Survival in breast cancer patients with a delayed DIEP flap breast reconstruction after adjustment for socioeconomic status and comorbidity.

PURPOSE: Overall survival in breast cancer patients receiving a delayed deep inferior epigastric perforator (DIEP) flap breast reconstruction is better than in those without delayed breast reconstruction. This study aimed at determining the impact of socioeconomic status (SES) and comorbidity on these observations. MATERIALS AND METHODS: This matched cohort study included all consecutive women undergoing a delayed DIEP flap reconstruction at Karolinska University Hospital, Sweden, between 1999 and 2013. Controls had not received any delayed breast reconstruction and were relapse-free after a corresponding follow-up interval. Matching was by year of and age at mastectomy, tumour stage and lymph node status. Charlson Comorbidity Index (CCI) and socioeconomic data were obtained from national registers. Associations with breast cancer-specific (BCSS) and overall survival (OS) were investigated by Kaplan-Meier survival estimates and Cox proportional hazard regression analysis. RESULTS: Women in the DIEP group (N = 254) more often continued education after primary school (88.6% versus 82.6%, P = 0.026), belonged to the high-income group (76.0% versus 63.1%, P < 0.001), were in a partnership (57.1% versus 55.7%, P = 0.024) and healthier (median CCI 1.00 (range 0-13) versus 2.00 (range 0-16), P = 0.021) than the control group (N = 729). After adjustment for tumour and treatment factors, SES and comorbidity, OS remained significantly better for the DIEP group than the control group (HR 2.27, 95% CI 1.44-3.55). CONCLUSION: Women with a delayed DIEP flap reconstruction are a subgroup of higher socioeconomic status and better health. Higher survival estimates for the DIEP group persisted after adjusting for those differences, suggesting the presence of further unmeasured covariates.

Risk factors for post-operative complications after sentinel lymph node biopsy for cutaneous melanoma: Results from a large cohort study.

BACKGROUND: A sentinel lymph node (SLN) biopsy is a common surgical procedure for cutaneous melanoma. Our aim was to evaluate risk factors for early post-operative complications after SLN biopsy and to examine the impact of complications on health care resource utilisation. METHODS: We performed a retrospective cohort study including all adult patients who underwent a SLN biopsy for cutaneous melanoma in the Stockholm region from 2006 to 2014. Data of patient and tumour characteristics were collected from medical records, as well as information on complications and outpatient visits within 30 days from surgery. Risk factors were evaluated through logistic regression. RESULTS: Out of 886 patients who underwent SLN biopsy during the study period, 109 (12.3%) had one or several post-operative complications. The most common complication was a wound infection (7.7%), followed by seroma (6.4%). The risk of a post-operative complication was increased in patients with diabetes (odds ratio (OR) = 10.0, 95% confidence interval (CI) 4.0-24.6), who had inguinal location of SLN (OR = 2.7, 95% CI 1.7-4.3), who were male (OR = 1.9, 95% CI 1.2-2.9) and who had ulceration of the primary tumour (OR = 1.6, 95% CI 1.0-2.6). Individuals with post-operative complications had more visits to the outpatient clinic (p < 0.05). CONCLUSION: Complications after SLN biopsy affect 12.3% of patients. Our results suggest that patients with diabetes, who had inguinal SLN biopsy and who were male have increased risk, and this might warrant more intense post-operative surveillance.

Autologous fat transplantation alters gene expression patterns related to inflammation and hypoxia in the irradiated human breast.

BACKGROUND: Radiation-induced fibrosis, an adverse effect of breast cancer treatment, is associated with functional and cosmetic impairment as well as surgical complications. Clinical reports suggest improvement following autologous fat transplantation, but the mechanisms underlying this effect are unknown. A global gene expression analysis was undertaken to identify genetic pathways dysregulated by radiation and evaluate the impact of autologous fat transplantation on gene expression. METHODS: Adipose tissue biopsies were taken synchronously from irradiated and contralateral non-irradiated breasts, before and 1 year after autologous fat transplantation. Whole-genome gene expression analyses were performed, and Hallmark gene set analysis used to explore the effect of radiotherapy and autologous fat transplantation on gene expression. RESULTS: Forty microarrays were analysed, using bilateral biopsies taken from ten patients before and after autologous fat transplantation. Forty-five pathways were identified among the 3000 most dysregulated transcripts after radiotherapy in irradiated compared with non-irradiated breast (P ≤ 0·023; false discovery rate (FDR) no higher than 0·026). After autologous fat transplantation, 575 of the 3000 genes were again altered. Thirteen pathways (P ≤ 0·013; FDR 0·050 or less) were identified; the top two canonical pathways were interferon-γ response and hypoxia. Correlative immunohistochemistry showed increased macrophage recruitment in irradiated tissues. CONCLUSION: The present findings contribute to understanding of how autologous fat transplantation can ameliorate radiation-induced fibrosis. This further supports the use of autologous fat transplantation in the treatment of radiation-induced fibrosis. Surgical relevance Clinical studies have indicated that autologous fat transplantation (AFT) stimulates regression of chronic inflammation and fibrosis caused by radiotherapy in skin and subcutaneous fat. However, there is a paucity of biological evidence and the underlying processes are poorly understood. Human data are scarce, whereas experimental studies have focused mainly either on the effect of irradiation or AFT alone. The present results indicate that radiotherapy causes dysregulated gene expression in fibrosis-related pathways in adipose tissues in humans. They also show that AFT can cause a reversal of this, with several dysregulated genes returning to nearly normal expression levels. The study provides biological evidence for the impact of AFT on radiation-induced dysregulated gene expression in humans. It supports the use of AFT in the treatment of radiation-induced fibrosis, associated with severe morbidity and surgical challenges.

Risk of recurrence and death in patients with breast cancer after delayed deep inferior epigastric perforator flap reconstruction.

BACKGROUND: Postmastectomy reconstruction using a deep inferior epigastric perforator (DIEP) flap is increasingly being performed in patients with breast cancer. The procedure induces extensive tissue trauma, and it has been hypothesized that the release of growth factors, angiogenic agonists and immunomodulating factors may reactivate dormant micrometastasis. The aim of the present study was to estimate the risk of breast cancer recurrence in patients undergoing DIEP flap reconstruction compared with that in patients treated with mastectomy alone. METHODS: Each patient who underwent delayed DIEP flap reconstruction at Karolinska University Hospital, Sweden, between 1999 and 2013, was compared with up to four controls with breast cancer who did not receive a DIEP flap. The control patients were selected using incidence density matching with respect to age, tumour and nodal status, neoadjuvant therapy and year of mastectomy. The primary endpoint was breast cancer-specific survival. Survival analysis was carried out using Kaplan-Meier survival estimates and Cox proportional hazard regression analysis. RESULTS: The analysis included 250 patients who had 254 DIEP flap reconstructions and 729 control patients. Median follow-up was 89 and 75 months respectively (P = 0·053). Breast cancer recurrence developed in 50 patients (19·7 per cent) in the DIEP group and 174 (23·9 per cent) in the control group (P = 0·171). The 5-year breast cancer-specific survival rate was 92·0 per cent for patients with a DIEP flap and 87·9 per cent in controls (P = 0·032). Corresponding values for 5-year overall survival were 91·6 and 84·7 per cent (P < 0·001). After adjustment for tumour and patient characteristics and treatment, patients without DIEP flap reconstruction had significantly lower overall but not breast cancer-specific survival. CONCLUSION: The present findings do not support the hypothesis that patients with breast cancer undergoing DIEP flap reconstruction have a higher rate of breast cancer recurrence than those who have mastectomy alone.

Physical Activity and Exercise Interventions in the Workplace Impacting Work Outcomes: A Stakeholder-Centered Best Evidence Synthesis of Systematic Reviews.

BACKGROUND: The prevention of work disability is beneficial to employees and employers, and mitigates unnecessary societal costs associated with social welfare. Many service providers and employers have initiated workplace interventions designed to reduce unnecessary work disability. OBJECTIVE: To conduct a best-evidence synthesis of systematic reviews on workplace interventions that address physical activities or exercise and their impact on workplace absence, work productivity or financial outcomes. METHODS: Using a participatory research approach, academics and stakeholders identified inclusion and exclusion criteria, built an abstraction table, evaluated systematic review quality and relevance, and interpreted the combined findings. A minimum of two scientists participated in a methodological review of the literature followed by a consensus process. RESULTS: Stakeholders and researchers participated as a collaborative team. 3363 unique records were identified, 115 full text articles and 46 systematic reviews were included, 18 assessed the impact of physical fitness or exercise interventions. 11 focused on general workers rather than workers who were absent from work at baseline; 16 of the reviews assessed work absence, 4 assessed productivity and 6 assessed financial impacts. CONCLUSION: The strongest evidence supports the use of short, simple exercise or fitness programs for both workers at work and those absent from work at baseline. For workers at work, simple exercise programs (1-2 modal components) appear to provide similar benefits to those using more complex multimodal interventions. For workers off-work with subacute low back pain, there is evidence that some complex exercise programs may be more effective than simple exercise interventions, especially if they involve workplace stakeholder engagement, communication and coordination with employers and other stakeholders. The development and utilization of standardized definitions, methods and measures and blinded evaluation would improve research quality and strengthen stakeholder-centered guidance.

Mental Health Interventions in the Workplace and Work Outcomes: A Best-Evidence Synthesis of Systematic Reviews.

BACKGROUND: Mental health issues in the workplace are a growing concern among organizations and policymakers, but it remains unclear what interventions are effective in preventing mental health problems and their associated organizational consequences. This synthesis reports on workplace mental health interventions that impact absenteeism, productivity and financial outcomes. OBJECTIVE: To determine the level of evidence supporting mental health interventions as valuable to work outcomes. METHODS: Databases were searched for systematic reviews between 2000 and 2012: Medline, EMBASE, the Cochrane Database of Systematic Reviews, DARE, CINAHL, PsycINFO and TRIP. Grey literature searches included health-evidence.ca, Rehab+, National Rehabilitation Information Center (NARIC), and Institute for Work and Health. The assessment of articles for inclusion criteria and methodological quality was conducted independently by two or more researchers, with differences resolved through consensus. RESULTS: The search resulted in 3363 titles, of which 3248 were excluded following title/abstract review, with 115 articles retrieved for full-text review. 14 articles finally met the inclusion criteria and are summarized in this synthesis. CONCLUSION: There is moderate evidence for the effectiveness of workplace mental health interventions on improved workplace outcomes. Certain types of programs, such as those incorporating both mental and physical health interventions, multicomponent mental health and/or psychosocial interventions, and exposure in vivo containing interventions for particular anxiety disorders had a greater level of research evidence to support their effectiveness.

Social Support and Supervisory Quality Interventions in the Workplace: A Stakeholder-Centered Best-Evidence Synthesis of Systematic Reviews on Work Outcomes.

BACKGROUND: There is controversy surrounding the impact of workplace interventions aimed at improving social support and supervisory quality on absenteeism, productivity and financial outcomes. OBJECTIVE: To determine the value of social support interventions for work outcomes. METHODS: Databases were searched for systematic reviews between 2000 and 2012 to complete a synthesis of systematic reviews guided by the PRISMA statement and the IOM guidelines for systematic reviews. Assessment of articles for inclusion and methodological quality was conducted independently by at least two researchers, with differences resolved by consensus. RESULTS: The search resulted in 3363 titles of which 3248 were excluded following title/abstract review, leaving 115 articles that were retrieved and underwent full article review. 10 articles met the set inclusion criteria, with 7 focusing on social support, 2 on supervisory quality and 1 on both. We found moderate and limited evidence, respectively, that social support and supervisory quality interventions positively impact workplace outcomes. CONCLUSION: There is moderate evidence that social support and limited evidence that supervisory quality interventions have a positive effect on work outcomes.

Job demand and control interventions: a stakeholder-centered best-evidence synthesis of systematic reviews on workplace disability.

BACKGROUND: Physical and psychological job demands in combination with the degree of control a worker has over task completion, play an important role in reducing stress. Occupational stress is an important, modifiable factor affecting work disability. However, the effectiveness of reducing job demands or increasing job control remains unclear, particularly for outcomes of interest to employers, such as absenteeism or productivity. OBJECTIVE: This systematic review reports on job demand and control interventions that impact absenteeism, productivity and financial outcomes. METHODS: A stakeholder-centered best-evidence synthesis was conducted with researcher and stakeholder collaboration throughout. Databases and grey literature were searched for systematic reviews between 2000 and 2012: Medline, EMBASE, the Cochrane Database of Systematic Reviews, DARE, CINAHL, PsycINFO, TRIP, health-evidence.ca, Rehab+, National Rehabilitation Information Center (NARIC), and Institute for Work and Health. Articles were assessed independently by two researchers for inclusion criteria and methodological quality. Differences were resolved through consensus. RESULTS: The search resulted in 3363 unique titles. After review of abstracts, 115 articles were retained for full-text review. 11 articles finally met the inclusion criteria and are summarized in this synthesis. The best level of evidence we found indicates that multimodal job demand reductions for either at-work or off-work workers will reduce disability-related absenteeism. CONCLUSION: In general, the impacts of interventions that aim to reduce job demands or increase job control can be positive for the organization in terms of reducing absenteeism, increasing productivity and cost-effectiveness. However, more high quality research is needed to further assess the relationships and quantify effect sizes for the interventions and outcomes reviewed in this study.

A prospective study of the effectiveness of early intervention with high-risk back-injured workers--a pilot study.

INTRODUCTION: It was postulated that workers, at the sub-acute stage after injury, respond differently to clinical and occupational interventions offered in a workers' compensation environment. Individual worker risk of disability, it was further believed, would influence the effectiveness of early intervention. The objective of the current pilot study was to evaluate return to work (RTW) outcomes following proactive, combined clinical, occupational and case management-based interdisciplinary early intervention, provided in a workers' compensation environment 4-10 weeks of onset of back pain, to workers with medium and high risk for disability. METHODS: The project was a controlled study comparing conventional workers' compensation case management with integrated, interdisciplinary and multimodal early intervention (hereinafter referred to as "EI"). At baseline, risk status was determined by a validated Risk for Disability Questionnaire by Carragee et al. (Spine 5(1):24-35, 2005). Seventeen workers at high risk of protracted disability and 20 workers at moderate risk of disability received conventional case management, and 17 workers assessed at high risk of protracted disability and 18 workers at moderate risk of disability received the Early Intervention. RESULTS: At 3 months post back pain onset, no statistically significant differences were identified in RTW outcomes between conventional case management and the Early Intervention. However, by 6 months post back pain onset, workers at high risk of work disability who received the Early Intervention were significantly more likely to RTW than high risk workers who received conventional case management. In contrast, moderate risk workers continued to exhibit no statistically significant differences in RTW outcomes. CONCLUSION: Multimodal Early Intervention in the workers' compensation case management context is likely effective for workers with sub-acute back pain who are at high risk of occupational disability. The comprehensive Early Intervention is, however, likely redundant for workers who are not at high risk for disability and should not be applied indiscriminately. Further studies are required to determine longer-term Early Intervention outcomes, and to replicate the findings using a randomized control design. Also, with a larger sample size, it will be possible to determine predictors of occupational outcomes.

Quantitative oral dosing of water soluble and lipophilic contaminants in the Japanese medaka (Oryzias latipes).

Quantitative oral dosing in fish can be challenging, particularly with water soluble contaminants, which can leach into the aquarium water prior to ingestion. We applied a method of bioencapsulation using newly hatched brine shrimp (Artemia franciscana) nauplii to study the toxicokinetics of five chlorinated and brominated halogenated acetic acids (HAAs), which are drinking water disinfection by-products. These results are compared to those obtained in a previous study using a polybrominated diphenyl ether (PBDE-47), a highly lipophilic chemical. The HAAs and PBDE-47 were bioencapsulated using freshly hatched A. franciscana nauplii after incubation in concentrated solutions of the study chemicals for 18 h. Aliquots of the brine shrimp were quantitatively removed for chemical analysis and fed to individual fish that were able to consume 400-500 nauplii in less than 5 min. At select times after feeding, fish were euthanized and the HAA or PBDE-47 content determined. The absorption of HAAs was quantitatively similar to previous studies in rodents: rapid absorption with peak body levels occurring within 1-2 h, then rapidly declining with elimination half-life of 0.3-3 h depending on HAA. PBDE-47 was more slowly absorbed with peak levels occurring by 18 h and very slowly eliminated with an elimination half-life of 281 h.

Head and neck squamous cell carcinoma transcriptome analysis by comprehensive validated differential display.

Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples. The resulting 820 nonredundant sequences were analysed by high throughput bioinformatics analysis. Human proteins were identified for 73% (596) of the DD sequences. A large proportion (>50%) of the remaining unassigned sequences match ESTs (expressed sequence tags) from human tumours. For the functionally annotated proteins, there is significant enrichment for relevant biological processes, including cell motility, protein biosynthesis, stress and immune responses, cell death, cell cycle, cell proliferation and/or maintenance and transport. Three of the novel proteins (TMEM16A, PHLDB2 and ARHGAP21) were analysed further to show that they have the potential to be developed as therapeutic targets.

Pelvic organ prolapse and urinary incontinence in women with surgically managed rectal prolapse: a population-based case-control study.

PURPOSE: This study aimed to investigate the prevalence of genital prolapse surgery and urinary incontinence in female patients operated on for rectal prolapse compared with a matched control group without rectal prolapse. METHODS: Fifty-two patients with a history of abdominal rectal prolapse surgery and 200 randomly selected age-matched and gender-matched control subjects without rectal prolapse received an extensive health care history survey. RESULTS: Response rate in the patient group was 48 of 52 (92 percent) and 165 of 200 (82 percent) in the control group. Rectal prolapse was associated with an increased risk of surgery for uterine prolapse (odds ratio = 3.1; 95 percent confidence interval = 1.4-6.9) and vaginal wall prolapse (odds ratio = 3.2; 95 percent confidence interval = 1.3-7.8). Mean age at hysterectomy because of uterine prolapse was 54.7 years in the patient group compared with 62.6 years in the control group (P < 0.01). Mean age at vaginal wall prolapse surgery was 60.2 years in the patient group compared with 66.6 years in the control group (P < 0.05). There were no significant differences between the cohorts regarding prevalence or age at debut of urinary incontinence. CONCLUSION: Our results indicate a strong association between rectal and genital prolapse surgery suggesting that diagnosis of rectal prolapse necessitating surgical intervention should prompt a multidisciplinary pelvic floor assessment.

Cefalea cervicogénica: bases anatómicas I / Cervicogenic headache: anatomical bases I

La generación de dolor de cabeza desde estructuras cervicales no es un concepto nuevo. Aunque no existe consenso en grupos expertos, muchos estudios han tratado de dar luz al asunto y establecer criterios clínicos para el diagnóstico diferencial, como también proveer un tratamiento adecuado. Es entonces imperativo disponer de bases anatomofisiológicas para su mejor comprensión. La emergencia de los nervios, su distribución cutánea, y sus relaciones anatómicas conforman un esquema de distribución sensitiva cérvico-cráneo-facial que nos permitiría explicar y asociar a algunos síndromes dolorosos de esta región. Este estudio incluyó una muestra de doce disecciones (n=12) de la región posterior cervical efectuada hasta el plano de los músculos semiespinosos. Diferentes estructuras anatómicas que se relacionan o podrían generar dolor de cabeza son descritas. Es así, como por ejemplo, comprobamos que el nervio occipital mayor, en su recorrido, puede estar sometido a tensión, atrapamiento o presiones en el paso a través del músculo semiespinoso, en el ojal fascio-muscular o bien al pasar entre las inserciones téndino musculares del esplenio y trapecio respectivamente. De este modo podría postularse una correlación anatomopatológica dentro de las posibles etiologías del síndrome cervicooccipital.

Predicting return to work after low back injury using the Psychosocial Risk for Occupational Disability Instrument: a validation study.

INTRODUCTION: This paper reports on the predictive validity of a Psychosocial Risk for Occupational Disability Scale in the workers' compensation environment using a paper and pencil version of a previously validated multimethod instrument on a new, subacute sample of workers with low back pain. METHODS: A cohort longitudinal study design with a randomly selected cohort off work for 4-6 weeks was applied. The questionnaire was completed by 111 eligible workers at 4-6 weeks following injury. Return to work status data at three months was obtained from 100 workers. Sixty-four workers had returned to work (RTW) and 36 had not (NRTW). RESULTS: Stepwise backward elimination resulted in a model with these predictors: Expectations of Recovery, SF-36 Vitality, SF-36 Mental Health, and Waddell Symptoms. The correct classification of RTW/NRTW was 79%, with sensitivity (NRTW) of 61% and specificity (RTW) of 89%. The area under the ROC curve was 84%. CONCLUSIONS: New evidence for predictive validity for the Psychosocial Risk-for-Disability Instrument was provided. IMPLICATIONS: The instrument can be useful and practical for prediction of return to work outcomes in the subacute stage after low back injury in the workers' compensation context.

Psychosocial factors predictive of occupational low back disability: towards development of a return-to-work model.

This paper focuses on the identification and testing of potential psychosocial factors contributing to an integrated multivariate predictive model of occupational low back disability. Psychosocial predictors originate from five traditions of psychosocial research: psychopathological, cognitive, diathesis-stress, human adaptation and organizational psychology. The psychosocial variables chosen for this study reflect a full range of research findings. They were investigated using 253 subacute and chronic pain injured workers. Three outcome measures were utilized: return-to-work status, duration of disability and disability costs. The key psychosocial predictors identified were expectations of recovery and perception of health change. Also implicated, but to a lesser degree, were occupational stability, skill discretion at work, co-worker support, and the response of the workers' compensation system and employer to the disability. All psychosocial models were better at predicting who will return than who will not return to work.

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC).

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a large-scale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12-13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets.

Survivin mRNA expression is elevated in malignant urothelial cell carcinomas and predicts time to recurrence.

BACKGROUND: Expression of the inhibitor of apoptosis protein survivin is up-regulated in many tumors of epithelial origin and frequently shows a relationship with disease prognosis. MATERIALS AND METHODS: We investigated survivin mRNA expression in 32 urothelial cell carcinomas by use of real-time quantitative PCR. Expression values were normalized to transcript levels of the housekeeping gene cyclophilin. RESULTS: All bladder tumor tissues expressed survivin mRNA. The median normalized survivin mRNA expression values were 0.26 for superficial tumors (n = 17) and 0.78 for invasive tumors (n = 15). A significant relationship with increasing pathological stage (p < 0.001) and grade (p < 0.001) was observed. Although survivin mRNA expression did not relate to disease progression or the patient survival period, patients with superficial bladder tumors and normalized survivin values over 0.26 had an increased risk of recurrence (log-rank test: p = 0.018). CONCLUSION: Our results suggest that quantitative measurement of survivin mRNA 1) can identify invasive and high-grade urothelial cell carcinomas and 2) may be used as an indicator for early recurrence of superficial tumors.

Assessing pain behaviour of low-back pain patients in real time: concurrent validity and examiner sensitivity.

Several systems for measuring pain behaviour have been developed for clinical settings. The present study reports on a real-time system for coding five categories of pain behaviour for low-back pain patients: guarding, touching, sounds, words, and facial expression. Unique features of the system are the use of refined measures of facial expression and integration of the measurements with a standardized physical examination. 176 sub-acute and chronic low-back pain patients underwent a physical examination while their pain behaviour was coded. Concurrent measures of subjective pain, medically-incongruent signs, and independent global ratings of pain behaviour were taken. Analyses indicated that the pain behaviours, particularly guarding and facial expression, varied systematically with the alternative measures, supporting the concurrent validity of the behaviour observation system. While pain behaviours, especially use of words and facial expressions, were significantly associated with the examiners' independent ratings, the strength of the associations suggested that, in the absence of direct training, examiners' performance was relatively poor. Implications for training of clinicians in detecting pain behaviour are discussed.

Dichloroacetate toxicokinetics and disruption of tyrosine catabolism in B6C3F1 mice: dose-response relationships and age as a modifying factor.

Dichloroacetate (DCA) is a rodent carcinogen commonly found in municipal drinking water supplies. Toxicokinetic studies have established that elimination of DCA is controlled by liver metabolism, which occurs by the cytosolic enzyme glutathione-S-transferase-zeta (GST-zeta). DCA is also a mechanism based inhibitor of GST-zeta, and a loss in GST-zeta enzyme activity occurs following repeated doses or prolonged drinking water exposures. GST-zeta is identical to an enzyme that is part of the tyrosine catabolism pathway known as maleylacetoacetate isomerase (MAAI). In this pathway, GST-zeta plays a critical role in catalyzing the isomerization of maleylacetoacetate to fumarylacetoacetate. Disruption of tyrosine catabolism has been linked to increased cancer risk in humans. We studied the elimination of i.v. doses of DCA to young (10 week) and aged (60 week) mice previously treated with DCA in their drinking water for 2 and 56 weeks, respectively. The diurnal change in blood concentrations of DCA was also monitored in mice exposed to three different drinking water concentrations of DCA (2.0, 0.5 and 0.05 g/l). Additional experiments measured the in vitro metabolism of DCA in liver homogenates prepared from treated mice given various recovery times following treatment. The MAAI activity was also measured in liver cytosol obtained from treated mice. Results indicated young mice were the most sensitive to changes in DCA elimination after drinking water treatment. The in vitro metabolism of DCA was decreased at all treatment rates. Partial restoration ( approximately 65% of controls) of DCA elimination capacity and hepatic GST-zeta activity occurred after 48 h recovery from 14 d 2.0 g/l DCA drinking water treatments. Recovery from treatments could be blocked by interruption of protein synthesis with actinomycin D. MAAI activity was reduced over 80% in liver cytosol from 10-week-old mice. However, MAAI was unaffected in 60-week-old mice. These results indicate that in young mice, inactivation and re-synthesis of GST-zeta is a highly dynamic process and that exogenous factors that deplete or reduce GST-zeta levels will decrease DCA elimination and may increase the carcinogenic potency of DCA. As mice age, the elimination capacity for DCA is less affected by reduced liver metabolism and mice appear to develop some toxicokinetic adaptation(s) to allow elimination of DCA at rates comparable to naive animals. Reduced MAAI activity alone is unlikely to be the carcinogenic mode of action for DCA and may in fact, only be important during the early stages of DCA exposure.

Reliability of the lumbar flexion, lumbar extension, and passive straight leg raise test in normal populations embedded within a complete physical examination.

STUDY DESIGN: The study measured the reliability of the passive straight leg raise (SLR) test and lumbar range of motion (LROM) tests measured as continuous variables embedded within a comprehensive physical examination. OBJECTIVES: To determine the reliability of the SLR and LROM test scores when they are measured with a Cybex electronic inclinometer (Lumex, Inc., New York, NY) within a physical examination. SUMMARY OF BACKGROUND DATA: Good published empirical reliability exists for the Cybex and for SLR and LROM tests when the measurements are taken in isolation from other physical examination procedures. Reliability of the Cybex for continuous SLR and LROM measurement within a physical examination has not been assessed, however. METHODS: Forty-five participants were seen by one of two physician/physiotherapist teams. Participants were examined by both team members. The first examiner conducted the first tests and retested 1 week later (intrarater reliability). The second examined the participants the day after their first appointment (inter-rater reliability). RESULTS: Only two scores showed substantial reliability (defined as r > or = 0.60). These scores were left (r = 0.81) and right (r = 0.79) SLR intrarater reliability. All other scores fell below the specified cutoff. CONCLUSIONS: SLR and LROM scores used clinically are collected during comprehensive physical examinations. Most scores gathered under these conditions were not reliable. These findings have implications for the use of clinically derived SLR and LROM scores.