Randomized control trial for evaluation of a hands-free pointer for surgical instruction during laparoscopic cholecystectomy.

INTRODUCTION: Training surgeons in minimally invasive surgery (MIS) requires surgical residents to operate under the direction of a consultant. The inability of the instructing surgeon to point at the laparoscopic monitor without releasing the instruments remains a barrier to effective instruction. The wireless hands-free surgical pointer (WHaSP) has been developed to aid instruction during MIS. METHODS: The objective of this study was to evaluate the effectiveness and likeability of the WHaSP as an instructional tool compared with the conventional methods. Data were successfully collected during 103 laparoscopic cholecystectomy procedures, which had been randomized to use or not use the WHaSP as a teaching tool. Audio and video from the surgeries were recorded and analyzed. Instructing surgeons, operating surgeons, and camera assistants provided feedback through a post-operative questionnaire that used a five-level Likert scale. The questionnaire results were analyzed using a Mann-Whitney U test. RESULTS: There were no negative effects on surgery completion time or instruction practice due to the use of the WHaSP. The number of times an instructor surgeon pointed to the laparoscopic screen with their hand was significantly reduced when the WHaSP was utilized (p < 0.001). The questionnaires showed that WHaSP users found it to be comfortable, easy to use, and easy to control. Compared to when the WHaSP was not used, users found that communication was more effective (p = 0.002), locations were easier to communicate (p < 0.001), and instructions were easier to follow (p = 0.005). CONCLUSIONS: The WHaSP system was successfully used in surgery. It integrated seamlessly into existing equipment within the operating room and did not affect flow. The positive outcomes of utilizing the WHaSP were improved communication in the OR, improved efficiency and safety of the surgery, easy to use, and comfortable to wear. The surgeons showed a preference for utilizing the WHaSP if given a choice.

CCR5 blockade is well tolerated and induces changes in the tissue distribution of CCR5+ and CD25+ T cells in healthy, SIV-uninfected rhesus macaques.

BACKGROUND: CCR5 is a main co-receptor for HIV, but also homes lymphocytes to sites of inflammation. We hypothesized that inhibition of CCR5 signaling would reduce HIV-associated chronic immune activation. METHODS: To test this hypothesis, we administered an antagonistic anti-CCR5 monoclonal antibody (HGS101) to five uninfected rhesus macaques (RMs) and monitored lymphocyte dynamics in blood and tissue. RESULTS: CCR5 blockade resulted in decreased levels of CCR5+ T cells in blood and, at later timepoints, in lymph nodes. Additionally, the levels of CD25+ T cells increased in lymph nodes, but decreased in blood, bone marrow, and rectal mucosa. Finally, a profile of gene expression from HGS101-treated RMs revealed a subtle, but consistent, in vivo signature of CCR5 blockade that suggests a mild immune-modulatory effect. CONCLUSIONS: Treatment with anti-CCR5 antibody induces changes in the tissue distribution of CCR5+ and CD25+ T cells that may impact on the overall levels of immune activation during HIV and SIV infection.

Is patient-centred care a good thing?

THE PROBLEM: Rehabilitation professionals recognize the need to adopt a social as well as a medical model of disability, but the full implications of a social orientation towards disability are less easily accepted. If the physical environment can both produce and alleviate disability, so also can the social environment. If disablement is not to be seen as the problem of one individual then problems in rehabilitation must be 'owned' not solely by a single patient but also by other people implicated in a situation. It follows that 'patient-centred care', where a professional directs assessments and interventions towards one person, has shortcomings in rehabilitation. THEORETICAL CONSIDERATIONS: A human systems model, shifting the focus of rehabilitation towards relationships, enables rehabilitation problems to be seen as provisional and context-dependent; the relational context of problems is clarified, and the positive and negative effects of professional power are more apparent. CLINICAL IMPLICATIONS: Rehabilitation practitioners using a systemic approach would no longer view 'carers' and other significant individuals as mere bystanders but would integrate them within rehabilitation's ethical and therapeutic system. Professionals would more readily recognize their roles within such a system, and would be better positioned to manage their negative as well as their positive effects.

B-cell homeostasis requires complementary CD22 and BLyS/BR3 survival signals.

Peripheral B-cell numbers are tightly regulated by homeostatic mechanisms that influence the transitional and mature B-cell compartments and dictate the size and clonotypic diversity of the B-cell repertoire. B-lymphocyte stimulator (BLyS, a trademark of Human Genome Sciences, Inc.) plays a key role in regulating peripheral B-cell homeostasis. CD22 also promotes peripheral B-cell survival through ligand-dependent mechanisms. The B-cell subsets affected by the absence of BLyS and CD22 signals overlap, suggesting that BLyS- and CD22-mediated survival are intertwined. To examine this, the effects of BLyS insufficiency following neutralizing BLyS mAb treatment in mice also treated with CD22 ligand-blocking mAb were examined. Combined targeting of the BLyS and CD22 survival pathways led to significantly greater clearance of recirculating bone marrow, blood, marginal zone and follicular B cells than either treatment alone. Likewise, BLyS blockade further reduced bone marrow, blood and spleen B-cell numbers in CD22(-/-) mice. Notably, BLyS receptor expression and downstream signaling were normal in CD22(-/-) B cells, suggesting that CD22 does not directly alter BLyS responsiveness. CD22 survival signals were likewise intact in the absence of BLyS, as CD22 mAb treatment depleted blood B cells from mice with impaired BLyS receptor 3 (BR3) signaling. Finally, enforced BclxL expression, which rescues BR3 impairment, did not affect B-cell depletion following CD22 mAb treatment. Thus, the current studies support a model whereby CD22 and BLyS promote the survival of overlapping B-cell subsets but contribute to their maintenance through independent and complementary signaling pathways.

On doing nothing: descriptions of sleep, fatigue, and motivation in encephalitis lethargica.

Epidemics of encephalitis lethargica (EL), from 1917 to the 1930s, are an important milestone in the history of movement disorders. Today, the two best-known features of EL are somnolence and parkinsonism but the full clinical picture was variable and complex. States of wakeful inactivity--as opposed to drowsiness--were often described both in the acute and postacute stages and were referred to in the EL literature as "lethargy" or "torpor." The study described here is based on a survey of clinical descriptions published in English, French, and German from 1917 to 1942. Its focus is on the history of clinical ideas, rather than applying modern pathophysiological concepts retrospectively. Descriptions of lethargy are explored as a way of elucidating concepts of sleep, fatigue, and motivation during the study period. The literature described many patients who had (1) lethargy without interruption in consciousness; (2) slowness of movement and catalepsy without other prominent parkinsonian features; and (3) apathy and lack of initiative without severe disorders of mood or thought content. Hence observers distinguished a state of wakeful inactivity from primary disorders of sleep, movement and behavior. Contemporaneous accounts suggest that writers had difficulty in reconciling their observations with preexisting concepts; there still may be limitations in our ability to describe and classify the clinical states connected during the epidemic era with the term "lethargy."

Using systemic approaches, methods and techniques in rehabilitation medicine.

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is 'The trainee demonstrates a knowledge of benefits and limitations of counselling approaches, specifically in this article systemic family therapy.'

In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice.

B lymphocytes are required for the pathogenesis of autoimmune diabetes in NOD mice. Previous studies established that a lymphopenic transitional (TR) B cell compartment reduces the competitive constraint on the entry of newly emerging TR B cells into the splenic follicle (FO), thereby disrupting a peripheral negative selection checkpoint in NOD mice. Thus, development of clinically feasible immunotherapeutic approaches for restoration of appropriate negative selection is essential for the prevention of anti-islet autoimmunity. In this study we hypothesized that in vivo neutralization of the B lymphocyte stimulator (BLyS/BAFF) may enhance the stringency of TR-->FO selection by increasing TR B cell competition for follicular entry in NOD mice. This study demonstrated that in vivo BLyS neutralization therapy leads to the depletion of follicular and marginal zone B lymphocytes. Long-term in vivo BLyS neutralization caused an increased TR:FO B cell ratio in the periphery indicating a relative resistance to follicular entry. Moreover, in vivo BLyS neutralization: 1) restored negative selection at the TR-->FO checkpoint, 2) abrogated serum insulin autoantibodies, 3) reduced the severity of islet inflammation, 4) significantly reduced the incidence of spontaneous diabetes, 5) arrested the terminal stages of islet cell destruction, and 6) disrupted CD4 T cell activation in NOD mice. Overall, this study demonstrates the efficacy of B lymphocyte-directed therapy via in vivo BLyS neutralization for the prevention of autoimmune diabetes.

It's About Time: Examining the Effect of Interviewer-Quoted Survey Completion Time Estimates on Survey Efficiency.

Declining response rates may introduce bias into survey results and increase costs. Two national surveys, the National Immunization Survey (NIS) and the NIS-Teen, were used to study the impact of survey length, as stated by the interviewer, and inclusion of a topic of interest to respondents on response rates. The two studies included comparisons of the standard survey instruments to revised, condensed instruments. The NIS study also included variations of the standard survey with sections considered of interest for parental respondents, the Parental Concerns Module (PCM), which contained questions about parents' thoughts and beliefs about vaccinations. The outcomes of interest were differences in the response rates and resulting survey costs in each of the study conditions. The shortened instruments resulted in higher response rates compared to both the standard instruments and the instruments including the PCM and reduced the overall time needed to complete an interview. Based on these results, the NIS and NIS-Teen questionnaires were both shortened.

Mastery Learning - does the method of learning make a difference in skills acquisition for robotic surgery?

BACKGROUND: Few studies compare the effectiveness of blocked vs random practice conditions in minimally invasive surgery training, and none have evaluated these in robotic surgery training. METHODS: The dV-Trainer® and the da Vinci® Surgical System (dVSS) were used to compare practice conditions. Forty-two participants were randomized into blocked and random practice groups. Each participant performed five tasks: Ring Walk, Thread the Rings, Needle Targeting, Suture Sponge and Tubes Level 2. Transfer to the dVSS was also assessed. RESULTS: No significant differences were observed between the two groups, except for a few instances. For example, during Ring Walk, the random group performed significantly faster than the blocked group (100.78 ± 5.26 s vs 121.59 ± 5.26 s, p < 0.01). CONCLUSIONS: The study results do not follow the current evidence presented in the education literature. This is the first time that blocked versus random practice was tested for robotic surgery training.

Murine islet allograft tolerance upon blockade of the B-lymphocyte stimulator, BLyS/BAFF.

BACKGROUND: Immunologic rejection is a major barrier to successful long-term outcomes in clinical transplantation. The importance of B lymphocytes-and their secretory products, alloantibodies-in the pathogenesis of allograft rejection is accepted. Furthermore, it is now clear that the dominant regulator of peripheral B-cell homeostasis and tolerance is the B-lymphocyte stimulator (BLyS), also referred to as the B-cell activating factor (BAFF). Recently, a novel class of clinical immunotherapeutic agents specific for BLyS, and its family of cytokines, has emerged for the treatment of B-cell-mediated diseases. In this study, we demonstrate the potential utility of BLyS-directed immunotherapy in preventing allograft rejection using a murine islet transplantation model. METHODS: A transient period of mature peripheral B-cell depletion was induced by means of in vivo BLyS neutralization using a murine analog of the monoclonal antibody, Benlysta. Subsequently, fully major histocompatibility complex-mismatched islets were transplanted into naïve diabetic mice followed by a short course of rapamycin. RESULTS: After BLyS neutralization, indefinite islet allograft survival was achieved. Induction therapy with rapamycin was necessary, but not sufficient, for the achievement of this long-term graft survival. The tolerant state was associated with (1) abrogation of the donor-specific antibody response, (2) transient preponderance of immature/transitional B cells in all lymphoid organs, (3) impaired CD4 T-cell activation during the period of B-cell depletion, and (4) presence of a "regulatory" cytokine milieu. CONCLUSIONS: In vivo BLyS neutralization effectively induces humoral tolerance and promotes long-term islet allograft survival in mice. Therefore, B-lymphocyte-directed immunotherapy targeting the homeostatic regulator, BLyS, may be effective in promoting transplantation tolerance.

B lymphocyte stimulator expression in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis patients.

OBJECTIVE: To assess the expression of B lymphocyte stimulator (BLyS) in patients with pediatric systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA). METHODS: Blood samples collected from patients with pediatric SLE (n = 56) and patients with JIA (n = 54) at the beginning and end of a 6-month interval were analyzed for plasma BLyS protein levels by enzyme-linked immunosorbent assay and for blood leukocyte full-length BLyS and DeltaBLyS messenger RNA (mRNA) levels by quantitative real-time polymerase chain reaction (normalized to 18S expression). Healthy siblings (n = 34) of these patients served as controls. RESULTS: In pediatric SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels were each significantly elevated, and plasma BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were correlated with disease activity. In contrast, plasma BLyS protein levels were normal in JIA despite blood leukocyte BLyS mRNA levels being elevated to degrees similar to those in pediatric SLE. Among JIA patients, neither BLyS parameter was correlated with disease activity. In both pediatric SLE and JIA, the BLyS expression profiles remained stable at 6 months. CONCLUSION: Our findings indicate that, as previously noted in adult SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels are elevated in pediatric SLE. The correlation of plasma BLyS protein levels with disease activity points to BLyS as a candidate therapeutic target in pediatric SLE. Contrary to previous observations in adults with rheumatoid arthritis, plasma BLyS protein levels are normal in JIA despite elevated blood leukocyte BLyS mRNA levels. The absence of correlation between either of the BLyS parameters and disease activity in JIA calls for circumspection prior to assigning BLyS as a candidate therapeutic target in this disorder.

Neuropsychiatric interpretations of postencephalitic movement disorders.

This study reviews the impact of encephalitis lethargica (EL) on concepts of behaviour and movement during the 1920s and 1930s. Clinicopathological correlations were imprecise but supported the role of subcortical structures in complex patterns of motor behaviour. This possibility challenged the widely assumed hegemony of the cerebral cortex. There was a perceived link between involuntary movements and reduced impulse control and also between parkinsonism and a defect in volition. Contemporary observers interpreted postencephalitic phenomena such as oculogyria in psychodynamic as well as in neurophysiological terms. EL also gave some support to the idea that neuroses such as obsessional neurosis and hysteria might have an organic basis. These speculations recently have acquired more credibility. The large amount of literature on EL and its sequelae could perhaps make further contributions to understanding the pathology of voluntary movement and action.

The 'Impact on Participation and Autonomy': acceptability of the English version in a multiple sclerosis outpatient setting.

To elicit the opinion of multiple sclerosis (MS) patients about the acceptability of a newly designed participation questionnaire--the 'Impact on Participation and Autonomy' (IPA), 35 MS outpatients who had completed an English version of the IPA questionnaire (IPA-E) were interviewed. Patients were recruited consecutively from outpatients attending the MS clinic. They were invited to answer 15 short questions during a 20-minute interview after signing a consent form and completing the IPA-E questionnaire. Completion time of the IPA-E questionnaire was 19.3 +/- 4.7 minutes. Most respondents believed that the IPA-E items were easy or very easy to understand (83%), relevant (more than 74%), not embarrassing (more than 97%) and 94% considered that no items should be removed. Three additional topics were suggested: 'looking after children; 'the extent of information on current services'and information about 'treatment progress' Among the eight domains of the IPA, most respondents considered mobility to be the most important and education the least important. The IPA-E was found to be acceptable and relevant to a sample of MS outpatients, although it could have been enhanced by items on parental or family roles.

Design features of portable wheelchair ramps and their implications for curb and vehicle access.

This study evaluated a range of portable wheelchair ramps to highlight the effect of different product features on ease of use when wheelchair users climb curbs or access vehicles. Twelve portable ramps were evaluated. Although all the ramps were designed to load powered wheelchairs into motor vehicles, they were manufactured in different designs. The ramps were based on a "singlewide" platform or "channel" design. Some ramps had fixed dimensions, whereas others could be reduced in size because they were telescopic or designed to allow folding. Overall, the ramps could be divided into four subgroups on the basis of their key features. These were horizontally and longitudinally folding ramps, telescopic ramps, and ramps with fixed dimensions. The telescopic ramps could be subdivided into "U"-shaped gutter ramps and reverse profile ramps. Product appraisals and trials involving wheelchair users and caregivers of wheelchair users were done to evaluate each of these ramp designs. Although wheelchair ramps are available in a wide range of designs and configurations, we found that no single ramp design successfully met the needs of all wheelchair users or their caregivers. The evaluation highlighted a number of specific problems and potential hazards. Some ramps were found to move during a maneuver, showed poor stability when used with some vehicles, or were too narrow to allow wheelchair castors to pass through the channel without jamming. Some features, such as handles and locking mechanisms, influenced the ease with which the caregivers could use the ramps. Wheelchair users preferred the wide platform ramps because they were able to drive up these with ease and little preparation. The caregivers preferred folding or telescopic channel ramps because these were easier to handle and store.

BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases.

BLyS and APRIL are two members of the TNF superfamily that are secreted by activated myeloid cells and have costimulatory activity on B cells. BLyS and APRIL share two receptors, TACI and BCMA, whereas a third receptor, BAFF-R, specifically binds BLyS. Both BLyS and APRIL have been described as homotrimeric molecules, a feature common to members of the TNF superfamily. In this study, we show that APRIL and BLyS can form active heterotrimeric molecules when coexpressed and that circulating heterotrimers are present in serum samples from patients with systemic immune-based rheumatic diseases. These findings raise the possibility that active BLyS/APRIL heterotrimers may play a role in rheumatic and other autoimmune diseases and that other members of the TNF ligand superfamily may also form active soluble heterotrimers.