Clinical Study The Clinical Investigation of Disparity of Utility Values Associated with Gallstone Disease: A Pilot Study

. Purpose. The utility evaluation was an effective method to incorporate all of the contributing variables for multiple diseases into one outcome measure. A cross-sectional study was conducted to assess the utility values associated with varying states of gallstone disease among outpatient clinics participants at a teaching hospital in Taipei, Taiwan. Methods. The utility values were measured by using time trade-off method. A total of 120 outpatient clinics participants (30 subjects with no gallstone disease, 30 subjects with single stone, 30 subjects with multiple stones, and 30 subjects with cholecystectomy) evaluated utility values from January 1, 2006 to December 31, 2006. The diagnosis of gallstone disease was performed by a panel of specialists using ultrasound sonography. Results. The overall mean utility value was 0.89 ± 0.13 (95% CI: 0.87-0.91) indicating that study participants were willing to trade about 11% (95% CI: 9-13%) of their remaining life in return for being free of gallstone disease perpetually. The significant associated factors of utility values based on the multiple linear regression analysis were older age and different degrees of gallstone disease. Conclusion. Our results found that in addition to older age, multiple stones and cholecystectomy could influence utility values from the patient's preference-based viewpoint

The Clinical Investigation of Disparity of Utility Values Associated with Gallstone Disease: A Pilot Study

Purpose. The utility evaluation was an effective method to incorporate all of the contributing variables for multiple diseases into one outcome measure. A cross-sectional study was conducted to assess the utility values associated with varying states of gallstone disease among outpatient clinics participants at a teaching hospital in Taipei, Taiwan. Methods. The utility values were measured by using time trade-off method. A total of 120 outpatient clinics participants (30 subjects with no gallstone disease, 30 subjects with single stone, 30 subjects with multiple stones, and 30 subjects with cholecystectomy) evaluated utility values from January 1, 2006 to December 31, 2006. The diagnosis of gallstone disease was performed by a panel of specialists using ultrasound sonography. Results. The overall mean utility value was 0.89±0.13 (95% CI: 0.87–0.91) indicating that study participants were willing to trade about 11% (95% CI: 9–13%) of their remaining life in return for being free of gallstone disease perpetually. The significant associated factors of utility values based on the multiple linear regression analysis were older age and different degrees of gallstone disease. Conclusion. Our results found that in addition to older age, multiple stones and cholecystectomy could influence utility values from the patient’s preference-based viewpoint

Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia

Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, “Chen Pi.” Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4H/PDE4L) ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation

Factors Related to Significant Improvement of Estimated Glomerular Filtration Rates in Chronic Hepatitis B Patients Receiving Telbivudine Therapy

Background and Aim. The improvement of estimated glomerular filtration rates (eGFRs) in chronic hepatitis B (CHB) patients receiving telbivudine therapy is well known. The aim of this study was to clarify the kinetics of eGFRs and to identify the significant factors related to the improvement of eGFRs in telbivudine-treated CHB patients in a real-world setting. Methods. Serial eGFRs were calculated every 3 months using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The patients were classified as CKD-1, -2, or -3 according to a baseline eGFR of ≥90, 60–89, or <60 mL/min/1.73 m2, respectively. A significant improvement of eGFR was defined as a more than 10% increase from the baseline. Results. A total of 129 patients were enrolled, of whom 36% had significantly improved eGFRs. According to a multivariate analysis, diabetes mellitus (DM) (p=0.028) and CKD-3 (p=0.043) were both significantly related to such improvement. The rates of significant improvement of eGFR were about 73% and 77% in patients with DM and CKD-3, respectively. Conclusions. Telbivudine is an alternative drug of choice for the treatment of hepatitis B patients for whom renal safety is a concern, especially patients with DM and CKD-3

An Evaluation of the Additive Effect of Natural Herbal Medicine on SARS or SARS-like Infectious Diseases in 2003: A Randomized, Double-blind, and Controlled Pilot Study

Natural herbal medicine (NHM) has been used to control infectious diseases for thousands of years. In view of the possible beneficial effect of NHM on SARS, we conducted this study to examine whether NHM is of any benefit as a supplementary treatment of SARS or SARS-like infectious disease. This was a randomized, double-blind, placebo-controlled trial. Twenty-eight patients fulfilled the WHO inclusion criteria and our exclusion criteria. All enrolled patients received routine western-medicine treatment. Patients were randomly allocated to one of the three supplementary treatment groups: NHM A (Group A, n = 9) NHM B (Group B, n = 9) or placebo (Group C, n = 10). Chest X-ray was done every 1 or 2 days for every patient. Reading radiologists use a standard 0–3 scoring system (0: no infiltration; 1: focal haziness or even small patchy lesion; 2: ground glass picture; 3: lobar consolidation) according to the severity of infiltration in each lung field (three lung fields in both right and left lungs). The main outcome measurements were the improving chest radiographic scores (IRS) and the duration (days) till improvement (DI). One patient from the placebo group passed away. Patients from NHM A took less days before showing improvement (6.7 ± 1.8) compared with placebo group (11.2 ± 4.9), which showed statistical significance (P = 0.04). The cases were too few to be conclusive, the initial observations seem to indicate NHM appears to be safe in non-criticallly ill patients and clinical trials are feasible in the setting of pandemic outbreaks

Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: Conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation

AbstractAimRefractory ventricular fibrillation, resistant to conventional cardiopulmonary resuscitation (CPR), is a life threatening rhythm encountered in the emergency department. Although previous reports suggest the use of extracorporeal CPR can improve the clinical outcomes in patients with prolonged cardiac arrest, the effectiveness of this novel strategy for refractory ventricular fibrillation is not known. We aimed to compare the clinical outcomes of patients with refractory ventricular fibrillation managed with conventional CPR or extracorporeal CPR in our institution.MethodThis is a retrospective chart review study from an emergency department in a tertiary referral medical center. We identified 209 patients presenting with cardiac arrest due to ventricular fibrillation between September 2011 and September 2013. Of these, 60 patients were enrolled with ventricular fibrillation refractory to resuscitation for more than 10min. The clinical outcome of patients with ventricular fibrillation received either conventional CPR, including defibrillation, chest compression, and resuscitative medication (C-CPR, n=40) or CPR plus extracorporeal CPR (E-CPR, n=20) were compared.ResultsThe overall survival rate was 35%, and 18.3% of patients were discharged with good neurological function. The mean duration of CPR was longer in the E-CPR group than in the C-CPR group (69.90±49.6min vs 34.3±17.7min, p=0.0001). Patients receiving E-CPR had significantly higher rates of sustained return of spontaneous circulation (95.0% vs 47.5%, p=0.0009), and good neurological function at discharge (40.0% vs 7.5%, p=0.0067). The survival rate in the E-CPR group was higher (50% vs 27.5%, p=0.1512) at discharge and (50% vs 20%, p=0. 0998) at 1 year after discharge.ConclusionsThe management of refractory ventricular fibrillation in the emergency department remains challenging, as evidenced by an overall survival rate of 35% in this study. Patients with refractory ventricular fibrillation receiving E-CPR had a trend toward higher survival rates and significantly improved neurological outcomes than those receiving C-CPR

SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Infection

The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic Helicobacter pylori (H. pylori) infection. Nuclear translocation is thought to be important for p38 function, but no nuclear translocation signals have been found in the protein and no nuclear carrier proteins have been identified for p38. We have investigated the role of small ubiquitin-related modifier (SUMO) in the nuclear transfer of p38 in response to H. pylori infection. Exposure of human AGS cells to H. pylori induced the activation of p38 and the expression of SUMOs, especially SUMO-2. SUMO knockdown counteracted the effect of H. pylori infection by decreasing the resulting p38 mediated cellular apoptosis through a reduction in the nuclear fraction of phosphorylated p38. We identified a non-covalent interaction between SUMOs and p38 via SUMO interaction motifs (SIMs), and showed that SUMO-dependent nuclear transfer of p38 was decreased upon mutation of its SIMs. This study has identified a new pathway of p38 nuclear translocation, in response to H. pylori infection. We conclude that in the presence of H. pylori SUMO-2 has a major role in regulating nuclear levels of p38, through non-covalent SUMO-p38 interactions, independent of the p38 phosphorylation state

Plasma Low-Density Lipoprotein Cholesterol Correlates With Heart Function in Individuals With Type 2 Diabetes Mellitus: A Cross-Sectional Study

Background: Heart failure is a frequent complication of type 2 diabetes mellitus (T2DM). Plasma cholesterol, particularly the proatherogenic low-density lipoprotein (LDL) cholesterol, impairs heart function by promoting atheroma formation and ventricular dysfunction. Considering the established effect of cholesterol on the cardiovascular system, we hypothesized that plasma LDL cholesterol may influence left ventricular function in individuals with T2DM.Methods: This cross-sectional study was conducted at a tertiary care hospital in Taiwan. Enrollment criteria were patients exceeding 21 years of age with T2DM who received antidiabetic and cholesterol-lowering medications. Candidates were excluded if they had heart failure, acute cardiovascular events, or familial hypercholesterolemia. Participants received blood sampling for plasma lipids after a 12-h fast, followed by transthoracic echocardiography in the cardiology clinic.Results: The study enrolled 118 participants who were divided into two groups according to their plasma LDL cholesterol levels. Demographic characteristics including age (69.7 vs. 66.9 years, P = 0.159), body mass index (26.2 vs. 25.9 kg/m2, P = 0.66), diabetes duration (5.4 vs. 5.1 years, P = 0.48), hemoglobin A1c (7.2 vs. 7.5%, P = 0.225), and systolic blood pressure (129 vs. 130 mm Hg, P = 0.735) were similar between these groups. Moreover, all participants received similar antihypertensive medications. Participants with lower plasma LDL cholesterol levels had better heart function, as measured by the left ventricular ejection fraction (LVEF), than patients with higher LDL cholesterol levels (58.0 vs. 50.5%, P = 0.022). Multivariate regression analysis also showed an inverse correlation between plasma LDL cholesterol and left ventricular function (β coefficient: −0.110, P = 0.024).Conclusion: This study observed an inverse correlation between plasma LDL cholesterol and heart function in individuals with T2DM. Patients with higher levels of plasma LDL cholesterol had worse left ventricular function. Therefore, plasma LDL cholesterol may be a modifiable risk factor of heart failure in diabetes, but prospective studies are necessary to confirm this finding

Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice

Chia-Che Tsai1, Chih-Hsien Chang1, Liang-Cheng Chen1, Ya-Jen Chang1, Keng-Li Lan2, Yu-Hsien Wu1, Chin-Wei Hsu1, I-Hsiang Liu1, Chung-Li Ho1, Wan-Chi Lee1, Hsiao-Chiang Ni1, Tsui-Jung Chang1, Gann Ting3, Te-Wei Lee11Institute of Nuclear Energy Research, Taoyuan, 2Cancer Center, Taipei Veterans General Hospital, Taipei, 3National Health Research Institutes, Taipei, Taiwan, ROCBackground: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated.Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM&amp;reg; computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared.Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% &amp;plusmn; 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 &amp;plusmn; 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188Re-liposomes provided better survival time (increased by 34.6% of life span; P &amp;lt; 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P &amp;lt; 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU).Conclusion: The use of 188Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that 188Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.Keywords: biodistribution, dosimetry, 5-fluorouracil, micro-SPECT/CT, 188Re-liposome