Large-volume paracentesis in the management of ascites in children.

BACKGROUND: Large-volume paracentesis has been evaluated for both therapeutic and diagnostic purposes in the management of ascites in cirrhotic adults. There are no published data relating to the safety, efficacy, or methods of this procedure in children. The objective of this study was to characterize the authors' initial experience with large-volume paracentesis (> 50 ml/kg of ascites) for removal of tense abdominal ascites in the pediatric population. METHODS: Retrospective chart review was performed of 21 large-volume paracentesis sessions in seven children (ages 6 months-18 years) with tense ascites that did not respond to other measures. RESULTS: Mean volume removed was 3,129 +/- 2,966 ml (mean +/- standard deviation) or 118 +/- 56 ml/kg over 2.9 +/- 3.7 hours by a 16-gauge intravascular catheter in 6 sessions, by an 18-gauge intravascular catheter in three sessions, and by a 15-gauge fenestrated, stainless-steel paracentesis needle in 12 sessions. Large-volume paracenteses performed with the paracentesis needle had significantly shorter duration of drainage and faster flow rates than those performed with the intravascular catheter. The only complication encountered was decreased urine output in one session. CONCLUSIONS: Large-volume paracentesis is a safe and effective therapeutic method for managing tense abdominal ascites in children. The use of the paracentesis needle significantly improved the speed and efficiency of large-volume paracentesis compared with the intravascular catheter.

Microvillous inclusion disease: report of a case with atypical features.

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.

Microvillous inclusion disease: report of a case with atypical features.

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.

Transglutaminase antibodies in children with a genetic risk for celiac disease.

OBJECTIVES: The transglutaminase (TG) antibody test is accurate in identifying celiac disease in symptomatic children. We sought to determine the positive predictive value of this test in asymptomatic children at genetic risk for celiac disease. STUDY DESIGN: Asymptomatic children with a genetic risk for celiac disease were studied to investigate the relationships between TG antibody titer, small bowel histology, growth, and clinical features. Small bowel biopsy histology was graded by using the system of Marsh. RESULTS: Of 30 children with a positive TG antibody test result, 21 (70%) had definite (Marsh score 2 or 3) and 4 (13%) had possible (Marsh score 1) biopsy evidence of celiac disease. TG antibody titer correlated with Marsh score (r = 0.569, P <.01). There was an inverse correlation between Marsh score and height z score (r = -0.361, P =. 05). CONCLUSIONS: In this group of asymptomatic children screened because of a genetic risk, TG antibodies have a positive predictive value of 70% to 83% for biopsy evidence of celiac disease and may identify children before clinical features of celiac disease develop.

A trial of oats in children with newly diagnosed celiac disease.

OBJECTIVE: To determine whether consumption of oats is safe in children with newly diagnosed celiac disease who are starting a gluten-free diet. STUDY DESIGN: We conducted a self-controlled, open-label, 6-month trial of a commercial oat breakfast cereal product. Primary outcome variables were small bowel histomorphology and anti-tissue transglutaminase IgA antibody titer. RESULTS: The 10 children who completed the study were 6.8 +/- 4.0 (mean +/- SD) years of age and 5 were male. Over 6.6 +/- 0.7 months, they consumed 24 grams of oat cereal per day, or 1.2 +/- 0.9 g/kg/d. Compared with start of study, at completion there was a significant decrease in biopsy score (P <.01), intra-epithelial lymphocyte count (P <.005), anti-tissue transglutaminase IgA antibody titer (P <.01), and number of symptoms (P <.01). CONCLUSIONS: We conclude that consumption of a commercially available oat cereal product for 6 months is safe for children with celiac disease beginning a gluten-free diet. Studies are needed to determine the long-term safety of including oat cereal in the gluten-free diet.

One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies.

Type 1 diabetes and celiac disease are both immunologic disorders where specific HLA alleles are associated with disease risk. We have developed a radioassay for autoantibodies to tissue transglutaminase (tTG) following the report that this enzyme is 'the' endomysial autoantigen (EMA) of celiac disease. The radioassay for transglutaminase autoantibodies is similar to that utilized for detecting anti-islet autoantibodies. The 'cut-off' for the IgA autoantibody assay was established as 3 x 100th percentile of 184 healthy control subjects at an index of 0.05. Ninety-eight of 847 patients with type 1 diabetes (11.6%) had tissue transglutaminase autoantibodies (tTG). All EMA-positive patients were positive (49/49) for transglutaminase autoantibodies, as were 49/540 EMA-negative patients. Twenty transglutaminase-positive patients consented to intestinal biopsy and 15 biopsies were positive for celiac disease. All patients with a transglutaminase level greater than 0.70 (13/13) had a positive biopsy, while none (0/3) with a level <0.3 had a positive biopsy. The prevalence of transglutaminase autoantibodies was higher in diabetic patients with HLA DQ2 or DQ8. One third of DQ2 homozygous patients (22/68) expressed transglutaminase autoantibodies vs. less than 2% of patients lacking DQ2 or DQ8. A simple radioassay for IgA transglutaminase autoantibodies detects all endomysial antibody positive patients and detects transglutaminase autoantibodies in 5% of endomysial autoantibody negative patients. The prevalence of transglutaminase autoantibodies is associated with DQ2 and DQ8 and in particular DQ2 homozygosity. Autoimmunity to transglutaminase is remarkably prevalent amongst patients with type 1 diabetes expressing certain class II HLA alleles.

Serologic testing for inflammatory bowel disease.

OBJECTIVES: To determine the accuracy of anti-neutrophil cytoplasmic antibodies (ANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCA) in distinguishing patients with inflammatory bowel disease from patients with other disorders, seen in a pediatric gastroenterology clinic setting, and in distinguishing ulcerative colitis (UC) from Crohn's disease (CD). STUDY DESIGN: Serum samples from 120 children with new or established diagnoses of UC (n = 25) or CD (n = 20) and control children (n = 74) were analyzed in blinded fashion for the presence of IgG ANCAs and IgA and IgG ASCA. RESULTS: The highest sensitivity for detecting inflammatory bowel disease, 71%, was achieved by using ANCAs and ASCA together. The best test for UC was ANCAs, which had a sensitivity of 80%. However, the ANCA pattern characteristic of UC, perinuclear ANCAs eliminated by DNAse, had a sensitivity of 60%. High-titer ANCAs were specific for UC, whereas ASCA were specific for CD. CONCLUSIONS: Testing for ANCAs and ASCA together did not achieve sensitivity necessary for population screening. However, ANCAs and ASCA may be helpful in evaluating children suspected of having inflammatory bowel disease and in distinguishing UC from CD.

Does retrograde warm blood cardioplegic perfusion provide better protection of ischemic areas than antegrade warm blood cardioplegic perfusion? A magnetic resonance study in pig hearts.

OBJECTIVE: The purpose of this study was to determine whether retrograde continuous normothermic blood cardioplegic perfusion provides better protection to ischemic areas of the left and right ventricles than does antegrade continuous normothermic blood cardioplegic perfusion. Localized phosphorus 31 magnetic resonance spectroscopy was used to monitor the changes in energy metabolism and intracellular pH in the ventricles of pig hearts. METHODS: Ten isolated pig hearts received 20 minutes of antegrade continuous normothermic blood cardioplegic perfusion for collection of control (baseline) data, followed by 60 minutes of either antegrade continuous normothermic blood cardioplegic perfusion (n = 5) or retrograde continuous normothermic blood cardioplegic perfusion (n = 5) with occlusion of the left anterior descending and the right coronary arteries. The hearts were then subjected to antegrade continuous normothermic blood cardioplegic perfusion for 20 minutes. The perfusion pressures were maintained between 80 and 100 mm Hg and between 38 and 43 mm Hg during antegrade and retrograde continuous normothermic blood cardioplegic perfusions, respectively. Intracellular pH and creatine phosphate, inorganic phosphate, and adenosine triphosphate levels were measured continuously in each ventricle by means of localized phosphorus 31 magnetic resonance spectroscopy with 2 surface coils. RESULTS: Both antegrade and retrograde continuous normothermic blood cardioplegic perfusion resulted in a significant increase in inorganic phosphate level and decreases in creatine phosphate level, adenosine triphosphate level, and intracellular pH. No significant differences in these changes were observed between the two groups. The creatine phosphate and adenosine triphosphate levels were significantly lower in the right ventricle than in the left ventricle during retrograde continuous normothermic blood cardioplegic perfusion. On reperfusion, the inorganic phosphate level, creatine phosphate level, and intracellular pH recovered completely; however, no recovery in the adenosine triphosphate level was seen in the ventricles of either group. CONCLUSIONS: Retrograde continuous normothermic blood cardioplegic perfusion does not provide better protection to ischemic areas of the ventricles than does antegrade continuous normothermic blood cardioplegic perfusion under our experimental conditions.

Symptomatic colonic polyps in childhood: not so benign.

BACKGROUND: The clinical spectrum of symptomatic polyps and the frequency of familial polyposis is not well defined in children. In the present study, a series of children with juvenile polyposis coli (JPC) and non-JPC polyps were studied. METHODS: Children with symptomatic colonic polyps and negative family history of polyps were ascertained by review of endoscopic records. Juvenile polyposis coli was defined as 10 or more juvenile polyps or any juvenile polyp in a relative of an index case of JPC. Polyps were tested for Ki-ras mutations, p53 overexpression, and aneuploidy. RESULTS: Seventy-eight children (age range, 0.4-18 years) were identified, all evaluated for lower gastrointestinal bleeding. Nine (12%) had JPC, 66 (84%) had isolated juvenile polyps, and 3 (4%) had other types of polyps. The JPC and non-JPC groups were similar in age (p = 0.4) and symptom duration (p = 0.3). The JPC group had more polyps (p = 0.0001), and greater likelihood of anemia (p = 0.01), polyps with adenomatous change (p = 0.03), and right-colon polyps (p = 0.001). In three of eight JPC families, polyps were identified in asymptomatic first-degree relatives. No abnormalities in Ki-ras, p53, or aneuploidy were identified. CONCLUSIONS: Juvenile polyposis coli is common in children with symptomatic polyps, and is associated with anemia, right-colon polyps, and adenomas. The risk of polyps and of colorectal cancer in relatives of persons with JPC requires further study.

Quality-of-life factors in adolescent inflammatory bowel disease.

Little is known about the specific psychosocial factors that influence quality of life in adolescents with newly diagnosed inflammatory bowel disease (IBD). We adapted a model by Garrett and Drossman to assess adolescent adjustment to recent-onset IBD. Thirty adolescent-parent pairs completed a set of standardized questionnaires. The inclusion criteria were adolescents 12-18 years of age with Crohn's disease or ulcerative colitis of < 5 years' duration. Adolescents' health-related quality-of-life scores significantly correlated with satisfaction and degree of closeness with their social support members, such as parents. An unexpected finding was that the adolescents included more extended family than peers in their social support networks. Also of note was that parental coping styles rather than adolescent coping styles significantly correlated with adolescents' quality-of-life health scores. Severity of illness did not correlate with adolescent quality-of-life health scores. There was significant agreement between adolescent and parental quality-of-life health scores and stressful event ratings. Adolescents with recent-onset IBD rely more on family members than their peers for emotional support, and they depend more on their parents' coping skills than their own. These findings may indicate lags in normal adolescent development. Adolescents and parents do communicate and share concerns with each other. Support programs for adolescents with IBD should reinforce existing coping skills and parent-adolescent communication while promoting normative development.

Outcome after exploratory laparoscopy for unexplained abdominal pain in childhood.

BACKGROUND: Abdominal pain in childhood is common yet frustrating when unexplained. OBJECTIVE: To describe the clinical features and outcome of 8 children (6 girls and 2 boys; mean[+/- SD] age, 13 +/- 2 years) with unexplained abdominal pain who underwent exploratory laparoscopy. SETTING: All 8 patients were examined at an academic pediatric gastroenterology center and referred for exploratory laparoscopy because of unexplained abdominal pain. Laparoscopy was offered after family agreement to pursue behavioral management if the pain and disability did not improve. RESULTS: In all 8 children, laparoscopy detected an anomaly at a site corresponding to that of the abdominal pain. Findings were adhesions in 7 children (3 colonic, 2 ileocecal, 1 gastric, and 1 appendiceal) and ovarian torsion in 1 child. At a mean follow-up of 12.6 months, the abdominal pain had completely resolved in 6 children, notably improved in 1 child, and continued unchanged in 1 child. Disability completely resolved in 2 of 3 children. CONCLUSIONS: In children with unexplained abdominal pain that is acute in onset, well described, and suggestive of peritoneal involvement, exploratory laparoscopy (1) successfully ends the cycle of abdominal pain in most cases; and (2) commonly identifies abnormalities, usually adhesions. However, whether laparoscopy, the placebo effect, or both promote the healing process is unclear. Further study is needed to develop criteria for referral for laparoscopic evaluation of unexplained abdominal pain.

Aspartate/glutamate-enriched blood does not improve myocardial energy metabolism during ischemia-reperfusion: a 31P magnetic resonance spectroscopic study in isolated pig hearts.

OBJECTIVE: Our objective was to test the effects of exogenous L-aspartate and L-glutamate on myocardial energy metabolism during ischemia-reperfusion. METHODS: Phosphorus 31-magnetic resonance spectroscopy was used to observe cellular energetics and intracellular pH in isolated pig hearts perfused with blood (group A, n = 8) or blood enriched with 13 mmol/L each of L-aspartate and L-glutamate (group B, n = 6). The hearts were subjected to 30 minutes of total normothermic ischemia and then reperfused for 40 minutes. Two hearts from each group were inotropically stimulated by titration with calcium after normokalemic reperfusion. Left ventricular function was measured with the use of a compliant balloon and oxygen consumption was calculated. RESULTS: Magnetic resonance spectroscopy showed no decrease in the rate of energy decline during ischemia for group B versus group A. No significant differences were observed between the two groups in terms of myocardial function, oxygen consumption, or the rate or extent of high-energy phosphate recovery after normokalemic reperfusion or inotropic stimulation. Inotropic stimulation of postischemic hearts, however, led to dramatic improvement in myocardial function in both groups (p < 0.05 for all parameters) and significant improvement in oxygen consumption (p = 0.01). CONCLUSIONS: In a normal, isolated, blood-perfused pig heart subjected to 30 minutes of total normothermic ischemia, (1) enrichment of the perfusate with aspartate/glutamate before and after ischemia affects neither myocardial energy metabolism during ischemia-reperfusion nor postischemic recovery of myocardial function or oxygen consumption and (2) inotropic stimulation can recruit significant postischemic function and sufficient aerobic respiration to support it, irrespective of aspartate/glutamate enrichment.

Circulating antioxidant concentrations in children with inflammatory bowel disease.

The mechanisms by which inflammatory bowel disease causes chronic injury to the gastrointestinal tract are poorly understood. To determine whether antioxidant defenses might be altered, we evaluated plasma antioxidant concentrations in 24 children with inflammatory bowel disease (12 with Crohn disease and 12 with ulcerative colitis) and in 23 healthy control subjects. Anthropometric measurements and disease activity scores were obtained. The groups were of similar age and sex distribution; most children had quiescent or mild disease. The children with Crohn disease were malnourished compared with the ulcerative colitis and control groups. Children with inflammatory bowel disease had decreased plasma ascorbic acid and increased glutathione peroxidase, glutathione, and alpha-tocopherol (vitamin E) concentrations compared with control subjects. These differences were found primarily in the children with Crohn disease. This study provides evidence that children with Crohn disease have alterations in circulating antioxidant defenses, possibly related to an ongoing oxidant stress.

Detection of group C rotavirus in infants with extrahepatic biliary atresia.

The purpose of this retrospective study was to examine liver tissue from patients with cholestatic disease for the presence of group C rotavirus RNA. The reverse transcriptase-polymerase chain reaction (PCR) for genes 5 and 6 was used, and the PCR products were subjected to liquid hybridization with a 32P-labeled probe. A second amplification with nested primers was also used. Samples from 32 subjects (20 with biliary atresia or choledochal cyst and 12 controls) were tested. Ten of 20 biliary atresia patients were positive for group C rotavirus RNA; no controls were positive (P < .003). Three of the positive patients were positive for both genes 5 and 6. Six of the 10 had > 1 sample that was positive. These data suggest a possible relationship between group C rotavirus and extrahepatic biliary atresia in the 10 patients in whom virus RNA was detected.

Antioxidants in pediatric gastrointestinal disease.

Oxidant stress seems to be involved in the pathogenesis of several important gastroenterologic disorders in infants and children. The question can still be asked, in most circumstances, whether the oxidant stress precedes, and therefore is involved in, tissue or cellular injury or is a result of injury and not of clinical importance. The data favor the former situation in several inflammatory conditions of the bowel and in a variety of liver diseases. Experimental and clinical testing of this possible basic mechanism of tissue injury over the next few years will shed light on the role of antioxidants in treating gastrointestinal disorders.

Evaluation of cardiac 31P magnetic resonance spectroscopy: reviewing NMR principles.

31P magnetic resonance spectroscopy (MRS) has been used for several decades as an analytical tool in cardiac research and is quickly emerging as a diagnostic tool, due to its ability to continuously and noninvasively monitor levels of high energy phosphates, inorganic phosphate, and intracellular pH in localized regions of the myocardium. This article provides a brief review of basic MRS principles, presents some current techniques of localized spectroscopy related to experimental and clinical cardiac research, and discusses their advantages and disadvantages.

Nursing case management for children with failure to thrive.

The case management approach is described for children with nonorganic failure to thrive in the pediatric tertiary care setting. An advanced practice nurse facilitated the organization of a planning committee, the construction of a care path, and the evaluation of the case management model. A 4-day care path is presented to show staff nursing functions in the nurse case manager role. Special issues are discussed for developing care paths for organic-based failure to thrive where parent reports can help guide health care interventions.

Antegrade and retrograde continuous warm blood cardioplegia: a 31P magnetic resonance study.

BACKGROUND: Retrograde normothermic blood cardioplegia has been shown to provide myocardial protection during certain bypass procedures. However, a number of animal studies have shown less than optimal myocardial protection with this technique. METHODS: Isolated, beating porcine hearts were perfused antegradely (aortic root pressure = 75 to 95 mm Hg) for 30 minutes. Arrest was induced and maintained for 60 minutes with high K+ blood cardioplegia delivered either antegradely (n = 8) or retrogradely (n = 8) (coronary sinus pressure = 35 to 55 mm Hg). Perfusate was switched to normokalemic blood for recovery of sinus rhythm (30 minutes). Intracellular pH, creatine phosphate, inorganic phosphate, and adenosine triphosphate were monitored continuously and noninvasively with phosphorus 31 magnetic resonance spectroscopy throughout the experiment, and functional variables (rate-pressure product and the positive and negative first derivatives of left ventricular pressure) were assessed concurrently. RESULTS: Antegrade cardioplegia maintained high-energy metabolites, intracellular pH, and myocardial function. Retrograde normothermic blood cardioplegia resulted in an increase in inorganic phosphate (197% +/- 15% of control) and a decrease in creatine phosphate (51% +/- 6% of control). There was no significant difference in myocardial function between the two groups (p > 0.05). The magnetic resonance spectroscopy data indicate ischemia occurred within 2 minutes of the initiation of retrograde perfusion. CONCLUSIONS: This study suggests that retrograde normothermic blood cardioplegia causes a transition of the myocardium to ischemic metabolism in the normal porcine heart.

Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy.

OBJECTIVE: To determine the outcome, in index patients followed at an American Center, of syndromic paucity of interlobular bile ducts (sPILBD; Alagille syndrome), with onset of cholestasis in infancy. DESIGN: Cohort. SETTING: Regional referral center for infants and children with liver disease. RESULTS: During the past 10 years, 26 unrelated children with sPILBD were identified. Fifteen (58%) are alive without liver transplantation at a median age of 12.1 years. Three (11%) died, all before 2 years of age. Eight patients (31%) underwent liver transplantation at a median age of 6.5 years; all eight are alive a median 5.4 years after transplantation. The most common factors contributing to the decision for transplantation were bone fractures, pruritus, and severe xanthoma. The predicted probability of reaching 19 years of age without transplantation is about 50%; however, with transplantation, the predicted probability of long-term survival is 87%. Of 26 patients 4 (15%) have had significant central nervous system disease, and two of them have died of intracranial hemorrhage. Of the four patients who underwent cholecystoportostomy or portoenterostomy, three required liver transplantation. CONCLUSIONS: Children with sPILBD identified in infancy because of cholestasis have a 50% probability of long-term survival without liver transplantation, a worse prognosis than other follow-up studies have reported. In selected patients, liver transplantation provides the opportunity for long-term survival with improved quality of life. Patients with sPILBD are at risk of having intracranial hemorrhage.