Are countries using global fund support to implement HIV drug resistance surveillance? A review of funded HIV grants

The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) is the largest funder of human immunodeficiency virus (HIV) prevention and treatment programs worldwide. Since 2002, the Global Fund has encouraged grant recipients to implement drug resistance surveillance (DRS) as part of treatment programs. We reviewed documentation of 147 grants funded in 2004-2008 (funding rounds 4-8) to assess grantees' use of funds to support HIV DRS. Overall, 94 grants (64%) described HIV DRS as part of the national treatment program. However, only 32 grants (22%) specifically documented DRS as a grant-funded activity. This review provides baseline information suggesting limited use by countries of Global Fund financing to support HIV DRS. Additional assessment is required to evaluate barriers to using Global Fund grants to support DRS.     

Results of a phase 4 trial of tacrobell® in liver transplantation patients: a multicenter study in South Korea

Background/Aims: This 26-week pilot study was performed in de novo liver transplant recipients to evaluate the efficacy of tacrobell capsule as an immunosuppressant drug after living donor liver transplant patients by determining the rate of acute cellular rejection after its use and evaluating its safety after transplantation. Methodology: From October 2005 to July 2007, 57 patients from four major medical centers in Seoul, South Korea were enrolled in the study. This open-label, noncomparative, multicenter pilot study lasted 26 weeks and assigned patients to receive tacrobell and corticosteroid after liver transplantation. Tacrobell (0.05mg/ kg/day, bid) and methylprednisolone were injected either on the day of the operation or on postoperative day one. A retrospective matched control group consisting of living donor liver transplant recipients at one center (Asan medical center) was used for comparison. Results: The rate of acute cellular rejection with tacrobell after 26 weeks of administration was 0.0% (95% CI, 0.0%-6.27%), which was below our hypothesized 36%. The most common drug-related adverse events included endocrine/nutritional disorders followed by gastrointestinal and hepatobiliary disorders. No patients died during the study period. The side effect profile of this drug was no different than other tacrolimus based immunosuppressants. Conclusions: Although our study was based on a low risk population and had a shortterm follow up, we conclude that tacrobell, as a generic tacrolimus, can be considered safe and effective in liver transplant patients.     

Assessment of In Vitro Dental Implant Primary Stability Using an Ultrasonic Method

Dental implants are used for oral rehabilitation. However, there remain risks of failure that depend on the implant stability. The objective of this study is to investigate whether quantitative ultrasound technique can be used to assess the amount of bone in contact with dental implants. Ten implants are first inserted in the bone samples. The 10 MHz ultrasonic response of each implant is measured using a dedicated device and an indicator I is derived based on the amplitude of the signal. Then, the implant is unscrewed by 2 π radians and the measurement is realized again. A statistical analysis of variance was carried out and revealed a significant effect of the amount of bone in contact with the implant on the values of I (p value < 10^?5). The results indicates the feasibility of quantitative ultrasound techniques to assess implant primary stability in vitro.     

Open channel block by KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane hydrochloride] of the heterologously expressed human ether-a-go-go-related gene K+ channels

KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane hydrochloride] is a newly synthesized class III antiarrhythmic drug and is known to be highly effective against various types of arrhythmias induced by coronary artery ligation, reperfusion, and programmed electrical stimulation. To understand the potential ionic mechanisms, we examined the effects of KCB-328, which encodes the rapidly activating delayed rectifier K(+) current in cardiac tissues, on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes. The amplitudes of steady-state currents and tail currents of HERG were decreased by KCB-328 dose dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by KCB-328 is voltage-dependent. IC(50) values at -30, -20, -10, 0, +10, +20, +30, and +40 mV were 7.6 +/- 0.5, 4.8 +/- 0.4, 3.2 +/- 0.3, 2.1 +/- 0.3, 1.7 +/- 0.2, 1.4 +/- 0.2, 1.3 +/- 0.1, and 1.2 +/- 0.1 microM, respectively. Induction of block depended on depolarization beyond the threshold for channel opening. In addition, time-dependent block developed slowly, with tau = 1.7 +/- 0.3 s (100 microM) at 0 mV, and was delayed by a stronger depolarization to +80 mV, at which HERG channel is inactivated. We can conclude that KCB-328 preferentially blocks open (or activated) HERG channels. The block of HERG current might in part explain the underlying ionic mechanism for the antiarrhythmic and proarrhythmic effect of KCB-328.     

The clinical impact of preoperative percutaneous drainage of abdominopelvic abscesses in patients with Crohn’s disease

Purpose

Although image-guided percutaneous drainage is increasingly being used to treat Crohn’s disease-related abdominopelvic abscesses, surgery is seldom avoided. The aim of this study was to compare outcomes following the treatment of intra-abdominal Crohn’s abscesses with percutaneous drainage followed by surgery to those after surgery alone.

Methods

We retrospectively reviewed the charts of patients treated for Crohn’s-related abdominopelvic abscesses at Mount Sinai Medical Center between April 2001 and June 2010. Patients who underwent drainage followed by surgery were compared to those who underwent surgery alone. Differences in operative and postoperative outcomes were compared.

Results

Seventy patients with Crohn’s disease-related abdominopelvic abscesses were identified, 38 (54%) of whom underwent drainage before surgery. Percutaneous drainage was technically successful in 92% of patients and clinically successful in 74% of patients. No differences in rate of septic complications (p?=?0.14) or need for stoma creation (p?=?0.78) were found. Patients who underwent percutaneous drainage had greater overall hospital lengths of stay (mean 15.8 versus 12.2?days, p?=?0.007); 8.6% of patients had long-term postponement of surgery after percutaneous drainage.

Conclusions

In our series, the treatment of Crohn’s abscesses with percutaneous drainage prior to surgery did not decrease the rate of postoperative septic complications.     

Quantum-dot-assisted fluorescence resonance energy transfer approach for intracellular trafficking of chitosan/DNA complex

Fluorescence resonance energy transfer (FRET) was employed to monitor the molecular dissociation of a chitosan/DNA complex with different molecular weights of chitosan. Chitosan with different molecular weights was complexed with plasmid DNA and the complex formation was monitored using dynamic light scattering and a gel retardation assay. As the chitosan molecular weight increased, a more condensed complex was prepared at various ratios of chitosan to DNA. Plasmid DNA and chitosan were separately labeled with quantum dots and Texas red, respectively, and the dissociation of the complex was subsequently monitored using confocal microscopy and fluorescence spectroscopy. As the chitosan molecular weight in the chitosan/DNA complex increased, the Texas red-labeled chitosan gradually lost FRET-induced fluorescence light when HEK293 cells incubated with chitosan/DNA complex were examined with confocal microscopy. This suggests that the dissociation of the chitosan/DNA complex was more significant in the high molecular weight chitosan/DNA complex. Fluorescence spectroscopy also monitored the molecular dissociation of the chitosan/DNA complex at pH 7.4 and pH 5.0 and confirmed that the dissociation occurred in acidic environments. This finding suggests that the high molecular weight chitosan/DNA complex could easily be dissociated in lysosomes compared to a low molecular weight complex. Furthermore, the high molecular weight chitosan/DNA complex showed superior transfection efficiency in relation to the low molecular weight complex. Therefore, it could be concluded that the dissociation of the chitosan/DNA complex is a critical event in obtaining the high transfection efficiency of the gene carrier/DNA complex.     

Differential involvement of GABA system in mediating behavioral and neurochemical effect of acupuncture in ethanol-withdrawn rats

In our previous study we demonstrated that acupuncture at Shenmen (HT7) points suppressed a decrease of accumbal dopamine (DA) release in ethanol-withdrawn rats. Furthermore, here we found that it inhibited behavioral withdrawal signs of ethanol. In an effort to better understand the mechanisms underlying this inhibition, the potential role of GABA receptor system in acupuncture was investigated. Male Sprague–Dawley rats were treated with 3 g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 48 or 72 h of ethanol withdrawal, acupuncture was applied at bilateral HT7 for 1 min. The selective GABA_A antagonist bicuculline and the selective GABA_B antagonist SCH 50911 were injected intraperitoneally 20 min before acupuncture, respectively. Importantly, suppressive effects of acupuncture on DA deficiency were completely abolished by SCH 50911, but not by bicuculline, whereas ameliorating effects of acupuncture on ethanol withdrawal syndrome were completely blocked either by SCH 50911 or bicuculline. These results suggest that acupuncture at specific acupoint HT7 may normalize the DA release in the mesolimbic system and attenuate withdrawal syndrome through the GABA_B receptor system in ethanol-withdrawn rats.     

Role of induction and consolidation chemotherapy in elderly acute myeloid leukemia patients

The present study sought to elucidate the role of induction and consolidation therapy in elderly patients. We retrospectively collected data of 477 patients who were aged over 60 years at the time of acute myeloid leukemia (AML) diagnosis. The median overall survival (OS) was 339 days in the induction group (n = 266) and 86 days in the best supportive care group (n = 211) (P < 0.001). In the induction group, the complete remission (CR) rate was 58.3 %, and treatment-related death was 15.4 %. Successful induction was related to good performance [Eastern Cooperative Oncology Group (ECOG <2)] [hazard ratio (HR) 3.215; P = 0.002]. Mortality correlated with failure to achieve CR (HR 4.059; P < 0.001) and poor performance status (ECOG >2) (HR 2.731; P = 0.035). In CR patients, poor karyotype and absence of consolidation (HR 2.313; P = 0.003) correlated with mortality. More than one cycle of consolidation was associated with better OS (P < 0.001). Lack of salvage therapy was associated with mortality in patients who did not achieve CR (HR 3.223; P = 0.005). Intensive induction in patients with good performance and >1 cycle of consolidation after CR may be the best strategy for improving OS in elderly AML patients.     

Limited feasibility in endovascular aneurysm repair using currently available graft in Korea

Despite the wide acceptance of endovascular aneurysmal repair in patients with abdominal aortic aneurysm (EVAR), stringent morphologic criteria recommended by manufacturers may preclude this treatment in patients with AAA. The purpose of this study was to investigate how many patients are feasible by Zenith and Excluder stent graft system, which are available in Korea. Eighty-two AAA patients (71 men, mean age 70 yr) who had been treated surgically or medically from January 2005 to December 2006 were included. Criteria for morphologic suitability (MS) were examined to focus on characteristics of aneurysm; proximal and distal landing zone; angulation and involvement of both iliac artery aneurysms. Twenty-eight patients (34.1%) were feasible in Zenith stent graft and 31 patients (37.8%) were feasible in Excluder. The patients who were excluded EVAR had an average of 1.61 exclusion criteria. The main reasons for exclusion were an unfavorable proximal neck (n=34, 41.5%) and problem of distal landing zone (n=25, 30.5%). There was no statistical significance among gender, age or aneurysm size in terms of MS. Only 32 patients (39%) who had AAA were estimated to be suitable for two currently approved grafts by strict criteria. However, even unfavorable AAA patients who have severe co-morbidities will be included in EVAR in the near future. Therefore, more efforts including fine skill and anatomical understanding will be needed to meet these challenging cases.