Pericytes modulate endothelial inflammatory response during bacterial infection.

Pericytes are located around blood vessels, in close contact with endothelial cells. We discovered that pericytes dampen pro-inflammatory endothelial cell responses. Endothelial cells co-cultured with pericytes had markedly reduced expression of adhesion molecules (PECAM-1 and ICAM-1) and proinflammatory cytokines (CCL-2 and IL-6) in response to bacterial stimuli (Brucella ovis, Listeria monocytogenes, or Escherichia coli lipopolysaccharide). Pericyte-depleted mice intraperitoneally inoculated with either B. ovis, a stealthy pathogen that does not trigger detectable inflammation, or Listeria monocytogenes, developed peritonitis. Further, during Citrobacter rodentium infection, pericyte-depleted mice developed severe intestinal inflammation, which was not evident in control mice. The anti-inflammatory effect of pericytes required connexin 43, as either chemical inhibition or silencing of connexin 43 abrogated pericyte-mediated suppression of endothelial inflammatory responses. Our results define a mechanism by which pericytes modulate inflammation during infection, which shifts our understanding of pericyte biology: from a structural cell to a pro-active player in modulating inflammation. IMPORTANCE: A previously unknown mechanism by which pericytes modulate inflammation was discovered. The absence of pericytes or blocking interaction between pericytes and endothelium through connexin 43 results in stronger inflammation, which shifts our understanding of pericyte biology, from a structural cell to a player in controlling inflammation.

3-D pain drawings-mobile data collection using a PDA.

A large number of the adult population suffers from some kind of back pain during their lifetime. Part of the process of diagnosing and treating such back pain is for a clinician to collect information as to the type and location of the pain that is being suffered. Traditional approaches to gathering and visualizing this pain data have relied on simple 2-D representations of the human body, where different types of sensation are recorded with various monochrome symbols. Although patients have been shown to prefer such drawings to traditional questionnaires, these pain drawings can be limited in their ability to accurately record pain. The work described in this paper proposes an alternative that uses a 3-D representation of the human body, which can be marked in color to visualize and record the pain data. This study has shown that the new approach is a promising development in this area of medical practice and has been positively received by patients and clinicians alike.

Neck pain and disability: a cross-sectional survey of the demographic and clinical characteristics of neck pain seen in a rheumatology clinic.

This hospital-based cross-sectional cohort study examines the clinical and demographic features of neck pain, disability (using the Northwick Park neck pain questionnaire) and relationships to handicap in employment. Of 173 consecutive referrals to a rheumatology clinic with neck pain, 70% had neck/arm pain without neurological involvement, 13% other conditions, 11% nerve involvement and 5% other spinal pain. 141 patients (mean age 50 years) had mechanical or degenerative neck pain, of which 13% was probably work-related and 13% was trauma-related. 44 had taken sickness absence for an average of 30 weeks. Comorbidities were frequent (lumbar pain 51%). Those in work were significantly less disabled than those not working (p = 0.001) and those off sick (p < 0.01). Those reporting sleep disturbance, tearfulness and crying were significantly more disabled (p = 0.0001) than those who did not. Neck pain in secondary care is complicated by physical and emotional comorbidities. Comprehensive management requires a biopsychosocial model of care.

Survey of the use of transport by recipients of a regional Electric Indoor/Outdoor Powered (EPIOC) wheelchair service.

PURPOSE: To determine the extent to which Electric Indoor/Outdoor Powered wheelchair (EPIOC) users travel in vehicles, their concerns about safety, any accidents occurring during transportation and difficulties with their equipment. METHOD: All 268 EPIOC users on the departmental database were sent a purpose-designed postal questionnaire asking whether the respondent:--used the chair during transportation and in what type of vehicle; understood clamping processes; had a 'mishap' or an 'accident'; felt safe during transportation and wished to comment. Replies from two mailings resulted in 203 usable replies (76%). Responses and comments were entered into an Excel database. RESULTS: Thirty-seven (18%) users did not use any transport. Of the 170 (82%) who did: 51% used Dial-a-Ride, 44% taxis, 41% ambulances, 37% local authority transport, 34% cars and others 17%. Twenty-one (12%) experienced 'mishaps'--8 toppled out of their chairs and 6 reported clamping-related accidents. Headrests were only used by 69 (41%). Thirty-four (19%) of 182 expressing a view about 'feeling safe' felt unsafe sometimes. Wheelchair users often feel vulnerable when being transported by public providers. DISCUSSION: Risks of vehicular travel by wheelchair users could be reduced with appropriate equipment and regular review of NHS prescriptions, education of users, wheelchair services and transport providers.

Changes in the quality of life in severely disabled people following provision of powered indoor/outdoor chairs.

PURPOSE: To determine the benefits for patients who received an electric powered inoor/outdoor chair (EPIOC) and to quantify their perceived changes to their quality of life. METHOD: Community-based cohort study of all patients provided with an EPIOC over 4 months; and followed up about 3 months later in a community served by a regional wheelchair service in North West London (population about 3.1 million) using the EuroQol EQ-5D with visual analogue scales for each of the five dimensions of the EQ-5D. RESULTS: Sixty-four wheelchair users were assessed initially and 51 completed follow up. Chair users showed no significant improvement in health state as measured by the EQ-5D after EPIOC provision. The visual analogue scales (VASs) indicated that, although perceived overall health state, independence and social life did not appear to improve, the dimensions of mobility, quality of life and pain/discomfort improved significantly on provision of an EPIOC. CONCLUSION: EPIOC users reported significant improvements in several important aspects of their lives; not just in mobility (as expected) but also in reduction of pain and discomfort. The use of VASs provided a more holistic set of outcome measures that demonstrate quality of life benefits beyond that of health state alone.

Conservative management of low back pain.

Back pain is prevalent worldwide, but back pain disability has reached epidemic proportions in many industrialised societies. Few patients have serious medical pathology or direct neurological involvement requiring surgery. Although the causes remain unclear, physical stress and its consequences on discs, facet joints and supporting soft tissues at work or leisure are important, sometimes aggravated by adverse psychosocial factors. Modern management emphasises the role of self-care, beginning in primary care with the first episode. Without root compression, bed rest should not exceed 48 hours. Emphasis is on encouraging a rapid return to physical fitness and other activities, including employment, acknowledging that returning to a normal life may require working through pain. Medication facilitates this. No one should remain in pain beyond six weeks without being referred to a specialist service for a physical and psychosocial assessment by appropriately trained professionals and with consultant support for investigation, pain management and rehabilitation when needed.

Introduction of a new NHS electric-powered indoor/outdoor chair (EPIOC) service: benefits, risks and implications for prescribers.

OBJECTIVE: To determine problems associated with electric-powered indoor/outdoor wheelchairs (EPIOCs) and the benefits perceived by their users. DESIGN: Hospital-based cohort study of all patients referred over a 19-month period. SETTING: Regional Wheelchair Service for North West London serving nine district wheelchair services. SUBJECTS: Of the 174 subjects referred, 10 withdrew their application or were found to be unsuitable at screening, 164 were assessed and 124 were prescribed chairs. One hundred and thirteen subjects were interviewed by telephone four months after provision of the chair. MAIN MEASURES: Demographic and diagnostic data; current chair usage; self-reported accidents and component faults were compared with those recorded in the unit records; new activities embarked on since delivery; and benefits reported for main carers. RESULTS: Seventeen 'mishaps' were reported by 15 users including tipping from chairs (6) and falls during transfers (3). Three probably reflected mechanical failure. Component failure was found in 39% of EPIOCs, mostly affecting control boxes (22), frames (10) and footrests (10). New activities were undertaken by 56 (50%) users, usually shopping and visits to friends/family. Eighty-five per cent of users felt that the chairs made life easier for their informal carers through increased independence, reducing transfers and reduced need for 'pushing'. CONCLUSIONS: The component failures and self-reported accidents (some potentially dangerous) have implications for the NHS, manufacturers, prescribers and users. EPIOCs enhance the independence of severely physically disabled individuals in the community and assist carers by lessening dependence and enhancing social interaction. This study demonstrated the need for follow-up of EPIOC users and chairs.

Subjective pain experience of people with chronic back pain.

BACKGROUND AND PURPOSE: Studies into the effect of pain experience on those who have it have largely focused on the views and interpretations of researchers gained by the use of assessment tools aimed at measuring pain. The purpose of this study was to explore and describe pain, as experienced by those with chronic back pain, and to document 'insider' accounts of how pain is perceived and understood by those who have it. METHOD: Unstructured interviews using the framework approach. Subjects were sampled for age, sex, ethnicity and occupation, from new referrals with back pain to a rheumatology outpatient clinic. Eleven subjects (5 M; 6 F) agreed to be interviewed. Interviews were unstructured, but followed a topic guide. Subjects were interviewed in English (nine) or their preferred language (two). Tape-recordings of interviews were transcribed verbatim and read in depth twice to identify the topics or concepts. Data were extracted in the form of words and phrases by use of thematic content analysis. The themes were pain description and amount of pain. An independent researcher reviewed the data and confirmed or contended the analysis. RESULTS: All subjects, except one, provided descriptors of the quality of their pain. The use of simile was common to emphasize both what the pain was, and what it was not. Five subjects expressed a loss of words in trying to describe their pain. Only 13 of 29 different pain descriptors used were commensurate with those in the McGill Pain Questionnaire (Melzack, 1983). Subjects had great difficulty quantifying their pain intensity. Several explained how the pain fluctuated, thus, quantifying pain at one point in time was problematic. Only one subject offered a numerical description of pain intensity. CONCLUSIONS: Subjects provided graphic and in-depth descriptions of their pain experience, but these bore little resemblance to commonly used assessment tools. The findings challenge the appropriateness of such formal instruments.

A cross-sectional survey of the clinical and psychological features of low back pain and consequent work handicap: use of the Quebec Task Force classification.

A hospital-based cross-sectional study examined 657 consecutive referrals with low back pain over two years to a district rheumatology service serving a population of about 250,000 people. Five hundred and thirty-eight had mechanical/degenerative low back pain. The mean age was 48.6 (range 18-80 SD 15.3) years; 64% were women. Patients with radiating pain or neurological deficit (Quebec Task Force classification) were significantly more disabled (Roland disability score p < 0.001) and depressed (Modified Zung score p < 0.05) than those without radiating pain. Women were more impaired (p = 0.02) than men but had similar disabilities (mean Roland score 11.7, range 0-24 SD 6.5). Fifty-three per cent of patients were receiving benefits and were significantly more likely to have musculoskeletal comorbidities than those in work (p < 0.025). It is concluded that the Quebec Task Force classification of low back pain impairment is a helpful descriptor and related to both physical and psychological disability and handicap in employment.

A finite-element model of oxygen diffusion in the pulmonary capillaries.

We determined the overall pulmonary diffusing capacity (DL) and the diffusing capacities of the alveolar membrane (Dm) and the red blood cell (RBC) segments (De) of the diffusional pathway for O2 by using a two-dimensional finite-element model developed to represent the sheet-flow characteristics of pulmonary capillaries. An axisymmetric model was also considered to assess the effect of geometric configuration. Results showed the membrane segment contributing the major resistance, with the RBC segment resistance increasing as O2 saturation (SO2) rises during the RBC transit: RBC contributed 7% of the total resistance at the capillary inlet (SO2 = 75%) and 30% toward the capillary end (SO2 = 95%) for a 45% hematocrit (Hct). Both Dm and DL increased as the Hct increased but began approaching a plateau near an Hct of 35%, due to competition between RBCs for O2 influx. Both Dm and DL were found to be relatively insensitive (2-4%) to changes in plasma protein concentration (28-45%). Axisymmetric results showed similar trends for all Hct and protein concentrations but consistently overestimated the diffusing capacities (approximately 2.2 times), primarily because of an exaggerated air-tissue barrier surface area. The two-dimensional model correlated reasonably well with experimental data and can better represent the O2 uptake of the pulmonary capillary bed.