Hereditary hemochromatosis in the post-HFE era

Following the discovery of the HFE gene in 1996 and its linkage to the iron overload disorder hereditary hemochromatosis (HH) there have been profound developments in our understanding of the pathogenesis of the biochemical and clinical manifestations of a number of iron overload disorders. This article provides an update of recent developments and key issues relating to iron homeostasis and inherited disorders of iron overload, with emphasis on HFE-related HH, and is based on the content of the American Association for the Study of Liver Diseases Single-Topic Conference entitled "Hemochromatosis: What has Happened After HFE?" which was held at the Emory Convention Center in Atlanta, September 7-9, 2007.     

Establishment of a multi-state experiential pharmacy program consortium

In 2002, a regional consortium was created for schools and colleges of pharmacy in Georgia and Alabama to assist experiential education faculty and staff members in streamlining administrative processes, providing required preceptor development, establishing a professional network, and conducting scholarly endeavors. Five schools and colleges of pharmacy with many shared experiential practice sites formed a consortium to help experiential faculty and staff members identify, discuss, and solve common experience program issues and challenges. During its 5 years in existence, the Southeastern Pharmacy Experiential Education Consortium has coordinated experiential schedules, developed and implemented uniform evaluation tools, coordinated site and preceptor development activities, established a work group for educational research and scholarship, and provided opportunities for networking and professional development. Several consortium members have received national recognition for their individual experiential education accomplishments. Through the activities of a regional consortium, members have successfully developed programs and initiatives that have streamlined administrative processes and have the potential to improve overall quality of experiential education programs. Professionally, consortium activities have resulted in 5 national presentations.     

The role of the renin-angiotensin system in atrial fibrillation and the therapeutic effects of ACE-Is and ARBS

Atrial fibrillation (AF) is the most common rhythm disturbance in medical practice and represents a very expensive health problem. AF can be managed with the prevention of thromboembolism and either a rate control of rhythm strategy. As both strategies have important limitations, probably a preventative strategy in patients at risk of developing arrhythmia can be a more attractive option. The renin-angiotensin system (RAS) seems to be involved in the genesis of arrhythmia by the following two mechanisms: 1. the induction of atrial fibrosis and structural remodelling by mitogen-activated protein kinase (MAPK) expression and reduction of collagenase activity; 2. the induction of electrical remodelling by shortening of the atrial effective refractory period (AERP) and of the action potential duration. For these reasons it has been hypothesized that angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II receptor blockers (ARBs) may play a role in preventing AF recurrence. The aim of the present review was to analyse evidence supporting the usefulness of RAS inhibition in patients with AF in order to focus on which specific subset of patients it would most favour. After reviewing the literature, we conclude that, although many studies and meta-analysis have supported the advantage of RAS block in preventing AF recurrence, it is premature to recommend the use of ACE-Is and ARBs specifically for the prevention of AF. However we believe that as these drugs are safe and manageable, they should be considered the drugs of choice in patients with AF and coexisting clinical conditions such as hypertension, coronary disease, heart failure and diabetes mellitus.     

Pain and Mortality Risk in a Cohort of HIV-Infected Persons with Alcohol Use Disorders

Pain has been associated with increased risk for mortality in some studies. We analyzed data from a cohort study [HIV-longitudinal interrelationships of viruses and ethanol (HIV-LIVE)] of HIV-infected persons with alcohol use disorders enrolled 2001–2003 to explore whether reporting moderate or greater pain interference was associated with mortality. The main independent variable was pain that at least moderately interfered with work based on a single question from the SF-12. Primary analyses dichotomized at “moderately” or above. Cox proportional hazards models assessed the association between pain interference and death adjusting for demographics, substance use, CD4 count, HIV viral load and co-morbidities. Although significant in unadjusted models (HR = 1.58 (95 % CI 1.03–2.41; p value = 0.04)), after adjusting for confounders, ≥moderate pain interference was not associated with an increased risk of death [aHR = 1.30 (95 % CI 0.81–2.11, p value = 0.28)]. Among HIV-infected persons with alcohol use disorders, we did not detect a statistically significant independent association between pain interference and risk of death after adjustment for potential confounders.     

Investigation of Linezolid Resistance in Staphylococci and Enterococci

The objective of this study was to investigate an apparent increase in linezolid-nonsusceptible staphylococci and enterococci following a laboratory change in antimicrobial susceptibility testing from disk diffusion to an automated susceptibility testing system. Isolates with nonsusceptible results (n = 27) from Vitek2 were subjected to a battery of confirmatory testing which included disk diffusion, Microscan broth microdilution, Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution, gradient diffusion (Etest), 23S rRNA gene sequencing, and cfr PCR. Our results show that there is poor correlation between methods and that only 70 to 75% of isolates were confirmed as linezolid resistant with alternative phenotypic testing methods (disk diffusion, Microscan broth microdilution, CLSI broth microdilution, and Etest). 23S rRNA gene sequencing identified mutations previously associated with linezolid resistance in 16 (59.3%) isolates, and the cfr gene was detected in 3 (11.1%) isolates. Mutations located at positions 2576 and 2534 of the 23S rRNA gene were most common. In addition, two previously undescribed variants (at positions 2083 and 2345 of the 23S rRNA gene) were also identified and may contribute to linezolid resistance.     

Construction and Periplasmic Expression of the Anti-EGFRvIII ScFv Antibody Gene in Escherichia coli

In the previous study, we constructed an expression vector carrying the anti-EGFRvIII scFv antibody gene with V_H-linker-V_L orientation. The proteins were successfully produced in the periplasmic space of Escherichia coli. In this study, we substituted the inserted DNA with V_L-linker-V_H orientation of the anti-EGFRvIII scFv gene and analyzed its expression in E. coli. The DNA fragment was amplified from its cloning vector (pTz-rscFv), subsequently cloned into a previous expression vector containing the pelB signal sequence and his-tag, and then transformed into E. coli TOP10. The recombinant plasmids were characterized by restriction, PCR, and DNA sequencing analyses. The new anti-EGFRvIII scFv antibody proteins have been successfully expressed in the periplasmic compartment of E. coli Nico21(DE3) using 0.1 mM final concentration of IPTG induction. Total proteins, soluble periplasmic and cytoplasmic proteins, solubilized inclusion bodies, and extracellular proteins were analyzed by SDS-PAGE and Western Blot analyses. The results showed that soluble scFv proteins were found in all fractions except from the cytoplasmic space.     

The use and impact of quality of life assessment tools in clinical care settings for cancer patients,with a particular emphasis on brain cancer: insights from a systematic review and stakeholder consultations

Purpose

Patient-reported data are playing an increasing role in health care. In oncology, data from quality of life (QoL) assessment tools may be particularly important for those with limited survival prospects, where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting, particularly those with brain cancer. It also examines facilitators and challenges, and provides implications for policy and practice.

Design

We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit.

Results

The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient–physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address.

Conclusion

Our findings suggest that the use of QoL tools in cancer patients may improve patient–physician communication and have the potential to improve care, but the tools are not currently widely used in clinical practice (in brain cancer nor some other cancer contexts) although they are in clinical trials. There is a need for further research and stakeholder engagement on how QoL tools can achieve most impact across cancer and patient contexts. There is also a need for policy, health professional, research and patient communities to strengthen information exchange and debate, support awareness raising and provide training on tool design, use and interpretation.