CD84 is markedly up-regulated in Kawasaki disease arteriopathy.

The major goals of Kawasaki disease (KD) therapy are to reduce inflammation and prevent thrombosis in the coronary arteries (CA), but some children do not respond to currently available non-specific therapies. New treatments have been difficult to develop because the molecular pathogenesis is unknown. In order to identify dysregulated gene expression in KD CA, we performed high-throughput RNA sequencing on KD and control CA, validated potentially dysregulated genes by real-time reverse transcription-polymerase chain reaction (RT-PCR) and localized protein expression by immunohistochemistry. Signalling lymphocyte activation molecule CD84 was up-regulated 16-fold (P < 0·01) in acute KD CA (within 2 months of onset) and 32-fold (P < 0·01) in chronic CA (5 months to years after onset). CD84 was localized to inflammatory cells in KD tissues. Genes associated with cellular proliferation, motility and survival were also up-regulated in KD CA, and immune activation molecules MX2 and SP140 were up-regulated in chronic KD. CD84, which facilitates immune responses and stabilizes platelet aggregates, is markedly up-regulated in KD CA in patients with acute and chronic arterial disease. We provide the first molecular evidence of dysregulated inflammatory responses persisting for months to years in CA significantly damaged by KD.

Histological chorioamnionitis and neurodevelopmental outcome in preterm infants.

OBJECTIVE: The objective of this study is to examine the neurodevelopmental outcome at 30 to 42 months corrected age of preterm infants with histological chorioamnionitis (HCA). STUDY DESIGN: The study design is a retrospective cohort study with a prospective follow-up. All surviving infants with birth gestational age <29 weeks, born between 2000 and 2006, who had a neurodevelopmental assessment at 30 to 42 months corrected age were included. We compared the neurodevelopmental outcomes of infants with or without HCA. RESULT: Of the 384 infants, 197 (51%) were born to mothers with evidence of HCA. Infants with HCA were of lower gestational age (26 weeks vs 26.6 weeks) and more likely to have intraventricular hemorrhage (27.9% vs 14.4%), periventricular leukomalacia (2.5% vs 0%) and retinopathy of prematurity ≥ stage 3 (31.4% vs 22.4%). On univariate analysis, infants with HCA were more likely to have cerebral palsy (12.6% vs 6.4%, P=0.04). There was no significant difference in the incidence of cognitive delay, deafness, blindness, or total major disabilities between the two groups. After adjusting for perinatal variables, HCA was associated with increased risk of cerebral palsy (odds ratio (OR): 2.45; 95% confidence interval (CI) 1.11 to 5.40), but not for total major disabilities (OR: 1.22; 95% CI: 0.64 to 2.34). There was a trend towards increased risk of cerebral palsy with HCA with funisitis. CONCLUSION: HCA is associated with increased risk of cerebral palsy at 30 to 42 months corrected age in preterm infants.

Histological chorioamnionitis and bronchopulmonary dysplasia: a retrospective cohort study.

OBJECTIVE: To examine the association between histological chorioamnionitis (HC) with or without fetal inflammatory response (FIR) and bronchopulmonary dysplasia (BPD) in preterm infants. STUDY DESIGN: We conducted a retrospective cohort study of infants born at <29 weeks gestation admitted to the neonatal intensive care unit from 2000 to 2006, who had placental histology. We compared the incidence of BPD among three groups: No HC group, HC without FIR group and HC with FIR group. The multivariable model based on generalized estimating equation was fitted to estimate the adjusted risk ratios (aRR) and 95% confidence intervals (CIs) for BPD and combined outcome of BPD or death. RESULT: Of 529 infants, 84 (16%) had HC without FIR, 186 (35%) had HC with FIR and 259 (49%) had no HC. Compared with the no HC group, HC with and without FIR group infants were of lower gestational age and singleton births. Multivariable modeling based on generalized estimating equation revealed that HC with FIR is associated with decreased risk of both BPD (aRR 0.88, 95% CI 0.81 to 0.95) and the combined outcome of BPD or death (aRR 0.91, 95% CI 0.86 to 0.97). HC without FIR showed a trend toward reduction in BPD (aRR 0.93, 95% CI 0.86 to 1.00). CONCLUSIONS: HC with FIR is associated with decreased risk of both BPD and the combined outcome of BPD or death in preterm infants.

Mucosal inflammation in a genetic model of spontaneous type I diabetes mellitus.

The BioBreeding (BB) rat provides a model of spontaneous type I diabetes mellitus that closely resembles the human disease. Diabetes-prone BB rats demonstrate increased intestinal permeability prior to the development of insulinitis. Studies suggest that alterations in intestinal permeability can lead to increased intestinal inflammatory activity. Diabetes-prone (BBdp) and diabetes-resistant (BBdr) BB rats were examined at 45 days and at >70 days of age following the development of clinical disease (BBd). In separate experiments, tissue was assayed for myeloperoxidase (MPO) or fixed for histological assessment and immunohistochemistry. Blood was obtained for leukocyte MPO measurements and morphological assessment of circulating leukocytes. MPO activity was significantly elevated in the distal small intestine of 45-day-old BBdp rats. In contrast, at >70 days of age, MPO activity was significantly increased throughout the small intestine of BBd and non-diabetic BBdp rats. Subsequently, all measurements were performed in >70-day-old rats. An increase in inflammatory infiltrate was noted in the distal small intestine of BBd rats by light microscopy. Infiltrating cells were identified as bands (a maturing cell type of the neutrophil lineage) and mature neutrophils. The findings suggest diabetes susceptibility is associated with an increase in intestinal inflammatory activity.

Age-dependent changes in the regulation of cyclooxygenases in the gastrointestinal tract after gram-negative endotoxemia.

BACKGROUND: Cyclooxygenases (COXs) modulate prostaglandin synthesis in the gastrointestinal tract. Prostaglandins have been shown to have a cytoprotective effect on bowel mucosa in adults, but no similar data are available in neonates. Thus, the purpose of the current study was to evaluate age-dependent changes in gastrointestinal tract COX regulation after Escherichia coli lipopolysaccharide exposure in rats. METHODS: Stomach, small bowel, and large bowel COX-1 and COX-2 mRNA levels (reverse transcription polymerase chain reaction technique) and protein content (Western blot) were obtained from neonates (younger than 3 days old) and adult rats 18 hours after exposure to E. coli O111:B4 lipopolysaccharide toxin. Untreated animals served as controls. RESULTS: Stomach, small bowel, and large bowel tissue COX-1 mRNA levels in the newborn were significantly lower (P < 0.01) than in the adult. No age-dependent differences were found for COX-2 mRNA levels. After lipopolysaccharide exposure, no significant changes in COX-1 levels were seen at either age, whereas COX-2 mRNA levels were increased only in the stomach for both ages. Western blot analysis of small bowel tissue for COX-1 and COX-2 showed no lipopolysaccharide-induced changes in protein content, but the COX-1 content was significantly lower in the newborn (P < 0.01). CONCLUSIONS: In the rat, COX expression in the gastrointestinal tract is regulated in an age-dependent fashion. Lower COX-1 expression and a lack of observable increase in COX-2 mRNA levels in the newborn small bowel after endotoxemia may render the bowel more susceptible to bowel injury early in life.

Combination of renal agenesis with respiratory and alimentary tract atresia results in normal lung development.

The VACTERL complex comprises renal agenesis and atresias of the alimentary and respiratory tracts. We report on a case with this combination causing severe oligohydramnios but with normal lung development. The likely protective mechanism for pulmonary development was an increase in alveolar pressure and reduced alveolar fluid loss due to the esophageal-tracheal malformation. This suggests the possible treatment of oligohydramnios by tracheal occlusion.

Severe Kawasaki disease in infants: two fatal cases.

Kawasaki disease is a systemic vasculitis that manifests itself in many ways. Infants may present as atypical cases and commonly experience severe inflammatory changes. The two cases that are presented here highlight unusual severity and pathology. Patient 1 was a three-month-old infant with atypical Kawasaki disease who developed gangrenous lesions, and coronary and extracoronary artery aneurysms. Multiorgan failure ensued with diffuse cardiac and extracardiac aneurysms and thromboses at autopsy. Patient 2 was a five-month-old infant with Kawasaki disease, cholangitis and peripheral gangrene. Severe coronary artery aneurysms developed and he died following a myocardial infarction, despite multiple doses of intravenous immunoglobulin, acetylsalicylic acid (ASA) and corticosteroids. There is a higher occurrence of atypical disease and more severe vasculitis in infants with Kawasaki disease. Pathological changes are described, including coronary and extracardiac lesions. Patient 1 shows extensive peripheral gangrene and widespread aneurysms, and patient 2 illustrates severe cardiac complications with diffuse organ inflammation. Therapies including intravenous immunoglobulin, ASA, corticosteroids and antithrombotics are reviewed.

Disseminated bacille Calmette-Guérin infection in an infant with a novel deletion in the interferon-gamma receptor gene.

Six weeks after receiving BCG vaccination, a Canadian aboriginal infant presented with suspected sepsis, lymphadenopathy and hepatosplenomegaly. Lymph node biopsy revealed macrophages filled with acid-fast bacilli. Mycobacterium bovis was cultured from tissue specimens and there was evidence of concomitant cytomegalovirus disease. The infant died of disseminated BCG infection. A novel deletion at nucleotide 165 in the interferon-gamma receptor (IFN-gammaR1) was identified. The incidence of this mutation in the aboriginal population and the impact on the heterozygous state are unknown.

Comparative study of three different BACTEC culture media for the detection of bacteremia in ambulatory and hospitalized children.

To compare the yield of two aerobic and an anaerobic BACTEC blood culture media in detecting bacteremia in ambulatory and hospitalized care settings at a children's hospital, a prospective cohort study was completed. Over an 18-month period, equal blood volumes (minimum of 1 mL/bottle) were inoculated into a three-bottle culture set including aerobic BACTEC NR 6A, aerobic BACTEC PEDS Plus and anaerobic NR 7A broths. Chart reviews were completed on all children with bacteremia to determine whether the isolate was clinically significant based on predefined criteria. Among 5328 evaluable blood culture sets, 323 clinically significant organisms (110 from ambulatory and 213 from hospitalized children) were isolated. Most Streptococcus pneumoniae, Haemophilus species, and Neisseria or Moraxella species were recovered from children attending the emergency department or out-patient clinics. Important isolates in hospitalized children included most of the staphylococci and Enterobacteriaceae, and all group D enterococci, Gram-negative nonfermentative bacilli and all Candida species. Overall, significantly more isolates were detected only in the anaerobic bottle from ambulatory children (P<0.0001), including 13 of 54 (24%) patients with S pneumoniae bacteremias presenting to the emergency department. This study indicated that different BACTEC blood culture media combinations are needed in ambulatory and hospitalized pediatric care settings to ensure the optimal recovery of all types of isolates. Whereas aerobic blood culture bottles are adequate for detection of bacteremia in hospitalized children, the common occurrence of fastidious organisms mandates the need for a combined aerobic/anaerobic culture set in ambulatory pediatric care settings.

Metastatic renal cell carcinoma in a child: 11-year disease-free survival following surgery.

A child with metastatic renal cell carcinoma (RCC) is presented. This case is unusual in that the patient has remained disease free for 11 years following surgery and only one course of chemotherapy prior to thoracotomy. The management of metastatic RCC is reviewed and the genetic mechanisms leading to its development briefly discussed.

Middle cerebral artery dissection.

A 12-year-old girl had minor head trauma, with resultant mild headache, one day prior to onset of an apparently generalized tonic clonic seizure, right hemiparesis and dysphasia. A cranial CT scan showed evidence of a left middle cerebral artery infarct. Despite ventilation, fluid restriction, mannitol, thiopental infusion and intracranial pressure monitoring she deteriorated and died. Autopsy demonstrated dissection of the left middle cerebral artery with an intact internal carotid artery and no evidence of vasculitis. Middle cerebral artery dissection in children is very rare. Most reported cases are diagnosed at autopsy. The pathogenesis of cerebral artery dissection may include preceding minor head trauma or exertion and this should be sought for in the history.

Practice guidelines for ordering stool ova and parasite testing in a pediatric population. The Alberta Children's Hospital.

A comprehensive utilization review was done of all stool ova parasite examinations performed at a pediatric hospital during a 3-year period from June 1, 1989 to July 1, 1992. A total of 2,652 stool specimens were surveyed from 1,532 children. Forty-one percent (1,081) of the workload was from inpatients, 37% (976) was from emergency room (ER) visits/other outpatients, and 22% (233) was from patients attending the gastroenterology (GI) clinic. The prevalence of enteric parasites in hospitalized children was 4% (35 of 829) compared to rates of 10% (47 of 470) and 13% (30 of 233) for children attending the ER/other outpatient clinics and GI clinic, respectively. Giardia lamblia was found most often (31%[45 of 146]), followed by Dientamoeba fragilis (23%[33 of 146]), Entamoeba coli (16%[24 of 146]), Blastocystis hominis (13% [19 of 146]), Cryptosporidium (8% [12 of 146]), Endolimax nana (4% [6 of 146]), Enterobius vermicularis (2% [3 of 146]), Hymenolepis nana (2% [3 of 146]), and Iodamoeba buetschlii (1% [1 of 146]). Most children were colonized/infected with a single parasite (85%) with a much smaller number having two or more parasites. Only nine children (6%) who were immunocompetent and hospitalized for more than 4 days were found to have enteric parasites. Over the past 18 months, significant sustainable cost savings have resulted from the implementation of practice guidelines for ordering pediatric stool ova and parasite examinations.

Anti-neutrophil cytoplasmic antibody associated glomerulonephritis in a patient with Down's syndrome.

A 9-year-old boy with Down's syndrome developed a glomerulonephritis associated with crescents and anti-neutrophil cytoplasmic antibodies (ANCA). The patient also had type 1 diabetes mellitus, chronic lymphocytic thyroiditis, and bronchial asthma. Prednisone therapy resulted in an improvement in renal function and a reduction in ANCA titers.

Practice guidelines for ordering stool cultures in a pediatric population. Alberta Children's Hospital, Calgary, Alberta, Canada.

A comprehensive utilization review was done of all stool culture tests performed at a pediatric hospital during a 3-year period from June 1, 1989 through to July 1, 1992. A total of 4,460 stool culture specimens were surveyed from 3,420 children. Sixty percent (2,692) of the workload was from inpatients, 22% (1,001) was from emergency room (ER) visits and 18% (767) was from outpatient clinic/office visits. A total of 9% (294 of 3,420) of the children were confirmed to have enteric bacterial infection. Enteric infections in Southern Alberta follow a typical pattern, where most cases of Escherichia coli O157:H7, Salmonella sp and Campylobacter jejuni are diagnosed in the summer months between June and September. Marked differences were found in the overall stool culture positivity rate between hospitalized children (94 of 2,141, 4%), and ambulatory children attending the ER (176 of 892, 19%). Although a significant number of children had more than one stool culture done, most cases of enteric bacterial infections were diagnosed on the first stool sample (290 of 294, 98%). Most children (89 of 94, 95%) who were hospitalized because of an acute diarrheal illness had a bacteriological diagnosis confirmed within the first 4 days after admission (90 of 94, 96%), including immunocompromised children in the Oncology ward. Over the past year, significant sustainable cost savings have resulted from the implementation of practice guidelines for ordering pediatric stool cultures.

Hyperglycemia in diarrhea-associated hemolytic-uremic syndrome.

Hyperglycemia is a recognized complication of diarrhea-associated hemolytic-uremic syndrome (D + HUS). Hyperglycemia developed in 8 (6.6%) of 121 patients with D + HUS. A literature review revealed a further 11 patients with D + HUS who developed hyperglycemia. The mortality rate in this group of patients is high. Hyperglycemia is more common in patients with D + HUS uremic syndrome who are female, who have an elevated white blood cell count on admission, and who develop anuria or a central nervous system complication.

Allergic colitis in infancy: clinical and pathologic aspects.

This study prospectively evaluated 35 consecutive infants who presented with fresh blood mixed with stools. The mean age at onset of bleeding was approximately 4 weeks. All infants were otherwise asymptomatic and exhibited normal growth and physical examinations. None had evidence of a bleeding diathesis, viral or bacterial enteritis, or necrotizing enterocolitis. Consent for limited colonoscopy and biopsy was obtained for 34 infants. Twenty-five had macroscopic colitis and 10 infants had marked nodular lymphoid hyperplasia. Thirty-one infants had histopathological evidence of colitis characterized by a marked eosinophilic infiltrate. Compared with 19 controls (age, 4.1 +/- 3.6 months) the mean number of eosinophils per high-power field was greater in the patients with colitis. Patients with colitis also had an elevated mean absolute peripheral eosinophil count and a low mean serum albumin compared to control values. The 31 infants with colitis were receiving solely breast milk (10), cow's milk formula (9), soya formula (9), breast milk with cow's milk formula (2), or nutramigen (1) at the time of presentation. Nineteen infants had rapid resolution of frank bleeding and gradual correction of serum albumin with dietary change. While limited colonoscopy and biopsy were useful in establishing a definitive diagnosis, a low serum albumin and high peripheral eosinophil count suggested the diagnosis. Colitis characterized histologically by > 20 eosinophils per high-power field is a common cause of rectal bleeding in otherwise healthy young infants. Resolution of bleeding and increase in serum albumin after dietary change suggest that this is an allergic colitis: however, the pathogenesis of this disorder needs further clarification.