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Biomedical subjects

Petar Mamula

Publications and source records attributed to Petar Mamula.

At least 19 recordsLinked to original sources

Interventional upper endoscopy: the pediatric perspective.

Pediatric endoscopy has evolved from a purely observational modality into one with the potential for many therapeutic applications. Common therapeutic uses of endoscopy in children now include treatment of variceal bleeds and foreign body retrieval and newer procedures such as endoluminal gastroplication and endoscopic pyloromyotomy. Continuing research in pediatric endoscopy will allow pediatric gastroenterologists to perfect existing interventional endoscopic techniques and to learn to perform new ones.

Child↗

Predictors of immunomodulator use as early therapy in pediatric Crohn's disease.

GOALS: The goals of this study were to identify markers in a patient's presentation and disease progression that predict the need for the use of immunomodulators in a pediatric population. BACKGROUND: Although immunomodulator safety and efficacy have been documented in Crohn's disease, models for predicting outcome and the need for immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate) early in the disease course have not been investigated in children or adults. METHODS: Data on newly diagnosed Crohn's disease patients were prospectively collected within 3 weeks of diagnosis, 6 months after diagnosis, and 1 year after diagnosis. Information collected at each visit included medication use and disease activity assessment. RESULTS: A total of 57 patients who were followed for > or = 6 months were evaluated. Overall, 34 of 57 (59.6%) were started on immunomodulators within 1 year of diagnosis. Mean serum albumin (3.35 g/dL vs. 3.7 g/dL, P = 0.013) and hematocrit (33.3% vs. 35.9%, P = 0.023) at diagnosis were lower, and erythrocyte sedimentation rate (32 vs. 12, P = 0.011) at diagnosis was higher in patients who required immunomodulators. The total Pediatric Crohn's Disease Activity Index score as well as the physical examination score and patient recall score within the PCDAI at diagnosis were not different among those who received immunomodulators and those that did not. CONCLUSIONS: Immunomodulators are frequently used within 1 year of diagnosis in pediatric Crohn's disease. Lower serum albumin levels and hematocrit, and elevated erythrocyte sedimentation rate at diagnosis may predict the need for immunomodulators earlier in the disease course.

Adolescent↗

Treatment of iron deficiency anemia in pediatric inflammatory bowel disease.

Anemia is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) that is commonly overlooked, despite its significant impact on quality of life. Characteristic symptoms include chronic fatigue, headache, and subtle impairment of cognitive function, although some less common symptoms include dyspnea, dizziness, pica, angular stomatitis, shortened attention span, and esophageal webs. Several types of anemia are associated with IBD, but iron deficiency anemia (IDA) accounts for the majority of cases and others include anemia of chronic disease, anemia associated with vitamin deficiency (vitamin B12 and folate), autoimmune anemia, and anemia caused by medication used to treat IBD. The diagnosis of IDA relies on laboratory blood tests. Therefore, these tests should be obtained on a regular basis because characteristic symptoms may be absent or not readily recognized by patients and their clinicians. Complete blood count may suffice; however, iron studies and serum vitamin levels may be necessary to differentiate between specific types of anemia. During the diagnostic process, it is important to consider coexistence of different types of anemia, especially if no response to therapy is noted. The therapy for anemia is directed towards treatment of the underlying inflammatory process and supplemental therapy, depending on the type of deficiency. Iron deficiency anemia is treated with iron preparations, first orally, and if unresponsive or if associated with untoward adverse events leading to decrease in adherence with the therapeutic regimen, with intravenous preparations. Intramuscular therapy has been abandoned due to high rate of complications. Intravenous therapy may be administered as a multiple-dose regimen (intravenous iron sucrose and gluconate) or as a single intravenous dose (iron dextran), which is associated with a higher risk of allergic infusion reactions and requires obligatory test dose administration. Treatment with erythropoietin is reserved for a select subgroup of patients with anemia of chronic disease. With appropriate treatment, the majority of patients with IBD will have significant improvement or resolution of anemia, which can lead to a better quality of life. However, a high index of suspicion should be maintained in order to identify the precise cause of anemia and to prescribe the appropriate therapy.

Journal Article↗

Eosinophilic esophagitis: a 10-year experience in 381 children.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a disorder characterized by a severe, isolated eosinophilic infiltration of the esophagus unresponsive to aggressive acid blockade but responsive to the removal of dietary antigens. We present information relating to our 10-year experience in children diagnosed with EoE. METHODS: We conducted a retrospective study between January 1, 1994, and January 1, 2004, to evaluate all patients diagnosed with EoE. Clinical symptoms, demographic data, endoscopic findings, and the results of various treatment regimens were collected and evaluated. RESULTS: A total of 381 patients (66% male, age 9.1 +/- 3.1 years) were diagnosed with EoE: 312 presented with symptoms of gastroesophageal reflux; 69 presented with dysphagia. Endoscopically, 68% of patients had a visually abnormal esophagus; 32% had a normal-appearing esophagus despite a severe histologic esophageal eosinophilia. The average number of esophageal eosinophils (per 400 x high power field) proximally and distally were 23.3 +/- 10.5 and 38.7 +/- 13.3, respectively. Corticosteroids significantly improved clinical symptoms and esophageal histology; however, upon their withdrawal, the symptoms and esophageal eosinophilia recurred. Dietary restriction or complete dietary elimination using an amino acid-based formula significantly improved both the clinical symptoms and esophageal histology in 75 and 172 patients, respectively. CONCLUSIONS: Medications such as corticosteroids are effective; however, upon withdrawal, EoE recurs. The removal of dietary antigens significantly improved clinical symptoms and esophageal histology in 98% of patients.

Administration, Oral↗

Managing complicated Crohn's disease in children and adolescents.

The natural history of Crohn's disease is characterized by recurrent exacerbations. A small, but significant, number of pediatric patients with Crohn's disease are resistant to standard medical therapies. The goal of therapy in pediatric patients is not only to achieve and maintain clinical remission, but also to promote growth, development and improve quality of life. All of this needs to be achieved within a relatively short window of opportunity, before growth and development deficiencies become permanent. The standard therapy for pediatric patients with Crohn's disease consists of 5-aminosalicylic-acid compounds, antibiotics and enteral nutrition. Enteral nutrition has an excellent adverse-effect profile and, in addition to its therapeutic effect, positively impacts growth and nutritional status. Immunomodulating medications, such as azathioprine, 6-mercaptopurine and methotrexate, are frequently used to maintain remission, and to treat corticosteroid-dependent and perianal disease. Recently, biologic treatment with the anti-tumor-necrosis-factor-alpha antibody infliximab has dramatically changed the therapeutic approach. The long-term safety of this therapy still needs to be established. Limited data are available on other biologic therapies, which, at this point in time, are considered experimental and are only available through clinical trials.

Adolescent↗

Health-related quality of life improves in children and adolescents with inflammatory bowel disease after attending a camp sponsored by the Crohn's and Colitis Foundation of America.

PURPOSE: To describe the reported health-related quality of life (HRQOL) in children and adolescents with inflammatory bowel disease (IBD) after attending an IBD summer camp. METHODS: A prospective analysis of quality of life was completed at an overnight camp that was exclusively for patients with IBD, which was sponsored by the Crohn's and Colitis Foundation of America. The IMPACT-II questionnaire (Canada and United States) and the State-Trait Anxiety Inventory for Children were administered to the campers at the beginning and at the end of a 1-week camp to assess HRQOL and anxiety. The IMPACT-II questionnaire consists of 35 questions measuring 6 quality-of-life domains (i.e., bowel domain, systemic symptoms, emotional functioning, social functioning, body image, and treatment/interventions). The State-Trait Anxiety Inventory for Children consists of 2 different 20-item sets of questions. One set assesses state anxiety, and the other, trait anxiety. A repeated-measures multivariate analysis of variance was performed to determine the differences between scores attained before and after camp on the IMPACT-II questionnaire and in each of its domains. Paired sample t tests were performed on state and trait anxiety before and after camp. RESULTS: A total of 125 individuals consented to participate, but 61 patients (50 girls and 11 boys; age range, 9 to 16 y) completed the IMPACT-II questionnaire in full. Of those 61 patients, 47 had Crohn's disease and 14 had ulcerative colitis. There was statistically significant improvement between the mean (+/-SD) precamp total score (172.95 +/- 36.61) and the mean postcamp total score (178.71 +/- 40.97; P = 0.035), bowel symptoms scores (P = 0.036), social functioning scores (P = 0.022), and treatment interventions scores (P = 0.012). No difference was found between anxiety scores before and after camp on either the state or trait anxiety inventories (n = 55; P > 0.05). CONCLUSIONS: Overall, HRQOL improved in children after attending IBD summer camp. This exploratory study suggests that contributing factors for these improvements may be an increase in social functioning, a better acceptance of IBD symptoms, and less distress regarding treatment interventions, suggesting that a camp that is specifically designed for children with IBD may normalize the chronic illness experience. However, future research using a multimodal measurement approach is warranted to support these conclusions.

Adolescent↗

Infliximab in pediatric ulcerative colitis: two-year follow-up.

OBJECTIVES: The role of infliximab in treating pediatric ulcerative colitis (UC) is not defined. The authors previously have described their experience with the open label use of infliximab in nine children with moderate to severe UC. The aim of this study was to describe the outcome of these patients after a minimum 2-year follow-up and to describe the responses of eight additional patients to this medication. METHODS: The authors reviewed all pediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia from its first use until February 2003. Tolerance of the infusions and adverse events were recorded. RESULTS: Follow-up information for a minimum of 2 years was reviewed for the nine initial patients. A total of 73 infliximab infusions were administered to these patients. Seven of nine (78%) patients were considered to be responders to the initial dose of infliximab. Two of these patients became nonresponders within 9 months of the first dose of infliximab and underwent colectomy. Of the remaining five (56%) patients with sustained response, two continue to receive infliximab infusions and three are doing well without infliximab. One patient experienced an infusion reaction, and one experienced herpes zoster infection. We have treated eight additional UC patients with infliximab. Seven (88%) patients were considered responders. One responder experienced relapse within 2 months. Overall, a short-term improvement was seen in 14 of 17 (82%) patients, and sustained improvement in 10 of 16 (63%) patients followed up for more than 9 months. All five patients with severe or fulminant UC, unresponsive to 2 weeks of intravenous corticosteroid therapy, experienced improvement with infliximab. Infliximab was well tolerated. CONCLUSION: Infliximab is associated with short- and long-term clinical improvement in children and adolescents with moderate to severe UC.

Adolescent↗

Human antichimeric antibody in children and young adults with inflammatory bowel disease receiving infliximab.

INTRODUCTION: Pediatric studies on immunogenicity of infliximab have not been published. The aim of the study was to evaluate the prevalence of human antichimeric antibody (HACA), relationship to infusion reactions (IR), and the role of concomitant immunomodulatory therapies. METHODS: An inflammatory bowel disease (IBD) database was queried, and a retrospective review of patients who had HACA performed was undertaken. RESULTS: HACA was conclusively determined in 34 patients with IBD (14 male, Crohn disease/ulcerative colitis: 30/4), median age 14.8 years (range, 6.4-22.5 years). Twenty-nine (85.3%) patients were receiving immunomodulatory therapy. A total of 234 infliximab infusions were administered (mean, 6.9; range, 1-26). HACA was detected in 12 (35.3%) patients. IR occurred in 8 (23.5%) patients. HACA-positive patients had a higher proportion of infusions associated with IR than did HACA-negative patients (P < 0.01). HACA levels > or =8.0 microg/mL were more likely to be associated with IR (P = 0.03). Levels of > or = 8.0 microg/mL were more common in patients who had an average interval between infliximab infusions of 8 weeks or less (P = 0.04). Concomitant immunomodulatory therapy was associated with a lower risk of developing HACA (P = 0.02) and lower titer of HACA (P = 0.04). Patients did not have HACA at a greater rate when there was an extended interval (more than 12 weeks) between infliximab infusions (P = 0.89). CONCLUSIONS: In children and adolescents with IBD, HACA formation is related to IR and to the duration of response to treatment. Immunomodulatory agents seem to have a protective role against development of HACA or high titers of antibodies. The interval between infusions does not influence the development of HACA.

Adjuvants, Immunologic↗