Raynorda F Brown

Use of Infliximab in Pediatric Patients with Inflammatory Bowel Disease

BACKGROUND: The concentration of tumor necrosis factor, a proinflammatory cytokine, is increased in the gastrointestinal mucosa of patients with active Crohns disease (CD) and ulcerative colitis (UC). Neutralization of tumor necrosis factor decreases the mucosal inflammatory response of adults with CD. Little information is available on the use of monoclonal antibody to tumor necrosis factor (infliximab) in children and adolescents with CD or UC. OBJECTIVE: To evaluate the clinical response and side effects of patients to infliximab. METHODS: A retrospective review of data regarding 18 pediatric and adolescent patients with active CD (n = 15) and UC (n = 3) poorly controlled with conventional therapy. All patients received one to six intravenous infusions of infliximab 5 mg/kg, while receiving their usual medications. RESULTS: All patients experienced clinical improvement, including decrease in the frequency of stooling and resolution of extraintestinal symptoms such as arthropathy, malaise, and skin manifestations after treatment with infliximab. All but one patient had a documented decrease in the erythrocyte sedimentation rate. Prednisone dosage was tapered in all but two patients, and discontinued in seven patients. Intravenous infusion of infliximab was well tolerated. One patient developed a rash several days after the infusion. A patient who received six infliximab infusions developed recurrent Staphylococcus aureus infections, as well as septic arthritis and chronic osteomyelitis during the follow-up period, raising the issue of the long-term safety of infliximab. CONCLUSIONS: Treatment of our patients with refractory CD and UC with infliximab was associated with remarkable clinical improvement. Although the drug may have an important role in their management, further assessment of long-term safety and efficacy is needed.

Gastroesophageal reflux and Nissen fundoplication following percutaneous endoscopic gastrostomy in children.

BACKGROUND Abnormal gastroesophageal reflux after percutaneous endoscopic gastrostomy is a serious problem in neurologically impaired children. Protective fundoplication has been advocated. Whether esophageal pH monitoring before percutaneous endoscopic gastrostomy will predict later problems with gastroesophageal reflux is unclear. METHODS Eighty-five mostly neurologically impaired pediatric patients who underwent percutaneous endoscopic gastrostomy were studied retrospectively regarding complications, success of nutritional rehabilitation, and the incidence of pathologic gastroesophageal reflux. Follow-up period was 1 to 4 years. Twenty-four-hour esophageal pH monitoring was performed in 46 patients before percutaneous endoscopic gastrostomy. RESULTS There were no deaths. Two major complications occurred that required surgical intervention, and 14 minor complications occurred related to the procedure. Z-scores for weight increased significantly after percutaneous endoscopic gastrostomy. pH probe results were normal in 22 patients (group 1). Five required medical treatment for gastroesophageal reflux after percutaneous endoscopic gastrostomy, but only 1 (5%) later required Nissen fundoplication. pH probe results were abnormal in 24 patients (group 2). Nineteen required medical therapy for gastroesophageal reflux, and 7 (29%) later needed fundoplication (p < 0.05, incidence of fundoplication group 1 vs. group 2). Improvement in Z-scores was similar in patients requiring and not requiring fundoplication. CONCLUSIONS Percutaneous endoscopic gastrostomy is a safe and effective technique for long-term nutritional support in children. Abnormal gastroesophageal reflux is common. Normal findings in an esophageal pH study before percutaneous endoscopic gastrostomy may be predictive of a favorable outcome with respect to gastroesophageal reflux. This is in contrast to patients with abnormal results in pH studies before percutaneous endoscopic gastrostomy of whom a relatively large percentage may later require fundoplication. Improved nutritional status after percutaneous endoscopic gastrostomy does not appear to have an impact on the severity of gastroesophageal reflux.

Metastatic perivascular epithelioid cell tumor of the colon in a child.

Painless hematochezia in a school-age child is the hallmark of a juvenile colorectal polyp. Rarely do malignant gastrointestinal (GI) neoplasms present with painless rectal bleeding in childhood. We describe the clinical and pathological features of a PEComa of the sigmoid colon with regional metastases in an 11-year-old boy with painless hematochezia and mild anemia. The PEComa is a recently described tumor of unknown cellular origin and low-grade malignancy characterized by both smooth muscle and melanocytic differentiation. Most cases affect adult women, and most tumors are found in the uterus (1). To the best of our knowledge, this is the first report of a metastatic PEComa involving the GI tract of a child.

Association of the T allele of an intronic single nucleotide polymorphism in the colony stimulating factor 1 receptor with Crohn's disease: a case-control study

BackgroundPolymorphisms in several genes (NOD2, MDR1, SLC22A4) have been associated with susceptibility to Crohns disease. Identification of the remaining Crohns susceptibility genes is essential for the development of disease-specific targets for immunotherapy. Using gene expression analysis, we identified a differentially expressed gene on 5q33, the colony stimulating factor 1 receptor (CSF1R) gene, and hypothesized that it is a Crohns susceptibility gene. The CSF1R gene is involved in monocyte to macrophage differentiation and in innate immunity.MethodsPatients provided informed consent prior to entry into the study as approved by the Institutional Review Board at LSU Health Sciences Center. We performed forward and reverse sequencing of genomic DNA from 111 unrelated patients with Crohns disease and 108 controls. We also stained paraffin-embedded, ileal and colonic tissue sections from patients with Crohns disease and controls with a polyclonal antibody raised against the human CSF1R protein.ResultsA single nucleotide polymorphism (A2033T) near a Runx1 binding site in the eleventh intron of the colony stimulating factor 1 receptor was identified. The T allele of this single nucleotide polymorphism occurred in 27% of patients with Crohns disease but in only 13% of controls (X2 = 6.74, p < 0.01, odds ratio (O.R.) = 2.49, 1.23 < O.R. < 5.01). Using immunohistochemistry, positive staining with a polyclonal antibody to CSF1R was observed in the superficial epithelium of ileal and colonic tissue sections.ConclusionsWe conclude that the colony stimulating factor receptor 1 gene may be a susceptibility gene for Crohns disease.