Ventromedial frontal lobe plays a critical role in facial emotion recognition

The ventromedial prefrontal cortex has been implicated in a variety of emotion processes. However, findings regarding the role of this region specifically in emotion recognition have been mixed. We used a sensitive facial emotion recognition task to compare the emotion recognition performance of 7 subjects with lesions confined to ventromedial prefrontal regions, 8 subjects with lesions elsewhere in prefrontal cortex, and 16 healthy control subjects. We found that emotion recognition was impaired following ventromedial, but not dorsal or lateral, prefrontal damage. This impairment appeared to be quite general, with lower overall ratings or more confusion between all six emotions examined. We also explored the relationship between emotion recognition performance and the ability of the same patients to experience transient happiness and sadness during a laboratory mood induction. We found some support for a relationship between sadness recognition and experience. Taken together, our results indicate that the ventromedial frontal lobe plays a crucial role in facial emotion recognition, and suggest that this deficit may be related to the subjective experience of emotion.     

The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium

OBJECTIVE: Marrow-derived endothelial progenitor cells (EPCs) are important in the neovascularization that occurs in diverse conditions such as cardiovascular disorders, inflammatory diseases, and neoplasms. In rheumatoid arthritis (RA), synovial neovascularization propels disease by nourishing the inflamed and hyperproliferative synovium. This study was undertaken to investigate the hypothesis that EPCs selectively home to inflamed joint tissue and may perpetuate synovial neovascularization. METHODS: In a collagen-induced arthritis (CIA) model, neovascularization and EPC accumulation in mouse ankle synovium was measured. In an antibody-induced arthritis model, EPC recruitment to inflamed synovium was evaluated. In a chimeric SCID mouse/human synovial tissue (ST) model, mice were engrafted subcutaneously with human ST, and EPC homing to grafts was assessed 2 days later. EPC adhesion to RA fibroblasts and RA ST was evaluated in vitro. RESULTS: In mice with CIA, cells bearing EPC markers were significantly increased in peripheral blood and accumulated in inflamed synovial pannus. EPCs were 4-fold more numerous in inflamed synovium from mice with anti-type II collagen antibody-induced arthritis versus controls. In SCID mice, EPC homing to RA ST was 3-fold greater than to normal synovium. Antibody neutralization of vascular cell adhesion molecule 1 (VCAM-1) and its ligand component alpha4 integrin potently inhibited EPC adhesion to RA fibroblasts and RA ST cryosections. CONCLUSION: These data demonstrate the selective recruitment of EPCs to inflamed joint tissue. The VCAM-1/very late activation antigen 4 adhesive system critically mediates EPC adhesion to cultured RA fibroblasts and to RA ST cryosections. These findings provide evidence of a possible role of EPCs in the synovial neovascularization that is critical to RA pathogenesis.     

A comparison of epinephrine and norepinephrine in critically ill patients

Objective  To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients. Design  Prospective, double-blind, randomised-controlled trial. Setting  Four Australian university-affiliated multidisciplinary ICUs. Patients and participants  Patients who required vasopressors for any cause at randomisation. Patients with septic shock and acute circulatory failure were analysed separately. Interventions  Blinded infusions of epinephrine or norepinephrine to achieve a MAP ≥70 mmHg for the duration of ICU admission. Measurements  Primary outcome was achievement of MAP goal >24 h without vasopressors. Secondary outcomes were 28 and 90-day mortality. Two hundred and eighty patients were randomised to receive either epinephrine or norepinephrine. Median time to achieve the MAP goal was 35.1 h (interquartile range (IQR) 13.8–70.4 h) with epinephrine compared to 40.0 h (IQR 14.5–120 h) with norepinephrine (relative risk (RR) 0.88; 95% confidence interval (CI) 0.69–1.12; P = 0.26). There was no difference in the time to achieve MAP goals in the subgroups of patients with severe sepsis (n = 158; RR 0.81; 95% CI 0.59–1.12; P = 0.18) or those with acute circulatory failure (n = 192; RR 0.89; 95% CI 0.62–1.27; P = 0.49) between epinephrine and norepinephrine. Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study by attending clinicians. There was no difference in 28 and 90-day mortality. Conclusions  Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients. This study was presented at the Annual Congress of the European Society of Intensive Care Medicine in Berlin on October 10 2007. The presentation received the International Sepsis Forum prize for best abstract and paper. This study has been published in abstract form: Myburgh J.A., Higgins A., Jovanovska A., Lipman J., Ramakrishnan N., Santamaria J and the CAT Study Investigators. (2007). A comparison of epinephrine and norepinephrine on reversal of shock. Intensive Care Medicine 33 (Supplement 2): S197. Trial registration: The study was registered with Current Controlled Studies: ISRCTN number 92846592.     

Use of aerosolized aminoglycosides in the treatment of Gram-negative ventilator-associated pneumonia

BACKGROUND AND PURPOSE : Ventilator-associated pneumonia (VAP) in the surgical intensive care unit (ICU) is associated with substantial morbidity and mortality. Affected patients are at higher risk for infection with multi-drug-resistant (MDR) pathogens, often necessitating therapeutic regimens of two parenteral antibiotics. Aerosolized antibiotics achieve high alveolar concentrations and have been reported anecdotally to have value in the treatment of VAP. This study examined the role of aerosolized aminoglycosides in the treatment of VAP in surgical ICU patients. METHODS: We reviewed retrospectively the medical records of 22 patients who received aerosolized aminoglycosides in conjunction with parenteral antibiotics for VAP in the surgical ICU. Sixteen patients received inhaled tobramycin, and six received inhaled amikacin. Demographic information and data on the length of stay (LOS), mortality rate, days of antibiotic therapy, days of mechanical ventilation, and recurrence of VAP were collected. Results of bronchoscopic and sputum cultures were reviewed to identify bacterial pathogens and antimicrobial susceptibilities. RESULTS: The average duration of mechanical ventilation was 31 +/- 12 days, the mean ICU LOS was 41 +/- 13 days, and the mean hospital LOS was 71 +/- 25 days. There were three deaths. The average duration of mechanical ventilation after initiation of aerosolized antibiotics was 4.3 days. Seven patients (40%) developed recurrent pneumonia with the same pathogen, but only one had a change in antibiotic susceptibility pattern. There were no renal or pulmonary complications of aminoglycoside treatment. CONCLUSIONS: Ventilator-associated pneumonia in critically ill patients is associated with substantial morbidity, longer ICU stays, and prolonged mechanical ventilation. Along with systemic therapy, aerosolized aminoglycosides are valuable adjuncts in select patients with minimal risk of antibiotic resistance.     

Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries

The G101W founder mutation is the most common CDKN2A mutation in Italy, Spain, and France. As the background of modifying genes, environmental exposures, and sun behavior vary across countries, studying G101W carriers from distinct countries offers a unique opportunity to evaluate possible modifying factors in melanoma development. We evaluated 76 G101W cases and 59 carrier controls from France, Italy, Spain, and the United States. Hair color and dysplastic nevi distributions differed significantly in cases and controls across the 4 study groups. Cases also varied significantly for eye color, freckling, and nevi. The distribution of MC1R variants in cases differed significantly across study groups because 12% of Italian melanoma patients had > or =2 MC1R variants vs. >50% for the other case groups. Several MC1R covariates showed significant associations with melanoma risk in all groups combined and in the American, French, and Spanish samples; no significant findings were observed in the Italian sample. In multiple-case families, the number and type of MC1R variants varied significantly between multiple-primary-melanoma and single-primary-melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of MC1R variants increased. The variation in the effects of the cutaneous phenotypic and MC1R factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline CDKN2A mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered.     

News from the National Institute of General Medical Sciences (NIGMS)

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Investigating the Influence of Haemodynamic Stimuli on Intracranial Aneurysm Inception

We propose a novel method to reconstruct the hypothetical geometry of the healthy vasculature prior to intracranial aneurysm (IA) formation: a Frenet frame is calculated along the skeletonization of the arterial geometry; upstream and downstream boundaries of the aneurysmal segment are expressed in terms of the local Frenet frame basis vectors; the hypothetical healthy geometry is then reconstructed by propagating a closed curve along the skeleton using the local Frenet frames so that the upstream boundary is smoothly morphed into the downstream boundary. This methodology takes into account the tortuosity of the arterial vasculature and requires minimal user subjectivity. The method is applied to 22 clinical cases depicting IAs. Computational fluid dynamic simulations of the vasculature without IA are performed and the haemodynamic stimuli in the location of IA formation are examined. We observe that locally elevated wall shear stress (WSS) and gradient oscillatory number (GON) are highly correlated (20/22 for WSS and 19/22 for GON) with regions susceptible to sidewall IA formation whilst haemodynamic indices associated with the oscillation of the WSS vectors have much lower correlations.     

Sharps-related injuries in California healthcare facilities: pilot study results from the Sharps Injury Surveillance Registry.

BACKGROUND AND OBJECTIVES: In 1998, the California Department of Health Services invited all healthcare facilities in California (n = 2,532) to participate in a statewide, voluntary sharps injury surveillance project. The objectives were to determine whether a low-cost sharps registry could be established and maintained, and to evaluate the circumstances surrounding sharps injuries in California. RESULTS: Approximately 450 facilities responded and reported a total of 1,940 sharps-related injuries from January 1998 through January 2000. Injuries occurred in a variety of healthcare workers (80 different job titles). Nurses sustained the highest number of injuries (n = 658). In hospital settings (n = 1,780), approximately 20% of the injuries were associated with drawing venous blood, injections, or assisting with a procedure such as suturing. As expected, injuries were caused by tasks conventionally related to specific job classifications. The overall results approximate those reported by the Centers for Disease Control and Prevention's National Surveillance System for Health Care Workers and the University of Virginia's Exposure Prevention Information Network. CONCLUSION: These data further support findings from previous studies documenting the complex and persistent nature of sharps-related injuries in healthcare workers. In the future, mandated reporting using standardized forms and consistent application of decision rules would facilitate a more thorough analysis of injury events.