Neutrophilic panniculitis with myelodysplastic syndromes presenting as pustulosis: case report and review of the literature

Neutrophilic panniculitis associated with myelodysplastic syndromes is rare. We report a 59-year-old patient who initially was diagnosed with myelodysplastic syndrome (MDS) and developed a sudden onset of widespread pustulosis and erythematous indurated papules. Examination of skin biopsies of a papule lesion showed dense neutrophilic infiltration limited to the subcutaneous tissue. The pustules and papules disappeared completely after treatment with systemic corticosteroids. To our knowledge, only one patient was identified by MEDLINE search of the English-language literature.     

ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease

Tandem mass spectrometry was applied to detect derangements in the pathways of amino acid and fatty acid metabolism in N-ethyl-N-nitrosourea-treated (ENU-treated) mice. We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria, and clinical features resembling human maple syrup urine disease (MSUD), a severe genetic metabolic disorder caused by the deficiency of branched-chain alpha-keto acid dehydrogenase (BCKD) complex. However, the BCKD genes and enzyme activity were normal. Sequencing of branched-chain aminotransferase genes (Bcat) showed no mutation in the cytoplasmic isoform (Bcat-1) but revealed a homozygous splice site mutation in the mitochondrial isoform (Bcat-2). The mutation caused a deletion of exon 2, a marked decrease in Bcat-2 mRNA, and a deficiency in both BCAT-2 protein and its enzyme activity. Affected mice responded to a BCAA-restricted diet with amelioration of the clinical symptoms and normalization of the amino acid pattern. We conclude that BCAT-2 deficiency in the mouse can cause a disease that mimics human MSUD. These mice provide an important animal model for study of BCAA metabolism and its toxicity. Metabolomics-guided screening, coupled with ENU mutagenesis, is a powerful approach in uncovering novel enzyme deficiencies and recognizing important pathways of genetic metabolic disorders.     

Estimating the input function non-invasively for FDG-PET quantification with multiple linear regression analysis: simulation and verification with in vivo data

A novel statistical method, namely Regression-Estimated Input Function (REIF), is proposed in this study for the purpose of non-invasive estimation of the input function for fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) quantitative analysis. We collected 44 patients who had undergone a blood sampling procedure during their FDG-PET scans. First, we generated tissue time-activity curves of the grey matter and the whole brain with a segmentation technique for every subject. Summations of different intervals of these two curves were used as a feature vector, which also included the net injection dose. Multiple linear regression analysis was then applied to find the correlation between the input function and the feature vector. After a simulation study with in vivo data, the data of 29 patients were applied to calculate the regression coefficients, which were then used to estimate the input functions of the other 15 subjects. Comparing the estimated input functions with the corresponding real input functions, the averaged error percentages of the area under the curve and the cerebral metabolic rate of glucose (CMRGlc) were 12.13±8.85 and 16.60±9.61, respectively. Regression analysis of the CMRGlc values derived from the real and estimated input functions revealed a high correlation (r=0.91). No significant difference was found between the real CMRGlc and that derived from our regression-estimated input function (Students t test, P>0.05). The proposed REIF method demonstrated good abilities for input function and CMRGlc estimation, and represents a reliable replacement for the blood sampling procedures in FDG-PET quantification.     

Effects of X-ray radiation on the rheologic properties of platelets and lymphocytes

BACKGROUND: Blood is often irradiated before transfusion for severely immunocompromised patients to prevent a potentially fatal complication of transfusion-associated GVHD. STUDY DESIGN AND METHODS: This study evaluates the effects of X-ray radiation on platelet and lymphocyte rheology because the ability of these blood cells to deform is vital to their flow throughout the microvascular system. Micropipette aspiration experiments were conducted on platelets and lymphocytes exposed to X-ray radiation doses of 0 (control), 25, and 50 Gy. RESULTS: A significant increase in the Young modulus of elasticity was observed between control platelets and irradiated platelets at 25 Gy (p = 0.02) and 50 Gy (p = 0.03). Percent cell activation increased significantly in 25 Gy-irradiated platelets (p = 0.008). In addition, lymphocytes irradiated at 25 Gy have a higher viscosity than controls (p < 0.02). A significantly larger number of activated cells is found in the 50 Gy-irradiated lymphocyte population (p < 0.04). CONCLUSION: The changes in the deformability and activation of irradiated platelets and lymphocytes may reduce local blood flow and lead to intermittent blockage, which may cause a change of blood flow in microvasculatures.     

A prospective study characterizing full-length hepatitis B virus genomes during acute exacerbation

BACKGROUND & AIMS: Hepatitis B virus (HBV) evolves rapidly in patients with chronic hepatitis B, and HBV variation may trigger acute exacerbation. To study this relationship, we investigated full-length viral sequences before, during, and after exacerbation. METHODS: We prospectively studied 14 patients with exacerbation of hepatitis B, either spontaneously (n = 4) or after receiving various medical interventions (n = 10), and measured their serum alanine aminotransferase (ALT) and HBV DNA levels monthly. Full-length HBV genomes at baseline, at the peak of serum viral load, at ALT peak, and after ALT peak were obtained by polymerase chain reaction, sequenced, and compared. Replication activities of serial HBV variants were assayed by in vitro transfection. RESULTS: Serum viral load was increased in all exacerbations. Viral peak preceded ALT peak in 13 (93%) of the 14 patients. At virologic peak, 12 patients (86%) harbored viral genome identical to the corresponding baseline genome. At and after ALT peak, 9 (64%) and 7 (50%) of the viral genomes remained identical to baseline, respectively. Mean nucleotide change per genome was 0.2 at virologic peak but increased to 4.4 and 8.1 at and after ALT peak, respectively. The replication potential of the viral variant that emerged during or after exacerbation was equivalent to that at baseline. CONCLUSIONS: Most exacerbations were preceded by an upsurge of serum HBV identical to the preexisting HBV strain. After exacerbation, about half of the patients were repopulated by a different viral variant, which was likely a result of immune selection.