ImmuKnow: a new parameter in immune monitoring of pediatric liver transplantation recipients.

Lifelong immunosuppression is mandatory for optimal graft and patient survival following liver transplantation. Nevertheless, graft rejection or numerous adverse events associated with overimmunosuppression or underimmunosuppression cannot be completely avoided. The ImmuKnow assay measures cell-mediated immunity and is able to discern between conditions of overimmunosuppression and underimmunosuppression. The aim of this study was to evaluate the ImmuKnow assay in the evaluation of the immune function in pediatric liver transplant recipients and to assess its correlation with the patients' clinical and biochemical status. Eighty-nine whole blood samples were collected from 23 liver transplant recipients that were 1 to 18 years old. The net state of immune function was determined by the quantitative measurement of the intracellular adenosine 5-triphosphate level in CD4+ lymphocytes after phytohemagglutinin stimulation. Comprehensive clinical data were correlated with the ImmuKnow assay results. In 23 of the 28 samples collected during clinical quiescence, ImmuKnow results were correlated with the clinical status, expressing the patient's moderate immune function. However, a correlation between measured therapeutic drug levels and clinical quiescence was found in only 18 of the 28 samples. In 6 patients who suffered from clinical complications, ImmuKnow measurements showed a wide range of deviations, expressing the unstable immunological status of these patients. In conclusion, the ImmuKnow assay correlates with the clinical status of liver-transplanted children. It serves as a reliable and unique parameter of the cellular immune function. We conclude that the ImmuKnow assay, together with existing clinical tools, may allow for the immune monitoring of pediatric liver recipients.

Resting energy expenditure in children with cyanotic and noncyanotic congenital heart disease before and after open heart surgery.

BACKGROUND: Failure to thrive is a common problem in children with congenital heart disease (CHD). Resting energy expenditure (REE) in cyanotic and noncyanotic children with CHD before and after open heart surgery has hardly been investigated. METHODS: Twenty-nine children younger than 3 years of age with CHD (14 cyanotic and 15 noncyanotic CHD) who were referred for open heart surgery were enrolled. Data on dietary intake, anthropometric measurements, and indirect calorimetry parameters were measured 24 hours before the surgery, (day -1), and on day 5 after surgery. The measured REE was compared with the Schofield and World Health Organization (WHO) REE prediction equations. RESULTS: The mean +/- SD measured REE was similar in the cyanotic and noncyanotic children before and after surgery (before surgery: 57 +/- 13 and 58 +/- 9 kcal/kg per day, respectively; 5 days after surgery: 59 +/- 10 and 62 +/- 10 kcal/kg per day, respectively). Oxygen consumption (VO2) and carbon dioxide production (VCO2) did not change significantly before and after surgery and were similar in both groups. The measured REE for all children on day -1 and day 5 was similar to the calculated REE using the Schofield equation but was significantly different from the calculated REE using the WHO equation (p < .01). CONCLUSIONS: Significant changes in REE, VCO2, and VO2 were not observed before and 5 days after open heart surgery in children with CHD. These parameters (REE, VCO2, and VO2) were also similar in children with cyanotic versus noncyanotic CHD. The Schofield equation is more accurate than the WHO equation in predicting energy needs of children with CHD, but measurement of REE is preferred over calculation of REE.

[Porto-systemic shunts in children: Schneider Children's Medical Center experience].

UNLABELLED: Portal hypertension in the absence of liver disease in children remains a therapeutic challenge. Despite successful control of variceal bleeding in most children, the risk of massive GI bleeding and mechanical disturbance of a huge spleen associated with hypersplenism exists throughout life. Surgical shunt between the portal and systemic venous systems is considered a definitive solution for that problem. AIMS: We present our experience with the porto-systemic shunt for extrahepatic portal hypertension. PATIENTS AND METHODS: Nine children (mean age 11.4 years) with portal hypertension were referred for a shunt procedure during a 5-year period (1996-2001). We reviewed patients charts for clinical parameters before and after surgery as well as surgical data (type of shunt, portal pressure gradient). A mesocaval shunt was constructed in 5 children, a splenorenal shunt in 3 other children and one child with splenic vein thrombosis underwent splenectomy alone for presumed diagnosis of left sided portal hypertension. RESULTS: During a mean follow-up period of 21.2 months (range 6-63 months), the surgical shunt remained patent in 7 of the 8 children. An immediate drop in portal pressure and increased platelets count over time was noted in those 7 children. In two children high portal pressure persisted after surgery, including a child who underwent mesocaval shunt following a previous failed splenorenal shunt and another child who underwent splenectomy alone. None of the children bled following the shunt procedure and decreased splenic size was observed in the 3 children with massive splenomegaly. CONCLUSIONS: We suggest that the porto-systemic shunt is indicated for children with non-hepatic portal hypertension suffering with uncontrolled bleeding and those with massive splenomegaly associated with hypersplenism.

Comparison of two dosing methods for induction of response and remission with oral budesonide in active pediatric Crohn's disease: a randomized placebo-controlled trial.

BACKGROUND: Oral budesonide has been found to be comparable to systemic corticosteroids in mild to moderately active Crohn's disease (CD). Remission rates in pediatric studies to date have been suboptimal (47%-55%), even though patients with colonic involvement were excluded in some studies. In addition, the optimal pediatric dosing regimen has never been evaluated before. METHODS: This was a randomized, controlled, double-blind study in 70 children with mild or moderately active CD randomized to 1 of 2 groups: Group 1: Standard dose budesonide (9 mg/day) for 7 weeks followed by 6 mg budesonide daily for an additional 3 weeks. Group 2: Induction with 12 mg/day for the first month followed by the same regimen as Group 1. Outcome measures included a decrease in Pediatric Crohn's Disease Activity Index and remission rates. Patients with colonic disease were not excluded. RESULTS: At week 7 a clinical response was obtained in 51.4% in Group 1 versus 74.3% in Group 2. A significant decrease in C-reactive protein was seen only in Group 2. At the end of treatment, remission was obtained in 42.9% in Group 1 versus 65.7% in Group 2 (P = 0.054). There was no significant difference in adverse events or serum cortisol. CONCLUSIONS: Use of an induction dose of budesonide followed by a budesonide taper resulted in a trend to higher rates of clinical remission and a decrease in inflammation, without an increase in steroid-associated side effects. Budesonide was also useful for patients with ileocolonic disease.

Susceptibility-guided vs. empiric retreatment of Helicobacter pylori infection after treatment failure.

Successful eradication of Helicobacter pylori after failure of standard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin. We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance. Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results. Findings were compared with those for 49 control patients referred to our center for a (13)C-urea breath test. H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups. Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment. The difference remained significant in stratified and multivariate analysis. Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure.

Helicobacter pylori and Clostridium difficile in cystic fibrosis patients.

We describe the prevalence of H. pylori and toxigenic Clostridium difficile (CD) infection and its relationship with gastrointestinal symptoms and pancreatic sufficiency (PS) or insufficiency (PI) in cystic fibrosis (CF) patients. Stool specimens from 30 consecutive patients with CF, aged 1-44, and from 30 healthy similarly aged subjects were tested for the H. pylori antigen by specific monoclonal antibodies and for CD toxins by Tox A/B assay and Tox A assay. CF patients were assessed clinically and tested for specific H. pylori serum antibodies and for mutations. In CF patients, the prevalence of H. pylori antigen was 16.6% (5/30), compared to 30% (9/30) in controls. Of the 26 CF patients with PI, only 2 (7.6%) were infected by H. pylori, compared with 3 of the 4 (75%) patients with PS (P=0.001). H. pylori infection was diagnosed in 3 of 5 (60%) CF patients carrying mild mutations, compared to 1 of 25 (4%) CF patients carrying severe mutations (P=0.01). Fourteen of 30 (46.6%) stool specimens from CF patients tested positive in the ToxA/B assay, and 3 of 14 tested positive for ToxA. No significant differences in antibiotic use, severity of lung disease, PI, chronic abdominal pain, or genotype were found between the two groups. None of the controls was positive for CD toxins. Prevalence of H. pylori infection in CF patients was lower than in similarly aged non-CF controls. CF patients with PI or a history of distal intestinal obstruction syndrome and those carrying mutations associated with a severe phenotype were protected against H. pylori infection. Almost half of the CF patients were asymptomatic carriers of CD producing mostly toxin B. More studies are needed to confirm our results in a larger group of CF patients.

Association of Helicobacter pylori infection with Shigella gastroenteritis in young children.

OBJECTIVE: Helicobacter pylori infection is acquired mainly in early childhood. Much is unknown about the mode of transmission. The organism can be cultivated from cathartic stools and vomitus and is potentially transmissible during episodes of gastrointestinal tract illness. Because Shigella and Salmonella are common pathogens in enteric infections in children, we examined the association of H. pylori with Shigella and Salmonella infections in pediatric patients. METHODS: The study population included consecutive children aged 2-72 months hospitalized with acute gastroenteritis who had culture-proven shigellosis (N = 78) or salmonellosis (N = 76). Sixty-five healthy similarly aged children with culture-negative stools served as controls. Parents of cases were queried for personal and family characteristics and socioeconomic indicators. The stool specimens from all participants were tested for H. pylori antigen. RESULTS: On univariate analysis, Shigella gastroenteritis was significantly associated with H. pylori positivity (odds ratio, OR: 3.5, 95% confidence interval (CI): 1.5-8.8, p= 0.004) compared to controls. This association remained significant even after adjusting for living conditions, father's occupation, and father's education (OR = 3.38, 95% CI: 1.39-8.22, p= 0.007). Salmonella gastroenteritis was not associated with H. pylori positivity (OR = 1.1; 95% CI: 0.4-3.0, p= 0.8). CONCLUSION: H. pylori infection in young children is associated with Shigella gastroenteritis. This association warrants further investigation.

Use of quantitative ultrasound to assess osteopenia in children with Crohn disease.

BACKGROUND AND AIMS: Children with Crohn disease are at increased risk for osteopenia and osteoporosis. Early development of osteopenia can increase the lifetime risk for fractures and may be amenable to early intervention. The gold standard for measuring bone mineral density (BMD) and fracture risk is dual x-ray absorptiometry (DXA), but this involves some radiation and specialized programs for measuring BMD in children. Bone density Z scores were evaluated with quantitative ultrasound (QUS) using a novel portable device and were compared with DXA in children with Crohn disease. METHODS: Thirty-five children with documented Crohn disease (mean age 14.3 +/- 2.3 years) had speed of sound measured at the left radius and left tibia. Normative values for QUS Z scores were calculated from a cohort of 1,110 healthy children. A subgroup of 26 children with Crohn disease underwent both QUS and DXA. Z scores were calculated and compared for both groups. RESULTS: The mean Z score using lumbar spine DXA was -1.04 +/- 1.51 SD, compared with -0.15 +/- 1.49 SD, using the lowest Z score for QUS ( < 0.05). Using height adjusted DXA, 50% of children with Crohn disease had osteopenia, whereas QUS detected only 19.2% of these children ( < 0.05). Significantly fewer cases of osteopenia were detected using QUS at Z scores up to -2 SD. CONCLUSIONS: Quantitative ultrasound performed on the radius and tibia may not be sensitive enough to pick up osteopenia in children with Crohn disease.

Evaluation of oral budesonide for treatment of mild and moderate exacerbations of Crohn's disease in children.

OBJECTIVES: Oral budesonide has been found to be efficacious for mild to moderate Crohn's disease in adults, with equal improvement rates for budesonide and prednisone. We report the results of a retrospective study of budesonide treatment in mild to moderate Crohn's disease in children. STUDY DESIGN: Charts of patients treated with budesonide (n = 62) with a pediatric Crohn's Disease Activity Index of 12.5 to 40 were compared with a cohort of 58 age-matched patients treated with prednisone. RESULTS: Among children treated with budesonide, 48% had remission compared with 77% of the children treated with prednisone (P =.001). Among patients who had failed previous medical therapy with mesalamine, 59% had remission with budesonide (9 mg/day). Remission with prednisone occurred in 73% of children who failed to achieve remission with budesonide. Patients responding to budesonide had significantly milder disease compared with nonresponders who had remission while taking prednisone. CONCLUSIONS: Budesonide is useful in mild to moderate Crohn's disease in children. It is more effective than mesalamine and antibiotics but less effective than prednisone. Budesonide should be considered for first-line therapy in mild to moderate Crohn's disease.

Neoral dose monitoring using 2-hour cyclosporine post-dose levels in stable children with liver transplants: improvement in renal function.

In adult liver transplant recipiens, 2-h post-Neoral (C2) dose monitoring is associated with a lower incidence and severity of acute cellular rejection and improved renal function than C0 (trough level) monitoring. This study examined whether switching from C0 to C2 monitoring during maintenance also improves renal function in pediatric liver transplant recipients. Three boys aged 11-16 yr with stable graft function at 6-50 months after liver transplantation were switched from C0 to C2 monitoring. Median C0 was 148 ng/mL (range 100-186), and median C2 was 767 ng/mL (range 702-1187). At the time of conversion, C2 levels exceeded the recommended targets (0-6 months 1000 ng/mL; > 12 months 600 ng/mL in all children). Within 3 months, serum creatinine level decreased by a median of 42.8%, and glomerular filtration rate increased by a median of 86%. No clinical or biochemical evidence of rejection was noted during the 6-month follow-up. Our results suggest that in pediatric liver transplant recipients, C2 monitoring is associated with greater improvement in renal function than C0 monitoring; switching to C2 monitoring can correct cyclosporine-associated toxicity.

Resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime.

The resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime was tested in 138 isolates, including 28 from treatment failures. No resistance to tetracycline was detected. Resistance to amoxicillin was found in one isolate (MIC = 1.5 mg/L) from an untreated patient, and resistance to cefixime in two isolates from each group (P = 0.18). Resistance to metronidazole and clarithromycin was much higher in the isolates from treated than from untreated patients: 60.7% and 38.2% for metronidazole (MIC >or= 8 mg/L) (P = 0.03); 46.4% and 8.2% for clarithromycin (MIC >or= 2 mg/L) (P < 0.001). Therapeutic outcome would benefit from susceptibility testing, especially after treatment failure.

A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease.

OBJECTIVES: Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease. METHODS: A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease. RESULTS: Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P< 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P< 0.01). CONCLUSIONS: Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.