Vivekanand Singh

Symptoms and Subtypes in Pediatric Functional Dyspepsia: Relation to Mucosal Inflammation and Psychological Functioning

Objectives: The aim of the present study was to explore relations between antral or duodenal inflammatory cells and aspects of psychological functioning with clinical symptom presentation in children with functional dyspepsia (FD), as well as to determine whether histologic inflammation and/or psychopathology are differentially associated with FD subtypes as defined by the Rome II and Rome III criteria. Patients and Methods: One hundred pediatric patients with dyspepsia completed a standardized history and physical examination at initial evaluation. Patients and parents also completed a measure of psychological functioning. Subsequently, 63 of these patients underwent upper endoscopy with biopsy (4 patients excluded from analysis because of mucosal disease). Inflammatory cells in the mucosa of stomach and duodenum were enumerated. Associations between specific symptoms and FD subtypes with inflammatory cell densities and anxiety, depression, and somatization scores were examined. Results: Rome III subtypes were more robustly related to differences in mast cell densities and scores on psychologic subscales than was true for Rome II subtypes. At the individual symptom level, having pain wake the patient from sleep was associated with higher duodenal mast cell density. Bloating was associated with lower levels of general antral inflammation, as well as higher self-reported levels of anxiety and somatization. Early satiety and bothersome postprandial fullness also were associated with higher levels of self-reported anxiety and depression. Conclusions: The present study provides preliminary evidence for a relation between clinical presentation, specific types of inflammatory cell infiltrates, and aspects of psychological functioning in children with FD. Rome III subtyping, adopted for adult dyspepsia, may be relevant to the pediatric population.

Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing

Pediatric-onset inflammatory bowel disease (IBD) is known to be associated with severe disease, poor response to therapy, and increased morbidity and mortality. We conducted exome sequencing of two brothers from a non-consanguineous relationship who presented before the age of one with severe infantile-onset IBD, failure to thrive, skin rash, and perirectal abscesses refractory to medical management. We examined the variants discovered in all known IBD-associated and primary immunodeficiency genes in both siblings. The siblings were identified to harbor compound heterozygous mutations in IL10RA (c.784C>T, p.Arg262Cys; c.349C>T, p.Arg117Cys). Upon molecular diagnosis, the proband underwent successful hematopoietic stem cell transplantation and demonstrated marked clinical improvement of all IBD-associated clinical symptoms. Exome sequencing can be an effective tool to aid in the molecular diagnosis of pediatric-onset IBD. We provide additional evidence of the safety and benefit of HSCT for patients with IBD due to mutations in the IL10RA gene.

Antral Inflammatory Cells, Gastric Emptying, and Electrogastrography in Pediatric Functional Dyspepsia

The aims of the current study were to determine the activation states of antral eosinophils and mast cells and to evaluate the interactions of antral inflammatory cells with gastric emptying and electrogastrography (EGG) in 30 pediatric patients with functional dyspepsia. Eosinophil degranulation was moderate in 42% and extensive in 54% of patients. Mast cell degranulation was >50% in 81% of patients. Elevated mast cell density was associated with slower one hour gastric emptying and increased preprandial dysrhythmia. Mast cell density correlated with the preprandial percentage tachygastria. CD3+ cell density correlated with the preprandial percentage tachygastria also, but only in patients with increased eosinophil density. In conclusion, antral eosinophils and mast cells are significantly activated in pediatric functional dyspepsia. Mast cell density is associated with delayed gastric emptying and preprandial dysrhythmia, suggesting that there may be an interaction between antral inflammation and gastric electromechanical dysfunction in the pathophysiology of pediatric functional dyspepsia.

Umbilical Cord Lesions in Early Intrauterine Fetal Demise

CONTEXT The cause for intrauterine fetal demise (IUFD) occurring in early gestation in a high percentage of spontaneous abortions is unknown. OBJECTIVE To determine the association, if any, of umbilical cord abnormalities with early IUFD. DESIGN All cases of IUFD occurring within 16 weeks of gestation that presented to our hospitals between August 1998 and July 2001 were prospectively studied. Once the fetal demise was diagnosed, pregnancy was terminated by medical induction, such that the products of conception were largely delivered intact. Cases with an intact umbilical cord connecting the fetus and placenta were considered in the study, whereas disrupted cord and curettage material was excluded from the study. RESULTS A total of 153 early IUFD cases were seen during the period of study. The medical induction yielded intact products of conception in 122 cases, whereas 31 cases had to be completed by curettage, as the expulsion of the conceptus was incomplete. Thirteen of the 122 IUFD cases showed abnormalities of the umbilical cord. The cord lesions most frequently encountered were constriction and coiling abnormalities. Other lesions seen included hemorrhage, thrombosis, edema, and amniotic band. CONCLUSIONS A significantly high number (10.7%) of IUFD in early gestation are associated with umbilical cord abnormalities. Routine assessment of umbilical cords in early pregnancy might help to detect pregnancies at risk.

Fatal Pulmonary Tumor Embolism in a Child with Chondroblastic Osteosarcoma

Fatal embolic chondroblastic osteosarcoma to the lung is an extremely rare phenomenon. We report a case of a 15-year-old boy who developed bilateral pulmonary embolism shortly after resection of the right distal femur for chondroblastic osteosarcoma. The patient succumbed to right-sided heart failure 8 weeks later. An autopsy revealed extensive intravascular tumor emboli in the bilateral pulmonary arteries and their branches. No metastatic lesions were identified in the lungs. We review the clinical, radiologic, and pathologic findings of this patient and the literature.

Differentiating between congenital rhabdomyosarcoma versus fibromatosis of the pediatric tongue

Congenital rhabdomyosarcoma of the tongue is exceedingly rare. Fibromatosis of the tongue is also rare, and very difficult to distinguish from the spindle cell variant of rhabdomyosarcoma. Both appear histologically as spindle neoplasms replacing normal striated musculature of the tongue. The treatment protocol for the former has been developed by the Intergroup Rhabdomyosarcoma Studies (IRS) I-IV and requires surgery, radiation, and chemotherapy. For fibromatosis, complete surgical excision is usually adequate without additional therapy, although some cases of aggressive fibromatosis also require chemotherapy. With significant differences in appropriate treatment and prognosis, each entity must not be mistaken for the other. We review the differences in radiologic, histologic, and immunohistochemical (IHC) features of both entities.

Decreased Pregnane X Receptor Expression in Children with Active Crohn’s Disease

Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn’s disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn’s disease (CD) and 12 age- and sex-matched controls (aged 7–17yrs). The aim of this investigation was to compare the relative mRNA expression of PXR, cytochrome p450 3A4 (CYP3A4), and villin 1 (VIL1) (a marker of epithelial cell integrity) in the inflamed terminal ileum (TI) versus noninflamed duodenum of children with CD. Relative expression was determined via reverse transcription real-time quantitative polymerase chain reaction, data normalized to glyceraldehyde 3-phosphate dehydrogenase, and differences in gene expression explored via paired t tests. PXR expression was decreased in the inflamed TI versus noninflamed duodenum (TI = 1.88 ± 0.89 versus duodenum = 2.5 ± 0.67; P < 0.001) in CD, but not controls (TI = 2.11 ± 0.41 versus duodenum = 2.26 ± 0.61; P = 0.52). CYP3A4 expression was decreased in CD (TI = –0.89 ± 3.11 versus duodenum = 1.90 ± 2.29; P < 0.05), but not controls (TI = 2.46 ± 0.51 versus duodenum = 2.60 ± 0.60; P = 0.61), as was VIL1 (CD TI = 3.80 ± 0.94 versus duodenum = 4.61 ± 0.52; P < 0.001; controls TI = 4.30 ± 0.35 versus duodenum = 4.47 ± 0.40; P = 0.29). PXR expression correlated with VIL1 (r = 0.78, P = 0.01) and CYP3A4 (r = 0.52, P = 0.01) expression. In conclusion, PXR, CYP3A4, and VIL1 expression was decreased only in the actively inflamed small intestinal tissue in children with CD. Our findings suggest that inflammation has the potential to influence expression of genes, and potentially intestinal proteins, important to drug disposition and response. The observed differential patterns of gene expression support further investigation of the role of PXR in the pathogenesis and/or treatment of pediatric Crohn’s disease.

Angiomatoid Fibrous Histiocytoma with t(2;22)(q33;q12.2) and EWSR1 Gene Rearrangement

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of low malignant potential. The tumor is mostly seen in the deep dermis and subcutis of the lower extremities in children and young adults. Histologically, the tumor forms lobulated sheets of plump round to spindle cells surrounded by a fibrous pseudocapsule and lymphoid cuff. The cytogenetic and molecular hallmarks of AFH are not well defined. Only 4 of 30 reported cases of AFH have had karyotypic information. We present a case of AFH in the inguinal region of a 12-year-old girl. The tumor showed characteristic histological features, t(2;22)(q33;q12.2), and EWSR gene rearrangement by fluorescence in situ hybridization.

Plasma cell-rich acute cellular rejection of a transplanted kidney associated with antibody to the red cell Kidd antigen

Abstract:  Plasma cell‐rich acute cellular rejection of a transplanted kidney is described in association with the identification of serum antibody to the red cell Kidd antigen, Jk‐b, which is also found in the kidney. This antibody was formed without a history of a recent blood transfusion or exposure to intravenous immunoglobulin. The role this antibody could have in the rejection of the transplant is discussed.

Spitzoid Melanoma in a Child with Li-Fraumeni Syndrome

Spitzoid melanoma of childhood is a rare malignancy. The histological features are at the upper end of a range encompassing Spitz nevus and atypical Spitz tumor, the unifying features including large oval, fusiform or polygonal melanocytes with abundant homogeneous-appearing cytoplasma and large vesicular nuclei. The presence of a “bottom-heavy” pattern, strikingly enlarged nuclei and nucleoli in both the upper and lower portions of the lesion, and deep mitotic figures are among the findings that distinguish most of the Spitzoid melanomas from Spitz nevi and atypical Spitz tumors. There are no syndromic associations reported for this malignancy. We report the occurrence of choroid plexus carcinoma, Spitzoid melanoma, and myelodysplasia in a child who was found to carry a germline mutation for TP53. While choroid plexus carcinoma and myelodysplasia have relatively frequently been described, melanomas have been very rarely described in Li-Fraumeni syndrome. The association of Spitzoid melanoma with Li-Fraumeni syndrome, especially in a pediatric patient, has not been reported before.