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Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA) is associated with adverse outcomes in kidney transplantation. We evaluated i-IFTA in 429 indication- and 2052 protocol-driven biopsy samples from a longitudinal cohort of 362 kidney-pancreas recipients to determine its prevalence, time course, and relationships with T cell-mediated rejection (TCMR), immunosuppression, and outcome. Sequential histology demonstrated that i-IFTA was preceded by cellular interstitial inflammation and followed by IF/TA. The prevalence and intensity of i-IFTA increased with developing chronic fibrosis and correlated with inflammation, tubulitis, and immunosuppression era (P

We present a conceptual framework for modelling clinical guidelines as networks of concurrent processes. This enables the guide- line to be partitioned and distributed at run-time across a knowledge-based telemedicine system, which is distributed by definition but whose exact physical configuration can only be determined after design-time by considering, amongst other factors, the indi- vidual patient's needs. The framework was applied to model a clinical guideline for gestational diabetes mellitus and to derive a prototype that executes the guideline on a smartphone. The framework is shown to support the full development trajectory of a decision support system, including analysis, design and implementation.

Transplant glomerulopathy (TXG) presents a distinctive pattern of glomerular abnormalities. The aim of this study was to describe its sequential ultrastructural pathology. A paired cohort study of 228 protocol biopsies, from our longitudinal database (n = 1345), compared TXG (7 patients, 95 biopsies) and controls (8 patients, 133 biopsies). Ultrastructural morphometry and C4d immunoperoxidase were evaluated from implantation to 5 years after transplantation against sequential histology and functional changes. TXG was predated by early glomerular endothelial cell activation; typified by vacuolation, hypertrophy, serration and expansion of lamina rara interna from 39 +/- 23 days after transplantation. Endothelial cells were transformed into an activated phenotype, containing numerous mitochondria, Golgi and ribosomes. Transition from fenestrated to continuous endothelium, mesangial matrix expansion and podocyte fusion occurred late. Endothelial cell activation also occurred in peritubular capillaries (PTC) followed by basement membrane multi-lamination (p < 0.05-0.001). Light microscopy changes of TXG occurred at 2.3 years. PTC C4d deposition was intermittently expressed over time, correlating with endothelial abnormalities, glomerular C4d and donor-specific antibodies (DSA) (p < 0.05-0.001). In summary, endothelial and subendothelial ultrastructural abnormalities in glomerular and peritubular capillaries are sensitive, early markers of TXG, likely due to stimulation of endothelial cells into an activated phenotype by antibody-mediated sub-lytic complement deposition.

Sir,Malakoplakia and Whipple's disease are generally regarded as two discrete disease entities. Their occurrence in the same patient has not previously been reported. We report the case of 54‐year‐...

Case report Eosinophilic angiocentric fibrosis is a rare fibrotic lesion of the sinonasal and upper respiratory tract. We present a case of eosinophilic angiocentric fibrosis of the maxillary and sphenoid sinuses with infiltration by IgG4-positive plasma cells, raising the possibility of a relationship with IgG4-related sclerosing disease. A 34-year-old female with an unremarkable past medical history presented with a long history of left sided facial pain and congestion unresponsive to corticosteroid therapy. Serum IgG and serum IgG4 levels were not performed. Preoperative CT scans revealed a mass in the left maxillary and sphenoid sinuses. Biopsy of the mass showed fragments of dense fibrous tissue with a prominent concentric arrangement around blood vessels. There was a mild to moderate inflammatory infiltrate including lymphocytes, plasma cells and variable numbers of eosinophils. Isolated blood vessels showed vasculitis with leukocytoclasis. There was no evidence of granulomas, fungi or amyloid. The histological features were consistent with eosinophilic angiocentric fibrosis. Immunohistochemical stain for IgG4 showed the presence of numerous IgG4-positive plasma cells, raising the possibility of a link with IgG4-related sclerosing disease. IgG4-related sclerosing disease is a chronic inflammatory condition in which numerous IgG4 positive plasma cells are seen on immunohistochemical staining and is associated with elevation of serum IgG and IgG4 levels. Since it was first described in the pancreas (autoimmune pancreatitis) in 2001, IgG4-related sclerosing disease has been reported at many sites. As yet, it has not been reported in the sinonasal tract.

A solid-phase radioimmunoassay is described for the detection of antibodies to mouse hepatitis virus. Viruses were purified by velocity and isopycnic gradient centrifugation and 96-well plastic plates were coated with viral antigens. To allow the detection of most serotypes of low titered antisera, a pool of antigens from several viral serotypes were employed. The second antibody, an affinity-purified goat antimouse immunoglobulin, detects IgG, IgM and IgA antibodies. This assay is more sensitive than either the plaque reduction assay or the commercially available enzyme-linked immunosorbant assay and proved to be useful for screening mouse colonies for the presence of mouse hepatitis virus, following seroconversion in experimental animals and in the production of monoclonal antibodies to both structural and nonstructural proteins.