Hepatitis E Virus Superinfection: an Underrecognized Trigger of Acute Hepatitis B Virus Flare.

Hepatitis E virus (HEV) infection is a significant cause of acute hepatitis in endemic areas, such as parts of Asia, Africa, and Mexico, though HEV prevalence in the United States has been estimated between 6% and 20%. Chronic hepatitis B virus (HBV) infection affects about 1 per 1.4 million people in North America. Although well documented in Asia, HBV flare secondary to HEV superinfection is rarely reported in the United States. Here, we present a case of chronic undiagnosed HBV infection with acute flare secondary to HEV superinfection.

Rural-urban differences in the prevalence of cognitive impairment in independent community-dwelling elderly residents of Ojiya city, Niigata Prefecture, Japan.

BACKGROUND: This study aimed to examine rural-urban differences in the prevalence of cognitive impairment in Japan. METHODS: We targeted 592 residents aged 65 years and older who did not use long-term care insurance services in one rural and two urban areas in Ojiya City, Japan. Of these, 537 (90.7 %) participated in the study. The revised Hasegawa's dementia scale (HDS-R) was used to assess cognitive function, and cognitive impairment was defined as a HDS-R score ≤20. Lifestyle information was obtained through interviews. The prevalence of cognitive impairment was compared according to the levels of predictor variables by odds ratios (ORs) calculated by a logistic regression analysis. RESULTS: Mean age of participants was 75.7 years (SD 7.0). The prevalence of cognitive impairment was 20/239 (8.4 %) in the rural area and 6/298 (2.0 %) in the urban areas, for a total of 26/537 (4.8 %) overall. Men tended to have a higher prevalence of cognitive impairment (P = 0.0628), and age was associated with cognitive impairment (P for trend <0.0001). The rural area had a significantly higher prevalence of cognitive impairment (age- and sex-adjusted OR = 4.04, 95 % CI: 1.54-10.62) than urban areas. This difference was significant after adjusting for other lifestyle factors. CONCLUSIONS: The prevalence of cognitive impairment was higher in the rural area relative to urban areas in Ojiya city. This regional difference suggests the existence of potentially modifiable factors other than lifestyle in relation to cognitive impairment.

Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance.

PURPOSE: Although tyrosine kinase inhibitors have improved survival in advanced gastrointestinal stromal tumor (GIST), complete response is rare and most patients eventually fail the first-line treatment with imatinib. Sunitinib malate is the only approved second-line therapy for patients with imatinib-resistant or imatinib-intolerant GIST. The clinical benefit of sunitinib is genotype-dependent in regards to both primary and secondary mutations, with GIST patients harboring the KIT(AY502-3ins) exon 9 mutation being the most sensitive. EXPERIMENTAL DESIGN: As sunitinib resistance is now emerging, our goal was to investigate mechanisms of progression and to test the efficacy of novel tyrosine kinase inhibitor on these resistant mutants in vitro. N-ethyl-N-nitrosourea mutagenesis of Ba/F3 cells expressing the KIT(AY502-3ins) mutant was used to investigate novel patterns of resistant mutations evolving in the presence of sunitinib. RESULTS: Tumors from patients who developed sunitinib resistance after at least 1 year of radiographic response were analyzed, showing similar findings of a primary KIT(AY502-3ins) mutation and a secondary mutation in the KIT activation loop. Ba/F3 cells expressing these sunitinib-resistant double mutants showed sensitivity to both dasatinib and nilotinib. CONCLUSIONS: Sunitinib resistance in GIST shares similar pathogenetic mechanisms identified in imatinib failure, with acquisition of secondary mutations in the activation domain after an extended initial response to the drug. Moreover, in vitro mutagenesis with or without N-ethyl-N-nitrosourea of Ba/F3 cells expressing KIT(AY502-3ins) showed acquisition of secondary mutations restricted to the second kinase domain of KIT. In contrast, in vitro resistance to imatinib produces a broader spectrum of secondary mutations including mutations in both KIT kinase domains.

Malignant histiocytoses/disseminated histiocytic sarcoma with hemophagocytic syndrome in a patient with mediastinal germ cell tumor.

We describe a case of a 24-year-old man with a large anterior mediastinal mass showing a nonseminomatous germ cell tumor then subsequently developed hemophagocytic syndrome involving the bone marrow and liver. During the course of chemotherapy, he developed profound thrombocytopenia, eccymoses, and bleeding. He had moderate splenomegaly and splenectomy was performed to restore adequate hematologic reserve to permit further chemotherapy. The spleen showed marked erythrophagocytosis and markedly atypical histiocytes consistent with malignant histiocytoses. Atypical histiocytes stained positive for CD68, CD163, CD4, CD45 (LCA), and S-100. Cytogenetics studies were negative for i12p. The patient was refractory to therapy and ultimately died 5 months after diagnosis.

Evaluation of human serum albumin cobalt binding assay for the assessment of myocardial ischemia and myocardial infarction.

BACKGROUND: Clinical diagnoses were correlated with results of a Co(II)-albumin binding assay in 167 patients treated at an emergency department of a health maintenance organization. METHODS: Patients were evaluated as being nonischemic or potentially ischemic through standard coronary disease indicators [creatine kinase (CK), CK-MB, cardiac troponin I, and electrocardiographic findings] and were tested by a Co(II)-albumin binding assay. Samples were tested anonymously, and the study was double-blinded. The sensitivity and specificity of this assay for the detection of ischemia were evaluated by ROC curve analysis. Known Co(II) binding sites on albumin were analyzed by N-terminal amino acid sequencing. RESULTS: The mean absorbance units (ABSU) +/- 2 SD for non-myocardial ischemic and myocardial ischemic individuals measured at 470 nm were 0.43 +/- 0.10 and 0.63 +/- 0.25, respectively (P <0.0001). The area under the ROC curve was 0.95 [95% confidence interval (CI), 0.92-0.99], and at a cutoff value of 0.50 ABSU, sensitivity and specificity were 88% (78-94%) and 94% (86-98%), respectively, suggesting a high distinction between the two groups. When we compared non-acute myocardial infarction (AMI) and AMI ischemic individuals, the area under the ROC curve was 0.66 (95% CI, 0.53-0.79) and was considered a poor discriminator between these two groups. N-Terminal amino acid sequencing data for purified albumin showed normal amino acid residues for six of seven high-ABSU (> or =0.70) individuals and one nonischemic individual tested. However, only one individual with a high ABSU (0.80) had two missing amino acid residues (DA) from the N-terminal region. Clinical diagnosis for this patient did not reveal an ischemic event. CONCLUSIONS: The Co(II)-albumin binding test may serve as a useful diagnostic tool in emergency facilities for the assessment of myocardial ischemia. High and low ABSU were associated with myocardial ischemic individuals and non-myocardial ischemic individuals, respectively. However, the Co(II)-albumin binding was a poor discriminator between ischemic individuals with and without MI.