Oral ulceration in HIV infection: Investigation and pathogenesis

Oral ulcerations associated with HIV infection include recurrent aphthous ulcers (RAU). Whereas RAU prevalence is not increased, lesion severity is: among a group of HIV⁺ patients, 66% had the more severe herpetiform or major RAU. This increased severity suggests that HIV disease-related changes in the immune system may exacerbate RAU. In the peripheral blood of healthy subjects with RAU, CD4:CD8 cell ratios may be reversed and the proportion of T cell receptor-γδ⁺ cells increased. HIV disease-related immune system changes are characterized by reversed CD4:CD8, lowered CD4 cell counts and an inverse correlation between CD4 cell counts and per cent activated γδ lymphocytes. Adhesion molecules and cytokines involved in lymphocyte homing may be important in RAU pathogenesis: ICAM-I and ELAM are strongly expressed, and TNFα production is increased in peripheral blood lymphocytes of healthy patients with RAU. In patients with active HIV disease/AIDS, serum TNFα levels are increased. Thalidomide, which inhibits TNFα production, is effective treatment for RAU. Some RAU patients have vitamin B12 or folate deficiencies, levels of which are commonly low in HIV⁺/AIDS patients. However, in a case control study of HIV⁺ patients, vitamin B12- or folate-deficiencies were not found to be significant risk factors for RAU.     

Epstein-Barr virus BMRF-2 and BDLF-3 expression in hairy leukoplakia

Hairy leukoplakia (HL) is a lesion found on the side of the tongue of immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection. The lesion has unique histopathologic features and is characterised by high-level Epstein-Barr virus (EBV) replication, multiple EBV strains, and extensive inter-and intra-strain recombination. Expression of EBV genes spanning the entire viral life cycle from latency-associated genes to late, replicative genes has been detected in the lesion. HL thus provides a unique opportunity to study EBV expression in oral epithelium, and to study expression of novel EBV genes. We therefore constructed a cDNA library from an HL biopsy and detected expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs revealed few amino acid changes from the B95-8 sequence. Expression of both genes was localized to the lower prickle cell layer of the tongue epithelium. BMRF-2 protein expression was primarily detected in the cell nuclei of the upper prickle cell layer. BDLF-3 protein expression was observed in the perinuclear space and Golgi compartment. The function of these proteins is currently under investigation.     

Chronic-intermittent hypoxia: a model of sympathetic activation in the rat

This review focuses upon the development of a small animal model that incorporates exposure to chronic-intermittent hypoxia to produce systemic hypertension similar to that experienced by humans with the obstructive sleep apnea syndrome. It has been suggested that experimentally-induced hypertension, like human hypertension, is due to activation of the sympathetic nervous system. That hypothesis is supported by physiological studies carried out in humans with obstructive sleep apnea as well as in animals exposed to chronic-intermittent hypoxia. Furthermore, recent anatomical studies of exposed animals strongly suggested that activation was widespread and included cortical and brainstem components of the sympathetic system. Such findings, while illustrating the complexity of modeling human disease in animals, also demonstrate the heuristic value of chronic-intermittent hypoxia as an experimental approach.     

Establishment of a system to standardize acceptability criteria for alanine aminotransferase activity in donated blood

A multilaboratory study was conducted to develop a system for standardizing alanine aminotransferase (ALT) acceptability criteria ("cutoffs") for donated blood. Without standardized cutoffs, each laboratory must develop its own cutoff, and this may not make optimal use of ALT testing to reduce transmission of non-A, non-B hepatitis (NANB). Defining an ALT acceptability criterion in absolute terms is necessary because relative cutoffs based on local donor populations may be affected by the prevalence of NANB in each community. This study involved 16 laboratories using 23 different analytic systems. The ALT results of the analysis of a plasma reference sample could be used to translate mathematically a single, absolute cutoff to units applicable to each analytic system. The distribution of ALT results in 1.4 million donations from across the country was established; basing the cutoff on this sample avoids the problems inherent in using a local donor base to establish a cutoff. We propose the implementation of a system to standardize ALT acceptability criteria to an activity level defined by analysis of a nationwide donor sample.     

Centronuclear myopathies: genotype–phenotype correlation and frequency of defined genetic forms in an Italian cohort

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype–phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four ‘canonical’ genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood–adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.     

Innovative service delivery for secondary prevention of PTSD in at-risk OIF-OEF service men and women

Service personnel involved in Operation Enduring Freedom/Operation Iraqi Freedom are at high risk for trauma-related physical injury and emotional problems, including posttraumatic stress disorder (PTSD) and major depression. Although evidence-based psychotherapies are increasingly available and effective in treating symptoms of PTSD, a large number of service personnel are reluctant to seek mental health treatments due to both perceived stigma associated with these treatments and geographically-based barriers to care at specialized treatment facilities. The present investigation evaluates an innovation in service delivery designed to address these concerns. Specifically, we are comparing exposure-based therapy for PTSD delivered via traditional, in-person settings to the same exposure-based treatment delivered via telehealth technology. The proposed project is a prospective, randomized repeated measures design with two treatment groups (telehealth and in-person) assessed at pre-treatment, mid-treatment, post-treatment and 3- and 12-month follow-up points. Outcome measures ascertain longer-term effects of the treatments on three domains: clinical, process, and economic. Non-inferiority and superiority analyses will be conducted to determine symptom changes between pre-treatment, post-treatment, and follow-up time points between the two treatment conditions. The study will determine whether an exposure therapy for PTSD delivered via telehealth is at least as successful as the same exposure-based therapy delivered in-person in treating the symptoms of PTSD in both subthreshold and fully diagnosed cases.     

Coordinating Canada's research response to global health challenges: the Global Health Research Initiative

The Global Health Research Initiative (GHRI) involving the Canadian International Development Agency, the Canadian Institutes of Health Research, Health Canada and the International Development Research Centre seeks to coordinate Canada's research response to global health challenges. In light of numerous calls to action both nationally and internationally, an orientation to applied health policy and systems research, and to public health research and its application is required to redress global inequalities in wealth and health and to tackle well-documented constraints to achieving the United Nations Millennium Development Goals. Over the last four years, the GHRI has funded close to 70 research program development and pilot projects. However, longer-term investment is needed. The proposed dollars 100 million Teasdale-Corti Global Health Research Partnership Program is such a response, and is intended to support teams of researchers and research users to develop, test and implement innovative approaches to strengthening institutional capacity, especially in low- and middle-income countries; to generating knowledge and its effective application to improve the health of populations, especially those most vulnerable; and to strengthen health systems in those countries. While Canada stands poised to act, concerted leadership and resources are still required to support "research that matters" for health and development in low- and middle-income countries.     

Aqueductal stenosis 9 years after mumps meningoencephalitis: treatment by endoscopic third ventriculostomy

Introduction Hydrocephalus due to aqueductal stenosis following mumps meningoencephalitis is a rare condition, reported only in 16 cases in the literature. The pathogenetic role of the mumps virus in inducing aqueductal stenosis has been demonstrated experimentally in animal models and clinically proven in a few cases. Although obstructive in nature, the post-infectious etiology raises the question as to whether third ventriculostomy is the appropriate treatment.Patient We report a case of hydrocephalus due to pure aqueductal stenosis occurring in an 11-year-old boy who suffered from mumps meningoencephalitis 9 years previously. The boy was successfully treated by endoscopic third ventriculostomy.Conclusions The present case offers further evidence of the purely obstructive nature of the hydrocephalus induced by paramyxovirus meningoencephalitis, even if it did occur several years after the infectious disease. The pathogenesis of mumps-induced hydrocephalus and the rationale of treatment are discussed, and the literature is reviewed.