Crohn's Disease Presenting as Metabolic Myopathy: A Case Report.

Myopathies associated with systemic diseases results from several different disease processes. Myopathy as the initial presenting symptom in Crohn's disease is a rare presentation. We report a 20-yearr-old lady who presented with a painful proximal myopathy. On examination, she was malnourished with pallor, angular cheilitis, Bitots spots, and bilateral pitting pedal edema. Laboratory evaluation showed iron deficiency anemia, hypoalbuminemia, and very low vitamin D levels with elevated creatine phosphokinase levels. A possibility of osteomalacic metabolic myopathy due to vitamin D deficiency was considered. The malabsorption workup was negative. A colonoscopic biopsy showed noncaseating granulomatous inflammation suggestive of Crohn's disease. With supplementary therapy and specific treatment, she was asymptomatic at 6-months follow-up with no residual neurological deficits. A detailed history and an algorithmic approach will be very useful in making the differential diagnosis in any patient presenting with muscle weakness in myopathy associated with systemic illness.

Seronegative limbic encephalitis in association with Sjögren's syndrome: a rare case report.

Limbic encephalitis is often due to an autoimmune or paraneoplastic disease and is always a diagnostic challenge. We report a 31-year-old lady who presented with fever and proximal weakness to start with and afterwards developed refractory focal onset seizures and worsening cognition despite optimum treatment. Evaluation revealed hypokalemia with a normal anion gap metabolic acidosis. Magnetic resonance imaging (MRI) brain showed features of limbic encephalitis. Cerebrospinal fluid (CSF) showed lymphocytosis and CSF autoimmune, paraneoplastic and viral encephalitis panel were negative. However a blood ANA profile clinched the diagnosis when SS-A and Ro 52 were strongly positive. She was given steroids and subsequently plasma exchange. A labial gland biopsy confirmed the diagnosis of Sjögren syndrome. In cases of autoimmune limbic encephalitis with no identifiable cause, serological screening for rheumatological disorders is recommended. Sjögren syndrome is a rare aetiology for autoimmune limbic encephalitis. A detailed history and a step wise approach is always the key to the right diagnosis.

El-MAVEN: A Fast, Robust, and User-Friendly Mass Spectrometry Data Processing Engine for Metabolomics.

Analysis of large metabolomic datasets is becoming commonplace with the increased realization of the role that metabolites play in biology and pathophysiology. While there are many open-source analysis tools to extract peaks from liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and tandem mass spectrometry (LC-MS/MS) data, these tools are not very interactive and are suboptimal when a large number of samples are to be analyzed. El-MAVEN is an open-source analysis platform that extends MAVEN and provides fast, powerful, and interactive analysis capabilities especially for datasets containing over 100 samples. The El-MAVEN workflow is easy to use with just four steps from loading data to exporting of the results. Advanced analysis and software techniques such as multiprocessing, machine learning, and reduction of memory leaks are implemented so as to provide a seamless and interactive user experience. Results from El-MAVEN can be exported in a range of formats allowing continued analysis on other platforms. Additionally, El-MAVEN is also fully integrated with Polly™, a cloud-based analysis platform that provides a range of tools for flux analysis and integrative-omics analysis. El-MAVEN is a powerful tool that enables fast and efficient analysis of large metabolomic datasets to accelerate the process of gaining insight from raw data.

Mass spectrometric and physiological validation of a sensitive, automated, direct immunoassay for serum estradiol using the Architect.

BACKGROUND: Measurement of estradiol (E(2)) plays a critical role in the diagnosis and clinical management of reproductive disorders. The challenge for all currently available direct methods for measuring E(2) is to provide accuracy and precision across a wide dynamic range. METHODS: We describe the development and multi-site performance evaluation of a direct E(2) assay on the Architect i2000. Assay performance and method comparisons were performed by testing specimens from men, healthy women with regular menstrual cycles, and post-menopausal women using the Architect assay and isotope dilution, gas chromatography-mass spectrometry (ID/GC-MS). Reference intervals were established by testing prospectively collected daily blood draws from 42 healthy women, 72 postmenopausal women and 101 males. RESULTS: No unexpected cross-reactivity or interference was observed for over 40 compounds tested. Recovery was 100+/-10% in the presence of estrone and estriol. Functional sensitivity (%CV<20%) was <15 pg/ml.(1) The imprecision of the assay was <7.1% (total CV), <2.5%, and <2.3% for control sera containing 45, 190, and 600 pg/ml estradiol, respectively. The assay had a correlation of y=1.033 x+0.3156, r(2)=0.99, n=131 compared to ID/GC-MS. Reference intervals for the current Architect Estradiol assay are reported. CONCLUSIONS: Format changes resulted in dramatic improvement in the performance and accuracy of this direct, fully automated assay. The assay is standardized by ID/GC-MS. The assay is clinically useful for serum concentrations from 15 to >4000 pg/ml.

Millions of missing girls: from fetal sexing to high technology sex selection in India.

The morality and acceptability of using prenatal diagnosis for sex selection is being extensively debated around the world as advances in assisted reproductive technologies (ART) and embryology have enabled selective implantation of embryos of the desired sex (George and Dahiya, 1998; Savulescu, 1999; Raphael, 2002; Harris, 2005; Robertson, 2005; Snider, 2005). Sophisticated methods of separation of semen, originally developed for cattle breeding, are being used for human sex selection. Recently, non-invasive methods of fetal sex determination in the first trimester (from 6 weeks) of pregnancy have also emerged (Hahn and Chitty, 2005). Market forces that promote sex selection along with libertarian ideologues have assisted in blurring the ethical limits (Paul, 2001; President's Council on Bioethics, 2003). The widespread misuse of sex selection for eliminating girls before birth in India and among the Indian diaspora needs to be brought into the global 'intellectual discourse'. It is imperative that Western ethicists recognize the genocidal nature of sex selection taking place in certain Asian countries. Even if they believe that these trends will not affect mainstream Western societies, the promotion or tolerance of sex selection amounts to a 'crime of silence' against this ongoing genocide in China and India. I have been concerned with issues of the girl child in India for over two decades and sex selection among Asian Indians in North America (George et al., 1992; George et al., 1993; George and Dahiya, 1998). This article examines the missing millions of girls, but will not consider the 1980s campaign against fetal sex determination, Indian feminists' recognition of sex selection as violence against women (unlike several Western feminists, Moazam, 2004), or the Government's response to regulate prenatal diagnostic techniques in 1994 (George and Dahiya, 1998; George, 2002).

Changes in glutathione, glutathione-linked enzymes and hexose monophosphate shunt enzymes in senile cataract.

Changes in glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GSH-R), reduced glutathione (GSH), glutathione peroxidase (GSH-PO), transketolase (TK) and transaldolase (TA) were studied in lens and red blood cells (RBCs) to understand the possible biochemical mechanisms responsible for the development of senile cataract. The activity of G-6-PD was increased in lens, though not so in erythrocytes during cataractogenesis. A marked decrease was observed in GSH level and GSH-R activity in the lens and RBCs of the cataractous group. The activity of GSH-PO was remarkably high in lens but not in the erythrocytes during the maturity of cataract. The activity of TK decreased gradually in both the lens and erythrocytes. The activity of TA decreased in erythrocytes but increased in the lens with maturation of cataract.

Gastric Dysmotility and Gastroparesis.

Nutrition support in gastroparesis begins with encouraging smaller volume, low-fat, low-fiber meals and, if necessary, liquid caloric supplements. There should be a low threshold for placing a jejunal feeding tube either by laparoscopy or mini-laparotomy. Parenteral nutrition should be used only briefly during hospitalization and not encouraged or sustained as an outpatient. Metoclopramide is now the prokinetic of choice for patients who can tolerate this agent; subcutaneous administration is an important method that allows for continued guaranteed absorption. Low-dosage erythromycin also has a prokinetic role alone or in combination with metoclopramide. Domperidone, a centrally acting antiemetic and prokinetic, is only be available to US citizens who can access sources in Canada or Mexico. Antiemetics should be used extensively because nausea is a very severe debilitating symptom, which is under-appreciated and under-treated by physicians. We recommend scopolamine patches to gain maximal absorption, in spite of vomiting and unpredictable oral intakes. The 5-hydroxytryptamine-3 (5-HT3) antagonists ondansetron and granisetron are the most powerful agents. Relief bands using the P6 acupuncture point are useful adjunct. Special vigilance should be paid to situations that can undermine medical therapy or result in breakthrough symptoms, such as hyperglycemic events in patients with diabetes, migraine headaches, cyclic nausea and vomiting, menstrual cycles, rumination syndrome (psychogenic vomiting), and elevated herpes simplex titers. Most excitingly, the era of gastric electrical stimulation has arrived for patients not responding to standard medical therapy. The dramatic improvement in nausea and vomiting, as well as a sustained evidence of improved quality of life, gastric emptying, nutritional status, and decreased hospitalizations by this device are documented by long-term follow-up of more than a year for patients in this country and world-wide.