Neuroinvasive astrovirus (VA1-HMO-C) is an emerging life-threatening infection in immunocompromised hosts. We describe an 8-month-old child who died of VA1/HMO-C encephalitis following bone marrow transplantation. The diagnosis was only made post-mortem using RNA deep sequencing of the brain. Repeat analysis of the post-mortem brain tissue using PCR specific primers for VA1/HMO-C was positive. Astrovirus VA1/HMO-C should be included in the evaluation of patients with similar encephalitis.
From the Departments ofPathology, the Lancaster Moor Hospital, Lancaster, and the *Manchester Medical School, Manchester suMMARY A polyclonal antiserum to toxic shock syndrome toxin (TSST-1) and a standard immunoperoxidase technique were used on formalin fixed tissues from 50 cases of sudden infant death syndrome (SIDS) to determine if the syndrome was associated with bacterial infection. There was strong specific staining in the renal tubular cells in nine (18%) cases. A similar pattern of staining was seen in three ofa series of50 kidneys selected for comparison from a wide range ofnecropsy cases. The staining was finely granular within the cytoplasm of proximal convoluted tubular cells and diffuse in tubular cell nuclei. In an attempt to validate the staining pattern the immunoperoxidase technique was also performed on formalin fixed kidneys from rats which had been given intravenous injections ofcrude bacterial products containing TSST-1. These showed coarse granular cytoplasmic staining in proximal convoluted tubules with some diffuse nuclear staining. This pattern was not seen in controls injected with saline. These results indicate that TSST-1 might have a pathogenic role in some cases of SIDS.
Diffuse congenital hyperinsulinism in infancy (CHI-D) arises from mutations inactivating the KATP channel; however, the phenotype is difficult to explain from electrophysiology alone. Here we studied wider abnormalities in the β-cell and other pancreatic lineages. Islets were disorganized in CHI-D compared with controls. PAX4 and ARX expression was decreased. A tendency toward increased NKX2.2 expression was consistent with its detection in two-thirds of CHI-D δ-cell nuclei, similar to the fetal pancreas, and implied immature δ-cell function. CHI-D δ-cells also comprised 10% of cells displaying nucleomegaly. In CHI-D, increased proliferation was most elevated in duct (5- to 11-fold) and acinar (7- to 47-fold) lineages. Increased β-cell proliferation observed in some cases was offset by an increase in apoptosis; this is in keeping with no difference in INSULIN expression or surface area stained for insulin between CHI-D and control pancreas. However, nuclear localization of CDK6 and P27 was markedly enhanced in CHI-D β-cells compared with cytoplasmic localization in control cells. These combined data support normal β-cell mass in CHI-D, but with G1/S molecules positioned in favor of cell cycle progression. New molecular abnormalities in δ-cells and marked proliferative increases in other pancreatic lineages indicate CHI-D is not solely a β-cell disorder.
Background: Insulinomas are a rare cause of hyperinsulinaemic hypoglycaemia (HH) in children. The clinical features, investigations, management and histology of these rare pancreatic tumours in children have not been described in a large cohort of patients. Methods: We conducted a retrospective review of cases diagnosed between 2000 and 2012, presenting to two referral centres in the United Kingdom. Clinical, biochemical, imaging (magnetic resonance imaging (MRI) and 6-L-18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA) PET/CT scanning) and histological data were collected.
Objectives: To quantify islet cell nucleomegaly in controls and tissues obtained from patients with congenital hyperinsulinism in infancy (CHI) and to examine the association of nucleomegaly with proliferation.Methods: High-content analysis of histologic sections and serial block-face scanning electron microscopy were used to quantify nucleomegaly.Results: Enlarged islet cell nuclear areas were 4.3-fold larger than unaffected nuclei, and the mean nuclear volume increased to approximately threefold. Nucleomegaly was a normal feature of pediatric islets and detected in the normal regions of the pancreas from patients with focal CHI. The incidence of nucleomegaly was highest in diffuse CHI (CHI-D), with more than 45% of islets containing two or more affected cells. While in CHI-D nucleomegaly was negatively correlated with cell proliferation, in all other cases, there was a positive correlation.Conclusions: Increased incidence of nucleomegaly is pathognomonic for CHI-D, but these cells are nonproliferative, suggesting a novel role in the pathobiology of this condition.
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