Histamine, a vasoactive agent with vascular disrupting potential, improves tumour response by enhancing local drug delivery

Tumour necrosis factor (TNF)-based isolated limb perfusion (ILP) is an approved and registered treatment for sarcomas confined to the limbs in Europe since 1998, with limb salvage indexes of 76%. TNF improves drug distribution in solid tumours and secondarily destroys the tumour-associated vasculature (TAV). Here we explore the synergistic antitumour effect of another vasoactive agent, histamine (Hi), in doxorubicin (DXR)-based ILP and evaluate its antivascular effects on TAV. We used our well-established rat ILP model for in vivo studies looking at tumour response, drug distribution and effects on tumour vessels. In vitro studies explored drug interactions at cellular level on tumour cells (BN-175) and Human umbilical vein endothelial cells (HUVEC). There was a 17% partial response and a 50% arrest in tumour growth when Hi was combined to DXR, without important side effects, against 100% progressive disease with DXR alone and 29% arrest in tumour growth for Hi alone. Histology documented an increased DXR leakage in tumour tissue combined to a destruction of the TAV, when Hi was added to the ILP. In vitro no synergy between the drugs was observed. In conclusion, Hi is a vasoactive drug, targeting primarily the TAV and synergises with different chemotherapeutic agents

The long-term effects of naprapathic manual therapy on back and neck pain - Results from a pragmatic randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Back and neck pain are very common, disabling and recurrent disorders in the general population and the knowledge of long-term effect of treatments are sparse. The aim of this study was to compare the long-term effects (up to one year) of naprapathic manual therapy and evidence-based advice on staying active regarding non-specific back and/or neck pain. Naprapathy, a health profession mainly practiced in Sweden, Finland, Norway and in the USA, is characterized by a combination of manual musculoskeletal manipulations, aiming to decrease pain and disability in the neuromusculoskeletal system.</p> <p>Methods</p> <p>Subjects with non-specific pain/disability in the back and/or neck lasting for at least two weeks (n = 409), recruited at public companies in Sweden, were included in this pragmatic randomized controlled trial. The two interventions compared were naprapathic manual therapy such as spinal manipulation/mobilization, massage and stretching, (<it>Index Group</it>), and advice to stay active and on how to cope with pain, provided by a physician (C<it>ontrol Group</it>). Pain intensity, disability and health status were measured by questionnaires.</p> <p>Results</p> <p>89% completed the 26-week follow-up and 85% the 52-week follow-up. A higher proportion in the Index Group had a clinically important decrease in pain (risk difference (RD) = 21%, <it>95% CI: 10-30</it>) and disability (RD = 11%, <it>95% CI: 4-22</it>) at 26-week, as well as at 52-week follow-ups (pain: RD = 17%, <it>95% CI: 7-27 </it>and disability: RD = 17%, <it>95% CI: 5-28</it>). The differences between the groups in pain and disability considered over one year were statistically significant favoring naprapathy (p ≤ 0.005). There were also significant differences in improvement in bodily pain and social function (subscales of SF-36 health status) favoring the Index Group.</p> <p>Conclusions</p> <p>Combined manual therapy, like naprapathy, is effective in the short and in the long term, and might be considered for patients with non-specific back and/or neck pain.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN56954776.</p

How well do questionnaires on symptoms in neck-shoulder disorders capture the experiences of those who suffer from neck-shoulder disorders? A content analysis of questionnaires and interviews

<p>Abstract</p> <p>Background</p> <p>Previous research has indicated neck-shoulder disorders to have a fluctuating course incorporating a variety of symptoms. These findings awoke our interest to make a comparison between symptoms experienced by people affected with the disorder and the content of questionnaires that assess pain and other symptoms in neck-shoulder disorders. Thus the aims of this study were: -to explore the symptoms experienced by people with non-specific neck-shoulder problems, as well as experiences of nuances and temporal variations (fluctuations) of symptoms; -to investigate which sources were used in the development of ten questionnaires for assessing pain and other symptoms in the neck-shoulder; -to analyse the item content of the questionnaires; -to analyse the correspondence between the item content of the questionnaires and the symptoms described by the informants.</p> <p>Methods</p> <p>Content analysis of interviews with 40 people with non-specific neck-shoulder pain, and 10 questionnaires used to assess pain and other symptoms in neck-shoulder disorders.</p> <p>Results</p> <p>The interviews revealed a variety of symptoms indicating a bodily, mental/cognitive, and emotional engagement, and more general and severe symptoms than are usually considered in neck-shoulder questionnaires. Taking all questionnaires together many of the symptoms were considered, but most questionnaires only included a few of them. The informants were able to distinguish fluctuation of symptoms, and a variety of different qualities which were not usually considered in the questionnaires. Only two questionnaires had made use of the opinions of affected people in the development.</p> <p>Conclusion</p> <p>Few of the questionnaires had made use of the experiences of affected people in the development. The correspondence between the symptoms expressed by those affected and the content of the questionnaires was low. A variety of symptoms were expressed by the interviewees, and the participants were also able to distinguish nuances and fluctuations of symptoms. The present study points to the importance of other aspects than just pain and physical functioning as clinical trial outcome measures related to neck-shoulder disorders. To develop a condition-specific questionnaire, it is important to decide on the specific symptoms for the condition. Using the experiences of those affected, in combination with relevant research and professional knowledge, can enhance the validity of the questionnaires.</p

Protocol of a randomized controlled trial of the effectiveness of physician education and activation versus two rehabilitation programs for the treatment of Whiplash-associated Disorders: The University Health Network Whiplash Intervention Trial

Background: Whiplash injuries are an important public health problem that is associated with significant disability and high health care utilization. Recent cohort studies suggest that physician care may be the most effective treatment for patients with whiplash-associated disorders. However, these findings have not been tested in a randomized controlled trial. The purpose of this study is to determine which of physician care or two rehabilitation programs of care is most effective in improving recovery of patients with recent whiplash associated disorders. Methods and Design: We designed a pragmatic randomized clinical trial. A total of 444 participants (148 in each of three arms) who reside in Southern Ontario, Canada will be recruited from a large insurer. We will include individuals who are 18 years of age or older and who are diagnosed with Grade I or II Whiplash-associated Disorders. Participants will be randomized to physician-based education and activation or one of two rehabilitation programs of care currently in use in Ontario. Our primary outcome, self-rated global recovery and all secondary outcomes (neck pain intensity, whiplash disability, health-related quality of life, depressive symptomatology and satisfaction with care) will be measured at baseline by a trial coordinator and at 6 weeks, 3, 6, 9 and 12 months follow-up by an interviewer who is blind to the participants' baseline characteristics and treatment allocation. We will also collect information on general health status, other injuries, comorbidities, expectation of recovery, work status, pain coping, legal representation, and co-interventions. The primary intention-to-treat analysis will compare time to recovery between the three interventions. This trial will have 90% power at an alpha of 0.05 to detect a 20% difference in the rate of perceived recovery at one year. Secondary analyses will compare the health outcomes, rate of recurrence and the rate of adverse events between intervention groups. Conclusion: The results of this study will provide the public, clinicians and policy makers much needed evidence on the effectiveness of common approaches used to manage whiplash-associated disorders. © 2008 Côté et al; licensee BioMed Central Ltd

Range of shoulder motion in patients with adhesive capsulitis; Intra-tester reproducibility is acceptable for group comparisons

<p>Abstract</p> <p>Background</p> <p>Measurements of range of motion play a key role in shoulder research. The purpose of this study is to investigate intra-observer reproducibility of measurements of active and passive range of motion in patients with adhesive capsulitis.</p> <p>Methods</p> <p>The study was carried out in a population consisting of 32 patients with clinical signs of adhesive capsulitis. A specified measurement protocol was used, and range of motion in affected and non-affected shoulders was measured twice for each patient with a one-week interval.</p> <p>Results</p> <p>For most of the investigated individual movements, test-retest differences in range of motion score of more than approximately 15° are not likely to occur as a result of measurement error only. Point-estimates for the intraclass correlation coefficient ranged from 0.61 to 0.93.</p> <p>Conclusion</p> <p>Range of motion of patients with adhesive capsulitis can be measured with acceptable reproducibility in settings where groups are compared. Scores for individual patients should be interpreted with caution.</p

Proliferation and aneusomy predict survival of young patients with astrocytoma grade II

The clinical course of astrocytoma grade II (AII) is highly variable and not reflected by histological characteristics. As one of the best prognostic factors, higher age identifies rapid progressive A II. For patients over 35 years of age, an aggressive treatment is normally propagated. For patients under 35 years, there is no clear guidance for treatment choices, and therefore also the necessity of histopathological diagnosis is often questioned. We studied the additional prognostic value of the proliferation index and the detection of genetic aberrations for patients with A II. The tumour samples were obtained by stereotactic biopsy or tumour resection and divided into two age groups, that is 18–34 years (n=19) and 35 years (n=28). Factors tested included the proliferation (Ki-67) index, and numerical aberrations for chromosomes 1, 7, and 10, as detected by in situ hybridisation (ISH). The results show that age is a prognostic indicator when studied in the total patient group, with patients above 35 years showing a relatively poor prognosis. Increased proliferation index in the presence of aneusomy appears to identify a subgroup of patients with poor prognosis more accurately than predicted by proliferation index alone. We conclude that histologically classified cases of A II comprise a heterogeneous group of tumours with different biological and genetic constitution, which exhibit a highly variable clinical course. Immunostaining for Ki-67 in combination with the detection of aneusomy by ISH allows the identification of a subgroup of patients with rapidly progressive A II. This is an extra argument not to defer stereotactic biopsy in young patients with radiological suspicion of A II

The reliability of postural balance measures in single and dual tasking in elderly fallers and non-fallers

BACKGROUND: The purpose of this study was to determine the reliability of a forceplate postural balance protocol in a group of elderly fallers and non-fallers. The measurements were tested in single and dual-task conditions, with and without vision. METHODS: 37 elderly (mean age 73 +/- 6 years) community-dwellers were included in this study. All were tested in a single (two-legged stance) and in a dual-task (two-legged stance while counting backwards aloud in steps of 7's) condition, with and without vision. A forceplate was used for registering postural variables: the maximal and the root-mean-square amplitude in medio-lateral (Max-ML, RMS-ML) and antero-posterior (Max-AP, RMS-AP) direction, mean velocity (MV), and the area of the 95% confidence ellipse (AoE). Reliability of the test protocol was expressed with intraclass correlation coefficients (ICC), with 95% limits of agreement (LoA), and with the smallest detectable difference (SDD). RESULTS: The ICCs for inter-rater reliability and test-retest reliability of the balance variables were r = 0.70-0.89. For the variables Max-AP and RMS-AP the ICCs were r = 0.52-0.74. The SDD values were for variable Max-ML and Max-AP between 0.37 cm and 0.83 cm, for MV between 0.48 cm/s and 1.2 cm/s and for AoE between 1.48 cm2 and 3.75 cm2. The LoA analysis by Bland-Altman plots showed no systematic differences between test-retest measurements. CONCLUSION: The study showed good reliability results for group assessment and no systematic errors of the measurement protocol in measuring postural balance in the elderly in a single-task and dual-task condition