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Effect of a gluten-free diet on albuminuria in children with newly diagnosed celiac disease

Levine, Jeremiah; Hauptman, Leora; Moy, Libia; Trachtman, Howard
Background and objectives/UNASSIGNED:Altered gastrointestinal permeability in celiac disease (CD) is mediated by zonulin. The receptor for zonulin is expressed on podocytes. Therefore, we tested the effect of a gluten-free diet (GFD) on albuminuria in pediatric patients with newly diagnosed CD. Methods/UNASSIGNED:We performed a cohort study comparing urinary albumin (μg):creatinine (mg) ratio (ACR) in CD patients vs controls and in response to a GFD. Results/UNASSIGNED:Children with CD (n=46) had higher ACR compared to controls (n=21), 20.2±5.6 versus 8.4±1.1 μg/mg, P=0.16 and exceeded 30 μg/mg (microalbuminuria cut-off) in 7/46 cases. 17 patients had a follow-up assessment (interval 6.1±0.7 months) on a GFD. Baseline ACR was 20.7±5.2 that fell to 10.4±1.5 μg/mg, P=0.035. Conclusion/UNASSIGNED:Children and adolescents with newly diagnosed CD have low-grade albuminuria that is numerically higher than controls and that declined after implementation of a GFD. CD may be associated with reversible defects in the glomerular barrier.
PMCID:8336695
PMID: 34368799
ISSN: 2673-3633
CID: 5086952

Airway and esophageal eosinophils in children with severe uncontrolled asthma

Erkman, Jessica; Vaynblat, Allen; Thomas, Kristen; Segal, Leopoldo N; Levine, Jeremiah; Moy, Libia; Greifer, Melanie; Giusti, Robert; Shah, Rasik; Kazachkov, Mikhail
AIM/OBJECTIVE:Children with severe uncontrolled asthma (SUA) have a high burden of symptoms and increased frequency of asthma exacerbations. Reflux esophagitis and eosinophilic esophagitis are important co-morbid factors for SUA. Both are associated with the presence of eosinophils in esophageal mucosa. We hypothesized that esophageal eosinophils are frequently present and correlate with the presence of airway eosinophils in children with SUA. METHOD/METHODS:We performed a retrospective analysis of a prospective database of children who underwent "triple endoscopy" (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage [BAL] and endobronchial biopsy [EBB], and esophagogastroduodenoscopy with esophageal biopsy [EsB]) at our Aerodigestive Center for evaluation of SUA. Children with known cystic fibrosis, primary ciliary dyskinesia, and aspiration-related lung disease were excluded. RESULT/RESULTS:Twenty-four children (21 males) ages 2-16 years were studied. Elevated BAL eosinophils were found in 10 (42%) patients, endobronchial eosinophils in 16 (67%); 7 (29%) had endobronchial eosinophils without elevated BAL eosinophils. Esophageal eosinophils were found in 11 (46%) patients. There was a correlation between the amount of eosinophils in BAL and EBB (R = 0.43, P = 0.05) airway eosinophils, defined as elevated BAL and/or EBB eosinophils, correlated with esophageal eosinophils (R = 0.41, P = 0.047). CONCLUSION/CONCLUSIONS:We concluded that airway and esophageal eosinophils are frequently present in children with SUA.
PMID: 30353711
ISSN: 1099-0496
CID: 3373392

Aerodigestive dysbiosis in children with chronic cough

Kazachkov, Mikhail; Kapoor, Bianca C; Malecha, Patrick W; Wu, Benjamin G; Li, Yonghua; Levine, Jeremiah; Erkman, Jessica; Fitzgerald, Kathryn; Moy, Libia; Segal, Leopoldo N
In pediatric patients with chronic cough, respiratory culture techniques commonly yield negative results. Studies using culture-independent methods have found a high relative abundance of oral microbes in the lower airways, suggesting that the topographical continuity, and dynamics of the intraluminal contents of the aerodigestive system likely influence the lower airway microbiota. We hypothesize that in subjects with chronic cough, clinical diagnosis will correlate with distinct microbial signatures detected using culture-independent methods.
PMID: 29984544
ISSN: 1099-0496
CID: 3191752

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations

Kazachkov, Mikhail; Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Bar-Aluma, Bat-El; Spalink, Christy L; Barnes, Erin P; Amoroso, Nancy E; Balou, Stamatela M; Bess, Shay; Chopra, Arun; Condos, Rany; Efrati, Ori; Fitzgerald, Kathryn; Fridman, David; Goldenberg, Ronald M; Goldhaber, Ayelet; Kaufman, David A; Kothare, Sanjeev V; Levine, Jeremiah; Levy, Joseph; Lubinsky, Anthony S; Maayan, Channa; Moy, Libia C; Rivera, Pedro J; Rodriguez, Alcibiades J; Sokol, Gil; Sloane, Mark F; Tan, Tina; Kaufmann, Horacio
BACKGROUND:Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS:We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS:Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS:Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.
PMCID:6084453
PMID: 30053970
ISSN: 1532-3064
CID: 3216612

Association of airway esophageal eosinophils in children with refractory asthma and chronic cough [Meeting Abstract]

Erkman, J; Segal, L; Levine, J; Moy, L; Greifer, M; Giusti, R; Shah, R; Kazachkov, M
PURPOSE: Reflux esophagitis (ReE) and eosinophilic esophagitis (EoE) are associated with the presence of eosinophils in esophageal mucosa and are considered to be important co-morbid factors for chronic cough and asthma in adults. We hypothesize that esophageal eosinophils related to ReE and EoE are present in children with refractory asthma and chronic cough and correlate with airway eosinophilia. METHODS: We performed a retrospective analysis of medical records of children who underwent "triple endoscopy" (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy (EBB), and esophagogastroduodenoscopy with esophageal biopsy (EsB)) at our Aerodigestive Center for evaluation of refractory asthma and cough. Inclusion criteriawere cough for 8 weeks or more with no response to trial of antibiotics and systemic/inhaled corticosteroids (ICS), poor control of asthma symptoms, and/or airflowlimitations and air trapping despite use ICS or ICS/long-acting beta-agonist combination. Children with known cystic fibrosis, primary ciliary dyskinesia and aspiration into airway were excluded. RESULTS: Thirty-two children (22 males) met inclusion criteria. Nineteen had refractory asthma and 13 had chronic cough. There were no significant complications recorded after procedures including EBB. Eosinophils (>1%) were present in BAL of 8 (25%) children. EBB showed eosinophils in 17 (53%) children. There were a total of 19 children with eosinophils isolated from the airway (either BAL or EBB), 4 (21%) had them in BAL alone, 8 (42%) in EBB only, and 7 (37%) in both BAL and EBB. EoE was diagnosed in 6 children (19%) and ReE in 13 (41%). EsB revealed esophageal eosinophils in 47% of children. Presence of eosinophils in EsB was related to presence of eosinophils in EBB chi2 (1, N = 32), p = 0.026, but not BAL (p=0.89). CONCLUSIONS: ReE and EoE with esophageal eosinophils was present in 47% of children with refractory asthma and chronic cough. There is a significant relationship between airway and esophageal eosinophils, which becomes evident only when EBB is performed for detection of airway eosinophils. Further research is required for understanding the association of airway and esophageal eosinophilia in the development and management of refractory asthma and cough
EMBASE:619297567
ISSN: 1931-3543
CID: 2860212

Colitis as the Sole Initial Presentation of Chronic Granulomatous Disease: Histopathologic Clues to Diagnosis

Rosenbaum, Brooke E; Shenoy, Rivfka; Vuppula, Sharon; Thomas, Kristen; Moy, Libia; Kaul, Aditya
Chronic granulomatous disease (CGD) is a rare, inherited immunodeficiency disorder that reduces the superoxide generation ability of phagocytes, leading to recurrent infections and granulomatous inflammation. We report the case of a previously healthy 3-year-old boy who presented with classic features of Crohn's disease. Suspicion from histopathological assessment allowed early diagnosis and treatment for CGD before the onset of infections.
PMID: 27331854
ISSN: 1532-0987
CID: 2159192

Autoimmune hepatitis: a classic autoimmune liver disease

Moy, Libia; Levine, Jeremiah
AIH is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and production of autoantibodies. Based on the nature of the serum autoantibodies, two types of AIH are recognized: type 1 (AIH-1), positive for ANA and/or anti-smooth muscle antibody, and type 2 (AIH-2), defined by the positivity for anti-liver kidney microsomal type 1 antibody or for anti-liver cytosol type 1 antibody. AIH demonstrates a female preponderance with the female-to-male ratio of 4:1 in AIH-1 and 10:1 in AIH-2. Several genes confer susceptibility to AIH and influence clinical manifestation, response to treatment, and overall prognosis. Most are located within the human leukocyte antigen (HLA) region, which is involved in the presentation of antigenic peptides to T cells and thus in the initiation of adaptive immune responses. The strongest associations are found within the HLA-DRB1 locus. In patients with increased genetic susceptibility to AIH, immune responses to liver autoantigens could be triggered by molecular mimicry. Because of molecular mimicry, different environmental agents, drugs, and viruses might produce AIH. In AIH, T cells are numerically and functionally impaired, permitting the perpetuation of effector immune responses with ensuing persistent liver destruction. AIH is rare but highly treatable inflammatory condition of the liver. Subclinical and asymptomatic disease is common. AIH therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes. Clinical response to immunosuppressive therapy is characteristic and supports the diagnosis.
PMID: 25466500
ISSN: 1538-3199
CID: 1424792

Capsule endoscopy in the evaluation of patients with unexplained growth failure

Moy, Libia; Levine, Jeremiah
BACKGROUND: Poor weight gain and growth can be caused by many medical, nutritional, behavioral, and psychological factors. Crohn disease is one of the more common gastrointestinal etiologies associated with growth failure. The aim of this study is to determine the role of capsule endoscopy (CE) in the evaluation of older children and adolescents who were referred to a pediatric gastroenterology service for a chief complaint of unexplained growth failure. PATIENTS AND METHODS: We retrospectively reviewed the records of children with growth failure undergoing CE between August 2002 and November 2005. Height and weight (expressed as z scores) were recorded at least 6 months before study, at the time of the study, and at least 6 months post study. All of the patients had celiac disease and Crohn disease excluded using standard biochemical, radiologic, endoscopic, and histologic assessment. RESULTS: Seven children (4 males and 3 females) were included in the study-mean age 11.7+/-3.6 years. Indications for CE were growth failure associated with abdominal pain (3 patients), diarrhea and apthous ulcers (2 patients), delayed puberty (1 patient), or a family history of Crohn disease (1 patient). The mean z score for weight at the time of the study was 2.10+/-1.0 and for height was 1.50+/-0.7 All 7 children had normal small bowel series performed before the CE. All had both endoscopically and histologically normal esophagogastroduodenoscopy and colonoscopy. In 4 of 7 patients, multiple small bowel apthous ulcerations consistent with Crohn disease were identified by CE. All 4 patients who had abnormal CE were treated and started gaining weight. The mean z score for weight after 6 months of treatment was 1.35+/-1.2 and for height was 0.50+/-1.7. The mean z score for weight after treatment was significantly improved compared with the mean z score at diagnosis (P<0.05). CONCLUSIONS: In our study, 4 of the 7 older children and adolescents with unexplained growth failure and normal small bowel series were found to have Crohn disease involving the small intestine. In addition, we were able to show the improvement on the mean z score for weight after treatment of small bowel Crohn disease was instituted.
PMID: 19367183
ISSN: 0277-2116
CID: 587242

Wireless capsule endoscopy in the pediatric age group: experience and complications

Moy, Libia; Levine, Jeremiah
BACKGROUND: The development of wireless capsule endoscopy (CE) provides a unique opportunity to visualize the entire small bowel in a minimally invasive manner. Studies in adult patients have demonstrated that the disposable capsule is well tolerated and highly effective, but few studies have been done in children. The aims of our study were to compare the diagnostic yield of CE and small bowel series in children being evaluated for possible small intestine disease and to determine the risk of developing an adverse event following capsule endoscopy. PATIENTS AND METHODS: We retrospectively reviewed the records of all children who underwent CE at 1 institution between August 2002 and July 2005. Results of CE were compared with those of small bowel radiographic studies when available. RESULTS: There were 46 CE studies from 45 patients, 28 male and 17 female, with a mean age of 14.9 +/- 3.6 years and mean weight of 49.7 +/- 17.5 kg. The indications for CE included unresponsive Crohn disease (n = 16), possible intestinal polyps (n = 11), unexplained iron deficiency anemia (n = 7), growth failure (n = 5), unresponsive ulcerative colitis (n = 3), persistent abdominal pain (n = 1), protein-losing enteropathy (n = 1), and allergic enteropathy with occult gastrointestinal bleeding (n = 1). Of the 46 CE studies, 41 were completed and 5 were incomplete studies. Based on the CE, 9 patients were newly diagnosed with Crohn disease, 9 patients with Crohn disease were newly diagnosed with small bowel involvement, 8 patients had upper intestinal polyps, 1 patient had findings consistent with Menetrier disease, and 1 had a duodenal ulcer. Thirty-three patients had small bowel series before CE: 24 studies were normal, 6 had abnormal thickening of the small bowel, 2 had polyps, and 1 patient had antral narrowing. All 9 patients with abnormal small bowel series had abnormal CE studies. Of the 24 patients with normal small bowel series, 20 had completed CE studies, and in 10 children, the study was abnormal. Nine of the 45 subjects had adverse events. Five patients had delayed passage from the stomach, with 2 needing endoscopic retrieval of the CE, and 4 had delayed passage from the small intestine (>5 days), with 2 requiring surgical removal, 1 responding to steroids, and the final patient requiring an ileocolic resection 2 months after the CE for an undiagnosed ileal stricture. The only significant association noted was that older patients were more likely to have intestinal retention. CONCLUSIONS: CE provides a valuable tool in the evaluation of pediatric patients for possible small bowel disease. However, the risk of developing complications appears to be greater in the pediatric population, with 20% of our patients having an adverse event.
PMID: 17414156
ISSN: 0277-2116
CID: 587272

Capsule endoscopy as a diagnostic tool in the evaluation of graft-vs.-host disease [Case Report]

Silbermintz, Ari; Sahdev, Indira; Moy, Libia; Vlachos, Adrianna; Lipton, Jeffrey; Levine, Jeremiah
Capsule endoscopy is a relatively new technology that has allowed gastroenterologists to visualize the mucosa of the small intestine. This technology is playing an expanding role in both adult and pediatric gastroenterology. In this report, we present an 8-yr-old child following allogeneic hematopoietic cell transplantation who developed large volume bloody diarrhea requiring multiple packed red blood cell transfusions that was resistant to aggressive therapy for GVHD. The capsule endoscopy performed on this patient provided significant information not provided by upper endoscopy and colonoscopy that allowed for successful treatment changes. This case demonstrates that capsule endoscopy is a diagnostic tool that may play an important role in the assessment of patients, including children, with possible GVHD
PMID: 16573617
ISSN: 1397-3142
CID: 94610