David L. Zwick

Posttransplant lymphoproliferative disorder in pediatric renal transplantation

Abstractu2002Of 84 renal transplants performed in our center since 1986, six recipients (7.1%) developed posttransplant lymphoproliferative disorder (PTLD). All received quadruple immunosuppression with Minnesota anti-lymphoblastic globulin or anti-thymocyte globulin, methylprednisolone, cyclosporine, and azathioprine or mycophenolate mofetil. Five were seronegative for Epstein-Barr virus (EBV) when they received their renal transplant. All patients received prophylactic acyclovir treatment postrenal transplant and none developed a cytomegalovirus (CMV) infection. All patients were positive for EBV by serology and polymerase chain reaction at the time of diagnosis of PTLD. Clinical features at presentation included fever (6/6), adenopathy (4/6), hypertrophied adenoids (4/6), liver involvement (2/6), and allograft involvement (2/6), 2–78 months (4/6<6 months) postrenal transplant. Histopathology of PTLD tissue revealed T cell rich/ Hodgkin disease-like B cell PTLD in one patient, polymorphic PTLD in four, and monomorphic (large B cell lymphoma) PTLD in one. Immunophenotyping of the PTLD biopsy specimen revealed predominant T cells in three, mixed B and T cells in two patients, and B cell in one. No aneuploid populations were identified by flow cytometric DNA ploidy assay. DNA from the PTLD tissue revealed weak to moderate IgH gene rearrangement in four of six patients but no T cell receptor β-chain or c-myc gene rearrangement on Southern blot analysis. The child with monomorphic (large B cell lymphoma) PTLD was clonal with λ light chain restriction on immunophenotyping. Treatment consisted of reduced immunosuppression and ganciclovir/ acyclovir in all patients. CMV hyperimmune globulin was used as an adjunctive therapy in two patients. Chemotherapy was needed in only one patient. A single rejection episode occurred in two children following reduction in immunosuppression, which reversed following intravenous methylprednisolone therapy. PTLD resolved in all patients and at present all patients are alive with functional grafts 2–54 months post diagnosis. Our experience suggests that reduced immunosuppression and anti-viral treatment is adequate in most cases of PTLD, but chemotherapy and hyperimmune globulin therapy may be beneficial in cases resistant to first-line therapy. Since all but one of our patients were EBV seronegative at the time of transplant, vigilance is especially important for early detection of PTLD in this group of the pediatric renal transplant population.

Intracranial trigeminal nerve rhabdomyoma/choristoma in a child: A case report and discussion of possible histogenesis

Rhabdomyomas are rare tumors that usually arise within the heart, orocervical, or vulvovaginal regions. The cardiac tumors have a characteristic immature morphology, occur often in association with tuberous sclerosis, and are regarded as hamartomas rather than true neoplasms. The histogenesis of the extracardiac tumors and their true neoplastic nature are matters of controversy. We report the first case of a rhabdomyoma located inside the cranium. The intimate association with the mandibular division of the trigeminal nerve, the normal embryogenesis of the craniofacial muscles, and animal homograft and xenograft experiments provide a framework for considering this tumor, and possibly other rhabdomyomas, as a choristoma/hamartoma rather than a true neoplasm.

Independent and Combined Effects of Prolonged Inhaled Nitric Oxide and Oxygen on Lung Inflammation in Newborn Piglets

Clinical use of nitric oxide (NO) is usually in conjunction with high oxygen concentrations, the effects of which may include lung neutrophil accumulation, apoptosis and upregulation of antioxidant enzyme activity. To define the effects of NO on neutrophils from young piglets and its relationship to lung neutrophil dynamics during hyperoxia we exposed thirty piglets to room air (RA), RA+NO (50 ppm NO), O2 (FiO2≥0.96) or O2+NO for 5 days. Ten additional animals breathed RA+NO or O2+NO, then recovered in RA for 3 days before sacrifice. Neutrophil CD18 and intracellular oxidant production were measured by flow cytometry. Lung apoptosis were assessed by TUNEL assay. Lung myeloperoxidase, SOD and catalase were measured biochemically. When compared to RA group, there was significant reduction in neutrophil CD18 and intracellular oxidant production in the RA+NO group, but lung MPO was unchanged. The O2 and O2+NO groups did not differ in CD18 expression or in intracellular oxidant production, but had significant increase in lung myeloperoxidase compared to the RA group. Apoptosis increased significantly only in the O2+NO group. The O2 group showed significantly increased lung SOD and catalase activity compared to the RA group, whereas the RA+NO and O2+NO groups did not. We conclude that inhaled NO at 50 ppm decreases neutrophil CD18 expression as well as intracellular oxidant production. However, this effect does not impact lung neutrophil accumulation during concurrent hyperoxia. The combination of NO and O2 exposure produces an increase in lung apoptosis. Finally, NO may prevent upregulation of SOD and catalase activity during hyperoxia, potentially increasing injury.

Cerebral vasculitis in acute post-streptococcal glomerulonephritis

Neurological complications in acute post-streptococcal glomerulonephritis (APSGN) have been traditionally attributed to hypertensive encephalopathy. A 9-year-old girl with biopsy-documented APSGN developed seizures at a time she was normotensive and biochemically well balanced. Computed tomography of her brain was consistent with vasculitis, a finding which was also clinically supported by apparent vasculitic involvement of other organ systems. All clinical, laboratory and radiological abnormalities resolved with recovery from the APSGN. We suggest that on rare occasions neurological complications in APSGN may result from involvement of the central nervous system in multiorgan transient vasculitis.

Grasp biopsy, suction biopsy, and clinical history in the evaluation of esophagitis in infants 0-6 months of age

Fifty-three infants 0–6 months of age with abnormal 24-h intraesophageal pH monitoring were evaluated by esophageal suction biopsies and endoscopic grasp biopsies. Histologic esophagitis was present in 30% of the infants. Of the infants with esophagitis, 88% were accurately identified by suction biopsy, and 75% were accurately identified by endoscopic grasp biopsy. Suction biopsy alone was not significantly different from combined grasp and suction biopsy, while differences between grasp biopsy and combined biopsy approached significance (p = 0.051). Twelve clinical symptoms and 21 intraesophageal pH monitoring parameters were evaluated for their ability to predict esophagitis, and none were found to be useful. We conclude that endoscopic esophageal biopsy, while more costly, offers no advantage over suction biopsy for the detection of esophagitis in young infants.

Renal-pancreatic-hepatic dysplasia in siblings

Fewer than 20 children with complete renal-pancreatic-hepatic dysplasia have been reported since first described in 1959. We report two brothers with renal-pancreatic-hepatic dysplasia, one of whom had hypertrophic cardiomyopathy and pancreatic exocrine insufficiency, previously unreported associated findings.

Comparison Between Flow Cytometric and Cytogenetic Tumor Cell DNA Content Using a Simple Flow Sample Preparation Method: Ploidy Comparison of 86 Fresh Pediatric Tumors

A comparison of tumor ploidy by flow cytometry (FL) and cytogenetics (CYG) was made in 86 fresh pediatric solid (n = 47) and hematopoietic (n = 39) tumors using simple sampling and semiautomated proprietary FL preparation methods and defined histogram interpretive criteria. Tumor karyotypes with 44-48 chromosomes were regarded as CYG diploid and other chromosomal complements CYG aneuploid for comparison purposes. Five histograms were uninterpretable and nine cases failed to produce 15 or more metaphases for karyotyping. Mean G0/G1 peak coefficients of variation of all 86 cases were 2.7 and 3.0 for the diploid and aneuploid populations, respectively. Of the 72 eligible cases, 41 were concordant diploid and 16 concordant aneuploid with an overall concordance of 79%. The DNA index and karyotypic index correlation coefficient was 0.92 for the 16 concordant aneuploid cases. Analysis of the 15 discordant cases highlights the limitations of both methods and of the histogram interpretive criteria and indicates that FL is probably more sensitive for detection of tumor aneuploidy as defined and detected by these methods.

The Interrelationship of Hyperoxia and Nitric Oxide on the Neutrophil CD18 Receptor and Lung Myeloperoxidase in Piglets |[diams]| 1647

Nitric oxide (NO) down regulates the neutrophil CD18 receptor and is purported to decrease lung inflammation. However, in clinical situations, NO is used in the presence of oxygen (O2), a lung inflammatory gas.