Variant of Subclavian Steal in the Setting of Ipsilateral Common Carotid Artery Occlusion: Case Report

Subclavian steal is a well-described angiographic finding and clinical syndrome that rarely results in vertebrobasilar ischemic symptoms. In classic subclavian steal, left subclavian artery (SA) stenosis occurs proximal to the left vertebral artery (VA) origin. We report a symptomatic variant of this syndrome that occurred in the setting of left common carotid artery occlusion and anomalous origin of the left VA directly from the aortic arch. The steal and symptoms resolved after stenting of the left SA stenosis.     

The influence of cold water immersions on adaptation following a single bout of damaging exercise

The aim of this investigation was to elucidate the effects of cold water immersions (CWIs) following damaging exercise on the repeated bout effect (RBE). Sixteen males performed two bouts of drop jump exercise separated by 14–21 days. Participants were equally, but randomly assigned to either a CWI (12-min CWI at 15°C) or control group (12-min seated rest). Treatments were given immediately after the first exercise bout, 24, 48 and 72 h post-exercise. No interventions were given following the second bout. Maximum voluntary contraction (MIVC), soreness (DOMS), creatine kinase (CK), thigh girth and range of motion (ROM) were recorded before and for 96 h following the initial and repeated bouts of damaging exercise. All variables, except ROM, showed a significant time effect (P < 0.01) indicating the presence of muscle damage following the initial bout; there were no differences between the CWI and control groups after the initial bout. Following the repeated bout of exercise there was a significant attenuation in the reduction of MIVC (P = 0.002) and a reduction in DOMS (P < 0.001), which is indicative of the RBE. There were no significant differences between groups following the repeated bout of damaging exercise. These data show that CWI had no effect following damaging exercise and did not inhibit the RBE. Despite CWI being used routinely, its efficacy remains unclear and there is a need to elucidate the benefits of this intervention on recovery and adaptation to provide practitioners with evidence based practice.     

Approaches to reducing the most important patient errors in primary health‐care: patient and professional perspectives

We have previously reported a preliminary taxonomy of patient error. However, approaches to managing patients’ contribution to error have received little attention in the literature. This paper aims to assess how patients and primary care professionals perceive the relative importance of different patient errors as a threat to patient safety. It also attempts to suggest what these groups believe may be done to reduce the errors, and how. It addresses these aims through original research that extends the nominal group analysis used to generate the error taxonomy. Interviews were conducted with 11 purposively selected groups of patients and primary care professionals in Auckland, New Zealand, during late 2007. The total number of participants was 83, including 64 patients. Each group ranked the importance of possible patient errors identified through the nominal group exercise. Approaches to managing the most important errors were then discussed. There was considerable variation among the groups in the importance rankings of the errors. Our general inductive analysis of participants’ suggestions revealed the content of four inter‐related actions to manage patient error: Grow relationships; Enable patients and professionals to recognise and manage patient error; be Responsive to their shared capacity for change; and Motivate them to act together for patient safety. Cultivation of this GERM of safe care was suggested to benefit from ‘individualised community care’. In this approach, primary care professionals individualise, in community spaces, population health messages about patient safety events. This approach may help to reduce patient error and the tension between personal and population health‐care.     

Screening of Predicted Secreted Antigens from Mycobacterium bovis Reveals the Immunodominance of the ESAT-6 Protein Family

Results of previous studies utilizing bioinformatic approaches in antigen-mining experiments revealed that secreted proteins are among the most frequently recognized antigens from Mycobacterium bovis. Thus, we hypothesized that the analysis of secreted proteins is likely to reveal additional immunogenic antigens that can be used to increase the specificity of diagnostic tests or be suitable vaccination candidates for mycobacterial infections. To test this hypothesis, 382 pools of overlapping peptides spanning 119 M. bovis secreted and potentially secreted proteins were screened for the ability to stimulate a gamma interferon response in vitro using whole blood from tuberculin-positive reactor (TB reactor) cattle. Of the 119 proteins screened, 70 (59%) induced positive responses in the TB reactor animals to various degrees. Strikingly, all but one of the 15 ESAT-6 proteins tested were recognized by at least 30% of the TB reactor animals, with 12 of the 22 most commonly recognized antigens belonging to this protein family. Further analysis of these data demonstrated that there was no significant difference in immunogenicity between the ESAT-6 proteins that were components of potentially intact ESX secretory systems and those corresponding to additional partial esx loci. Importantly for vaccine design, antigenic epitopes in some highly conserved regions shared by numerous ESAT-6 proteins were identified. However, despite this considerable homology, peptide-mapping experiments also revealed that immunodominant peptides were located in regions of amino acid variability.The incidence of bovine tuberculosis (BTB), a zoonotic infection in cattle caused by Mycobacterium bovis, has been steadily rising in Great Britain over the last 20 years despite the current “test and slaughter” control policy (13). The desire for an effective cattle vaccine to help control the spread of infection has been acknowledged by the British government. To date, the only available vaccine for BTB is M. bovis bacillus Calmette-Guérin (BCG), which has shown various degrees of efficacy in cattle (6, 8, 35). Recent developments show that, using a heterologous prime-boost vaccine strategy, the efficacy of BCG vaccination is significantly improved following boosting with DNA (24), protein (36), or virus (30-32) subunit vaccines. However, vaccination with BCG results in sensitization of animals to bovine tuberculin and compromises the single intradermal comparative tuberculin test (SICCT) currently used for diagnosis of BTB. Thus, the identification of novel immunogenic proteins for use as vaccine candidates and/or as reagents in diagnostic tests able to differentiate M. bovis-infected and uninfected vaccinated animals is of high research priority.A longstanding concept in tuberculosis research is that active secretion of antigenic proteins by mycobacteria induces strong cellular immune responses in the host. Indeed, in our own antigen-mining experiments with M. bovis-infected cattle, we have previously observed that secreted proteins in general, and members of the ESAT-6 protein family in particular, are among the most frequently recognized antigens from M. bovis. The ESAT-6 protein family comprises 23 small proteins (approximately 100 amino acids) that show amino acid sequence similarity to either ESAT-6 or CFP-10, proteins encoded by the adjacent esxA and esxB genes, respectively, which are located at the ESX-1 locus. The genes encoding the 23 proteins that constitute the ESAT-6 family are dispersed throughout the genome, with the genes for 10 members located within the ESX-1 to ESX-5 loci; the genes encoding the other 13 members are not located within ESX loci 1 to 5. The ESX loci are thought to have originated through multiple duplication events, beginning with the ESX-4 locus (16).Of all the members of the ESAT-6 protein family, ESAT-6 and CFP-10 have been the most extensively investigated. Although lacking classical signal sequences, ESAT-6 and CFP-10 can be isolated from M. tuberculosis culture filtrate (7, 27) and are thought to be secreted via the ESX-1/type VII secretion system (3). ESAT-6 and CFP-10 form a stable, fully folded structure only when present as a heterodimer (23), the formation of which appears to be crucial for their secretion (17). Given that Rv0287 and Rv0288 (two ESAT-6 proteins that show homology to CFP-10 and ESAT-6, respectively) also form a heterodimer (20), it has been suggested that this may be a general, characteristic feature of all ESAT-6 couplets. Both ESAT-6 and CFP-10 have been demonstrated previously to be strong immunogens in numerous infection models, including humans (18, 22, 29), mice (5), cattle (2, 21), and guinea pigs (1, 15, 26). Furthermore, immune responses directed against other ESAT-6 proteins have been identified in M. bovis-infected cattle (1, 2, 12, 19). Lastly, antigenic epitopes in several ESAT-6 proteins have also been characterized in human studies (4, 25), although these experiments were performed with a limited number of individuals.The aim of the present study is to investigate the immunogenicity of potential M. bovis secreted antigens by using a cattle model of M. bovis infection. Pools of overlapping peptides representing the ESAT-6 protein family and a complete list of potentially secreted M. bovis antigens identified through in silico analysis of M. tuberculosis H37Rv were assessed for the ability to induce gamma interferon (IFN-γ) production in whole-blood assays. In addition, IFN-γ responses to individual peptides were evaluated to identify the immunodominant epitopes within antigenic proteins.     

Dopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery – An in vivo Molecular Imaging Study in Humans

Objectives:

To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.

Design:

Prospective study.

Setting:

Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [^99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.

Patients or Participants:

Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).

Measurements and Results:

Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.

Conclusion:

Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.

Citation:

Martins, RCS; Andersen ML; Garbuio SA; Bittencourt LR: Guindalini C; Shih MC; Hoexter MQ; Bressan RA; Castiglioni MLV; Tufik S. Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery – an in vivo molecular imaging study in humans. SLEEP 2010;33(2):243-251.     

Mesenchymal Stem Cells Arrest Intervertebral Disc Degeneration Through Chondrocytic Differentiation and Stimulation of Endogenous Cells

Degenerative disc disease (DDD) is a common disease which affects millions of people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have been shown to have the ability to arrest degeneration in rabbit and canine intervertebral discs. In this study, we have used the mouse model to investigate the mechanism of degeneration arrest. BMSC from Egfp transgenic mice were injected into the degenerated murine intervertebral discs induced by annular puncture. We found that BMSC could arrest the progressive degeneration of the discs with significant regeneration of the nucleus pulposus (NP). In the regeneration, expression of proteoglycan genes were upregulated and extracellular matrix (ECM) progressively accumulated in the NP after BMSC injection. Combined in situ hybridization and immunohistochemistry revealed that BMSC underwent chondrocytic differentiation in the regeneration process. Interestingly, BMSC-induced an increase of endogenous notochordal cells in NP and expression of chondrocytic markers. In this study, we have firstly shown that the BMSC could arrest the degeneration of the murine notochordal NP and contribute to the augmentation of the ECM in the NP by both autonomous differentiation and stimulatory action on endogenous cells.     

Expression of osteopontin in the rat retina: effects of excitotoxic and ischemic injuries

PURPOSE: The cytokine osteopontin (OPN) has been localized to the retinal ganglion cell layer in the normal rodent retina, prompting the suggestion that it could serve as a useful marker for identifying and quantifying such neurons in models of retinal and optic nerve neurodegeneration. In the present study, we characterized the time course and cellular localization of OPN expression in the rat retina after excitotoxic and ischemic injuries. METHODS: Excitotoxicity and ischemia-reperfusion experiments were performed by using standard techniques. Rats were killed at various time points, and the retinas were removed either for mRNA analysis or to be processed for immunohistochemistry. RESULTS: In the normal retina, double-labeling immunofluorescence indicated that OPN is expressed by the majority of, if not all, RGCs, since OPN was associated with more cells than Brn-3, but was colocalized with Thy1.1. NMDA, kainic acid, and ischemia-reperfusion all caused decreases in the total retinal levels of Thy1 and Brn-3 mRNAs, reflecting injury to RGCs, but a dramatic, short-lived upregulation in OPN mRNA. The source of the increased OPN signal after excitotoxic-ischemic insults is unlikely to be injured RGCs, as no alteration in the intensity of OPN immunostaining in RGCs was apparent. Instead, additional cells, mostly contained within the IPL, were identified as positive for OPN. Double-labeling immunofluorescence showed that ED1 always colocalized with OPN in these cells, indicating their status as activated microglia. CONCLUSIONS: OPN is exclusively expressed by RGCs in the physiological retina, but in response to retinal neurodegeneration is synthesized de novo by endogenous, activated microglia.