Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses.

A role for type II interferon (IFN-gamma) in resolving viral infection is suggested by the correlation of hepatitis C virus (HCV) clearance with enhancement of IFN-gamma-producing activated T cells in the resolution of acute HCV infection. Using vesicular stomatitis virus (VSV), a synergistic direct antiviral effect was documented using IFN-gamma1b and a potent, consensus type I IFN (IFN alfacon-1). Global expression profiling following EC50 exposure to IFN alfacon-1, IFN-gamma1b, or a cocktail of the two allowed the antiviral state to be correlated with induction of a subset of IFN-stimulated genes (ISGs). Genes identified through this analysis corresponded to classic antiviral components, ISGs more recently associated with direct antiviral functions, as well as expressed sequence tags (ESTs) and hypothetical proteins. The magnitude of these antiviral EC50-correlated expression events in human hepatoma (Huh7) cells exposed to clinically relevant doses of IFN alfacon-1, IFN-gamma1b, or a cocktail of the two was also probed because the standard of care for patients with chronic hepatitis C is type I IFN-containing regimens. Relative to type I IFNs used alone, the addition of type II IFN caused enhanced expression not only of many of the genes correlated with the direct antiviral state but also of genes involved in (1) antigen presentation to cytotoxic T lymphocytes (CTLs), (2) macrophage, natural killer (NK), and T helper 1 (Th1) cell recruitment and activation, (3) complement system function, (4) apoptosis, and (5) ISGs with unknown functions. As many of these processes are correlated clinically with resolution of chronic HCV infection, the combined use of these IFNs could display a beneficial effect on viral clearance in patients infected with HCV and other viruses through enhancement of one of these processes or of the direct antiviral state.     

Altered central micro-opioid receptor binding after psychological trauma.

BACKGROUND: Functional neuroimaging studies have detected abnormal limbic and paralimbic activation to emotional probes in posttraumatic stress disorder (PTSD), but few studies have examined neurochemical mechanisms that underlie functional alterations in regional cerebral blood flow. The mu-opioid neurotransmitter system, implicated in responses to stress and suppression of pain, is distributed in and is thought to regulate the function of brain regions that are implicated in affective processing. METHODS: Here we examined the micro-opioid system with positron emission tomography and the micro-opioid receptor-selective radiotracer [11C] carfentanil in 16 male patients with PTSD and two non-PTSD male control groups, with (n = 14) and without combat exposure (n = 15). Differences in micro-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions. RESULTS: Relative to healthy controls, both trauma-exposed groups had lower micro-opioid receptor BP2 in extended amygdala, nucleus accumbens, and dorsal frontal and insular cortex but had higher BP2 in the orbitofrontal cortex. PTSD patients exhibited reduced BP2 in anterior cingulate cortex compared with both control groups. Micro-opioid receptor BP2 in combat-exposed subjects without PTSD was lower in the amygdala but higher in the orbitofrontal cortex compared with both PTSD patients and healthy controls. CONCLUSIONS: These findings differentiate the general response of the micro-opioid system to trauma from more specific changes associated with PTSD.     

PR05POST‐OPERATIVE HAEMATOMAS IN MICROVASCULAR FREE FLAP RECONSTRUCTION OF THE HEAD AND NECK: THE INCIDENCE,AETIOLOGY AND OUTCOME MODIFICATIONS

Background Free tissue transfer using microvascular surgery has become a safe a reliable means to repair soft tissue and/or bony defects of the head and neck. Operative success reaches 98%, however the incidence of significant post‐operative complication is also relatively high (32%). One common and often severe complication is haematoma formation at either donor or recipient sites. The incidence of recipient site haematoma is reported at 6%, however the causes and outcomes of haematomas have not been well investigated. A retrospective historical analysis of both donor and recipient site wound haematoma was performed to identify causative factors and the effect on patient outcome. Methodology A five year review was conducted for microvascular free tissue transfer to defects in the head and neck at The Royal Melbourne Hospital, for the period from February 2001 until February 2006. The medical records of these 150 patients were reviewed for donor and recipient site wound haematoma and outcomes. Results Significant factors for the development of post‐operative haematomas included lood pressure control during the first post‐operative, correlating with the likelihood of developing either a donor or recipient site haematoma (p value < 0.001), drain‐tube outputs (both high and low), smoking and the use of pre‐operative NSAIDs. Conclusion There are significant reversible factors that contribute to the development of post‐operative haematomas in head and neck surgery. Close monitoring of patient blood pressure by theatre and recovery nursing staff, close monitoring of drain outputs, and pre‐operative counselling on the use of NSAIDs and smoking may all be useful in the prevention of haematoma formation.     

Evidence of sustained skeletal benefits from impact-loading exercise in young females: a 3-year longitudinal study.

The skeletal effects from intensive exercise throughout puberty are undefined. Forty-five female gymnasts and 52 controls were studied over 3 years, including a heredity aspect. The effects of size, maturity, exercise, and diet were identified using a multilevel regression model. Results demonstrated sustained skeletal benefits resulting from exercise throughout all stages of pubertal development. INTRODUCTION: Weight-bearing exercise is beneficial for peak bone mass development. However, whether skeletal benefits achieved with exercise are maintained if training remains intensive throughout the pubertal years is not entirely clear. The influence of familial resemblance for bone mass remains undefined in physically active versus inactive children. The aim of this study was to investigate the long-term influences of impact-loading exercise on bone quantity and quality in young females after controlling for growth, maturation, and hereditary factors. MATERIALS AND METHODS: At baseline, 45 gymnasts (G) and 52 normally active controls (C) 8-17 years of age were recruited. Anthropometry, diet, physical activity, and quantitative ultrasound (QUS) were measured annually for 3 consecutive years. DXA scans of total body (TB) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) were taken three times at 1-year intervals. A multilevel regression model was fitted, and the independent effects of body size, maturity, physical activity, and diet were identified over time. To assess heredity influences, 27 G mothers and 26 C mothers volunteered for cross-sectional measurements of anthropometry, QUS, and BMC/BMD. RESULTS AND CONCLUSIONS: Gymnasts were smaller and lighter (as were their mothers) than controls, but they had significantly higher QUS and axial and appendicular BMC and BMD, with > 170 g more bone mineral in TB across puberty (after adjustment for maturity [years from peak height velocity], height, weight, energy, and protein intake). Gymnasts had up to 24-51% higher BMC and 13-28% higher BMD, depending on skeletal site. These results provide evidence of sustained skeletal benefits from impact-loading exercise, which are unlikely to result entirely from heredity, throughout pubertal years.     

Resident parents and shorter hospital stay.

A total of 586 admissions for 12 medical conditions were reviewed. The stay of children accompanied by a resident parent was 31% shorter than those whose parents were not resident. Resident parents benefit the emotional well being of the child and increase hospital efficiency; accommodation for parents should therefore be an integral part of a unit admitting children.