BackgroundKawasaki disease is recognized as the most common cause of acquired heart disease in children in the developed world. Clinical, epidemiologic, and pathologic evidence supports an infectious agent, likely entering through the lung. Pathologic studies proposing an acute coronary arteritis followed by healing fail to account for the complex vasculopathy and clinical course.Methodology/Principal FindingsSpecimens from 32 autopsies, 8 cardiac transplants, and an excised coronary aneurysm were studied by light (n=41) and transmission electron microscopy (n=7). Three characteristic vasculopathic processes were identified in coronary (CA) and non-coronary arteries: acute self-limited necrotizing arteritis (NA), subacute/chronic (SA/C) vasculitis, and luminal myofibroblastic proliferation (LMP). NA is a synchronous neutrophilic process of the endothelium, beginning and ending within the first two weeks of fever onset, and progressively destroying the wall into the adventitia causing saccular aneurysms, which can thrombose or rupture. SA/C vasculitis is an asynchronous process that can commence within the first two weeks onward, starting in the adventitia/perivascular tissue and variably inflaming/damaging the wall during progression to the lumen. Besides fusiform and saccular aneurysms that can thrombose, SA/C vasculitis likely causes the transition of medial and adventitial smooth muscle cells (SMC) into classic myofibroblasts, which combined with their matrix products and inflammation create progressive stenosing luminal lesions (SA/C-LMP). Remote LMP apparently results from circulating factors. Veins, pulmonary arteries, and aorta can develop subclinical SA/C vasculitis and SA/C-LMP, but not NA. The earliest death (day 10) had both CA SA/C vasculitis and SA/C-LMP, and an “eosinophilic-type” myocarditis.Conclusions/SignificanceNA is the only self-limiting process of the three, is responsible for the earliest morbidity/mortality, and is consistent with acute viral infection. SA/C vasculitis can begin as early as NA, but can occur/persist for months to years; LMP causes progressive arterial stenosis and thrombosis and is composed of unique SMC-derived pathologic myofibroblasts.
The TTG is a very sensitive screen for CD, but positive predictive value improves with a positive EMA titer. To apply the new ESPGHAN guidelines, clinicians must understand the performance of their celiac serology tests.
To assess the synaptic vesicle protein synaptophysin as a potential marker for maturation in the human fetal brain, synaptophysin immunoreactivity (sIR) was prospectively studied in postmortem sections of 162 normal human fetal and neonatal brains of both sexes from 6 to 41 weeks' gestational age. There was a consistent temporal and spatial pattern of sIR in the hippocampus and cerebral neocortex. In the rostral hippocampus, sIR was first apparent in the molecular zone of the dentate gyrus at 12 weeks, followed by CA2 at 14 weeks, CA3 and CA4 at 15 to 16 weeks, and CA1 at 19 weeks; it was incomplete until 26 weeks. In frontal neocortex, sIR developed in a laminar pattern above and below the cortical plate as early as 12 weeks, around Cajal-Retzius neurons of the molecular zone at 14 weeks, surrounding pyramidal neurons of Layers 5 and 6 at 16 weeks, and at the surface of neuronal somata in Layers 2 and 4 at 22 weeks. At 33 weeks, Layers 2 and 4 still had less sIR than other layers. Uniform sIR among all cortical layers was evident at 38 weeks. Ascending probable thalamocortical axons were reactive as early as 12 weeks and were best demonstrated by 26 weeks, after which increasing sIR in the neuropil diminished the contrast. The sIR was preserved for more than 96 hours postmortem, even in severely autolytic brains. We conclude that synaptophysin is a reliable marker in human fetal brain and that sIR provides the means for objective assessment of cerebral maturation in normal brains and to enable interpretation of abnormal synaptic patterns in pathological conditions.
Rotavirus, the most common cause of severe, dehydrating gastroenteritis among children worldwide, annually causes approximately 500,000 deaths among children aged <5 years. The primary site of rotavirus infection is the small intestine. Pathologic investigations of patients who died of rotavirus infection are limited to data from a few reported autopsies, and dehydration with electrolyte imbalance is believed to be the major cause of death. Several recent reports suggest that children who died during a rotavirus illness were viremic before death, because rotavirus was detected at several extraintestinal sites. We report 3 rotavirus-associated deaths among children, 2 of whom had evidence of rotavirus genome in extraintestinal tissues detected by use of novel molecular diagnostic methods. The part played by rotavirus in fatal cases is unclear and requires additional investigation of diarrhea-associated deaths, because a better understanding might alter the approach to treatment and the need for antiviral therapy.
The case records of 15 infants with intrauterine infections due to group B p-haemolytic streptococci were traced from the records of two geographically separate centres over a 4-year period (1979)(1980)(1981)(1982). Six infants were stillborn and the other nine died within the first 6 h. All the infants weighed < 1000 g and were (28 weeks gestation. Placental examination in 14 of the 15 infants showed the presence of chorioamnionitis and funisitis. The infants also showed evidence of pneumonitis. Four infants had evidence of otitis media, two had evidence of an early meningitis. A history of antepartum bleeding was present in six infants and abundant retroplacental clot was noted in four of them. The membranes had been ruptured for >24 h in only three infants. In six of the infants the membranes were intact at the time of delivery. A history of intact membranes at the time of delivery does not exclude a diagnosis of an intrauterine infection with this organism, and this series of infants highlights the importance of routine bacteriologic studies of all perinatal deaths.
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