Melena due to telangiectasia in migraine

Migraine is a chronic neurological disorder characterized by headaches and extracephalic symptoms. We report a 73-year-old male patient with a history of migraines as well as several other chronic conditions including abdominal pain accompanied by nausea and vomiting, pain and ecchymosis of the limbs, dysmetropsia, syncope, and melena due to telangiectasia of the sigmoid colon. After a thorough evaluation of the migraine condition, we hypothesized that the patient’s melena due to telangiectasia of the sigmoid colon might in fact be a migraine-related phenomenon. In this report, we discuss a possible mechanism for melena due to telangiectasia in migraine patients, as well as “tips” for identifying subtle and/or unreported clinical features of migraine conditions

Writing Case Reports: Teaching and Tuition Techniques, and the Improvement of Clinical Diagnostic Reasoning

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Structured Didactic Education Program for Writing Case Reports Can Motivate Medical Students

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Ictal high‐frequency oscillations at 80–200 Hz coupled with delta phase in epileptic spasms

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88095/1/j.1528-1167.2011.03263.x.pd

Uncovering Potential Therapeutic Targets in Colorectal Cancer by Deciphering Mutational Status and Expression of Druggable Oncogenes

Numerous driver mutations have been identified in colorectal cancer (CRC), but their relevance to the development of targeted therapies remains elusive. The secondary effects of pathogenic driver mutations on downstream signaling pathways offer a potential approach for the identification of therapeutic targets. We aimed to identify differentially expressed genes as potential drug targets linked to driver mutations.Somatic mutations and the gene expression data of 582 CRC patients were utilized, incorporating the mutational status of 39,916 and the expression levels of 20,500 genes. To uncover candidate targets, the expression levels of various genes in wild-type and mutant cases for the most frequent disruptive mutations were compared with a Mann-Whitney test. A survival analysis was performed in 2100 patients with transcriptomic gene expression data. Up-regulated genes associated with worse survival were filtered for potentially actionable targets. The most significant hits were validated in an independent set of 171 CRC patients.Altogether, 426 disruptive mutation-associated upregulated genes were identified. Among these, 95 were linked to worse recurrence-free survival (RFS). Based on the druggability filter, 37 potentially actionable targets were revealed. We selected seven genes and validated their expression in 171 patient specimens. The best independently validated combinations were DUSP4 (p = 2.6 × 10-12) in ACVR2A mutated (7.7%) patients; BMP4 (p = 1.6 × 10-04) in SOX9 mutated (8.1%) patients; TRIB2 (p = 1.35 × 10-14) in ACVR2A mutated patients; VSIG4 (p = 2.6 × 10-05) in ANK3 mutated (7.6%) patients, and DUSP4 (p = 7.1 × 10-04) in AMER1 mutated (8.2%) patients.The results uncovered potentially druggable genes in colorectal cancer. The identified mutations could enable future patient stratification for targeted therapy

Levetiracetam improves symptoms of multiple chemical sensitivity : Case report

Multiple chemical sensitivity (MCS) is a disorder of unknown etiology with no effective treatment. Many clinicians accept that a diagnosis of somatic symptoms disorder (SSD) is an appropriate diagnostic category for MCS. We found that administration of levetiracetam improved recurrent symptoms of MCS in a patient. A 23-year-old female presented with recurrent multiple symptoms of musculoskeletal, airway or mucous membrane, heart/chest-related, gastrointestinal, cognitive, affective, neuromuscular, head-related, and skinrelated induced by exposure to diesel or gas engine exhaust, tobacco smoke, insecticide, gasoline, paint or paint thinner, cleaning products, fragrances, tar or asphalt, nail polish or hairspray, and new furnishings. Gastrointestinal, cognitive, and skin-related symptoms were precipitated by some food additives. She suffered partial seizures from the age of 17 years, and was diagnosed with right parietal lobe epilepsy. Administration of levetiracetam (250 mg/day) eliminated her MCS symptoms. Levetiracetam reduces the release of presynaptic neurotransmitter including glutamate by binding to presynaptic vesicle protein. A recent study established the presence of glutamatergic overactivation in somatization disorder, a form of SSD. Our case may indicate that a subset of patients with SSD have glutamatergic overactivation, which levetiracetam can normalize

Ongoing EEG artifact correction using blind source separation

Objective: Analysis of the electroencephalogram (EEG) for epileptic spike and seizure detection or brain-computer interfaces can be severely hampered by the presence of artifacts. The aim of this study is to describe and evaluate a fast automatic algorithm for ongoing correction of artifacts in continuous EEG recordings, which can be applied offline and online. Methods: The automatic algorithm for ongoing correction of artifacts is based on fast blind source separation. It uses a sliding window technique with overlapping epochs and features in the spatial, temporal and frequency domain to detect and correct ocular, cardiac, muscle and powerline artifacts. Results: The approach was validated in an independent evaluation study on publicly available continuous EEG data with 2035 marked artifacts. Validation confirmed that 88% of the artifacts could be removed successfully (ocular: 81%, cardiac: 84%, muscle: 98%, powerline: 100%). It outperformed state-of-the-art algorithms both in terms of artifact reduction rates and computation time. Conclusions: Fast ongoing artifact correction successfully removed a good proportion of artifacts, while preserving most of the EEG signals. Significance: The presented algorithm may be useful for ongoing correction of artifacts, e.g., in online systems for epileptic spike and seizure detection or brain-computer interfaces.Comment: 16 pages, 4 figures, 3 table

Identification of amino acids in antigen-binding site of class II HLA proteins independently associated with hepatitis B vaccine response

Background & aimsGenetic factors in class II human leukocyte antigen (HLA) have been reported to be associated with inter-individual variation in hepatitis B virus (HBV) vaccine response. However, the mechanism underlying the associations remains elusive. In particular, the broad linkage disequilibrium in HLA region complicates the localization of the independent effects of genetic variants. Thus, the present study aimed to identify the most probable causal variations in class II HLA loci involved in the immune response to HBV vaccine.MethodsWe performed a case-control study to assess whether HLA-DRB1, -DQB1, and -DPB1 4-digit alleles were associated with the response to primary HBV vaccination in 574 healthy Japanese students. To identify causative variants, we next assessed independently associated amino acid variants in these loci using conditional logistic regression analysis. Furthermore, to clarify the functional effects of these variants on HLA proteins, we performed computational structural studies.ResultsHLA-DRB1∗01:01, HLA-DRB1∗08:03, HLA-DQB1∗05:01, and HLA-DPB1∗04:02 were significantly associated with sufficient response, whereas HLA-DPB1∗05:01 was associated with poor response. We then identified amino acids independently associated with sufficient response, namely, leucine at position 26 of HLA-DRβ1 and glycine-glycine-proline-methionine at positions 84–87 of HLA-DPβ1. These amino acids were located in antigen-binding pocket 4 of HLA-DR and pocket 1 of HLA-DP, respectively, which are important structures for selective binding of antigenic peptides. In addition, the detected variations in HLA-DP protein were responsible for the differences in the electrostatic potentials of the pocket, which can explain in part the sufficient/poor vaccine responses.ConclusionHLA-DRβ1 position 26 and HLA-DPβ1 positions 84–87 are independently associated with anti-HBs production against HBV vaccine. Our results suggest that HBsAg presentation through these HLA pocket structures plays an important role in the inter-individual variability of HBV vaccination

Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer has significant morbidity and mortality worldwide. Good prognosis relies on an early diagnosis. The purpose of this study was to develop techniques for identifying cancer biomarkers in the serum of patients with pancreatic cancer.</p> <p>Methods</p> <p>Serum samples from five individuals with pancreatic cancer and five individuals without cancer were compared. Highly abundant serum proteins were depleted by immuno-affinity column. Differential protein analysis was performed using 2-dimensional differential in-gel electrophoresis (2D-DIGE).</p> <p>Results</p> <p>Among these protein spots, we found that 16 protein spots were differently expressed between the two mixtures; 8 of these were up-regulated and 8 were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2, which have not previously been implicated in pancreatic cancer, were observed. In an independent series of serum samples from 16 patients with pancreatic cancer and 16 non-cancer-bearing controls, increased levels of mannose-binding lectin 2 and myosin light chain kinase 2 were confirmed by western blot.</p> <p>Conclusions</p> <p>These results suggest that affinity column enrichment and DIGE can be used to identify proteins differentially expressed in serum from pancreatic cancer patients. These two proteins 'mannose-binding lectin 2 and myosin light chain kinase 2' might be potential biomarkers for the diagnosis of the pancreatic cancer.</p

Vascular clamping in liver surgery: physiology, indications and techniques

This article reviews the historical evolution of hepatic vascular clamping and their indications. The anatomic basis for partial and complete vascular clamping will be discussed, as will the rationales of continuous and intermittent vascular clamping