Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach

The definition of sudden infant death syndrome (SIDS) originally appeared in 1969 and was modified 2 decades later. During the following 15 years, an enormous amount of additional information has emerged, justifying additional refinement of the definition of SIDS to incorporate epidemiologic features, risk factors, pathologic features, and ancillary test findings. An expert panel of pediatric and forensic pathologists and pediatricians considered these issues and developed a new general definition of SIDS for administrative and vital statistics purposes. The new definition was then stratified to facilitate research into sudden infant death. Another category, defined as unclassified sudden infant deaths, was introduced for cases that do not meet the criteria for a diagnosis of SIDS and for which alternative diagnoses of natural or unnatural conditions were equivocal. It is anticipated that these new definitions will be modified in the future to accommodate new understanding of SIDS and sudden infant death.     

Adenovirus enterocolitis in pediatric patients following bone marrow transplantation: report of 2 cases and review of the literature

We report 2 cases of adenovirus enterocolitis in pediatric patients who underwent bone marrow transplantation. The first case involved a 17-year-old adolescent boy with combined immunodeficiency and non-Hodgkin lymphoma who developed chronic graft versus host disease and persistent adenovirus duodenitis. Case 2 involved a 3-year-old boy who received a mismatched unrelated bone marrow transplant for metachromatic leukodystrophy; the boy developed severe graft versus host disease and died of multiorgan failure. At autopsy, diffuse hemorrhagic enterocolitis with changes of severe graft versus host disease and extensive mucosal invasion by adenovirus was found. Awareness and early recognition of this uncommon complication of concomitant graft versus host disease and adenovirus infection could impact therapy and outcome of patients with bone marrow transplant.     

Lafora-like ground-glass inclusions in hepatocytes of pediatric patients: a report of two cases.

We report 2 cases of ground-glass hepatocyte inclusions occurring in pediatric patients. Case 1 had alpha-thalassaemia major and was receiving iron chelation therapy, whereas case 2 had trisomy 21 with a history of bone marrow transplantation for acute myeloid leukemia. The liver sections in both cases showed eosinophilic, periodic acid-Schiff diastase-positive intracytoplasmic inclusions that were negative for hepatitis B surface antigen. Immunohistochemically the inclusions showed positive staining with KM279, a monoclonal antibody against polyglucosan derived from Lafora inclusions. On electron microscopy, in case 1, intracytoplasmic inclusions were composed of degenerate organelles, glycogen, and irregular fibrillar structures; in case 2, they were composed of vesicular structures containing granular material. Ultrastructural changes in both cases differed from classical Lafora inclusions and ruled out hepatitis B surface antigen, glycogenosis type IV, and fibrinogen storage disease. Genetic analysis of the Lafora's disease genes performed in case 2 revealed no mutations. The development of hepatocyte cytoplasmic inclusions in both our cases could be related to medication effects, because similar inclusions were reported in patients using cyanamide. Drug-induced inclusions, mimicking Lafora's disease, should be included in the differential diagnosis of hepatocyte ground-glass inclusions.     

Lingeous conjunctivitis with tracheal obstruction. A case report, with light and electron microscopy findings.

A white male infant of 1 year had unilateral membranous conjunctivitis and severe laryngotracheobronchitis which required tracheostomy. Cultures from eye and throat swabs and of fluid suctioned through the tracheostomy grew many organisms, including H. influenzae, adenovirus type 3, and Candida species, but he had no specific immunologic disturbance. Ligneous conjunctivitis was diagnosed. The infant's general condition responded slowly to intensive therapy but the membrane continued to slough off the regrow. The excised membrane contained massive subepithelial deposits of eosinophilic material and a moderately vascular chronic inflammatory-cell infiltrate with numerous mast cells in the perivascular spaces and the hyaline membrane. The conjunctivitis cleared when treated with topical sodium cromoglycate (Intal), a known inhibitor of mediator release from mast-cell granules. The success of Intal therapy in this case supports the theory that mast cells are involved in the pathogenesis of ligneous conjunctivitis.     

Neuroepithelial bodies as airway oxygen sensors.

Since the discovery of neuroepithelial bodies (NEB) in the late 1930s, evidence has accumulated to suggest that these cells may function as hypoxia-sensitive airway sensors. Until recently, this hypothesis was based largely on morphological observations. The use of in vitro models of isolated NEB, combined with electrophysiological approaches, have provided direct evidence that NEB cells express a membrane-bound O2 sensor and are the transducers of hypoxic stimulus. Here, we review the historical evidence and current state of knowledge of the oxygen-sensing properties of NEB cells, comparison with other O2 sensing cells, as well as recent advances that have been made using molecular and electrophysiological techniques. The possible role of NEB in perinatal pulmonary pathophysiology is also discussed.     

Novel function of Oncostatin M as a potent tumour‐promoting agent in lung

Oncostatin M is a leukocyte product that has been reported to have anti‐proliferative effects directly on melanoma and other cancer cell lines in vitro. However, its function(s) in cancers in vivo appears complex and its roles in cancer growth in lungs are unknown. Here, we show that OSM promotes marked growth of tumour cells in mouse lungs. Local pulmonary administration of adenovirus vector expressing mouse OSM (AdOSM) induced >13‐fold increase in lung tumour burden of ectopically delivered B16‐F10 melanoma cells in C57BL/6 mice. AdOSM caused increases in tumour size (14 days post‐challenge), whereas control vector (Addel70) did not. AdOSM had no such action in C57BL/6 mice deficient in the OSM receptor beta chain (OSMRβ?/?), indicating that these effects required OSMRβ expression on non‐tumour cells in the recipient mice. AdOSM induced elevated levels of chemokines and inflammatory cells in the bronchoalveolar lavage (BAL) fluid, elevated arginase‐1 mRNA levels (60‐fold), and increased arginase‐1+immunostaining macrophage numbers in lungs. Adherent BAL cells collected from AdOSM‐treated mice expressed elevated arginase‐1 activity. In contrast to AdOSM‐induced effects, pulmonary over‐expression of IL‐1β (AdIL‐1β) induced neutrophil accumulation and iNOS mRNA, but did not modulate tumour burden. AdOSM also increased lung tumour load (>50‐fold) upon ectopic administration of Lewis lung carcinoma (LLC) cells in vivo. However, in vitro, neither recombinant OSM nor AdOSM infection stimulated B16‐F10 or LLC cell growth directly. We conclude that pulmonary over‐expression of OSM promotes tumour growth, and does so through altering the local lung environment with accumulation of M2 macrophages.