Case of Chronic Lymphocytic Leukemia with Unusual Chromosome Aberrations

Chronic lymphocytic leukemia is one of the most common leukemias in the western world and consists of many chromosome aberrations. We report the case of a 74-year-old male patient with chronic lymphocytic leukemia with complex variant translocations t(8;22)(q24;q11) and der(8)t(6;8)(p21;p21) identified by chromosome banding analysis and confirmed by fluorescence in situ hybridization analysis of interphase cells. Because of the rarity of these changes, possible molecular mechanisms associated with this karyotype are discussed.     

Reappraisal of the characteristics of glucose abnormalities in patients with chronic hepatitis C infection

OBJECTIVES: There is growing evidence suggesting the mutual link between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the impact of HCV infection on the suite of glucose abnormalities has rarely been investigated. The study aimed to determine the difference regarding the prevalence and the characteristics of glucose abnormalities between chronic hepatitis C (CHC) patients and community-based controls. It also aimed to investigate the related clinical, virological, and histological features of glucose abnormalities in HCV infection.
METHODS: Six hundred eighty-three CHC patients and 515 sex-/age-matched controls were included. Oral glucose tolerance test (OGTT) was performed in 522 CHC patients and 447 controls without known T2DM. Clinical data were assessed upon the different stages of glucose abnormalities based on OGTT results.
RESULTS: The prevalence of normoglycemia, IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively. There was a significant linear trend from normoglycemia to T2DM in terms of age, family history of T2DM, and advanced liver fibrosis in CHC patients. For those CHC patients without fibrosis, the prevalence of glucose abnormalities reached 67.9% high. All CHC patients carried a significantly higher prevalence than controls regarding those aged <65 yr. For those without known DM, there was a 3.5-fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70–4.56, P < 0.001).
CONCLUSIONS: CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested.     

Comparative Efficacy of Intra-Articular Steroid Injection and Distension in Patients With Frozen Shoulder: A Systematic Review and Network Meta-Analysis

Objective

To compare the efficacy of intra-articular (IA) steroid injection and distension in patients with frozen shoulder.

Effects of Wrist Weights on Kinematic and Myographic Movement Characteristics During a Reaching Task in Individuals With Parkinson Disease

Objective

To investigate the kinematic and myographic effects of weighted wrist cuffs on individuals with Parkinson disease (PD) during a reaching task.

GPCR dimerization in brainstem nuclei contributes to the development of hypertension

Background and Purpose

μ-Opioid receptors, pro-opiomelanocortin and pro-enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and μ receptor agonists given to the NTS dose-dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, μ receptors heterodimerize with α_2A-adrenoceptors. We hypothesized that α_2A-adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with μ receptors.

Experimental Approach

We microinjected μ-opioid agonists and antagonists into the NTS of rats and measured changes in BP. Formation of μ receptor/α_2A-adrenoceptor heterodimers was assessed with immunofluorescence and co-immunoprecipitation methods, along with proximity ligation assays.

Key Results

Immunofluorescence staining revealed colocalization of α_2A-adrenoceptors and μ receptors in NTS neurons. Co-immunoprecipitation revealed interactions between α_2A-adrenoceptors and μ receptors. In situ proximity ligation assays confirmed the presence of μ receptor/α_2A-adrenoceptor heterodimers in the NTS. Higher levels of endogenous endomorphin-1 and μ receptor/α_2A-adrenoceptor heterodimers were found in the NTS of hypertensive rats, than in normotensive rats. Microinjection of the μ receptor agonist [D-Ala², MePhe⁴, Gly⁵-ol]-enkephalin (DAMGO), but not that of the α_2A-adrenoceptor agonist guanfacine, into the NTS of normotensive rats increased μ receptor/α_2A-adrenoceptor heterodimer formation and BP elevation. The NO-dependent BP-lowering effect of α_2A-adrenoceptor agonists was blunted following increased formation of μ receptor/α_2A-adrenoceptor heterodimers in the NTS of hypertensive rats and DAMGO-treated normotensive rats.

Conclusions and Implications

Increases in endogenous μ receptor agonists in the NTS induced μ receptor/α_2A-adrenoceptor heterodimer formation and reduced the NO-dependent depressor effect of α_2A-adrenoceptor agonists. This process could contribute to the pathogenesis of hypertension.     

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency in Taiwan

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathic disease in Taiwan. The mass neonatal screening of G6PD deficiency by fluorometric spot test in Taiwan was started with a pilot program in 1984. The nationwide screening was started on July 1, 1987, and a follow-up system comprising of eighteen referral hospitals, including outlying islands, was organized for confirmatory test, medical care and genetic counseling. From July 1987 to December 1997, 2,971,192 heel blood samples collected on filter paper from 1,143 delivery units were screened by four neonatal screening centers. 46,570 cases were confirmed as G6PD deficiency is estimated to be around 2.1% (male 3.1%, female 0.9%) in Taiwan. The coverage rate of neonatal screening was 99% in 1997. To assess the reliability of the confirmatory test, an external quality assurance (QA) program for G6PD assay was developed. Periodically, 3 or 5 lyophilized quality control materials with different activities of G6PD were sent to each referral hospital by speed post delivery in dry ice. From January 1988 to June 1998, 85 QA services were performed. Two hundred and seven (13.5%) abnormal QA results were found, which were attributed to clerk (11.6%), procedural (16.4%), and instrumental errors (47.3%). In aid to confirm G6PD deficiency, a method to detect the G6PD mutation by using the dried blood samples was developed. The frequencies of the mutant alleles in Taiwan were determined to be 46.8% (1376G > T), 16.2% (1388G > A), 7.9% (95A > G), 6.5% (493A > G), 5.6% (392G >T), 4.6% (1024C > T), 0.5% (487G > A) and 0.5% (519C > G), respectively.     

Virus reactivation in high-risk non-Hodgkin’s lymphoma patients after autologous CD34+-selected peripheral blood progenitor cell transplantation

CD34⁺-selected peripheral blood progenitor cells (PBPCs) may not only reduce contaminated tumor cells but also compromise immunologic reconstitution and increase incidence of infections after transplantation. We analyzed the incidence of virus reactivation in CD34⁺-selected PBPCs autologous transplantation. From December 2001 to December 2004, ten high-risk aggressive non-Hodgkin’s lymphoma (NHL) patients were enrolled in a program of high-dose chemotherapy plus autologous CD34⁺-selected PBPCs support. Viral screening studies, including clinical symptoms, physical examinations, hepatitis B virus (HBV)-DNA, cytomegalovirus (CMV)-polymerase chain reaction (PCR), rapid diagnosis of fluorescent antibody stain for herpes-simplex virus (HSV), and viral culture from blood, fluid or tissue were performed weekly during the first 3 months and then monthly for 1 year. Two of four patients (50%) who were HBV carriers developed HBV reactivation. The other two HBV carriers who received prophylactic lamivudine therapy did not develop HBV reactivation. Two patients (20%) developed cytomegalovirus (CMV) infection, and three patients (30%) developed HSV infection in total ten serum-positive patients. The possibility of virus reactivation might increase in NHL patients undergoing autologous CD34⁺-selected PBPC transplantation. Administering prophylactic antivirus therapy and closely following patient’s clinical viral complications should be considered.     

Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial.

BACKGROUND: Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging. METHODS AND RESULTS: This multicenter, double-blinded phase 3 trial involved 784 patients at 54 sites. Each patient underwent 2 sets of gated single photon emission computed tomography myocardial perfusion imaging studies: an initial qualifying study with adenosine and a subsequent randomized study with either regadenoson (2/3 of patients) or adenosine. Regadenoson was administered as a rapid bolus (<10 seconds) of 400 mug. The primary endpoint was to demonstrate noninferiority by showing that the difference in the strength of agreement in detecting reversible defects, based on blinded reading, between sequential adenosine-regadenoson images and adenosine-adenosine images, lay above a prespecified noninferiority margin. Other prospectively defined safety and tolerability comparisons and supporting analyses were also performed. The average agreement rate based on the median of 3 independent blinded readers was 0.63 +/- 0.03 for regadenoson-adenosine and 0.64 +/- 0.04 for adenosine-adenosine-a 1% absolute difference with the lower limit of the 95% confidence interval lying above the prespecified noninferiority margin. Side-by-side interpretation of regadenoson and adenosine images provided comparable results for detecting reversible defects. The peak increase in heart rate was greater with regadenoson than adenosine, but the blood pressure nadir was similar. A summed symptom score of flushing, chest pain, and dyspnea was less with regadenoson than adenosine (P = .013). CONCLUSIONS: This phase 3 trial shows that regadenoson provides diagnostic information comparable to a standard adenosine infusion. There were no serious drug-related side effects, and regadenoson was better tolerated than adenosine.