significant reduction in glomerular fibrin deposition, extracepillary cell proliferation and urea retention occurred. Doses of 300 and 1000 units/kg/day were insufficient to modify fibrin deposition and cell proliferation. Defibrination with ancrod provided protection, judged by histological and functional criteria, comparable to 2000 units of heparin/kg/day; but fibrin could still be demonstrated in the glomeruli of animals treated with 2000 units of heparin/kg/day, contrasting with the virtual absence of fibrin in animals given ancrod.
The role of polymorphonuclear leucocytes (PMN) in the autologous phase of nephrotoxic nephritis (NTN) in the rabbit has been investigated. Depletion of circulating PMN by nitrogen mustard protected renal function and immunofluorescent examination showed reduction in glomerular fibrin deposition. Depletion of circulating PMN using a highly specific goat anti-PMN serum (APS) provided similar protection of renal function, highly significant reduction in proteinuria and histological and immunofluorescent examination showed reduced glomerular PMN infiltration, extracapillary cell proliferation and virtual absence of fibrin deposition. Although protection by nitrogen mustard may have been partly due to immunosuppression, no reduction in antibody response was detected in the APS-treated rabbits. The results implicate the polymorph as the principal injurious agent in this model of NTN, responsible directly or indirectly for both proteinuria and glomerular fibrin deposition.
Glomerulonephritis associated with antibody to glomerular basement membrane, shown by linear staining of the glomerular basement membrane with fluoresceinated anti-IgG antisera, was found in only 10 out of 400 (2.5%) renal biopsy specimens studied by immunofluorescence. Seven of these cases had rapidly progressive glomerulonephritis, five with lung haemorrhage (Goodpasture's syndrome) and two without, and three had less severe nephritis without lung haemorrhage. Circulating antibody to glomerular basement membrane, measured by a passive haemagglutination technique and by indirect immunofluorescence, was detected in the serum of all patients with rapidly progressive glomerulonephritis by both techniques but only by the passive haemagglutination method in two of the other three patients. Two patients died of their lung haemorrhage, one despite bilateral nephrectomy, and lung haemorrhage and circulating antibody to glomerular basement membrane persisted after bilateral nephrectomy in another patient.
Explore the source record for details and available documents.