Angelo Campanozzi

Gastrointestinal manifestations in children with cerebral palsy

We describe the prevalence and nature of gastrointestinal (GI) symptoms in 58 children affected by cerebral palsy (range: from 6 months to 12 years of age) referred to a pediatric neurology outpatient clinic. In each patient we assessed (GI) symptoms and defined the associated GI functional or structural abnormalities. Furthermore, we tried to correlate the type of GI dysfunction with findings on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain. Our results showed that 92% of children with cerebral palsy had clinically significant gastrointestinal symptoms. Swallowing disorders were present in 60% of patients, regurgitation and/or vomiting in 32%, abdominal pain in 32%, episodes of chronic pulmonary aspiration in 41% and chronic constipation in 74%. Dysfunction of the oral and/or pharyngeal phase of swallowing was found in 28 of 30 (93%) patients with swallowing disorders. Of the 45 patients with symptoms suggesting gastroesophageal reflux, 41 (91%) had an abnormal pH-monitoring and/or esophagitis. Furthermore, a significant delay in the scintigraphic gastric emptying of liquids was found in 12 of 18 patients (67%) and an abnormal esophageal motility in 11 of the 18 (61%) investigated patients. In 25 patients with chronic constipation evaluation of colonic transit showed a delay at level of the proximal segments of the colon in 13 (52%), at level of the left colon and rectum in 9 (36%) and in 3 (12%) at level of the rectum only. Computed tomography and/or magnetic resonance imaging were normal in 5 (9%) and abnormal in 53 (91%) of the 58 children with cerebral palsy. No GI symptom was significantly associated with any kind of abnormal neuroimaging. In conclusion, children with cerebral palsy exhibited diffuse GI clinical manifestations, mostly due to disorders of GI motility. The GI symptoms seemed not to be related to any specific finding on CT or MRI of the brain.

Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure

Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc-modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease.

Omeprazole and high dose ranitidine in the treatment of refractory reflux oesophagitis.

Thirty two consecutive patients (age range 6 months-13.4 years) with severe reflux oesophagitis were randomised to a therapeutic trial for eight weeks during which they received either standard doses of omeprazole (40 mg/day/1.73 m2 surface area) or high doses of ranitidine (20 mg/kg/day). Twenty five patients completed the trial (12 on omeprazole, 13 on ranitidine). At entry and at the end of the trial patients underwent symptomatic score assessment, endoscopic and histological evaluation of the oesophagus, and simultaneous oesophageal and gastric pH measurement; results are given as median (range). Both therapeutic regimens were effective in decreasing clinical score (omeprazole before 24.0 (15-33), after 9.0 (0-18); ranitidine before 19.5 (12-33), after 9.0 (6-12)), in improving the histological degree of oesophagitis (omeprazole before 8.0 (6-10), after 2.0 (0-60); ranitidine before 8.0 (8-10), after 2.0 (2-6), and in reducing oesophageal acid exposure, measured as minutes of reflux at 24 hour pH monitoring (omeprazole before 129.4 (84-217), after 44.6 (0.16-128); ranitidine before 207.3 (66-306), after 58.4 (32-128)) as well as intragastric acidity, measured as median intragastric pH (omeprazole before 2.1 (1.0-3.0), after 5.1 (2.2-7.4); ranitidine before 1.9 (1.6-4), after 3.4 (2.3-5.3)). Serum gastrin concentration was > 150 ng/l in four patients on omeprazole and in three patients on ranitidine. It is concluded that in children with refractory reflux oesophagitis high doses of ranitidine are comparable with omeprazole for the healing of oesophagitis and relief of symptoms; both drugs resulted in efficacious reduction of intragastric acidity and intra-oesophageal acid exposure.

Prevalence and Natural History of Gastroesophageal Reflux: Pediatric Prospective Survey

OBJECTIVE. The prevalence and natural history of gastroesophageal reflux in infants have been poorly documented. The aim of this study was to evaluate the prevalence and natural history of infant regurgitation in Italian children during the first 2 years of life. METHODS. A detailed questionnaire, according to the Rome II criteria, was completed by 59 primary care pediatricians to assess infant regurgitation in consecutive patients seen in their office over a 3-month period. A total of 2642 patients aged 0 to 12 months were prospectively enrolled during this 3-month period. Follow-up was performed at 6, 12, 18, and 24 months of age. RESULTS. A total of 313 children (12%; 147 girls) received the diagnosis of infant regurgitation. Vomiting was present in 34 of 313 patients. Their score for the Infant Gastroesophageal Reflux Questionnaire was 8.51 ± 4.75 (mean ± SD). Follow-up visits were conducted to the end in 210 of 313 subjects. Regurgitation had disappeared in 56 of 210 infants by the first 6 months of age, in 128 by the first 12 months, in 23 at 18 months, and in 3 patients by the first 24 months. At follow-up, 1 of 210 patients had developed a gastroesophageal reflux disease with esophagitis, proven endoscopically and histologically; another patient received a diagnosis of cow milk protein intolerance. The Infant Gastroesophageal Reflux Questionnaire score reached 0 after 8.2 ± 3.9 months in breastfed infants (89 of 210) and after 9.6 ± 4.1 months in artificially fed infants. CONCLUSIONS. We found that 12% of Italian infants satisfied the Rome II criteria for infant regurgitation. Eighty-eight percent of 210 infants who had completed a 24-month follow-up period had improved at the age of 12 months. Only 1 patient later turned out to have gastroesophageal reflux disease. Use of breast milk was associated with a shorter time necessary to reach an Infant Gastroesophageal Reflux Questionnaire score of 0.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Background: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. Methods: In 1996 an IBD register of disease onset was established on a national scale. Results: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohns disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996–2003 an increase of IBD incidence from 0.89 to 1.39/105 inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. Conclusions The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Autoimmune thyroid disease and celiac disease in children.

Background: Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD. Methods: Five hundred seventy‐three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty‐three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty‐six of the patients with CD (median age, 9 years) had been following a gluten‐free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid‐stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti‐TSH receptor antibodies, and thyroid echographic pattern were considered. Results: Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten‐free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty‐four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002). Conclusions: The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten‐free diet, may justify a thyroid status assessment at diagnosis and at follow‐up evaluation of children with CD. JPGN 37:63‐66, 2003.

Hospital-acquired malnutrition in children with mild clinical conditions

OBJECTIVE Little is known about the incidence and risk factors of hospital-acquired malnutrition in children with mild illness (grade 1 clinical conditions) and its timing of occurrence. The aim of this study was to recognize any early stage of denutrition and possible risk factors leading to nutritional deterioration in children hospitalized due to mild clinical conditions. METHODS Four hundred ninety-six children (age 1-192 mo) with mild clinical conditions were studied. Weight and height were measured. Weight was assessed daily and body mass index (BMI) Z-score was calculated for all patients. RESULTS Children with a BMI Z-score <-2 SD on admission showed a mean BMI decrease at the end of their hospital stay, which was significantly higher than in children who showed a better nutritional condition at admission. Risk factors for hospital-acquired malnutrition were an age <24 mo, a duration of hospital stay >5 d, fever, and night-time abdominal pain. CONCLUSION Hospital stay has an impact on the nutritional status of children affected by mild clinical conditions. Children already malnourished on admission were found to be at risk for further nutritional deterioration during their hospital stay; and in all groups of children identified by their BMI Z-score at admission, nutritional status declined progressively.

Effects of Omeprazole on Mechanisms of Gastroesophageal Reflux in Childhood

Prolonged recordings of esophageal motility haveshown that dynamic changes of lower esophageal sphincter(LES) pressure such as transient LES relaxation and LESpressure drifts are the most common mechanisms underlying gastroesophageal reflux (GER). Thecoexistence of a delayed gastric emptying has also beenreported in a high proportion of patients with refluxdisease. However, not much information is available on the effects of antireflux therapy on thepathogenetic mechanisms of GER. The purpose of thisstudy was to determine in a group of children withsevere reflux disease the effect of omeprazole therapy on motor changes of LES underlying GER as wellas on gastric emptying time. Twenty-two children (medianage: 6.6 years) with GER disease, refractory to combinedranitidine and cisapride administration, entered into an eight-week omeprazole course.Ten subjects with moderate GER disease served ascontrols (median age: 6.0 years). Before and afteromeprazole administration, the following variables were assessed: esophagitis grading, fasting and fedsimultaneous prolonged recording of distal esophagealsphincter pressure (with a sleeve catheter) andintraesophageal pH, LES and esophageal peristalsisamplitude, and gastric emptying time of a mixedsolid-liquid meal (measured with gastric ultrasound). Ascompared to controls, patients showed a higher rate oftransient LES relaxation and LES pressure drift (P <0.01), a reduced amplitude of basal sphincter pressure(P < 0.01) and peristalsis (P < 0.05), and a moreprolonged gastric emptying time (P < 0.05). Afterending omeprazole, there was no significant change inany of the motor abnormalities of the esophagus and ingastric emptying time despite a marked improvement ofsymptoms and esophagitis in all patients. Sixteenpatients were symptomatic when reevaluated on a clinical basis two months after ending therapy. Weconclude that in children with severe GER disease, anabnormally high rate of both transient LES relaxationand LES pressure drift and slow gastric emptying are not affected by omperazole treatment, eventhough esophageal mucosal damage is markedly improved orcured. These abnormalities represent a primary motordisorder and can be implicated in the refractoriness of reflux disease.

Sterol profiling in red blood cell membranes and plasma of newborns receiving total parenteral nutrition.

Background and Objectives: Total parenteral nutrition (TPN) is a lifesaving therapy in children with intestinal failure, frequently complicated by liver dysfunction. Plant sterols (phytosterols) of lipid emulsions have been supposed to contribute to cholestasis in TPN-treated children. The present study aimed to evaluate the plasma and red blood cell membrane (RBCM) phytosterol levels in newborns after a short period of TPN. Patients and Methods: Phytosterols, cholesterol, and other sterol levels were quantified by gas chromatography-mass spectrometry in 15 healthy control infants, 22 patients after TPN, and 11 patients before TPN. Sterols of lipid emulsions were quantified. Results: Plasma and RBCM phytosterol levels were, respectively, on average 56 μmol/L and 83 μmol/g per protein in patients after TPN, 13 μmol/L and 15 μmol/g per protein in patients before TPN, and 9 μmol/L and 13 μmoL/g per protein in control infants (P < 0.05 for differences). The days of TPN and the total amount of infused lipids correlated significantly with RBCM phytosterol (P < 0.05); correlations for plasma were positive but not significant. No correlation was observed with plasma bilirubin, γ-glutamyltransferase, or alanine transaminase. Conclusions: Plasma and RBCM phytosterols increase significantly in newborns after a short period of TPN. Higher phytosterol levels were observed in some patients that could have been due to their individual variability in phytosterol metabolism and/or clearance. A greater accumulation of phytosterols in membranes may induce TPN-related cholestasis.

Postinfectious Functional Gastrointestinal Disorders in Children: A Multicenter Prospective Study

OBJECTIVES To prospectively investigate the occurrence of postinfectious functional gastrointestinal disorders (FGIDs), diagnosed according to the Rome III criteria, in children with acute diarrhea of different infectious etiology. STUDY DESIGN This was a prospective cohort multicenter study. Children 4-17 years of age presenting with acute diarrhea who tested positive for an enteric infection were recruited within 1 month from the episode and matched with control subjects of similar age and sex. Symptoms were evaluated with a validated questionnaire for FGIDs at the time of enrollment in the study and after 3 and 6 months. RESULTS A total of 64 patients (36 boys; median age 5.3 years; age range 4.1-14.1 years) were recruited, 32 subjects in each arm. Infections included rotavirus (56.8%), salmonella (30%), adenovirus (6.6%), norovirus (3.3%), and Giardia lamblia (3.3%). FGIDs were significantly more common in exposed patients compared with controls within 1 month from acute diarrhea (40.6% vs 12.5% [P = .02, relative risk (RR) = 1.9]), 3 months (53% vs 15.6% [P = .003, RR = 2.2]), and 6 months (46.8% vs 15.6% [P = .01, RR = 1.9]) later. No correlation was found between different etiologies, age, or sex, and any type of FGIDs. Among exposed children, abdominal pain-related FGIDs were significantly more frequent compared with controls after 6 months from infection (P = .04, RR = 1.7). CONCLUSION This prospective cohort multicenter study supports postinfectious FGIDs as a true entity in children. There seems to be a significant increase in abdominal pain-related FGIDs after acute diarrhea in children within 1 month and 3 and 6 months later.