Etanercept Therapy for Psoriasis in a Patient with Numerous Comorbidities

A recent study demonstrated an association between psoriasis and dilated cardiomyopathy. Tumour necrosis factor alpha (TNFα) may be involved in the pathogenesis of dilated cardiomyopathy and therefore, anti-TNFα agents may play a role in the treatment of dilated cardiomyopathy. The case of a 51-year-old woman with severe psoriasis and numerous comorbidities including dilated cardiomyopathy is described. During treatment with etanercept, the patient’s psoriasis improved rapidly without any worsening of her other conditions. Etanercept was safe and effective in the treatment of severe psoriasis in a patient with numerous comorbidities, including dilated cardiomyopathy.     

Accelerator mass spectrometry best practices for accuracy and precision in bioanalytical (14)C measurements

Accelerator mass spectrometers have an energy acceleration and charge exchange between mass definition stages to destroy molecular isobars and allow single ion counting of long-lived isotopes such as (14)C (t?=5370 years.). 'Low' voltage accelerations to 200 kV allow laboratory-sized accelerator mass spectrometers instruments for bioanalytical quantitation of (14)C to 2-3% precision and accuracy in isolated biochemical fractions. After demonstrating this accuracy and precision for our new accelerator mass spectrometer, we discuss the critical aspects of maintaining quantitative accuracy from the defined biological fraction to the accelerator mass spectrometry quantitation. These aspects include sufficient sample mass for routine rapid sample preparation, isotope dilution to assure this mass, isolation of the carbon from other sample combustion gasses and use of high-efficiency biochemical separations. This review seeks to address a bioanalytical audience, who should know that high accuracy data of physiochemical processes within living human subjects are available, as long as a (14)C quantitation can be made indicative of the physiochemistry of interest.     

Surveillance and diagnosis of hepatocellular carcinoma in patients with cirrhosis

Early identification of hepatocellular carcinoma (HCC) is more frequent because of surveillance programs for HCC worldwide. The optimal strategy of surveillance in cirrhosis is a current topical issue. In terms of diagnosis, recent advances in non-invasive imaging technology, including various techniques of harmonic ultrasound, new ultrasound contrast agents, multi-slice helical computed tomography and rapid high quality magnetic resonance, have all improved the accuracy of diagnosis. Consequently the role of liver biopsy in diagnosis of HCC has declined. The imaging diagnosis relies on the hallmark of arterial hypervascularity with portal venous washout. However, with recent advances in genomics and proteomics a great number of potential serum and tissue markers have been identified and are being developed as new candidate markers for both diagnosis and prognosis of hepatocellular carcinoma, and may increase the need for liver biopsy.     

Ganglioglioma arising in a Peutz-Jeghers patient: a case report with molecular implications

The Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder caused by inactivating germline mutations in the serine–threonine kinase gene LKB1, is characterized by mucocutaneous pigmentation, multiple gastrointestinal hamartomatous polyps, and by an increased risk for developing tumors involving several different organs. To date, no brain tumors have been described in PJS patients. In this report, we describe a case of ganglioglioma in a 22-year-old PJS patient. Single-strand conformation polymorphism-Heteroduplex analysis evidenced an abnormal pattern in exon 6 of the LKB1 gene. Sequencing revealed a 821delTinsAC mutation creating a termination codon 29 nucleotides downstream (p.Asn274fsX11). RNA studies showed an out-of-frame LKB1 isoform derived from the wild type allele and generated by exon 4 skipping. Since the LKB1 gene is expressed in the fetal and adult brain, our data would suggest its likely involvement in the pathogenesis of a subset of gangliogliomas.     

Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous disorders characterized by progressive spasticity of the lower limbs. Mutations in the SPG4 gene, which encodes spastin protein, are responsible for up to 45% of autosomal dominant cases. OBJECTIVE: To search for disease-causing mutations in a large series of Italian patients with HSP. DESIGN: Samples of DNA were analyzed by direct sequencing of all exons in SPG4. Samples from a subset of patients were also analyzed by direct sequencing of all exons in SPG3A, SPG6, SPG10, and SPG13. SETTING: Molecular testing facility in Italy. PATIENTS: Sixty unrelated Italian patients with pure (n = 50) and complicated (n = 10) HSP. MAIN OUTCOME MEASURES: Mutations in SPG4, SPG3A, SPG6, SPG10, and SPG13. RESULTS: We identified 12 different mutations, 8 of which were novel, in 13 patients. No mutations of any of the other HSP genes tested were found in 15 patients with sporadic pure HSP who did not have mutations in the SPG4 gene. CONCLUSIONS: The overall rate of mutation in the SPG4 gene within our sample was 22%, rising to 26% when only patients with pure HSP were considered. The negative result obtained in 15 patients without mutations in SPG4 in whom 4 other genes were analyzed (SPG3A, SPG6, SPG10, and SPG13) indicate that these genes are not frequently mutated in sporadic pure HSP.