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My scholarly pursuits are primarily focused on the study of death and disease in the pediatric population. Most notably to characterize pediatric tumor pathology, evaluate abnormalities of the juvenile reproductive system, demonstrate the histologic and ultrastructural changes of metabolic disorders on specific organs, and elucidate new scientific techniques to aid in the study of childhood disease.1. Ovarian Surface Epithelial Neoplasms:Ovarian cancer is the fifth most common cause of malignancy in adult women; with those involving the surface epithelium of the ovary being the most common. In stark contrast, ovarian neoplasms account for approximately 1% of all childhood malignancies with those affecting the epithelium being extraordinarily rare. It is partially due to their low frequency that little is known about the overall incidence, histologic subtypes, optimal treatment strategies, and natural history of ovarian surface epithelial neoplasms in children.2. Liver Pathology in Mitochondrial DNA Depletion Syndrome: Mitochondrial disorders are rare causes of childhood disease and dysfunction. Syndromes caused by depletion of mitochondrial DNA (mtDNA) are exceptionally rare, but can often cause devastating outcomes. These depletion syndromes are caused by anomalous mtDNA or nuclear DNA encoding for mitochondrial proteins resulting in a quantitative reduction in mtDNA and abnormal oxidative phosphorylation. To date, three genes have been implicated in this process MPV17, polymerase gamma, and deoxyguanosine kinase. In neonates, these abnormalities most often manifest with hepatic and neurologic dysfunction; the hepatocerebral phenotype. Recognition of the clinical signs and symptoms of mitochondrial DNA depletion coupled with the histologic and ultrastructural features can result in early diagnosis and optimal treatment.3. Liver Explant Pathology In Argininosuccinate Lyase Deficiency:Argininosuccinate (ASA) lyase deficiency is the second most common urea cycle disorder in the pediatric population. It manifests in either a neonatal or late onset form with seizures, lethargy, and often hyperammonemia. Due to the risk of cognitive impairment, children are closely followed by monitoring serum ammonia levels and treated with arginine supplementation, dietary restriction, and recently liver transplantation. Characterization of the histologic features of livers in children with ASA lyase deficiency will aid pathologists in providing prompt diagnoses and allow clinicians to impart early therapy before the onset of life threatening complications and cognitive impairment.4. Tissue Microarray Analysis of Small Volume Cellular Suspensions:The use of small volume tissue samples in tissue microarray analysis has been plagued by inefficiency and poor reproducibility. Therefore, tissue samples such as cerebrospinal fluid, pleural fluid, bone marrow aspirates, and fine needle aspirates are often excluded from scientific research. A new technique developed by a team of researchers at Stanford University School of Medicine has made utilization of these low volume tissue samples possible. In fact, this technique can be used to establish diagnoses and confirm other ancillary testing results, such as gene expression arrays.
Efficacy Study of Preconception Treatment of an Asymptomatic Bacterial Infection in an Infertility Population
Bacterial vaginosis (BV) is a common vaginal infection characterized by a pathologic shift in
the normal vaginal flora. BV has been associated with a number of poor reproductive outcomes,
including infertility, preterm labor and premature rupture of membranes. If BV does disrupt
normal embryologic development, then the treatment of BV prior to conception may improve
implantation rates and other pregnancy outcomes in the infertile population.
This is a prospective, randomized, double-blind, placebo-controlled trial in which infertile
women undergoing intrauterine insemination or embryo transfer are screened for BV prior to
treatment. Those patients who screen positive for BV will then be randomized into the
treatment arm(metronidazole 500mg by mouth twice daily for 7 days) or the control arm
(placebo by mouth twice daily for 7 days). The primary outcome, positive pregnancy test rate
(i.e. biochemical pregnancy rate), will then be assessed. Secondary outcomes, such as
clinical pregnancy rate, miscarriage rate, and live birth rate will also be examined.
Stanford is currently not accepting patients for this trial.
For more information, please contact Jamie Massie, MD, 650-498-7408.
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Development of Radiation Free Whole Body Magnetic Resonance (MR) Imaging Technique for Staging Children With Cancer
A research study on the diagnosis of spread of disease for children who have been diagnosed
with solid tumors using a new whole body imaging technique and a new MR contrast agent
(ferumoxytol). Standard tests that are used to determine the extent and possible spread of a
child's disease include magnetic resonance (MR) imaging, computed tomography (CT), Positron
Emission Tomography (PET) as well as bone scanning, and metaiodobenzylguanidine (MIBG)
scanning. The purpose of this study is to determine if newer imaging tests referred to as
whole body diffusion-weighted MR and whole body PET/MR can detect the extent and spread of
the disease as accurately or even better as the standard tests (CT, MR and/or PET/CT). The
advantage of the new imaging test is that it is associated with no or significantly reduced
radiation exposure compared to standard CT and PET/CT imaging tests. The results of whole
body MR and PET/MR will be compared with that of the conventional, standard imaging studies
for tumor detecting.