The Use of Fibers, Herbal Medicines and Spices in Children with Irritable Bowel Syndrome: A Narrative Review.

The pathophysiology of irritable bowel syndrome in children involves multiple factors. Thus, treatment options are variable, targeting both diet and the child's and parents' behavior via pharmacological and psychological interventions or neuromodulation. Parents are increasingly interested in complementary and alternative therapies for children with irritable bowel syndrome, especially when other treatments have been tried without relieving the child's symptoms. This paper examines current evidence for the benefits and side effects of herbal remedies and spices in pediatric patients with IBS. The benefits of peppermint oil, STW5, psyllium fiber, Curcuma, ginger, and other herbal medicines are discussed based on findings in the current literature.

New diagnostic and therapeutic procedures applied in pediatric esophageal achalasia in a pediatric tertiary center: A case series.

Achalasia is an esophageal motor disorder that is rare in children. While the condition is uncommon, it is especially difficult to diagnose in pediatric patients; however, the ability to form a diagnosis has progressed markedly with the advent of esophageal high-resolution manometry (HRM). The aim of the present study was to highlight particularities of the diagnosis, based on esophageal HRM, as well as the treatment of achalasia in children. The current study analyzed cases of achalasia from a single pediatric tertiary center, Clinical Emergency Hospital for Children (Cluj-Napoca, Romania). The clinical data and the results of the investigations of seven children with achalasia, the first children to be evaluated using esophageal HRM in the center, were reported. The patients were aged between 11 and 18 years. All the patients were newly diagnosed with achalasia, except for one. The duration of symptoms was between 4 months and 2 years in the newly diagnosed patients. All the patients were assessed with conventional esophageal manometry and/or esophageal HRM. A multidisciplinary team contributed to the diagnosis and the management of achalasia. A total of 4 children diagnosed with type II achalasia were treated with peroral endoscopic myotomy (POEM) and 3 of the patients were treated with pneumatic dilations. Overall, achalasia is a rare but challenging condition in children. A diagnosis starts with a clinical suspicion based on swallowing disorders and upper digestive endoscopy, and is confirmed by esophageal HRM. Therapy should be adapted to the type of achalasia, the age of the children and the severity. In the present study, a relatively recent treatment option, POEM, was applied in pediatric patients with minor immediate adverse events. The report of these cases adds to the limited experience of using HRM and POEM in children with achalasia.

Rectum sizes: Assessment by ultrasonography in children with functional constipation.

AIM: This study aimed to compare the transverse diameter and thickness of the anterior wall of the rectum in children with normal bowel movement and children with functional constipation in different age groups. Another objective was to find correlations of rectum sizes with faecal incontinence and constipation duration. METHODS: In the study, we included children with normal bowel movement and functional constipation diagnosed based on the Rome III and Rome IV criteria. We collected clinical data from the parents. We measured the rectum transverse diameter and the thickness of the anterior wall by abdominal ultrasound. RESULTS: The study included 65 children, 31 with normal bowel movement and 34 with functional constipation. The rectum transverse diameter and the thickness of the anterior wall had statistically significant higher values in patients with constipation (P < 0.05). There was a moderate and significant correlation between the duration of the disease (mean ± standard deviation = 31.7 ± 33.1 months) and rectum transverse diameter (r = 0.54; P = 0.0009). The rectum transverse diameter correlated moderately with the presence of faecal incontinence (r = 0.62; P = 0.003), but the thickness of the anterior wall did not correlate with this symptom (r = 0.02; P = 0.39). CONCLUSIONS: We found statistically significant differences between the transverse rectal diameter and thickness of the rectum anterior wall, measured by abdominal ultrasound, in children with functional constipation compared with normal defaecation patterns. Faecal incontinence and long-term constipation were correlated with the increased rectum diameter.

Changes in the parameters of the rectoanal inhibitory reflex in children with functional constipation and large rectum.

BACKGROUND: Abdominal ultrasound and anorectal manometry are part of the investigations used to assess children with functional constipation. This study aimed at assessing the changes in the characteristics of the rectoanal inhibitory reflex (RAIR) in children with functional constipation and correlating them with the dimensions of the rectum, measured by abdominal ultrasound. A secondary objective was to compare the rectum size in children with and without constipation. METHOD: We retrospectively reviewed the clinical data and investigations results of 51 children (mean age±standard deviation (SD) = 5.8±3.5 years) with functional constipation who came to our clinic between January 2013 and February 2020. The assessment of these patients included both the assessment of the transverse diameter of the rectal ampulla by abdominal ultrasound and anorectal manometry. The studied parameters of RAIR were: the minimal volume of air necessary to induce RAIR, in all the patients with functional constipation, and in 20 of them, relaxation time, latency and relaxation percentage. A control group was formed of 27 children (mean age±SD = 5.1±4 years) without digestive diseases and with normal intestinal transit, who were assessed by abdominal ultrasound. RESULTS: The mean value ±SD of the volume of air necessary to induce RAIR was 21.9±12.1 cm3 air. There was no correlation between the rectum transverse diameter and the minimal air volume that triggered RAIR (r=-0.01, p=0.94). The mean value ±SD of the transverse diameter of the rectum in patients with functional constipation was 39±14 mm, and in children without constipation 26±6 mm (p<0.05). The mean duration of the symptoms in children with functional constipation was 2.8 years. CONCLUSIONS: There were no correlations between the volume of air that induced the RAIR and the transverse diameter of the rectum in children with functional constipation. The transverse diameter of the rectum was increased in children with long-term functional constipation.

The value of abdominal ultrasonography compared to colonoscopy and faecal calprotectin in following up paediatric patients with ulcerative colitis.

AIM: To evaluate the value of abdominal ultrasonography (US) in the follow-up of paediatric patients with ulcerative colitis (UC) compared to faecal calprotectin (FC) and colonoscopy. MATERIAL AND METHOD: In this retrospective study we enrolled 30 paediatric patients previously diagnosed with UC, examined by abdominal US and colonoscopy within the same week. FC was also determined during the same week. Disease activity was established using the paediatric ulcerative colitis activity index (PUCAI). The global endoscopic activity was evaluated using the Mayo endoscopic subscore. RESULTS: Endos-copy revealed pathological findings of active disease in 27 out of 30 patients; 3 patients were in endoscopic remission. Only 18 of them had clinical active disease (PUCAI >10), [sensitivity (Se) 66.7% and specificity (Sp) 33% of PUCAI in detecting endoscopic active disease). Twenty-three (76.7%) patients had FC >250 mcg/g, but in 2 of these cases the colonoscopy was normal (Se 77.8% and Sp 33.3% in detecting active disease). At US examination, pathological findings (increased bowel wall thickness, hypervascularity, lymphadenopathies, and/or mesenteric inflammatory fat) were found in 27 patients (90%), all with endoscopic active disease (agreement US - colonoscopy, at patient level, k=1.0, p<0.001, Se 100% and Sp 100%). At seg-ment level (totally 180 bowel segments examined by US), the overall agreement between US and colonoscopy was k=0.767, p<0.001, Se 86.5%, Sp 90.1%. Of the 27 patients with US pathological findings in any of colonic segments, 23 had FC >250 mcg/g (85.1%). The inter-observer agreement for the US measurements had an overall ICC of 0.926 with p<0.001. CONCLUSION: Abdominal US findings demonstrate a good to excellent concordance with endoscopic examination and are correlated with elevated FC levels. Therefore, US appears as an accurate technique in assessing activity in patients with UC and might replace colonoscopic evaluation for the follow-up.

B cell-activating factor (BAFF) in children with inflammatory bowel disease.

BACKGROUND: Assessing the inflammation is important in the follow-up of paediatric patients with inflammatory bowel disease (IBD). We aim to evaluate the value of B cell-activating factor (BAFF) in paediatric IBD as a potential biomarker for follow-up. METHOD: We determined BAFF in serum and faeces and faecal calprotectin (CP) in 32 IBD children-16 Crohn's disease (CD) and 16 ulcerative colitis (UC). Twenty-six healthy children and 10 children with irritable bowel syndrome (IBS) were included as controls. RESULTS: No differences were found in serum BAFF between IBD, IBS, and healthy group: 1037.35, 990.9 and 979.8 pg/ml, respectively, all p > 0.05, but faecal BAFF was higher in the IBD group: 15.1, 8.5 and 8.2 pg/ml, respectively, p < 0.05, and higher in the UC group (55.975 pg/ml) compared to the CD group (10.95 pg/ml), p = 0.015. Splitting the IBD group in relation to the CP level, the serum BAFF had no significantly different values between the subgroups, but the faecal BAFF was significantly higher in the >250 µg/g subgroup. Cut-off values of BAFF were calculated. CONCLUSION: Faecal BAFF is a promising marker for monitoring the children with IBD, higher levels of BAFF being correlated with high CP. IMPACT: Faecal BAFF is a promising marker in monitoring the children with IBD, higher levels of BAFF being correlated with high faecal calprotectin. To our knowledge, this is the first paediatric study concerning BAFF evaluation in IBD. Faecal BAFF levels could be considered a potential non-invasive marker in monitoring IBD activity in paediatric population with clinically mild or inactive disease.

Ganglioneuroblastoma in children.

INTRODUCTION: Neuroblastoma ranks third among pediatric malignancies. CASE REPORT: The case of a 3-year-old child is presented, who suddenly had frequent, unproductive, emetic cough; fever; and weight loss. Lung X-ray showed an opacity situated in the posterior superior mediastinum. Thoracic ultrasound revealed a slightly inhomogeneous, hypoechoic mass located in the posterior superior mediastinum. Computed tomography evidenced a tumor mass with homogeneous appearance in the costo-vertebral groove. Histological examination confirmed the diagnosis of ganglioneuroblastoma. CONCLUSION: Although history and clinical examination provided few elements, diagnosis was made based on imaging and histopathological examination.

Ultrasonographic findings in hyperimmunoglobulin D syndrome: a case report.

Hyperimmunoglobulin D syndrome due to mevalonate kinase deficiency is a rare autoinflammatory disease with digestive tract involvement. We report an 11-year female child who has presented since the age of 1 year, bouts of fever, rash, joint swelling, pulmonary consolidation, lymph node involvement and hepatosplenomegaly. Hyperimmunglobulin D and increased urinary mevalonic acid were detected. The ultrasonographic features of hepatosplenomegaly ranged from increment in size to pseudotumoral involvement, with hypoechogenic masses without apparent wall. Abdominal CT during a disease flare showed hypodense, hypoenhancing nodular lesions, suggesting metastases. Nevertheless, a thorough search for malignancy was negative and the masses disappeared after the flare. Mevalonate kinase deficiency may add to the causes of hepatosplenic and pulmonary inflammatory pseudotumors.

Celiac disease in toddler with atypical onset. Case report.

Celiac disease is a chronic immune-mediated disorder induced in genetically susceptible individuals after ingestion of gluten proteins. An early diagnosis is of highest importance. Ultrasound might show small-bowel intussusception. We present a toddler with one month history of diarrhea and abdominal ultrasound showing ileo-ileal intussusception. Specific serological markers for celiac disease were positive. The duodenal endoscopy showed normal architecture but pathology indicated fully developed celiac disease (Marsh 3c). In conclusion, toddlers, who have even a short history of diarrhea with ultrasound showing ileo-ileal intussusception, can be suspected of celiac disease by positive serologic markers and can be confirmed by duodenal biopsy and pathology.

Bowel elastography - a pilot study for developing an elastographic scoring system to evaluate disease activity in pediatric Crohn's disease.

UNLABELLED: The diagnosis and monitoring of Crohn's disease (CD) represents a diagnosis challenge in which imaging plays an important role. AIM: In the present paper we aim to demonstrate the role of sonoelastography (SE), performed in addition to hydrosonography (HS), in the evaluation of CD in children and to propose a scoring system for the appreciation of disease activity. MATERIAL AND METHOD: All the patients included into the study were diagnosed with CD and had underwent HS and SE as part of the imaging evaluation. In selected cases magnetic resonance enterography (MRE) was also performed. SE aspects were classified into three types, each corresponding to a specific bowel wall pattern: normal or remission (type A), inflammation (type B) and fibrosis (type C); this classification represents the basis of the scoring system. For the purpose of statistical analysis each evaluated bowel segment became an individual case. RESULTS: Forty eight bowel segments were evaluated by SE: 21 type A, 20 type B and 7 type C. Statistically significant correlations were found between the intestinal wall HS changes, presence of complications, activity markers and the SE score. The HS assessment of the periintestinal area correlated only partially with SE score, while certain SE scores also proved to be predictors for the presence of complications or for increased values of the disease activity markers. CONCLUSIONS: SE, along with HS, represents a reliable investigation in the correct diagnosis and monitoring of pediatric patients with CD and the SE scoring system may be introduced as a method for the assessment of disease activity.

IgA anti-tissue transglutaminase antibodies, first line in the diagnosis of celiac disease.

BACKGROUND: According to the 2008 celiac disease working group run by Dr. A. Fassano under the auspices of the Federation of International Societies of Pediatric Gastroenterology, Hepatology and Nutrition, celiac disease is a chronic immune-mediated enteropathy characterized by gluten sensitivity, which can affect any organ or system, having a wide range of clinical manifestations of variable severity. The serological diagnosis of celiac disease is based on high sensitivity and specificity tests. The measurement of IgA anti-tissue transglutaminase antibodies by ELISA is universally accepted in the screening of celiac disease. METHODS: Using the gold standard represented by IgA anti-endomysium antibodies in a group of 890 children investigated during 2008-2009, we aimed to evaluate IgA anti-tissue transglutaminase antibodies (tTG IgA), as well as to establish their prevalence in associated diseases. RESULTS: Following the measurement of tTG IgA in the entire group, we obtained: sensitivity 773%, positive predictive value 55.2%, specificity 93.1%, negative predictive value 973%, p = 0.000, and in tTG IgA associations we obtained the value 0.51 for the ROC curve area. We found associations of tTG IgA with type 1 diabetes mellitus (235% prevalence), protein-calorie malnutrition (0.89% prevalence), and intestinal malabsorption (0.56% prevalence). CONCLUSIONS: Our results have a high specificity and sensitivity in the screening of celiac disease, while requiring a second method of confirmation.

Romanian experience in child celiac disease diagnosis.

Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reveals the following: "celiac disease is a chronic immune-mediated enteropathy characterized by sensitization to gluten. That can affect any organ or system, with a wide range of clinical manifestations of variable severity". Thus, in recent years, clinical picture of celiac disease has changed the old paradigm--bowel disease with villous atrophy and malnutrition, being replaced with the new paradigm--multi-organ autoimmune disease, affecting many organs and systems throughout but with more less specific symptoms, which undiagnosed leads to delayed diagnosis, at a late-onset disease and long-term major complications as the risk of cancer. According to this consensus "the serological diagnosis of celiac disease is based on high sensitivity and specificity tests", but in line with changing clinical features of celiac disease, its diagnosis has undergone significant changes in recent years. These changes in the diagnosis of celiac disease, we have decided to analyze them.

Clinical and ultrasound approach to achalasia in a child. Case report.

Achalasia is a primary esophageal motor disorder of unknown etiology characterized by insufficient lower esophageal sphincter (LES) relaxation in response to deglution. We present the case of a child diagnosed with asthma, with no response to asthma treatment. On account of associating dysphagia, regurgitation of food and weight loss he was given an abdominal ultrasound that revealed a massive dilated and narrowing of its distal segment esophagus. Ultrasound examination proved to be a good diagnostic tool, reorienting from the initial asthma diagnosis to the correct achalasia diagnosis, confirmed through barium swallow, upper digestive endoscopy and esophageal manometry. Esocardiomiotomy with antireflux technique was performed with excellent results.

Pharmacokinetic interaction between fluoxetine and metoclopramide in healthy volunteers.

The pharmacokinetic interaction of fluoxetine with metoclopramide in healthy volunteers was evaluated. A dose of 20 mg metoclopramide in combination with 60 mg fluoxetine was administered to 24 healthy male volunteers in a two treatment study design, separated by 8 days in which the fluoxetine alone was administered as a single p.o. dose daily. Plasma concentrations of metoclopramide were determined during a 24 h period following drug administration. Metoclopramide plasma concentrations were determined by a validated HPLC method. Pharmacokinetic parameters of metoclopramide were calculated using non-compartmental analysis. In the two periods of treatment, the mean peak plasma concentrations (Cmax) were 44.02 ng/ml (metoclopramide alone) and 62.72 ng/ml (metoclopramide after pre-treatment with fluoxetine). The times taken to reach Cmax and tmax, were 1.15 h and 1.06 h, respectively. The total areas under the curve (AUC(0-infinity)) were 312.61 ng.h/ml and 590.62 ng.h/ml, respectively. The half-life values (t1/2) were 5.52 h and 8.47 h. Statistically significant differences were observed for both AUC(0-infinity) and t1/2 of metoclopramide when administered alone or after 8 days treatment with fluoxetine. The experimental data demonstrate the pharmacokinetic interaction between fluoxetine and metoclopramide and suggest that the observed interaction may be clinically significant, but its relevance has to be confirmed.

No effect of short term ranitidine intake on diclofenac pharmacokinetics.

The pharmacokinetics of diclofenac sodium in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibited the metabolism of the non-steroidal anti-inflammatory drug. Diclofenac sodium 50 mg (tablets) in combination with ranitidine 150 mg (tablets) were administered to 14 healthy human volunteers in a two treatment study design, separated by 5 days in which the ranitidine alone was administrated in single p.o. doses twice daily. Plasma concentrations of diclofenac were determined during a 12 hour period following drug administration. Diclofenac plasma concentrations were determined by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis. In the two periods of treatments, the mean peak plasma concentrations Cmax were 1503.9 ng/ml (diclofenac alone) and 1742.5 ng/ml (diclofenac and ranitidine). The time taken to reach the peak, Tmax, was 0.85 hrs, and 0.82 hrs, respectively. The areas under the curve (AUC0-6) were 1479.9 ng x hr/ml and 1650.3 ng x hr/ml, respectively. Statistically insignificant difference was observed in these pharmaco-kinetic parameters of diclofenac sodium when administered alone or after 5 days of treatment with ranitidine. The experimental data did not suggest any consistent effects of ranitidine upon the pharmacokinetics of diclofenac sodium.

Pharmacokinetic interaction study between ranitidine and metoclopramide.

The pharmacokinetics of metoclopramide in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibit the metabolism of the gastrointestinal prokinetic drug. Metoclopramide 20 mg (tablets) in combination with ranitidine 150 mg (tablets) were administered to 14 healthy human volunteers in a two treatment study design, separated by 5 days in which the ranitidine alone was administrated in single p.o. doses twice daily. Plasma concentrations of metoclopramide were determined during a 24 hour period following drug administration. Metoclopramide plasma concentrations were determined by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis. In the two periods of treatments, the mean peak plasma concentrations Cmax were 44 ng/ml (metoclopramide alone) and 49.2 ng/ml (metoclopramide and ranitidine). The time taken to reach the peak, Tmax, was 1.15 hrs, and 1.21 hrs, respectively. The total areas under the curve (AUC) was 314.3 ng.hr/ml and 354.06 ng.hr/ml, respectively. The half-life (T 1/2) was 5.6 hr and 6.7 hr. A statistically significant difference was observed for both AUC and half-life of metoclopramide when administered alone or after 5 days of treatment with ranitidine. The experimental data proved the pharmacokinetic interaction between ranitidine of metoclopramide, and suggest monitoring adverse effects in patients.

[Effectiveness of antireflux therapy in asthmatic children with gastroesophageal reflux disease]. / Eficienta terapiei antireflux la copiii astmatici cu boala de reflux gastroesofagian.

There is an increased interest within literature regarding the relationship between gastro-esophageal reflux disease and asthma. The study was performed to assess the efficiency of antireflux therapy in asthmatic children. In a group of asthmatic children (n = 34, 22 male, age range: 2, 5-17 years) the pulmonary function tests were made by means of spirometry in those patients in which reflux disease was diagnosed by means of 24h esophageal pH-monitoring and upper digestive endoscopy. All these patients were reevaluated by means of spirometry 3 months after the antireflux therapy with ranitidine and cisapride added to antiasthmatic therapy. Three months later the results showed a significant decrease in frequency of asthma exacerbations from 3.18 +/- 4.86 to 0.45 +/- 0.80 (p = 0.016). There is also a significant increase of FEV1 (p = 0.04) and of FEV1/FVC (p = 0.018) in asthmatic patients with reflux disease and a positive symptomatic index, and of FEV1/FVC (p = 0.002) in all asthmatic children with abnormal gastro-esophageal reflux respectively. In conclusion, by adding antireflux therapy in asthmatic children there is a significant improvement in clinical and some of functional parameters.

[Gastroesophageal reflux in asthmatic children: prevalence and pathogenic role]. / Refluxul gastro-esofagian patologic la copii cu astm bronsic: prevalenta si rol patogenetic.

The relationship of gastroesophageal reflux disease and asthma is controversial. This study was performed to assess the prevalence of pathologic gastroesophageal reflux and its effect on pulmonary function tests in asthmatic children. The following study protocol was performed in a group of asthmatic children (n = 34, 22 male, age range: 2, 5-17 years): diagnosis of pathologic gastroesophageal reflux by means of 24h esophageal pH-monitoring; diagnosis of reflux esophagitis by means of upper digestive endoscopy and pulmonary function tests by means of spirometry. The results show a high prevalence (87%) of pathologic gastroesophageal reflux in asthmatic children. Additionally, there is an inverse correlation (r = -0.67) between the severity of pathologic gastroesophageal reflux and FEV1/FVC. In conclusion, there is a high prevalence of pathologic gastro-esophageal reflux in asthmatic children, contributing to asthma severity.