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Ines Daguet,1,2 Kayla Bergeron-Vezina,1,2 Marie-Philippe Harvey,1,2 Marylie Martel,1,2 Alexia Coulombe-Leveque,1– 3 Guillaume Leonard1– 3 1Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; 2Research Centre on Aging, CIUSSS de l’Estrie - CHUS, Sherbrooke, QC, Canada; 3School of Rehabilitation, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, CanadaCorrespondence: Guillaume LeonardResearch Centre on Aging, CIUSSS de l’Estrie – CHUS, 1036, rue Belvédère Sud, Sherbrooke, Québec J1H 4C4, CanadaTel +1 819-780-2220 Ext 45246Fax +1 819-820-6864Email guillaume.leonard2@usherbrooke.caBackground and Purpose: Aging is associated with an impairment of diverse physiological functions, including nociception. For example, older adults in comparison to young adults, show an overall increase in pain thresholds, reflecting a decline in pain sensitivity and changes in the nociceptive pathways. These results are, however, debated as they were not always replicated depending on the stimulus modality, duration, and location. The aim of the current study was to determine how the temporal evolution of pain intensity during a continuous tonic heat pain test is influenced by aging. More specifically, we wanted to 1) assess the effect of age on initial peak and late-phase pain and 2) determine whether potential age effects depend on the stimulation site.Participants and Methods: 13 young adults (average of 27.9 years old) and 13 older adults (average of 67.5 years old) participated in this study. Experimental heat pain was evoked on an appendicular (forearm) and axial (lower-back) body region, using a thermode (2-minute stimulation at a constant, individually-adjusted temperature). During the nociceptive stimulation, participants used a computerized visual analogue scale to continuously rate their pain.Results: We show that initial peak (0– 30 seconds) pain sensation was significantly lower in older adults compared to young adults, while late-phase (30– 120 seconds) pain sensation was similar across the two age groups. These results hold true for both stimulation sites, suggesting the existence of an age effect on both appendicular and axial body regions.Conclusion: The lower magnitude of initial peak pain observed in older adults, which affects both appendicular and axial body regions, could reflect generalized peripheral or central alterations of the nociceptive system in older adults. These alterations in older adults could have significant clinical impacts, such as an increased vulnerability to injury or an underestimation of the severity of their pain condition.Keywords: pain, experimental pain, age, aging, elderly, psychophysics

Francis Houde, 1– 3 Marie-Philippe Harvey, 1, 3 Pierre-François Tremblay Labrecque, 1, 3 Francis Lamarche, 1, 3 Alexandra Lefebvre, 1, 3 Leonard Guillaume 1, 3 1Research Center on Aging, CIUSSS de l’Estrie - CHUS, Université de Sherbrooke, Sherbrooke, Québec, Canada; 2Research Center of the Centre hospitalier universitaire de Sherbrooke (CHUS), CIUSSS de l’Estrie – CHUS, Université de Sherbrooke, Sherbrooke, Québec, Canada; 3Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Québec, CanadaCorrespondence: Leonard GuillaumeCentre de recherche sur le vieillissement, CIUSSS de l’Estrie - CHUS, 1036, rue Belvédère Sud, Sherbrooke, Québec J1H 4C4, CanadaTel +1 (819) 829-7131 ext. 45246Fax +1 (819) 820-6864Email guillaume.leonard2@usherbrooke.caPurpose: Complex regional pain syndrome (CRPS) is a rare neuropathic pain condition characterized by sensory, motor and autonomic alterations. Previous investigations have shown that transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) can alleviate pain in various populations, and that a combination of these treatments could provide greater hypoalgesic effects. In the present case report, we describe the effect of tDCS and TENS treatment on pain intensity and unpleasantness in a patient suffering from chronic CRPS.Results: The patient was a 37-year-old woman, suffering from left lower limb CRPS (type I) for more than 5 years. Despite medication (pregabalin, tapentadol, duloxetine), rehabilitation treatments (sensorimotor retraining, graded motor imagery) and spinal cord stimulation (SCS), the participant reported moderate to severe pain. Treatments of tDCS alone (performed with SCS turned off during tDCS application, 1 session/day, for 5 consecutive days) did not significantly decrease pain. Combining tDCS with TENS (SCS temporarily turned off during tDCS, 1 session/day, for 5 consecutive days) slightly reduced pain intensity and unpleasantness.Discussion: Our results suggest that combining tDCS and TENS could be a therapeutic strategy worth investigating further to relieve pain in chronic CRPS patients. Future studies should examine the efficacy of combined tDCS and TENS treatments in CRPS patients, and other chronic pain conditions, with special attention to the cumulative and long-term effects and its effect on function and quality of life.Keywords: chronic pain, neuropathic pain, electrotherapy, peripheral electrical stimulation, peripheral nerve stimulation, non-invasive brain stimulation

Inès Daguet,1,2 Kayla Bergeron-Vézina,1,2 Marie-Philippe Harvey,1,2 Marylie Martel,1,2 Guillaume Léonard2,3 1Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada; 2Research Center on Aging, Institute of Geriatrics of Sherbrooke, Sherbrooke, QC, Canada; 3École de réadaptation, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada Purpose: Placebo analgesia refers to a perceived reduction in pain intensity following the administration of a simulated or otherwise medically ineffective treatment. Previous studies have shown that many factors can influence the magnitude of placebo analgesia. However, few investigations have examined the effect of age on placebo analgesia, and none have done it in the context of electrotherapeutic interventions. The objective of this study is to compare the placebo response induced by sham transcutaneous electrical nerve stimulation (TENS) between young and older individuals, using an experimental heat-pain paradigm.Patients and methods: Twenty-two young (21–39 years) and 22 older (58–76 years) healthy adults participated in this comparative study. Experimental heat pain was evoked with a thermode (2-min stimulation at a constant individually adjusted temperature) applied on the lumbar region. Participants were asked to evaluate the intensity of their pain using a computerized visual analog scale. Experimental pain was induced before and after an unconditioned placebo intervention (placebo TENS) applied for 25 min.Results: In young individuals, no significant pain reductions were noted, whereas in older individuals, a statistically significant pain reduction was observed after the placebo stimulation (P

Marie-Philippe Harvey,1,2 Dominique Lorrain,1,3 Marylie Martel,1,2 Kayla Bergeron-Vezina,1 Francis Houde,1,2 Mario Séguin,2,4 Guillaume Léonard1,2,5 1Research Centre on Aging, CIUSSS de l’Estrie-CHUS, 2Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3Department of Psychology, Université de Sherbrooke 4Department of Neurosurgery, Centre Hospitalier Universitaire de Sherbrooke, 5School of Rehabilitation, Université de Sherbrooke, Sherbrooke, QC, Canada Background: The prevalence of chronic pain and sleep disturbances substantially increases with age. Pharmacotherapy remains the primary treatment option for these health issues. However, side effects and drug interactions are difficult to control in elderly individuals.Aims: The objective of this study was to assess the feasibility of conducting a randomized sham-controlled trial and to collect preliminary data on the efficacy of transcranial direct current stimulation (tDCS) to reduce pain and improve sleep in older adults suffering from chronic pain.Methods: Fourteen elderly individuals (mean age 71±7 years) suffering from chronic pain and sleep complaints were randomized to receive either anodal tDCS, applied over the primary motor cortex (2 mA, 20 minutes), or sham tDCS, for 5 consecutive days. Pain was measured with visual analog scales, pain logbooks and questionnaires, while sleep was assessed with actigraphy, sleep diaries and questionnaires.Results: There were no missing data for pain and sleep measures, except for actigraphy, that generated several missing data. Blinding was maintained throughout the study, for both the evaluator and participants. Active but not sham tDCS significantly reduced pain (P

Knee osteoarthritis (OA) is a painful condition characterized by joint and bone changes. A growing number of studies suggest that these changes only partially explain the pain experienced by individuals with OA. The purpose of the current study was to evaluate if corticospinal and bulbospinal projection measurements were interrelated in patients with knee OA, and to explore the relationship between these neurophysiological measures and temporal summation (excitatory mechanisms of pain) on one hand, and clinical symptoms on the other. Twenty-eight (28) patients with knee OA were recruited. Corticospinal projections were measured using transcranial magnetic stimulation, while bulbospinal projections were evaluated with a conditioned pain modulation (CPM) protocol using a counter-irritation paradigm. Validated questionnaires were used to document clinical and psychological manifestations. All participants suffered from moderate to severe pain. There was a positive association between corticospinal excitability and the effectiveness of the CPM (r s = 0.67, p = 0.01, n = 13). There was also a positive relationship between pain intensity and corticospinal excitability (r s = 0.45, p = 0.03, n = 23), and between pain intensity and temporal summation (r s = 0.58, p = 0.01, n = 18). The results of this study highlight some of the central nervous system changes that could be involved in knee OA and underline the importance of interindividual variability to better understand and explain the semiology and pathophysiology of knee OA.

Objective: Endogenous pain inhibition can be investigated using conditioned pain modulation (CPM). CPM efficacy has been reported to be influenced by various factors, such as gender and cardiovascular (autonomic) activity. The aim of this study is to describe the effect of pharmacological manipulations of autonomic activity on CPM efficacy., Methods: Thirty healthy participants were enrolled to assess CPM efficacy in 4 experimental sessions. The first session consisted of the determination of baseline CPM effectiveness. The three following sessions were performed in a randomized order and consisted of the injection of (1) esmolol, (2) ephedrine, or (3) placebo, before the conditioning stimulus. Pain intensity induced by using a contact heat stimulation thermode was compared before and after a cold-pressure conditioning stimulus to evaluate CPM effectiveness., Results: Our results show that inhibiting sympathetic nervous activity with esmolol did not have a significant effect on CPM. Conversely, enhancing sympathetic nervous activity with ephedrine increased CPM effectiveness in healthy women but decreased it in men., Conclusions: Increasing sympathetic activity with adrenergic agonists, such as ephedrine, could improve CPM effectiveness in women. It will be interesting to verify if the same results are present in patients suffering from chronic pain and if adrenergic agonists could have better therapeutic effects in women showing reduced CPM effectiveness., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Marie-Philippe Harvey et al.)

Introduction: Chronic pain is a significant health problem and is particularly prevalent amongst the elderly. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been proposed to reduce chronic pain. The aim of this study was to evaluate and compare the efficacy of active and sham tDCS in reducing pain in older individuals living with chronic musculoskeletal pain., Materials and Methods: Twenty-four older individuals (mean age: 68 ± 7 years) suffering from chronic musculoskeletal pain were randomized to receive either anodal tDCS over the contralateral motor cortex (2 mA, 20 min; n = 12) or sham tDCS (20 min; n = 12) for five consecutive days. Pain logbooks were used to measure pain intensity. Questionnaires (McGill Pain Questionnaire, Brief Pain Inventory, Beck Depression Inventory [BDI], Beck Anxiety Inventory, Pain Catastrophizing Scale [PCS], and Margolis Pain Drawing and Scoring System [MPDSS]) were also used to assess pain in its globality., Results: Analysis of pain logbooks revealed that active tDCS led to a reduction in daily average pain intensity (all p ≤ 0.04), while sham tDCS did not produce any change ( p = 0.15). Between-group comparisons for change in pain intensity reduction between active and sham tDCS showed a trend during treatment ( p = 0.08) which was significant at the follow-up period ( p = 0.02). Active tDCS also improved scores of all questionnaires (all p ≤ 0.02), while sham tDCS only reduced MPDSS scores ( p = 0.04). Between-group comparisons for the pain-related outcomes showed significant differences for BDI et PCS after the last tDCS session., Conclusions: These results suggest that anodal tDCS applied over the primary motor cortex is an effective modality to decrease pain in older individuals. tDCS can also improve other key outcomes, such as physical and emotional functioning, and catastrophic thinking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Harvey, Martel, Houde, Daguet, Riesco and Léonard.)

Background: Many primary care patients receive both medical and chiropractic care; however, interprofessional relations between physicians and chiropractors are often suboptimal which may adversely affect care of shared patients. We surveyed Canadian family physicians in 2010 to explore their attitudes towards chiropractic and re-administered the same survey a decade later to explore for changes in attitudes., Methods: A 50-item survey administered to a random sample of Canadian family physicians in 2010, and again in 2019, that inquired about demographic variables, knowledge and use of chiropractic. Imbedded in our survey was a 20-item chiropractic attitude questionnaire (CAQ); scores could range from 0 to 80 with higher scores indicating more positive attitudes toward chiropractic. We constructed a multivariable regression model to explore factors associated with CAQ scores., Results: Among eligible physicians, 251 of 685 in 2010 (37% response rate) and 162 of 2429 in 2019 (7% response rate) provided a completed survey. Approximately half of respondents (48%) endorsed a positive impression of chiropractic, 27% were uncertain, and 25% held negative views. Most respondents (72%) referred at least some patients for chiropractic care, mainly due to patient request or lack of response to medical care. Most physicians believed that chiropractors provide effective therapy for some musculoskeletal complaints (84%) and disagreed that chiropractic care was beneficial for non-musculoskeletal conditions (77%). The majority agreed that chiropractic care was a useful supplement to conventional care (65%) but most respondents (59%) also indicated that practice diversity among chiropractors presented a barrier to interprofessional collaboration. In our adjusted regression model, attitudes towards chiropractic showed trivial improvement from 2010 to 2019 (0.31 points on the 80-point CAQ; 95%CI 0.001 to 0.62). More negative attitudes were associated with older age (- 1.55 points for each 10-year increment from age 28; 95%CI - 2.67 to - 0.44), belief that adverse events are common with chiropractic care (- 1.41 points; 95% CI - 2.59 to - 0.23) and reported use of the research literature (- 6.04 points; 95% CI - 8.47 to - 3.61) or medical school (- 5.03 points; 95% CI  - 7.89 to - 2.18) as sources of knowledge on chiropractic. More positive attitudes were associated with endorsing a relationship with a specific chiropractor (5.24 points; 95% CI 2.85 to 7.64), family and friends (4.06 points; 95% CI 1.53 to 6.60), or personal treatment experience (4.63 points; 95% CI 2.14 to 7.11) as sources of information regarding chiropractic., Conclusions: Although generally positive, Canadian family physicians' attitudes towards chiropractic are diverse, and most physicians felt that practice diversity among chiropractors was a barrier to interprofessional collaboration., (© 2021. The Author(s).)

Background: Past studies have shown that pain memories are often inaccurate, a phenomenon known as mnemonic pain bias. Pain memories are thought to play an important role on how future pain is felt. Recent evidence from our laboratory suggests that individuals who exaggerate past pain display increased superior temporal gyrus (STG) activity during the encoding of experimental painful stimulations, suggesting that this brain structure plays an important role in pain memories., Objective: /hypothesis. To determine whether a virtual lesion paradigm, targeting the STG during pain encoding, can affect long-lasting pain memories. We hypothesized that interfering with the activity of the STG would attenuate mnemonic bias., Methods: Randomized double-blind study with two parallel groups. Participants received either sham (n = 21) or real (n = 21) transcranial magnetic stimulation (TMS - virtual lesion paradigm) over the STG during pain encoding (milliseconds after the administration of a painful stimuli). Pain intensity and unpleasantness were evaluated using a visual analog scale (VAS; 0 to 10) immediately after the painful event, and at recall, 2 months later. The mnemonic pain bias (calculated by subtracting the pain scores obtained at recall from the pain score obtained during encoding) was compared between the two groups for both pain intensity and unpleasantness., Results: Participants in both groups did not differ in terms of age and gender (real TMS = 27 years ± 9, 43% female; sham TMS = 25 years ± 4, 49% female; p > 0.64). The mnemonic bias related to pain intensity was similar in both groups (p = 0.83). However, the mnemonic bias related to pain unpleasantness was lower in the real TMS group (p = 0.04)., Conclusions: Our results provide the first evidence that the STG, is causally involved in the formation of biased memories of pain unpleasantness., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to evaluate cortical function and corticospinal pathway in normal and pathological aging. Yet, the metrologic properties of TMS-related measurements is still limited in the aging population. Objectives: The aim of this cross-sectional study was to document the reliability and smallest detectable change of TMS measurements among community-dwelling seniors. A secondary objective was to test if TMS measurements differ between elders based on lifestyle, medical and socio-demographic factors. Methods: Motor evoked potentials (MEPs) elicited by single-pulse TMS were recorded in the first dorsal interosseous (FDI) in 26 elderly individuals (mean age = 70 ± 3.8 years). Resting motor threshold (rMT), MEP amplitudes and contralateral silent period (cSP) were measured on two separate occasions (1-week interval), and the standard error of the measurement (SEM eas ), intraclass correlation coefficient (ICC), and smallest detectable change in an individual (SDC indv ) were calculated. Lifestyle, medical and socio-demographic factors were collected using questionnaires. TMS-related outcomes were compared using independent sample t -test based on the presence of chronic health diseases, chronic medication intake, obesity, history of smoking, physical activity levels, gender, and level of education. Results: rMT and cSP measures were the most reliable outcomes, with the lowest SEM eas and highest ICCs, whereas MEP amplitude-related measures were less reliable. SDC indv levels were generally high, even for rMT (7.29 %MSO) and cSP (43.16-50.84 ms) measures. Although not systematically significant, results pointed toward a higher corticospinal excitability in elderly individuals who were regularly active, who had no chronic medical conditions and who did not take any medication. Conclusion: Even though SDC indv levels were relatively high, these results show that rMT and cSP are the most reliable outcomes to investigate age-related changes in the corticomotor system and suggest that the influence of factors such as lifestyle habits and medications on TMS measures should be investigated further.

A previous study found that the modified version of the Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC-II) is a valid tool to assess pain in elderly individuals suffering from dementia and who are unable to communicate verbally. The primary objective of this study was to confirm the convergent validity of the PACSLAC-II using direct evaluation of long-term care residents in real-life situations, using two other well-validated pain assessment scales (i.e., PACSLAC and Pain Assessment in Advanced Dementia [PAINAD]). A secondary objective was to document and compare the time required to complete and score each assessment scale. During two potentially painful procedures (i.e., transfer/mobilization), 46 long-term care residents (mean age = 83 ± 10 years) suffering from dementia were observed by three independent evaluators, each using one of the assessment scales (randomly assigned). Correlational analyses and analysis of variance were used to evaluate the association between each scale and to compare scoring time. The PACSLAC (r = 0.61) and the PAINAD (r = 0.65) were both moderately associated with the PACSLAC-II (all p values < .001). The PAINAD's average scoring time (63 ± 19 seconds) was lower than the PACSLAC-II's (96 ± 2 seconds), which was lower than the PACSLAC's (135 ± 53 seconds) (all p values < .001). These results suggest that the PACSLAC-II is a valid tool for assessing pain in individuals with dementia. The time required to complete and score the PACSLAC-II was reasonable, supporting its usefulness in clinical settings., (Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Chronic abdominal and pelvic pain is a common condition that has significant impact on quality of life, and causes billions of dollars in direct and indirect costs. Emerging data suggest that transcranial direct current stimulation (tDCS), alone or in combination with transcutaneous electrical nerve stimulation (TENS), could be a promising therapeutic avenue to reduce chronic pain. The encouraging results coming from these studies prompted us to try combining TENS and tDCS in 4 of our patients who suffered from chronic abdominal/pelvic pain and to compare the effect with 5 other patients who received TENS alone. Pain intensity was assessed with a visual analog scale before, during and after the stimulation. We observed that there was a slight decrease in pain which was similar in both patient groups (TENS alone and TENS combined with tDCS). These observations suggest that combining TENS and tDCS in patients suffering from chronic pelvic and/or abdominal pain produces no additional benefit, compared to TENS alone. Future studies, looking at the effect of several/consecutive TENS and tDCS sessions should be conducted., Competing Interests: Conflict-of-interest statement: Léonard G has received research funding from Fonds de recherche en santé du Québec; Watier A and Dufort Rouleau É are employees of the Sherbrooke University Hospital Centre; Watier A and Léonard G are employees of the University of Sherbrooke.

The interaction between pain and the motor system is well-known, with past studies showing that pain can alter corticomotor excitability and have deleterious effects on motor learning. The aim of this study was to better understand the cortical mechanisms underlying the interaction between pain and the motor system. Experimental pain was induced on 19 young and healthy participants using capsaicin cream, applied on the middle volar part of the left forearm. The effect of pain on brain activity and on the corticomotor system was assessed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), respectively. Compared to baseline, resting state brain activity significantly increased after capsaicin application in the central cuneus (theta frequency), left dorsolateral prefrontal cortex (alpha frequency), and left cuneus and right insula (beta frequency). A pain-evoked increase in the right primary motor cortex (M1) activity was also observed (beta frequency), but only among participants who showed a reduction in corticospinal output (as depicted by TMS recruitment curves). These participants further showed greater beta M1-cuneus connectivity than the other participants. These findings indicate that pain-evoked increases in M1 beta power are intimately tied to changes in the corticospinal system, and provide evidence that beta M1-cuneus connectivity is related to the corticomotor alterations induced by pain. The differential pattern of response observed in our participants suggest that the effect of pain on the motor system is variable from on individual to another; an observation that could have important clinical implications for rehabilitation professionals working with pain patients.

Despite its widespread clinical use, the efficacy of transcutaneous electrical nerve stimulation (TENS) remains poorly documented in elderly individuals. In this randomized, double-blind crossover study, we compared the efficacy of high-frequency (HF), low-frequency (LF), and placebo (P) TENS in a group of 15 elderly adults (mean age: 67 ± 5 years). The effect of HF-, LF-, and P-TENS was also evaluated in a group of 15 young individuals (26 ± 5 years; same study design) to validate the effectiveness of the TENS protocols that were used in the elderly group. Each participant came to the laboratory on 3 separate occasions to receive, in random order, HF-, LF-, and P-TENS. Pain intensity and pain perception thresholds were assessed before, during, and after TENS, using an experimental heat pain paradigm. For the young group, there was a significant decrease in pain intensity during and after HF- and LF-TENS when compared with baseline, with both HF- and LF-TENS being superior to P-TENS. In the older group, HF- and LF-TENS did not reduce pain when compared with baseline and no difference was observed between the 2 active TENS sessions and P-TENS. High-frequency, LF-, and P-TENS all increased pain thresholds in young individuals, whereas in older individuals, only LF-TENS increased pain thresholds. Taken together, these results suggest that TENS is effective in young, but not in older, individuals. Future studies should be conducted to confirm these results in pain populations and to identify strategies that could enhance the effect of TENS in the elderly.

Background: Low back pain (LBP) is one of the most frequent musculoskeletal conditions in industrialized countries and its economic impact is important. Spinal manipulation therapy (SMT) is believed to be a valid approach in the treatment of both acute and chronic LBP. It has also been shown that SMT can modulate the electromyographic (EMG) activity of the paraspinal muscle. The purpose of this study was to investigate, in a group of patients with low back pain, the persistence of changes observed in trunk neuromuscular responses after a spinal manipulation (SMT)., Methods: Sixty adult participants with LBP performed a block of 5 flexion-extension movements. Participants in the experimental group (n=30) received lumbar SMT whereas participants in the control group (n=30) were positioned similarly for the treatment but did not receive SMT. Blocks of flexion-extension movements were repeated immediately after the manipulation as well as 5 and 30 minutes after SMT (or control position). EMG activity of paraspinal muscles was recorded at L2 and L5 level and kinematic data were collected to evaluate the lumbo-pelvic kinematics. Pain intensity was noted after each block. Normalized EMG, pain intensity and lumbo-pelvic kinematics were compared across experimental conditions., Results: Participants from the control group showed a significant increase in EMG activity during the last block (30 min) of flexion-extension trials in both flexion and full-flexion phases at L2. Increase in VAS scores was also observed in the last 2 blocks (5 min and 30 min) in the control group. No significant group x time interaction was seen at L5. No significant difference was observed in the lumbo-pelvic kinematics., Conclusion: Changes in trunk neuromuscular control following HVLA spinal manipulation may reduce sensitization or muscle fatigue effects related to repetitive movement. Future studies should investigate short term changes in neuromuscular components, tissue properties and clinical outcomes.

Purpose: The goal of the present study was to quantify the high-velocity, low-amplitude spinal manipulation biomechanical parameters in two cohorts of students from different teaching institutions. The first cohort of students was taught chiropractic techniques in a patient-doctor positioning practice setting, while the second cohort of students was taught in a "complete practice" manipulation setting, thus performing spinal manipulation skills on fellow student colleagues. It was hypothesized that the students exposed to complete practice would perform the standardized spinal manipulation with better biomechanical parameters., Methods: Participants (n = 88) were students enrolled in two distinct chiropractic programs. Thoracic spine manipulation skills were assessed using an instrumented manikin, which allowed the measurement of applied force. Dependent variables included peak force, time to peak force, rate of force production, peak force variability, and global coordination., Results: The results revealed that students exposed to complete practice demonstrated lower time to peak force values, higher peak force, and a steeper rate of force production compared with students in the patient-doctor positioning scenario. A significant group by gender interaction was also noted for the time to peak force and rate of force production variables., Conclusion: The results of the present study confirm the importance of chiropractic technique curriculum and perhaps gender in spinal manipulation skill learning. It also stresses the importance of integrating spinal manipulation skills practice early in training to maximize the number and the quality of significant learner-instructor interactions.

Objective: To determine whether Helicobacter pylori eradication is an effective treatment for Australian patients with chronic immune thrombocytopenic purpura (ITP)., Design, Setting and Patients: Retrospective analysis of clinical records of a consecutive series of ITP patients referred to a gastrointestinal surgeon in a tertiary referral hospital for laparoscopic splenectomy between August 2005 and November 2007., Main Outcome Measures: Platelet response (measured at least 3-monthly) following successful H. pylori eradication therapy (confirmed by urea breath test 4 weeks later)., Results: Of 16 patients, seven were H. pylori-negative and underwent laparoscopic splenectomy. Nine were H. pylori-positive and successfully underwent H. pylori eradication therapy; five of the nine had an initial platelet response. Four patients had platelet counts > 100 x 10(9)/L (reference range, 140-450 x 10(9)/L) and were off all immunosuppression at 9 months; three had a sustained response beyond 12 months. One patient had an initial response at 3 months (15 x 10(9)/L to 208 x 10(9)/L), but relapsed 4 months after H. pylori eradication and underwent splenectomy with platelet count recovery. The remaining four patients showed no platelet response and subsequently underwent splenectomy., Conclusion: Larger prospective studies are needed to fully ascertain the role of H. pylori in Australian patients with ITP. However, H. pylori eradication is simple and safe. H. pylori screening and eradication should be considered before immunosuppression or splenectomy.

The complexity of information technology systems has increased to approximate that of biological organisms, with a similar unpredictability of behaviour. With several million lines of code, a modern computer operating system, still can only be compared in complexity to a bacterial genome. However, just as unpredictable mutations continuously arise in the 3000 million haploid base pairs of human code and cause much misery and disease, undiscovered errors lie buried in the accumulated machine code which make up our world. As in human genetics, the difficulty is often distinguishing the harmless polymorphisms from the dangerous or lethal mutations. Similarly there is uncertainty about the impact of errors in data-handling code, which make up the "Year 2000 Problem". Over the remaining months it is vital that critical systems are checked for year 2000 compliance so as to avoid potentially serious disruption.

Objective: To determine blood products used, clinical outcomes and frequency of haemostatic complications of massive blood transfusion., Design and Setting: Retrospective review of the medical records of patients receiving more than 10 units of blood in 24 hours at a tertiary referral hospital in 1993., Patients: Forty-three patients fulfilled this criterion. The major reasons for massive transfusion were trauma (46%; 20 patients), gastrointestinal bleeding (21%; nine patients) and leaking abdominal aortic aneurysm (14%; six patients)., Main Outcome Measures: Blood products used, platelet count ( < 50 x 10(9)/L in first 48 h), prothrombin time (PT) and activated partial thromboplastin time (APTT) (twice normal in first 48 h), microvascular bleeding, and survival., Results: The 43 patients used 824 units of packed cells 15.2% of the total used in 1993), 457 units of fresh frozen plasma (FFP) (17.1% of the 1993 total) and 370 units of platelets (14.8% of the 1993 total). Overall, these patients consumed 16% of the total number of units of blood product used in 1993 for 1478 transfusion episodes. The overall survival rate was 60%. Severe coagulopathy occurred in 19 patients (44%) (mortality rate, 74%), and 13 (31%) had severe thrombocytopenia ( < 50 x 10(9)/L). There was no significant correlation between the severity of coagulopathy/thrombocytopenia and total units transfused, or between the age of the units of blood and development of coagulopathy or microvascular bleeding., Conclusions: Severe coagulopathy is common after massive transfusions. In the absence of clear correlation with the number of units transfused, "formula" replacement with plasma and platelets is unlikely to avoid the problem. Duration of tissue hypoperfusion and platelet consumption are likely to be more important than simple haemodilution of coagulation factors.

The -198 T-->C and the -175 T-->C transitions involving the proximal gamma-globin gene promoter are associated with the hereditary persistence of fetal hemoglobin (HPFH) phenotype and have been demonstrated to increase promoter activity in erythroid cells using transient and stable transfection systems. The above base changes are thought to alter the binding of different transcription regulatory proteins. Another mutation of the proximal gamma-globin promoter, -158 C-->T, has been less clearly linked to the HPFH phenotype but has been associated with increased G gamma activity. In the present paper, the -198 T-->C, -175 T-->C and -158 C-->T mutations both singly and in various combinations were evaluated by an in vitro expression assay. gamma-Globin promoters were transfected by electroporation into K562 human erythroleukemia cells and their activity measured in a human growth hormone (hGH) reporter gene assay. A novel cotransfectant was used to assess transfection efficiency. Results confirmed the previously reported upregulation of gamma-globin activity with the -198 T-->C and -175 T-->C HPFH mutations and a cooperative effect on promoter activity when both these mutations are present in cis. No effect of the -158 C-->T mutation was seen either alone or in combination with the -175 T-->C and -198 T-->C mutations.

Transgenic mice were produced from two 13 kb constructs containing the fetal (gamma) globin genes. Each construct consisted of a G gamma globin gene linked to one of two alternative A gamma genes. The first construct contained a normal G gamma gene plus an A gamma gene with the -198 T-->C hereditary persistence of fetal haemoglobin (HPFH) mutation. In the second, a normal G gamma gene was linked to a A gamma gene with a -222 to -225 four base pair deletion in the promoter. This latter mutation has been associated with low A gamma expression in humans. Both A gamma genes in these constructs also contained the 3' flanking enhancer. The two different constructs showed expression throughout gestation from day 11 yolk sac, through the fetal period and for a variable time during the first three postnatal weeks. Thereafter, no expression of any of the gamma-globin genes was seen in adult erythroid tissues. Transcription from the normal G gamma and HPFH A gamma genes in the first construct paralleled each other in developmental timing, with a proportionate excess of A gamma more evident in later gestation. G gamma and A gamma mRNA transcripts from the normal G gamma + 4 bp deletional A gamma construct were unable to be distinguished because of a 3' G gamma-like conversion in the deletional A gamma gene. Combined gamma-globin expression from the two genes in this second construct was detectable until just after birth, as seen with the individual genes in the first construct.(ABSTRACT TRUNCATED AT 250 WORDS)

The A gamma fetal globin genes from a large Australian kindred with nondeletional A gamma hereditary persistence of fetal hemoglobin (HPFH) were cloned and sequenced. The -198 T----C mutation (British type HPFH) was demonstrated upstream of the A gamma gene on one allele. On the other allele, a 4-deletion was identified -222 to -225 bp upstream from the cap site. The 4-bp deletion allele was associated with a number of variations in the A gamma gene sequence: anA gamma T transition, in the second exon (T----C at +402 relative to the cap site); a HindIII polymorphism in the second intron; and a G gamma-like sequence in the 3' untranslated region (TCAC in place of CTCT, creating a SacI site). An association between the -222 to -225 deletion, the A gamma T polymorphism, and the second intron HindIII polymorphism has previously been reported. In addition, linkage of the HindIII polymorphism with the G gamma-like sequence in the 3' untranslated region of A gamma has also been described. The case described here is unique, with all four changes present in the one A gamma gene. It is also noteworthy because there is simultaneous occurrence of high (HPFH) and low (-222 to -225 deletion) expression mutants in the same patient. Despite the presence of the 4-bp deletion, the resulting hematological phenotype remained that of HPFH. When the 4-bp deletion promoter was studied in a K562-cell transient expression assay, there was found to be no statistically significant reduction in activity compared to the control A gamma promoter. The possible reasons for the observed differences between the in vivo and in vitro activity of this mutation are discussed.

The rare association of alpha thalassaemia and mental retardation has been described previously. Molecular studies of the alpha globin cluster in these cases have been heterogeneous, with some patients having large deletions while in others the alpha globin complex appears to be intact (non-deletional). The non-deletional cases form a distinct group whose features include severe mental retardation, haematological changes of haemoglobin H (Hb H) disease, developmental defects, and unusual patterns of inheritance. To date, five cases have been described with non-deletional alpha thalassaemia-mental retardation. We present here a further example of a young male of Northern European origin who appears to have the non-deletional form of the disease. Clinical features included severe mental retardation, Hb H disease, and developmental defects similar to those reported previously. DNA mapping, including pulsed field electrophoresis, showed no evidence of deletions within the alpha globin cluster. Karyotypic analysis indicated an increase in random breakage, which has been observed previously in one case of deletional alpha thalassaemia-mental retardation. Profuse Hb H bodies and Hb H on electrophoresis were consistent with Hb H disease. However, the latter was present at a relatively low level (1.6%) and, as well, the mean corpuscular volume (82.8 fl) and mean corpuscular haemoglobin (26.4 pg) were surprisingly high. Our findings are compared to other cases described with the non-deletional Hb H-mental retardation syndrome.

During a 28 month period, 77 Hickman catheters were inserted in 66 patients with hematological disorders. Complete follow-up was possible for 72 catheter insertions. Catheters remained in situ for a median period of 77 days (range 5-474 days). Fourteen (19%) catheters required removal because of complications which included sepsis, blockage, or displacement. Catheter-related infection was the major complication and Staphylococcus epidermidis and diphtheroids (Corynebacterium species) were the organisms most commonly isolated.