North American Journal of Medicine and Science
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Biomarkers of Abnormal Energy Metabolism in Children with Autism Spectrum Disorder
Get PDFBiomarkers of mitochondrial disease were studies in 133 consecutive autism spectrum disorder patients to determine the prevalence of abnormalities in biomarkers of mitochondrial disease. Biomarkers included traditional biomarkers of mitochondrial disease (lactate, alanine), fatty-acid oxidation defects (acyl-carnitine panel) and recently described novel biomarkers of detecting mitochondrial dysfunction in individuals with autism spectrum disorder (alanine-to-lysine ratio, creatine kinase, aspartate transaminase). Biomarkers were collected in the morning fasting state. Abnormal biomarker values were verified by repeat testing. For those with abnormal acyl-carnitine panels, secondary disorders of fatty acid metabolism were ruled out. Abnormalities in lactate, alanine-to-lysine ratio and acyl-carnitine panels occurred in over 30% of children on initial testing. Among the patients with abnormal biomarkers who had repeated testing, abnormalities were confirmed about half of the time except for alanine which was only confirmed 20% of the time. Elevation in alanine-to-lysine ratio was associated with epilepsy and elevation in multiple acyl-carnitines was associated with regression. In order to confirm the significance of certain biomarkers, a wide variety of mitochondrial biomarker values were compared between specific subgroups of children with abnormal biomarkers and matched children without any abnormalities in biomarkers. Lactate, alanine-to-lysine ratio and acyl-carnitine panel groups demonstrated abnormalities in multiple mitochondrial biomarkers, confirming the validity of these biomarkers of mitochondrial dysfunction. This study demonstrates that multiple biomarkers of mitochondrial dysfunction are elevated in a significant portion of children with autism spectrum disorder and lend support to the notion that disorders of energy production may affect a significant subset of children with autism
The Advances in Molecular Biology of Hepatoblastoma: Implications for Diagnostic Pathology
Get PDFAs the most common pediatric liver malignancy, hepatoblastoma (HB) accounts for more than 90% of primary hepatic malignant tumors in children less than five years of age in the US, and its incidence has been increasing in the past decades. Despite extensive studies, the pathogenesis of HB remains to be elucidated. Multiple signaling pathways may be involved in the oncogenic process of HB. The best characterized pathways include the canonical Wnt/beta-catenin pathway, the hepatocyte growth factor (HGF)/c-Met signaling pathway, the Notch pathway and the Hedgehog pathway. In addition, signaling molecules associated with these signaling pathways have been shown to be potential novel tumor markers for HB. Preoperative chemotherapy is the current standard of care for HB. Highly sensitive and specific tumor markers are not only important for the accurate diagnosis of HB but are also essential for predicting its clinical behaviors and prognosis. This review summarizes the recent advances in the molecular aspects of HB with a focus on the pathogenic signaling pathways and tumor markers. Their implications for diagnostics and prognostics are also discussed from a pathologist’s point of view
Antipsychotics Medication Use and its Metabolic Challenges for Autism Spectrum Disorders
Get PDFThere has been a growth in the knowledge about autism and autism spectrum disorders (ASD) in the United States and worldwide. As the prevalence rates have grown, so has the awareness of the need to develop effective and safe treatments for children with ASD. In addition to the behavioral interventions such as applied behavioral analysis, parent training, and adaptive skills training, there has been an increase in the use of medications for the treatment of ASD symptoms. At this time, there are two antipsychotics approved by the FDA for the use in children with ASD, risperidone and aripiprazol. Generally, the use of this classification has been more recently associated with changes in metabolic function in children. The purpose of this article is to review briefly the use of psychotropic medications, focusing on antipsychotics, and discuss the metabolic risks and risk factors associated with their use within children with autism
Simultaneous Therapeutic Plasma Exchange in Parallel with Cardiopulmonary Bypass for Prevention of HLA-Antibody Mediated Rejection in a Pediatric Double-Transplant Patient
Get PDFTherapeutic plasma exchange (TPE) has been used peri-operatively to prevent antibody-mediated rejection (AMR) in pre-sensitized solid organ transplant patients. Intraoperative TPE during cardiopulmonary bypass (CPB) has been reported in neonates receiving ABO-incompatible cardiac transplants, as well as in adults undergoing cardiac surgery. To our knowledge, intraoperative TPE in parallel with CPB (TPE-CPB) for prevention of human leukocyte antigen (HLA)-AMR has not been reported in pediatric cardiac transplantation. A 13 year old female with dilated cardiomyopathy, status post orthotopic cardiac transplant at 5 months of age, presented for cardiac re-transplantation due to end-stage heart failure and renal transplantation for end stage renal disease. Histocompatibility testing was weakly positive for antibodies to HLA-DQ6, with weakly positive donor crossmatch. In order to minimize ischemic time of the donor heart, TPE was performed while on CPB, immediately prior to cardiac transplantation. Apheresis machine access and return lines were connected via stopcocks to the CPB via proximal and distal ports, respectively, on the venous/low pressure side of the CPB circuit, before the CPB pump and oxygenator. The apheresis access line pressure alarm was set to 10 mm Hg less than the CPB pump pressure, to avoid pressure alarms and apheresis pump shutdown. The procedure was well tolerated, without complications. The subsequent renal transplant was uneventful. Post-operatively, no AMR was seen, and the patient continues to have good cardiac and renal function. Intraoperative TPE-CPB is feasible and safe, and may be considered for reduction of HLA antibody level immediately prior to cardiac transplantation in pediatric patients.
Solitary Intracranial Plasmacytoma Located in the Clivus: A Diagnostic and Theraputic Challenge
Get PDFSolitary intracranial plasmacytoma (SIP) is a rare entity. To date, only 20 cases of SIP have been reported in English literature. Occasionally, SIP is comprised of atypical plasma cells which may not be plasma cell-appearing at all. As a result, pathologic diagnosis is extremely challenging, especially on frozen sections. A recent case demonstrating this profile is reported here. The patient was a 40-year-old white male who originally presented with diplopia. MRI revealed an enhancing non-infiltrating mass (5 x 4 x 3 cm) within the clivus. A transnasal endoscopic biopsy was done. Frozen sections showed sheets of pleomorphic cells with abundant eosinophilic cytoplasm and round/oval nuclei with stippled chromatin. On touch prep, naked nuclei with homogenous/salt and pepper chromatin, mild crush artifacts and rare plasmacytoid cells were noted. A frozen section diagnosis of "unclassified neoplasm, defer to permanent sections" was made. Immunohistochemical analysis on permanent sections showed that tumor cells were positive for CD138, CD56, kappa light chain, BCL-1 and negative for chromogranin A and lambda light chain. The Ki67 proliferation index was 5-10%. The immunostaining pattern was consistent with plasmacytoma. A subsequent complete work up for systemic disease revealed normal bone marrow biopsy, normal flow cytometry, and negative skeletal survey. The patient did have a serum M-spike of 0.75 g/dL but his quantitative immunoglobulins, kappa or lamda free light chains and beta-2 microglobulin were within normal limits. The patient was treated by radiation therapy accompanied by high-dose dexamethasone. However, four months post-radiation, repeat MRI showed a similar mass in the same area. His serum M-spike had dropped to 0.3 g/dL during his radiation therapy, but persisted at this level subsequently. The diagnosis of persistent residual plasmacytoma was reached. The patient underwent gamma knife radiosurgery and tolerated the procedure well. This case demonstrated that SIP should be considered as one of the differential diagnoses for intracranial tumor of unknown origin
Factors Associated with Colorectal Cancer Screening Among Cambodians, Vietnamese, Koreans and Chinese Living in the United States
Get PDFThe purpose of this community-based participatory study was to identify factors associated with colorectal cancer (CRC) screening compliance and non-compliance among Cambodians, Vietnamese, Koreans and Chinese men and women 50 years and older living in the United States. A cross-sectional design was used in the study. The completed sample included 815 Asian Americans which included Cambodians (N=215), Vietnamese (N=195), Koreans (N=94) and Chinese (N=311). A 95-item questionnaire was developed and pilot tested for content validity and reliability. An in-person data collection approach was utilized and participants were given choice in responding in English or their native language. Of the 815 participants, 79.1% (N=645) reported never-screened, 7.9% (N=64), non-compliance, and 13.0% (N=106) compliance. Education was significantly associated with never-screened for CRC for Vietnamese and Chinese; employment status for Cambodians and Koreans; lack of health insurance for Cambodians, Korean and Chinese; English fluency and years lived in the U.S. for Vietnamese, Koreans, and Chinese. Less acculturated Asian Americans were more likely to be never screened, but differentially across ethnic subgroups. Barriers to screening included lack of knowledge, language, transportation, and time. Increased culturally-targeted public awareness and education programs are needed to improve CRC screening and compliance among high risk Asian American ethnic subgroups.
Weekly Biological Variability of Urinary Organic Acids
Get PDFUse of LC-MS/MS methods has improved sample preparation and increased throughput for the measurement of 40 or more organic acids in urine. In order to assess the significance of abnormalities that might be attributed to nutritional inadequacies or other metabolic disturbances, the week-to-week variation of results due to normal physiological responses needs to be established. This study determined the biological variability for 37 organic acids plus hippuric acid, D-arabinitol and 8-hydroxy-2’-deoxyguanosine in overnight urine specimens from eight weekly samples submitted by 22 healthy adults. For the 40 analytes, CVb values varied from 12.3 to 74.3. Fourteen of the analytes had CVb values less than 30 and another 19 of them were less than 50. Multiple analytes displayed the property of increasing variability with concentration that may be characteristic of most intermediary metabolites. Linear regression line slopes for CVb vs. concentration were tabulated to assist the use of this information. The 40 analytes display biological variability in the range of disease risk markers such as serum lipoprotein cholesterol concentrations, cancer markers and thyroid hormones. The likelihood of a single measurement being representative of the true mean concentration varies with the analyte and the level found. Data reported here demonstrate reliability of results of urinary organic acid profiling performed under the reported analytical conditions
Accuracy of Touch Preparation versus Frozen Section for Intraoperative Diagnosis of Sentinel Lymph Node Metastases in Breast Cancer with Emphasis on Micrometastases
Get PDFThe sensitivity of intraoperative diagnosis of sentinel lymph node (SLN) metastases in breast cancer is variably low. The purpose of this study was to review the pros and cons of frozen section (FS) and touch preparation (TP) methods, particularly in micrometastases. Intraoperative TP or FS was performed on the SLN of consecutive breast cancer patients from 2007 to 2009. Sensitivity, specificity, and overall accuracy of detecting positive SLNs were calculated for FS and TP groups. There were 396 patients with SLN biopsy. 124 (31.3 %) patients had at least one positive SLN. A total of 1270 lymph nodes were examined intraoperatively, 133 with FS and 1137 with TP. FS was significantly more sensitive than TP, 82.6% and 49.6%, respectively (p<0.0001). There were a total of 57 SLNs with micrometastases. FS was performed on 10 and TP on 47. The sensitivity of FS was 50% and for TP, 19.3% (p<0.0001). Of the 10 positive SLNs using FS, 3 were negative on permanent sections (PS). We conclude that FS is superior to TP as a method of detecting micrometastases in SLNs. However, a significant subset of patients who had positive SLNs on FS became negative on PS. This raises the possibility that some negative SLNs on FS might have been understaged.
Primary Adrenal Leiomyosarcoma: Case Report and Review of Literature
Get PDFPrimary adrenal leiomyosarcomas are rare and usually symptomatic at presentation. The presentation of a large adrenal mass should raise suspicion of adrenal leiomyosarcoma as a differential diagnosis. To our knowledge, primary adrenal leiomyosarcoma has been reported in 20 cases in the English literature. Here we describe a case of primary adrenal leiomyosarcoma in a 76-year-old Caucasian female. The patient complained of right upper quadrant abdominal pain for 2 months. Contrast-enhanced magnetic resonance imaging showed a heterogeneous 10.5 cm adrenal mass with a suspected inferior vena cava tumor thrombus without lymph node enlargement or distant metastasis. The patient underwent a right adrenalectomy, partial resection of the inferior vena cava and reconstruction of the inferior vena cava with a pericardial patch. Histopathologic examination was consistent with leiomyosarcoma. At 3 months postoperatively, a follow-up computed tomography scan of the chest, abdomen and pelvis without intravenous contrast was done that showed multiple bilateral pulmonary metastatic lesions, bilateral hilar and mediastinal lymphadenopathy, liver metastasis, a new mass at the head of the pancreas, and a new mass at the lower pole of the right kidney. The patient was deemed to be unfit for systemic chemotherapy, and was referred to the hospice service for palliative care. The patient died 4 months after surgery.
Recent Advances in Renal Cell Carcinoma Associated with Xp11.2 Translocations/TFE Gene Fusions
Get PDFRenal cell carcinoma associated with Xp11.2 translocations/TFE gene fusions (Xp11.2 RCC) has been classified as a distinct entity in the 2004 WHO classification of kidney tumors. Over the past seven years, aided by increased awareness, positive nuclear staining for TFE3, unique cytogenetic features, and modern molecular technology, more cases have been recognized as Xp11.2 RCC. This review summarizes the most recent advances in Xp11.2 RCC regarding to its clinical presentation, cytogenetic profile, histopathology, prognosis and treatment