Faculty Bibliography

OBJECTIVE: To determine whether children breast fed by mothers with silicone implants (BFSI) have increased urinary excretion of nitric oxide (NO) metabolites and neopterin, whether these are associated with esophageal dysmotility, and whether in vitro incubation of macrophages with silicone increases NO synthesis. METHODS: In a case-control study based on laboratory investigation, 38 BFSI children (17 male, 21 female, mean age 7.1 +/- 3.6 years, range 0.5-16.5) were compared with 30 controls (14 male, 16 female, mean age 8.4 +/- 3.5 years, range 2.5-17). Urinary NO was quantitated using the Griess reaction. Urinary neopterin was determined by radioimmunoassay. Murine macrophages were cultured with or without silicone and NO production assayed. RESULTS: Urinary NO and neopterin were significantly increased in BFSI children compared with controls. There was a significant inverse relationship between urinary neopterin excretion and the severity of esophageal dysfunction. In vitro nitrite production was nearly 60% higher in macrophages grown on silicone compared to other growth conditions. CONCLUSION: BFSI children have evidence of macrophage activation and this is associated with esophageal dysmotility. In vitro data support the proposal that silicone exposure causes macrophage activation.

OBJECTIVE: We determined systematically the prevalence of autoantibodies in children born to mothers with silicone breast implants and the relationships with clinical symptoms and methods of exposure. METHODS: Autoantibody expression was determined in 80 children born to mothers with silicone implants and in 42 controls. A clinical assessment score was assigned to each patient. Antinuclear antibodies as well as antibodies to mitochondrial, smooth muscle, striational, myocardial, parietal cell, reticulin tissues, or subcellular compartments were measured by indirect fluorescent assay. Antibodies to nRNP (U1-RNP/snRNP); Sm; SS-A; SS-B; Scl-70; thyroid microsome; immunoglobulin (Ig)G, IgM, and IgA antibodies to cardiolipin; and antibodies to native and denatured human types I and II collagen were measured by enzyme-linked immunosorbent assay. Serum complement components C3 and C4 and IgM rheumatoid factor were measured by nephelometry. RESULTS: Autoantibody prevalence was not significantly different between children born to mothers with silicone implants and controls. The presence of autoantibodies was not related to the children's clinical symptoms or to the method of exposure. CONCLUSIONS: Determination of autoantibody production is of limited clinical utility in the evaluation of children born to mothers with silicone breast implants.

: The purpose of this study was to evaluate the use of the acute-phase serum protein alpha1-antitrypsin (alpha1-AT) compared with the erythrocyte sedimentation rate (ESR), platelet count, and hemoglobin level in screening for inflammation in newly diagnosed and known patients with inflammatory bowel disease (IBD). The serum alpha1-AT level, ESR, platelet count, and hemoglobin values of 154 children who were initially evaluated for possible IBD, as well as of 113 children with known IBD, were compared to evaluate their value as markers of inflammatory activity. Of the 154 children evaluated for IBD, 103 did not have IBD, 28 were diagnosed with Crohn's disease (CD), and 23 were found to have ulcerative colitis (UC). The sensitivity and specificity for CD was for alpha1-AT, 100%, 92%; for ESR, 68%, 94%; and for UC was for alpha1-AT, 70%, 92%; for ESR, 61%, 94%. In the 113 children with known IBD (66 CD, 47 UC), the sensitivity and specificity for predicting disease activity was for CD for alpha1-AT, 94%, 59%; for ESR, 52%, 63%; and for UC was for alpha1-AT, 79%, 76%; and for ESR, 59%, 82%. The determination of serum alpha1-AT levels was more sensitive and specific than the ESR in the initial diagnosis of CD and in predicting subsequent disease activity in both CD and UC.

The current study evaluated immune response to silicon dioxide in children born to women with silicone breast implants. In part one of the study, the T lymphocytes of 21 of 24 such children were significantly stimulated by silicon dioxide (silica). Part two consisted of eleven children, four born preimplantation and seven born postimplantation. None of the preimplant offspring showed T cell responses to silica; five of the seven postimplant children were positive for T cell memory for silica. Part three was a blinded study based on statistically significant differences in T cell stimulation with silicon dioxide between postimplant children and controls. These findings indicate a common immune reaction, that of T cell memory, occurs in mothers and their children born after exposure to silicone mammary implants placed prior to pregnancy. Since not all such children were breast fed the result favors transplacental passage of immunogens such as silicone oligomers or through maternofetal cellular traffic.

OBJECTIVES: The optimal timing of surgical intervention for severe ulcerative colitis remains uncertain. Numerous reports recommend surgery within 10-14 days if clinical remission is not achieved. We undertook a study to follow the clinical course and long-term follow-up of patients with severe ulcerative colitis treated medically for longer than 14 days (n = 11). METHODS: We performed a retrospective review of all patients admitted to the hospital with a diagnosis of severe ulcerative colitis who were treated for more than 14 days. RESULTS: Nine percent of patients (n = 1) required surgery during their hospitalization. Ninety-one percent of patients (n = 10, mean age 8.6 yr, 7 M, 3 F) treated with medical and nutritional therapy for more than 14 days went into clinical remission. Of these, only 10% (n = 1) ultimately required surgery; 60% remain in clinical remission up to 83 months posthospitalization (mean follow-up, 49.5 months), whereas 30% suffer from mild to moderate colitis (mean follow-up, 26.3 months). CONCLUSIONS: These results do not support the recommendation for colectomy for refractory severe ulcerative colitis if remission is not noted within 2 wk of hospitalization.

We describe a child with cystic fibrosis who was treated with high-dose pancreatic enzyme replacement therapy and who had a prominent ascending colon stricture with submucosal fibrosis. Unlike prior reported cases, this patient's disease was more extensive, involving the entire colon, and was associated with chylous ascites.

OBJECTIVE: To determine whether breast-fed children of mothers with silicone implants are at increased risk for the development of sclerodermalike esophageal involvement compared with children not exposed to silicone implants. DESIGN: Case-series [corrected]. SETTING: Referral-based pediatric gastroenterology clinic. PATIENTS: Eleven children (mean age, 6.0 years; range, 1.5 to 13 years; six boys and five girls) referred for abdominal pain who were born to mothers who had silicone breast implants (eight breast-fed children and three bottle-fed) were compared with 17 patients (mean age, 10.7 years; range, 2 to 18 years; 11 boys and six girls) with abdominal pain who were not exposed to silicone implants. METHODS: All children underwent esophageal manometry and upper intestinal endoscopy with esophageal biopsy and were tested for antinuclear antibody and autoantibodies to Scl-70, centromere, ribonucleoprotein, Sm, Ro, La, and phospholipid. RESULTS: Six of the eight breast-fed children from mothers with silicone implants had significantly abnormal esophageal motility with nearly absent peristalsis in the distal two thirds of the esophagus and decreased lower sphincter pressure. Upper esophageal pressures and motility were normal. Compared with controls, the breast-fed children had significantly decreased lower sphincter pressure and abnormal esophageal wave propagation. These manometric abnormalities were not seen in the three bottle-fed children. There was no difference in the expression of autoantibodies in the breast-fed children compared with the bottle-fed children or controls. CONCLUSIONS: A relationship appears to exist between breast-feeding by mothers with silicone implants and abnormal esophageal motility. Studies evaluating larger numbers of children are needed to determine the extent of the risk.