Roopa Seshadri

A prospective school-based study of abdominal pain and other common somatic complaints in children.

OBJECTIVE To determine the prevalence and impact of pediatric abdominal pain (AP). STUDY DESIGN Prospective cohort study (12/2005-06/2006), with gastrointestinal and other symptoms assessed weekly. Anxiety, depression, functional disability, quality of life, somatization, coping, school absenteeism and medical care were assessed in 237 students in the third through eighth grades (11.8 years; 134 girls) from 2 public schools weekly. Complete data were obtained on 4606 of 5175 (89%) possible questionnaires. RESULTS Seventy-two percent of children reported >1 somatic symptom weekly, and 45% of children reported >1 gastrointestinal symptom weekly. The weekly prevalence of AP was 38%, and 90% of children reported AP at least once. AP persisted >4 consecutive weeks in 52% of children and was associated with higher anxiety (P < .001) and depression (P < .001) scores and worse quality of life (P < .001). Twenty-three percent of children missed school for AP (average, 2.3 days), and 10% of parents of those children missed work (average, 1.9 days). Presence of AP (P < .001) was independently associated with school absences. Four children (2%) sought medical attention. CONCLUSIONS AP is common in school-age children and is associated with worse quality of life, psychological co-morbidities, school absenteeism, and parental work absences.

Surgical results of posterior fossa decompression for patients with Chiari I malformation

IntroductionAn increasing number of children with Chiari I malformations are coming to the attention of neurosurgeons today, although a consensus on the surgical approach to these lesions has yet to be found.MethodsWe present a retrospective analysis of posterior fossa decompression (PFD) performed at our institution on 96 patients from 1989 to 2001. Statistical analyses based on clinical and radiographic presentation and the types of surgical procedures used formed the basis for our review.ResultsMost of the patients with hydromyelia underwent duraplasty procedures with or without tonsillar manipulation. In contrast, most patients without hydromyelia underwent bony decompression with dural scoring and intraoperative ultrasound. PFD with bony decompression and dural scoring showed a 72% success rate, compared with 68% for duraplasty. Dural opening was not more likely to improve or arrest hydromyelia. The group subjected to duraplasty, however, had a significantly higher complication rate. Patients under the age of 8 fared better than their older counterparts.ConclusionsOverall, we favor a tailored posterior fossa craniectomy with dural scoring as the initial surgical procedure in children with Chiari I malformation with or without a syrinx. This less invasive approach minimizes complications associated with dural opening and offers comparable success rates.

High-Dose Chemotherapy as Initial Salvage Chemotherapy in Patients With Relapsed Testicular Cancer

PURPOSE To assess the role of high-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer. PATIENTS AND METHODS From August 1992 to April 1998, 65 patients with testicular cancer were treated with high-dose carboplatin and etoposide followed by peripheral-blood stem-cell transplantation or autologous bone marrow transplantation rescue as initial salvage chemotherapy at Indiana University. An identical course was given after hematopoietic reconstitution. Postchemotherapy resection of residual disease was performed in selected patients with incomplete radiographic response associated with normalization of markers. The median follow-up was 39 months (range, 16 to 91 months). RESULTS Thirty-seven (57%) of the 65 patients are continuously disease-free. Three additional patients are disease-free with subsequent surgery. High-dose chemotherapy was associated with significant morbidity but no treatment-related mortality. CONCLUSION High-dose chemotherapy as initial salvage chemotherapy achieved impressive long-term survival with acceptable toxicity in patients with relapsed testicular cancer.

Type III Secretion Phenotypes of Pseudomonas aeruginosa Strains Change during Infection of Individuals with Cystic Fibrosis

ABSTRACT Pseudomonas aeruginosa is a frequent cause of respiratory exacerbations in individuals with cystic fibrosis. An important virulence determinant of this pathogen is its type III protein secretion system. In this study, the type III secretion properties of 435 P. aeruginosa respiratory isolates from 56 chronically infected individuals with cystic fibrosis were investigated. Although it had been previously reported that 75 to 90% of P. aeruginosa isolates from patients with hospital-acquired pneumonia secreted type III proteins, only 12% of isolates from cystic fibrosis patients did so, with nearly all of these isolates secreting ExoS and ExoT but not ExoU. Despite the low overall prevalence of type III protein-secreting isolates, at least one secreting isolate was cultured from one-third of cystic fibrosis patients. Interestingly, the fraction of cystic fibrosis patient isolates capable of secreting type III proteins decreased with duration of infection. Although 90% of isolates from the environment, the presumed reservoir for the majority of P. aeruginosa strains that infect patients with cystic fibrosis, secreted type III proteins, only 49% of isolates from newly infected children, 18% of isolates from chronically infected children, and 4% of isolates from chronically infected adults with cystic fibrosis secreted these proteins. Within individual patients, isolates of clonal origin differed in their secretion phenotypes, indicating that as strains persisted in cystic fibrosis patient airways, their type III protein secretion properties changed. Together, these findings indicate that following infection of cystic fibrosis patient airways, P. aeruginosa strains gradually change from a type III protein secretion-positive phenotype to a secretion-negative phenotype.

Combination Versus Sequential Doxorubicin and Docetaxel as Primary Chemotherapy for Breast Cancer: A Randomized Pilot Trial of the Hoosier Oncology Group

PURPOSE To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as primary chemotherapy of breast cancer. PATIENTS AND METHODS Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were randomly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery. Patients in arm A received sequential therapy with doxorubicin 75 mg/m(2) every 2 weeks for three cycles followed by docetaxel 100 mg/m(2) every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks for four cycles. Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups. RESULTS Forty patients were entered onto the trial. Pretreatment tumor size averaged 5.7 cm with clinically positive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, >/= 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in both groups, with an overall response rate of 87%, including 20% clinical complete remissions. Pathologic complete remission or residual in situ disease only was confirmed in five patients (12.8%). Patients who received sequential therapy had fewer positive lymph nodes (mean, 2.17 v 4.81; P <.037) at definitive surgery. CONCLUSION Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active. A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy.

Persistent Association of Nailfold Capillaroscopy Changes and Skin Involvement Over Thirty-Six Months With Duration of Untreated Disease in Patients With Juvenile Dermatomyositis

OBJECTIVE To determine the association of changes on nailfold capillaroscopy with clinical findings and genotype in children with juvenile dermatomyositis (DM), in order to identify potential differences in disease course over 36 months. METHODS At diagnosis of juvenile DM in 61 children prior to the initiation of treatment, tumor necrosis factor alpha (TNFalpha) -308 allele and DQA1*0501 status was determined, juvenile DM Disease Activity Scores (DAS) were obtained, and nailfold capillaroscopy was performed. The disease course was monitored for 36 months. Variations within and between patients were assessed by regression analysis. RESULTS At diagnosis, shorter duration of untreated disease (P = 0.05) and a lower juvenile DM skin DAS (P = 0.035) were associated with a unicyclic disease course. Over 36 months, end-row loop (ERL) regeneration was associated with lower skin DAS (P < 0.001) but not muscle DAS (P = 0.98); ERL regeneration and decreased bushy loops were associated with a shorter duration of untreated disease (P = 0.04 for both). At 36 months, increased ERL regeneration (P = 0.007) and improvement of skin DAS (P < 0.001) and muscle DAS (P = 0.025) were associated with a unicyclic disease course. CONCLUSION Early treatment of juvenile DM may lead to a unicyclic disease course. The non-unicyclic disease course usually involves continuing skin manifestations with persistent nailfold capillaroscopy changes. The correlation of nailfold capillaroscopy results with cutaneous but not with musculoskeletal signs of juvenile DM over a 36-month period suggests that the cutaneous and muscle vasculopathies have different pathophysiologic mechanisms. These findings indicate that efforts to identify the optimal treatment of cutaneous features in juvenile DM require greater attention.

Graft histology characteristics in long‐term survivors of pediatric liver transplantation

The factors that influence the long‐term histological outcome of transplanted liver allografts in children are not yet fully understood, and the role of surveillance biopsies in patients with normal graft function remains controversial. The aims of this study were to describe the long‐term graft histology of pediatric liver transplant recipients surviving at least 3 years and to analyze factors correlating with long‐term histological outcome. Histological slides of 63 long‐term liver transplant recipients were assessed for inflammation and fibrosis. The histological findings were correlated with clinical, biochemical, serological, and radiological findings. A significant proportion of biopsies from these patients showed some type of histological abnormalities, with fibrosis being observed in 61 (97%) patients. Duration of transplantation of >6 years and ≥grade 2 inflammation were significantly associated with advanced fibrosis. We could not identify any correlation between ≥stage 3 fibrosis and donor age, cold and warm ischemia time, history of de novo autoimmune hepatitis, hepatic artery thrombosis, chronic rejection, or alanine aminotransferase, aspartate aminotransferase, and gamma‐glutamyl transferase values. In conclusion, liver fibrosis appears to be a common finding in long‐term pediatric liver transplant survivors. The cause of this fibrosis is uncertain, and normal alanine aminotransferase, aspartate aminotransferase, and gamma‐glutamyl transferase levels do not exclude the presence of significant fibrosis. Liver Transpl 14:1582–1587, 2008.

Performance of a rapid antigen-detection test and throat culture in community pediatric offices: Implications for management of pharyngitis

OBJECTIVES. The goals were to establish performance characteristics of a rapid antigen-detection test and blood agar plate culture performed and interpreted in community pediatric offices and to assess the effect of the pretest likelihood of group A streptococcus pharyngitis on test performance (spectrum bias). METHODS. Two throat swabs were collected from 1848 children 3 to 18 years of age who were evaluated for acute pharyngitis between November 15, 2004, and May 15, 2005, in 6 community pediatric offices. One swab was used to perform the rapid antigen-detection test and a blood agar plate culture in the office and the other was sent to our laboratory for blood agar plate culture. Clinical findings were used to calculate the McIsaac score for each patient. The sensitivities of the office tests were calculated, with the hospital laboratory culture results as the criterion standard. RESULTS. Thirty percent of laboratory blood agar plate cultures yielded group A streptococcus (range among sites: 21%–36%). Rapid antigen-detection test sensitivity was 70% (range: 61%–80%). Office culture sensitivity was significantly greater, 81% (range: 71%–91%). Rapid antigen-detection test specificity was 98% (range: 98%–99.5%), and office culture specificity was 97% (range: 94%–99%), a difference that was not statistically significant. The sensitivity of a combined approach using the rapid antigen-detection test and back-up office culture was 85%. Among patients with McIsaac scores of >2, rapid antigen-detection test sensitivity was 78%, office culture sensitivity was 87%, and combined approach sensitivity was 91%. Positive diagnostic test results were significantly associated with McIsaac scores of >2. CONCLUSIONS. The sensitivity of the office culture was significantly greater than the sensitivity of the rapid antigen-detection test, but neither test was highly sensitive. The sensitivities of each diagnostic modality and the recommended combined approach were best among patients with greater pretest likelihood of group A streptococcus pharyngitis.

Association of epigenetic inactivation of RASSF1A with poor outcome in human neuroblastoma

Purpose: To investigate the prevalence and potential clinical significance of epigenetic aberrations in neuroblastoma (NB). Experimental Design: The methylation status of 11 genes that are frequently epigenetically inactivated in adult cancers was assayed in 13 NB cell lines. The prevalence of RASSF1A and TSP-1 methylation was also analyzed in 56 NBs and 5 ganglioneuromas by methylation-specific PCR. Associations between the methylation status of RASSF1A and TSP-1 and patient age, tumor stage, tumor MYCN status, and patient survival were evaluated. Results: Epigenetic changes were detected in all 13 NB cell lines, although the pattern of gene methylation varied. The putative tumor suppressor gene RASSF1A was methylated in all 13 cell lines, and TSP-1 and CASP8 were methylated in 11 of 13 cell lines. Epigenetic changes of DAPK and FAS were detected in only small numbers of cell lines, whereas none of the cell lines had methylation of p16, p21, p73, RAR-β2, SPARC, or TIMP-3. RASSF1A was also methylated in 70% of the primary NB tumors tested, and TSP-1 methylation was detected in 55% of the tumors. RASSF1A methylation was significantly associated with age >1 year (P < 0.01), high-risk disease (P < 0.016), and poor survival (P < 0.001). In contrast, no association between TSP-1 methylation and prognostic factors or survival was observed. Conclusions: Our results suggest that epigenetic inactivation of RASSF1A may contribute to the clinically aggressive phenotype of high-risk NB.

Identification of overweight status is associated with higher rates of screening for comorbidities of overweight in pediatric primary care practice

OBJECTIVES. The goals were to determine whether primary care provider identification of children as overweight was associated with additional screening or referrals and whether the types and numbers of visits to primary care differed for overweight and nonoverweight children. METHODS. Sequential parents/guardians at 13 diverse pediatric practices completed an in-office survey addressing health habits and demographic features. Medical records of each child from a sample of families were reviewed. Data were abstracted from the first visit and from all visits in the 14-month period before study enrollment. Analyses were limited to children ≥2 years of age for whom BMI percentile could be calculated. RESULTS. The analytic sample included 1216 children (mean age: 7.9 years; 51% male) from 777 families (parents were 43% white, 18% black, 34% Hispanic, and 5% other; 49% of families had a child receiving Medicaid/uninsured). Among overweight children (BMI of ≥95th percentile; n = 248), 28% had been identified as such in the record. Screening or referral for evaluation of comorbidities was more likely among overweight children who were identified in the record (54%) than among overweight children who were not identified (17%). Among children at risk of overweight (BMI of 85th to 94th percentile; n = 186), 5% had been identified as such in the record and overall 15% were screened/referred. In logistic regression modeling, the children identified as overweight/at risk of overweight had 6 times greater odds of receiving any management for overweight. CONCLUSIONS. Low rates of identification of overweight status and evaluation or referrals for comorbidities were found. Identification of overweight status was associated with a greatly increased rate of screening for comorbidities.