Fatal Epstein-barr Virus Myocarditis in a Child with Repetitive Myocarditis

Fatal Epstein-Barr virus (EBV) myocarditis occurred in a 9-year-old female with a history of two prior discrete episodes of myocarditis, the first associated with chicken pox and the second of undetermined origin. Serologic studies during the fatal episode were characteristic of acute EBV infection, and EBV genome was detected by polymerase chain reaction (PCR) amplification of DNA extracted from cutopsy heart and liver. PCRs for enteroviruses and cardiac viral culture were negative. An intense mononuclear cell infiltrate in the myocardium consisted entirely of T cells, without identifiable B cells. Human leukocyte antigen HLA-DR analysis using frozen tissue obtained postmortem revealed antigens DR4 and DR13. DR4 is associated with some autoimmune disorders, as well as idiopathic dilated cardiomyopathy. We postulate that an aberrant immune response, possibly associated with the DR4 locus, was responsible for the repetitive episodes of myocarditis in this patient.     

Metastatic Intracranial Chordoma in a Child with Massive Pulmonary Tumor Emboli

A 27-month-old boy of Hispanic background developed multiple cranial nerve palsies, difficulty swallowing, bloody nasal discharge, and irritability. Radiographic evaluations showed extensive destruction of the clivus by a large tumor that invaded the sphenoid bone, left cavernous sinus, ethmoid sinus, nasal cavity, and left orbit. Multiple pulmonary nodules were also noted. The bone marrow and spinal fluid showed no evident tumor cells. Transnasal biopsy revealed a chordoma. Treatment was initiated with a combination of ifosfamide, mesna, and etoposide along with radiation therapy to the cranial tumor. Shifting pulmonary densities were noted on serial films. Despite some clinical improvement, the child developed rapidly progressive hypoxemia 3 weeks after admission and died. Autopsy showed persistent viable tumor in the primary site and massive pulmonary arteriolar tumor emboli, infarcts, and widespread lung parenchymal metastases. No other sites of tumor involvement were discovered. This is the second child reported with intracranial chordoma, pulmonary metastases at diagnosis, and early death attributed to pulmonary tumor emboli.     

Arteriovenous malformation mimicking recurrent medulloblastoma

Magnetic resonance imaging (MRI) is becoming the method of choice for evaluation of central nervous system tumors. However, the sensitivity of this modality raises concern that new lesions in patients previously diagnosed with a brain tumor may not necessarily represent recurrent disease. We report a patient previously treated with surgery, radiotherapy, and chemotherapy for a medulloblastoma who developed a new lesion in the floor of the fourth ventricle. Histologic review following excision revealed an arteriovenous malformation. © 1994 Wiley-Liss, inc.     

Blending Prevention Research and Practice in Schools: Critical Issues and Suggestions

Prevention Science -     

Molecular and pharmacological characterization of genes encoding urotensin-II peptides and their cognate G-protein-coupled receptors from the mouse and monkey

Urotensin-II (U-II) and its receptor (UT) represent novel therapeutic targets for management of a variety of cardiovascular diseases. To test such hypothesis, it will be necessary to develop experimental animal models for the manipulation of U-II/UT receptor system. The goal of this study was to clone mouse and primate preproU-II and UT for pharmacological profiling. Monkey and mouse preproU-II genes were identified to encode 123 and 125 amino acids. Monkey and mouse UT receptors were 389, and 386 amino acids, respectively. Genomic organization of mouse genes showed that the preproU-II has four exons, while the UT receptor has one exon. Although initially viewed by many exclusively as cardiovascular targets, the present study demonstrates expression of mouse and monkey U-II/UT receptor mRNA in extra-vascular tissue including lung, pancreas, skeletal muscle, kidney and liver. Ligand binding studies showed that [125I]h U-II bound to a single sites to the cloned receptors in a saturable/high affinity manner (Kd 654+/-154 and 214+/-65 pM and Bmax of 1011+/-125 and 497+/-68 fmol mg-1 for mouse and monkey UT receptors, respectively). Competition binding analysis demonstrated equipotent, high affinity binding of numerous mammalian, amphibian and piscine U-II isopeptides to these receptors (Ki=0.8 - 3 nM). Fluorescein isothiocyanate (FITC) labelled U-II, bound specifically to HEK-293 cells expressing mouse or monkey UT receptor, confirming cell surface expression of recombinant UT receptor. Exposure of these cells to human U-II resulted in an increase in intracellular [Ca2+] concentrations (EC50 3.2+/-0.8 and 1.1+/-0.3 nM for mouse and monkey UT receptors, respectively) and inositol phosphate (Ip) formation (EC50 7.2+/-1.8 and 0.9+/-0.2 nM for mouse and monkey UT receptors, respectively) consistent with the primary signalling pathway for UT receptor involving phospholipase C activation.     

Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human breast cancer and ovarian cancer xenografts

In cell culture, the compound317615^.2HCl, a potent inhibitor ofVEGF-stimulated HUVEC proliferation, wasnot very effective against MX-1 breastcancer cells (IC₅₀ = 8.1 M) orSKOV-3 ovarian carcinoma cells (IC₅₀ =9.5 M). Exposure to combinations ofpaclitaxel or carboplatin and317615^.2HCl with MX-1 cells in cultureresulted in cell survival that reflectedprimarily additivity of the two agents.Exposure of SKOV-3 cells to paclitaxel orcarboplatin along with 317615^.2HClresulted in cell survivals that reflectedadditivity of 317615^.2HCl withpaclitaxel and greater-than-additivecytotoxicity with carboplatin.Administration of 317615^.2HCl orallytwice daily to nude mice bearingsubcutaneous MX-1 tumors or SKOV-3 tumorsresulted in a decreased number ofintratumoral vessels as determined by CD31and CD105 staining with decreases of 35%and 43% in MX-1 tumors and 60% and 75%in SKOV-3 tumors, respectively.317615^.2HCl was an active antitumoragent against the MX-1 xenograft andincreased the tumor growth delay producedby paclitaxel by 1.7-fold and the tumorgrowth delay produced by carboplatin by3.8-fold. Administration of317615^.2HCl also increased the tumorgrowth delay produced by fractionatedradiation therapy in the MX-1 tumor.Treatment with 317615^.2HCl aloneincreased the lifespan of animals bearingintraperitoneal SKOV-3 xenografts by 1.9fold compared with untreated controlanimals. The combination of paclitaxel and317615^.2HCl resulted in 100% 120-daysurvival of SKOV-3 bearing animals.Administration of 317615^.2HCl alongwith carboplatin to animals bearing theSKOV-3 tumor produced a 1.8-fold increasein lifespan compared with carboplatinalone. 317615^.2HCl is a promising newantiangiogenic agent that is in early phaseclinical testing.     

Prophylactic indomethacin reduces grades III and IV intraventricular hemorrhages when compared to early indomethacin treatment of a patent ductus arteriosus.

OBJECTIVE: To determine the relative risk of severe intraventricular hemorrhage (IVH) between two very early indomethacin treatment strategies. STUDY DESIGN: Retrospective chart review of infants <29 weeks gestation and <1350 g who received either indomethacin prophylaxis or very early echocardiography with indomethacin treatment only if the ductus arteriosus was patent. RESULTS: A total of one hundred and two infants received prophylactic indomethacin (pINDO). Echochardiography was performed on 158 infants, of whom 117 received indomethacin. Infants receiving pINDO had lower gestational age, but similar birth weight, gender, race, antenatal steroid exposure, delivery mode, Apgar scores, and need for resuscitation as infants evaluated by echocardiography. Grades III to IV IVH was observed less frequently in infants who received pINDO (OR 0.27, 95% CI 0.10 to 0.77, p=0.014). Frequency of side effects and recurrent patent ductus arteriosus did not differ between treatment groups. CONCLUSION: pINDO reduces severe IVH when compared to an early echocardiography strategy.