Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B

BACKGROUND: Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS: In this phase 3, double-blind trial, we randomly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis). RESULTS: Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated (70 percent), as compared with 174 of 287 such patients in the lamivudine group (61 percent, P=0.01). More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus (HBV) DNA levels according to a polymerase-chain- reaction assay (90 percent vs. 72 percent, P<0.001) and normalization of alanine aminotransferase levels (78 percent vs. 71 percent, P = 0.045). The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine (5.0 vs. 4.5 log [on a base-10 scale] copies per milliliter, P<0.001). There was no evidence of resistance to entecavir. Safety and adverse-event profiles were similar in the two groups. CONCLUSIONS: Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine. The safety profile of the two agents was similar, and there was no evidence of viral resistance to entecavir. Copyright © 2006 Massachusetts Medical Society.published_or_final_versio

Photothermal treatment of glioma; an in vitro study of macrophage-mediated delivery of gold nanoshells

One of the major factors that limits the treatment effectiveness for gliomas is the presence of the blood–brain barrier (BBB) which protects infiltrating glioma cells from the effects of anti-cancer agents. Circulating monocytes/macrophages (Ma) have a natural ability to traverse the intact and compromised BBB and loaded with anti cancer agents could be used as vectors to target tumors and surrounding tumor infiltrated tissue. Nanoshells (NS) are composed of a dielectric core (silica) coated with an ultrathin gold layer which converts absorbed near-infrared light (NIR) to heat with an extremely high efficacy and stability. We have investigated the effects of exposure to laser NIR on multicell human glioma spheroids infiltrated with empty (containing no nanoshells) or nanoshell loaded macrophages. Our results demonstrated that; (1) macrophages could efficiently take up bare or coated (PEGylated) gold NS: (2) NS loaded macrophages infiltrated into glioma spheroids to the same or, in some cases, to a greater degree than empty Ma; (3) NIR laser irradiation of spheroids incorporating NS loaded macrophages resulted in complete growth inhibition in an irradiance dependent manner, and (4) spheroids infiltrated with empty macrophages had growth curves identical to untreated control cultures. The results of this study provide proof of concept for the use of macrophages as a delivery vector of NS into gliomas for photothermal ablation and open the possibility of developing such regimens for patient treatment

Factors Associated with Hepatitis B Testing Among Vietnamese Americans

Chronic hepatitis B and hepatitis B-associated liver cancer is a major health disparity among Vietnamese Americans, who have a chronic hepatitis B prevalence rate of 7–14% and an incidence rate for liver cancer six times that of non-Latino whites. Describe factors associated with hepatitis B testing among Vietnamese Americans. A population-based telephone survey conducted in 2007–2008. Vietnamese Americans age 18–64 and living in the Northern California and Washington, DC areas (N = 1,704). Variables included self-reports of sociodemographics, health care factors, and hepatitis B-related behaviors, knowledge, beliefs, and communication with others. The main outcome variable was self-reported receipt of hepatitis B testing. The cooperation rate was 63.1% and the response rate was 27.4%. Only 62% of respondents reported having received a hepatitis B test and 26%, hepatitis B vaccination. Only 54% knew that hepatitis B could be transmitted by sexual intercourse. In multivariable analyses, factors negatively associated with testing included: age 30–49 years, US residence for &gt;10 years, less Vietnamese fluency, lower income, and believing that hepatitis B can be deadly. Factors positively associated with testing included: Northern California residence, having had hepatitis B vaccination, having discussed hepatitis B with family/friends, and employer requested testing. Physician recommendation of hepatitis B testing (OR 4.46, 95% CI 3.36, 5.93) and respondent's request for hepatitis B testing (OR 8.37, 95% CI 5.95, 11.78) were strongly associated with test receipt. Self-reports of hepatitis B testing among Vietnamese Americans remain unacceptably low. Physician recommendation and patient request were the factors most strongly associated with test receipt. A comprehensive effort is needed to promote hepatitis B testing in this population, including culturally-targeted community outreach, increased access to testing, and physician education

Complications and pitfalls of lumbar interlaminar and transforaminal epidural injections

Lumbar interlaminar and transforaminal epidural injections are used in the treatment of lumbar radicular pain and other lumbar spinal pain syndromes. Complications from these procedures arise from needle placement and the administration of medication. Potential risks include infection, hematoma, intravascular injection of medication, direct nerve trauma, subdural injection of medication, air embolism, disc entry, urinary retention, radiation exposure, and hypersensitivity reactions. The objective of this article is to review the complications of lumbar interlaminar and transforaminal epidural injections and discuss the potential pitfalls related to these procedures. We performed a comprehensive literature review through a Medline search for relevant case reports, clinical trials, and review articles. Complications from lumbar epidural injections are extremely rare. Most if not all complications can be avoided by careful technique with accurate needle placement, sterile precautions, and a thorough understanding of the relevant anatomy and contrast patterns on fluoroscopic imaging

Cocaine-induced renal infarction: report of a case and review of the literature

BACKGROUND: Cocaine abuse has been known to have detrimental effects on the cardiovascular system. Its toxicity has been associated with myocardial ischemia, cerebrovascular accidents and mesenteric ischemia. The pathophysiology of cocaine-related renal injury is multifactorial and involves renal hemodynamic changes, alterations in glomerular matrix synthesis, degradation and oxidative stress, and possibly induction of renal atherogenesis. Renal infarction as a result of cocaine exposure, however, is rarely reported in the literature. CASE PRESENTATION: A 48 year-old male presented with a four-day history of severe right flank pain following cocaine use. On presentation, he was tachycardic, febrile and had severe right costovertebral angle tenderness. He had significant proteinuria, leukocytosis and elevated serum creatinine and lactate dehydrogenase. Radiographic imaging studies as well as other screening tests for thromboembolic events, hypercoagulability states, collagen vascular diseases and lipid disorders were suggestive of Cocaine-Induced Renal Infarction (CIRI) by exclusion. CONCLUSION: In a patient with a history of cocaine abuse presenting with fevers and flank pain suggestive of urinary tract infection or nephrolithiasis, cocaine-induced renal infarction must be considered in the differential diagnosis. In this article, we discuss the prior reported cases of CIRI and thoroughly review the literature available on this disorder. This is important for several reasons. First, it will allow us to discuss and elaborate on the mechanism of renal injury caused by cocaine. In addition, this review will demonstrate the importance of considering the diagnosis of CIRI in a patient with documented cocaine use and an atypical presentation of acute renal injury. Finally, we will emphasize the need for a consensus on optimal treatment of this disease, for which therapy is not yet standardized

Sustainability of donor programs: evaluating and informing the transition of a large HIV prevention program in India to local ownership

Sustainability is the holy grail of many development projects, yet there is limited evidence about strategies that effectively support transition of programs from donor funding to national governments. The first phase of Avahan, the India AIDS Initiative supported by the Bill and Melinda Gates Foundation (2003&#x2013;2009), aimed to demonstrate an HIV/AIDS prevention program at scale, primarily targeted at high-risk groups. During the second phase (2009&#x2013;2013), this large-scale program will be transitioned to its natural owners: the Government of India and local communities. This paper describes the evaluation design for the Avahan transition strategy.A detailed logic model for the transition was developed. The Avahan transition strategy focuses on three activities: 1 enhancing capacities among communities, non-governmental organizations (NGOs), and government entities, in line with India&#x0027;s national AIDS control strategy; 2 aligning technical and managerial aspects of Avahan programs with government norms and standards; and 3 promoting and sustaining commitment to services for most-at-risk populations. It is anticipated that programs will then transfer smoothly to government and community ownership, become institutionalized within the government system, and support a sustained HIV/AIDS response.The research design evaluates the implementation and effectiveness of 1 activities undertaken by the program; 2 intermediate effects including the process of institutionalization and the extent to which key Avahan organizational procedures and behaviors are integrated into government systems; and 3 overarching effects namely the impact of the transition process on the sustained delivery of HIV/AIDS prevention services to high-risk groups. Both qualitative and quantitative research approaches are employed so that the evaluation will both assess outcomes and explain why they have occurred.It is unusual for donor-supported projects in low- and middle-income countries to carefully plan transition processes, and prospectively evaluate these. This evaluation is designed so as to both inform decision making throughout the transition process and answer larger questions about the transition and sustainability of donor programs

Nanohybrids of Silver Particles Immobilized on Silicate Platelet for Infected Wound Healing

Silver nanoparticles supported on nanoscale silicate platelets (AgNP/NSP) possess interesting properties, including a large surface area and high biocide effectiveness. The nanohybrid of AgNP/NSP at a weight ratio 7/93 contains 5-nm Ag particles supported on the surface of platelets with dimensions of approximately 80×80×1 nm3. The nanohybrid expresses a trend of lower cytotoxicity at the concentration of 8.75 ppm Ag and low genotoxicity. Compared with conventional silver ions and the organically dispersed AgNPs, the nanohybrid promotes wound healing. We investigated overall wound healing by using acute burn and excision wound healing models. Tests on both infected wound models of mice were compared among the AgNP/NSP, polymer-dispersed AgNPs, the commercially available Aquacel, and silver sulfadiazine. The AgNP/NSP nanohybrid was superior for wound appearance, but had similar wound healing rates, vascular endothelial growth factor (VEGF)-A levels and transforming growth factor (TGF)-β1 expressions to Aquacel and silver sulfadiazine

Differential CARM1 expression in prostate and colorectal cancers

<p>Abstract</p> <p>Background</p> <p>Coactivator-associated arginine methyltransferase 1 (CARM1) functions as a transcriptional coactivator of androgen receptor (AR)-mediated signaling. Correspondingly, overexpression of CARM1 has been associated with the development of prostate cancer (PCa) and its progression to androgen-independent PCa. In our preliminary study, however, the promoting effects of CARM1, with regard to androgen-stimulated AR target gene expression were minimal. These results suggested that the AR target gene expression associated with CARM1 may result primarily from non-hormone dependent activity. The goal of this study was to confirm the pattern of expression of CARM1 in human tumors and determine the mechanism of action in CARM1 overexpressed tumors.</p> <p>Methods</p> <p>Tissue microarray was used to determine the pattern of expression of CARM1 in human cancers by immunohistochemistry. CARM1 expression was also evaluated in prostate and colorectal surgical specimens and the clinical records of all cases were reviewed. In addition, a reporter transcription assay using the prostate-specific antigen (PSA) promoter was used to identify the signaling pathways involved in non-hormone-mediated signal activation associated with CARM1.</p> <p>Results</p> <p>The tissue microarray showed that CARM1 was particularly overexpressed in the colorectal cancers while CARM1 expression was not prevalent in the prostate and breast cancers. Further studies using surgical specimens demonstrated that CARM1 was highly overexpressed in 75% of colorectal cancers (49 out of 65) but not in the androgen-independent PCa. In addition, CARM1's coactivating effect on the entire PSA promoter was very limited in both androgen-dependent and androgen-independent PCa cells. These results suggest that there are other factors associated with CARM1 expression in PSA regulation. Indeed, CARM1 significantly regulated both p53 and NF-κB target gene transcription.</p> <p>Conclusions</p> <p>The results of this study suggest that, in addition to its role in activation of steroid receptors, CARM1 functions as a transcriptional modulator by altering the activity of many transcriptional factors, especially with regard to androgen independent PCa and colorectal cancers.</p

Caucasian Infants Scan Own- and Other-Race Faces Differently

Young infants are known to prefer own-race faces to other race faces and recognize own-race faces better than other-race faces. However, it is entirely unclear as to whether infants also attend to different parts of own- and other-race faces differently, which may provide an important clue as to how and why the own-race face recognition advantage emerges so early. The present study used eye tracking methodology to investigate whether 6- to 10-month-old Caucasian infants (N = 37) have differential scanning patterns for dynamically displayed own- and other-race faces. We found that even though infants spent a similar amount of time looking at own- and other-race faces, with increased age, infants increasingly looked longer at the eyes of own-race faces and less at the mouths of own-race faces. These findings suggest experience-based tuning of the infant's face processing system to optimally process own-race faces that are different in physiognomy from other-race faces. In addition, the present results, taken together with recent own- and other-race eye tracking findings with infants and adults, provide strong support for an enculturation hypothesis that East Asians and Westerners may be socialized to scan faces differently due to each culture's conventions regarding mutual gaze during interpersonal communication