Recapitulating pathophysiology of skeletal muscle diseases in vitro using primary mouse myoblasts on a nanofibrous platform.

Tissue engineering approaches are used to mimic the microenvironment of the skeletal muscle in vitro. However, the validation of a bioengineered muscle as a model to study diseases is inadequate. Here, we present polycaprolactone nanofibers as a robust platform that mimics cellular organization and recapitulates critical functions of the myotubes observed in vivo. We isolated myoblasts from mice following a simplified protocol and cultured them on aligned nanofibers. Myotubes grown on aligned nanofibers maintained alignment for 14 days and exhibited a time-dependent increase in levels of p-AKT upon insulin stimulation. Treatment with matrix-assisted integrin inhibitor led to reduction in p-AKT levels, underscoring the critical role of environment on the biological processes. We demonstrate the suitability of myotubes grown on nanofibrous platform to study corticosteroid-induced muscle degeneration. This study, thus, demonstrates that aligned nanofibers retain myotubes in culture for longer duration and recapitulate the functions of skeletal muscle under pathophysiological conditions.

Further evidence for specific IFIH1 mutation as a cause of Singleton-Merten syndrome with phenotypic heterogeneity.

Singleton-Merten syndrome (MIM 182250) is an autosomal dominant inherited disorder characterized by early onset periodontitis, root resorption, osteopenia, osteoporosis, and aortic valve or thoracic aorta calcification. The disorder can have significant intrafamilial phenotypic variability. Here, we present a mother and daughter with Singleton-Merten syndrome harboring a previously described pathogenic missense mutation, c.2465G>A p.(Arg822Gln), in IFIH1 (interferon induced with helicase C domain 1), encoding MDA5 (Melanoma Differentiation-Associated protein 5). These data confirm the pathogenicity of IFIH1 c.2465G>A p.(Arg822Gln) for Singleton-Merten syndrome and affirm the striking phenotypic heterogeneity of this disorder. In addition, we expand the Singleton-Merten phenotype by adding severe systemic lupus erythematosus (SLE) to the clinical picture. Investigations of known SLE genes as well as a single nucleotide polymorphism suggested to be involved in development of SLE were normal.

Novel STAC3 Mutations in the First Non-Amerindian Patient with Native American Myopathy.

Native American myopathy (NAM) is an autosomal recessive congenital myopathy, up till now exclusively described in Lumbee Indians who harbor one single homozygous mutation (c.1046G>C, pW284S) in the STAC3 gene, encoding a protein important for proper excitation-contraction coupling in muscle. Here, we report the first non-Amerindian patient of Turkish ancestry, being compound heterozygous for the mutations c.862A>T (p.K288*) and c.432+4A>T (aberrant splicing with skipping of exon 4). Symptoms in NAM include congenital muscle weakness and contractures, progressive scoliosis, early ventilatory failure, a peculiar facial gestalt with mild ptosis and downturned corners of the mouth, short stature, and marked susceptibility to malignant hyperthermia. This case shows that NAM should also be considered in non-Indian patients with congenital myopathy, and suggests that STAC3 mutations should be taken into account as a potential cause of malignant hyperthermia.

Myogenic bladder defects in mouse models of human oculodentodigital dysplasia.

To date, over 65 mutations in the gene encoding Cx43 (connexin43) have been linked to the autosomal-dominant disease ODDD (oculodentodigital dysplasia). A subset of these patients experience bladder incontinence which could be due to underlying neurogenic deterioration or aberrant myogenic regulation. BSMCs (bladder smooth muscle cells) from wild-type and two Cx43 mutant lines (Cx43(G60S) and Cx43(I130T)) that mimic ODDD exhibit a significant reduction in total Cx43. Dye transfer studies revealed that the G60S mutant was a potent dominant-negative inhibitor of co-expressed Cx43, a property not equally shared by the I130T mutant. BSMCs from both mutant mouse strains were defective in their ability to contract, which is indicative of phenotype changes due to harbouring the Cx43 mutants. Upon stretching, Cx43 levels were significantly elevated in controls and mutants containing BSMCs, but the non-muscle myosin heavy chain A levels were only reduced in cells from control mice. Although the Cx43(G60S) mutant mice showed no difference in voided urine volume or frequency, the Cx43(I130T) mice voided less frequently. Thus, similar to the diversity of morbidities seen in ODDD patients, genetically modified mice also display mutation-specific changes in bladder function. Furthermore, although mutant mice have compromised smooth muscle contraction and response to stretch, overriding bladder defects in Cx43(I130T) mice are likely to be complemented by neurogenic changes.

Rehabilitation of scapular dyskinesis: from the office worker to the elite overhead athlete.

The scapula functions as a bridge between the shoulder complex and the cervical spine and plays a very important role in providing both mobility and stability of the neck/shoulder region. The association between abnormal scapular positions and motions and glenohumeral joint pathology has been well established in the literature, whereas studies investigating the relationship between neck pain and scapular dysfunction have only recently begun to emerge. Although several authors have emphasised the relevance of restoring normal scapular kinematics through exercise and manual therapy techniques, overall scapular rehabilitation guidelines decent for both patients with shoulder pain as well as patients with neck problems are lacking. The purpose of this paper is to provide a science-based clinical reasoning algorithm with practical guidelines for the rehabilitation of scapular dyskinesis in patients with chronic complaints in the upper quadrant.

Electropalatography as an adjunct to nonspeech orofacial myofunctional disorder assessments: a feasibility study.

The purpose of this study was to determine if electropalatography (EPG) would be a useful adjunct and feasible option for those conducting clinical assessments of individuals with suspected nonspeech orofacial myofunctional disorders (NSOMD). Three females (two adults, one child) were referred by their orthodontist for assessment of suspected NSOMD. Three adults and one child without NSOMD were recruited for the purpose of evaluating methodological construct, and to provide comparisons for participants with NSOMD. Using EPG, lingual-palatal timing and contact patterns of 105 saliva swallows (45 with NSOMD, 60 without NSOMD) were analyzed by compartmentalizing the sensor display and tracking the order and duration of activation. Lingual-palatal contact patterns were compared in terms of four stages: prepropulsion, propulsion, postpropulsion, release. Coding the lingual-palatal activation in an operationalized manner was a valuable adjunct for describing lingual-palatal timing and contact patterns. Participants with NSOMD showed unique lingual-palatal contact patterns that differed from the patterns of the participants without NSOMD, and from each other. EPG is a potential adjunct to the non-instrumental assessment of NSOMD. Larger scale investigations using EPG should proceed.

Immunomodulation and Biomaterials: Key Players to Repair Volumetric Muscle Loss.

Volumetric muscle loss (VML) is defined as a condition in which a large volume of skeletal muscle is lost due to physical insult. VML often results in a heightened immune response, resulting in significant long-term functional impairment. Estimates indicate that ~250,000 fractures occur in the US alone that involve VML. Currently, there is no active treatment to fully recover or repair muscle loss in VML patients. The health economics burden due to VML is rapidly increasing around the world. Immunologists, developmental biologists, and muscle pathophysiologists are exploring both immune responses and biomaterials to meet this challenging situation. The inflammatory response in muscle injury involves a non-specific inflammatory response at the injured site that is coordination between the immune system, especially macrophages and muscle. The potential role of biomaterials in the regenerative process of skeletal muscle injury is currently an important topic. To this end, cell therapy holds great promise for the regeneration of damaged muscle following VML. However, the delivery of cells into the injured muscle site poses a major challenge as it might cause an adverse immune response or inflammation. To overcome this obstacle, in recent years various biomaterials with diverse physical and chemical nature have been developed and verified for the treatment of various muscle injuries. These biomaterials, with desired tunable physicochemical properties, can be used in combination with stem cells and growth factors to repair VML. In the current review, we focus on how various immune cells, in conjunction with biomaterials, can be used to promote muscle regeneration and, most importantly, suppress VML pathology.

Periodontal Disease Impairs Muscle Recovery by Modulating the Recruitment of Leukocytes.

The purpose of this study is to analyze the impact of periodontal disease (PD) associated with physical exercise on inflammatory mediators and muscle repair. Twenty-four Wistar rats were divided into four groups: control (SH), healthy trained (TH), sedentary with PD (SP), and trained with PD (TP). PD was induced in groups SP and TP while the trained groups performed treadmill exercises for 8 weeks. For the analysis of IL-6, IL-10, TNF-α, and leukocyte count, we collected blood samples. Cryolesions were induced in the tibialis anterior and gastrocnemius, which were analyzed for morphological changes. The presence of PD modified leukocyte counts, while exercise showed an additive role. PD increased levels of IL-6, IL-10, and TNF-α, and physical exercise changed only values of IL-10. The association between physical exercise and PD was responsible for an increased concentration of leukocytes in the region of the inflammation. Serum levels of inflammatory markers were modified by PD and, when combined with exercise, may negatively modulate inflammation. The association between PD and physical exercise showed the most significant changes in the number of inflammatory cells and may negatively influence the process of muscle repair.

Neuromuscular disease and respiratory failure.

Neurologists should be able to anticipate and recognise the onset of respiratory failure in patients with neuromuscular disorders. Symptoms will differ depending on the speed of onset of the respiratory muscle weakness. Careful monitoring of respiratory function is particularly important in acute disorders such as Guillain-Barré syndrome. Patients with an unrecognised neuromuscular disorder may occasionally present with respiratory failure. Important investigations include vital capacity, mouth pressures, arterial blood gases, chest x ray and sometimes overnight respiratory monitoring. Patients with Guillain-Barré and other acute conditions may require short-term ventilatory support in the intensive care unit. Patients with some chronic disorders, such as motor neuron disease and Duchenne dystrophy, can be successfully treated with non-invasive ventilation, usually in collaboration with a respiratory physician. New-onset weakness of limb and respiratory muscles in the intensive care unit is usually due to critical illness myopathy or critical illness polyneuropathy, and treatment is supportive.

Postinjury Exercise and Platelet-Rich Plasma Therapies Improve Skeletal Muscle Healing in Rats But Are Not Synergistic When Combined.

BACKGROUND: Skeletal muscle injuries are the most common sports-related injury and a major concern in sports medicine. The effect of platelet-rich plasma (PRP) injections on muscle healing is still poorly understood, and current data are inconclusive. PURPOSE: To evaluate the effects of an ultrasound-guided intramuscular PRP injection, administered 24 hours after injury, and/or posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a recently established rat model of skeletal muscle injury that highly mimics the muscle trauma seen in human athletes. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 40 rats were assigned to 5 groups. Injured rats (medial gastrocnemius injury) received a single PRP injection (PRP group), daily exercise training (Exer group), or a combination of a single PRP injection and daily exercise training (PRP-Exer group). Untreated and intramuscular saline-injected animals were used as controls. Muscle force was determined 2 weeks after muscle injury, and muscles were harvested and evaluated by means of histological assessment and immunofluorescence microscopy. RESULTS: Both PRP (exhibiting 4.8-fold higher platelet concentration than whole blood) and exercise training improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%, and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar formation (collagen I) demonstrated the beneficial effect of the tested therapies in accelerating the muscle healing process in rats. PRP and exercise treatments stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and 2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer groups, respectively) and reduced scar formation in injured skeletal muscle (20%, 34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively). Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC expression, respectively), indicating that exercise therapies accelerated the muscle healing process witnessed by the more rapid replacement of the embryonic-developmental myosin isoform by mature muscle myosin isoforms. CONCLUSION: Intramuscular PRP injection and, especially, treadmill exercise improve histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries in athletes. However, there was not a synergistic effect when both treatments were combined, suggesting that PRP does not add any beneficial effect to exercise-based therapy in the treatment of injured skeletal muscle. CLINICAL RELEVANCE: This study demonstrates the efficacy of an early active rehabilitation protocol or single intramuscular PRP injection on muscle recovery. The data also reveal that the outcome of the early active rehabilitation is adversely affected by the PRP injection when the two therapies are combined, and this could explain why PRP therapies have failed in randomized clinical trials where the athletes have adhered to postinjection rehabilitation protocols based on the principle of early, active mobilization.

Postural alterations as a risk factor for temporomandibular disorders.

The aims of this study were to estimate frequency and assess postural alterations as a risk factor for temporomandibular disorders (TMD). Patients aged 10 to 15years (N=243, mean age 12. 6) seeking comprehensive dental care were analyzed according to RDC/ TMD. For static postural assessment, photographs were taken and analyzed by a physiotherapist following Kendall's model. Patients were divided into: A: without TMD (n=133); B: with muscle disorders (n=61); C: with disk displacement (N=49). No difference in age wasobserved between groups (p=0. 95). Significant association was observed between muscular TMD and alterations in spinal curves, head posture, and lower limbs: OR: 3. 40, 2. 44 and 2. 22 respectively. The most frequent types were hyperlordosis 23. 30 and 32. 78%; forward head posture 39. 85 and 52. 45%; and genu valgum 33. 08 and 45. 90% in A and B respectively. Alterations in head posture, vertebral curves and lower limbs could be considered risk factors for muscular TMD. The most frequent postural alterations were lumbar hyperlordosis, forward head posture and genu valgus.

Los objetivos de este estudio fueron estimar la frecuencia y evaluar las alteraciones posturales como factor de riesgo para trastornos temporomandibulares (TTM). Se evaluaron pacientes de 10 a 15 años (N= 243, edad media 12. 6) que concurrieron para atención odontológica integral utilizandolos protocolos CDI/TTM años. La evaluación postural estática, se j realizó mediante fotografías analizadas por un fisioterapeuta siguiendo el modelo de Kendall. Los pacientes se dividieron en f diferentes grupos según el diagnóstico: A: sin TTM (n = 133); B: con trastornos musculares (n = 61) y C: con desplazamiento del disco (n = 49). No se observaron diferencias entre los grupos en la edad (p = 0, 95). Se observó asociación significativa entre TTM muscular y alteraciones en las curvas espinales, la postura de la cabeza y los miembros inferiores: OR: 3, 40, 2, 44 y 2, 22 respectivamente. Los tipos más frecuentes fueron hiper-lordosis lumbar 23, 30 y 32, 78%; anteversión cefálica 39. 85 y 52. 45%; y genu valgum 33, 08 y 45, 90% en A y B, respectivamente. Las alteraciones en la postura de la cabeza, las curvas vertebrales y los miembros inferiores podrían considerarse factores de riesgo para los TTM musculares. Las alteraciones posturales más frecuentes fueron hiperlordosis lumbar, anteversión cefálica y genu valgo.

Double trouble in hereditary neuropathy: concomitant mutations in the PMP-22 gene and another gene produce novel phenotypes.

BACKGROUND: Mutations in the peripheral myelin protein 22 (PMP-22) gene are the most common cause of Charcot-Marie-Tooth neuropathy and may rarely occur in combination with other neurogenetic diseases. OBJECTIVE: To characterize 3 families having a mutation in PMP-22 in addition to another neurogenetic disease mutation. DESIGN: Clinical, electrophysiologic, and genetic evaluations were made of 3 families with more than 1 genetic neuromuscular disease. SETTING AND PATIENTS: Family members were evaluated in neurogenetic and muscular dystrophy clinics in a university medical center setting. RESULTS: Three unusual families were found: (1) 2 young brothers each having a PMP-22 duplication and a missense mutation in the GJB1 (Connexin-32) gene; (2) a 32-year-old woman having a PMP-22 duplication and a 1000-fold CTG repeat expansion in the DMPK gene (DM1 myotonic dystrophy); and (3) a 39-year-old man with a PMP-22 deletion and a missense mutation in the ABCD1 gene (adrenomyeloneuropathy). The mutations were "additive," causing a more severe phenotype than expected with each individual disease and coinciding with the important impact of each gene on peripheral nerve function. CONCLUSIONS: Individuals having 2 separate mutations in neuromuscular disease-related genes may develop unusually severe phenotypes. Neurologists should be alert to this possibility.

Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations.

We describe clinical, electrophysiological, histopathological and molecular features of a unique disease caused by mutations in the glycyl-tRNA synthetase (GARS) gene. Sixty patients from five multigenerational families have been evaluated. The disease is characterized by adolescent onset of weakness, and atrophy of thenar and first dorsal interosseus muscles progressing to involve foot and peroneal muscles in most but not all cases. Mild to moderate sensory deficits develop in a minority of patients. Neurophysiologically confirmed chronic denervation in distal muscles with reduced compound motor action potentials were features consistent with both motor neuronal and axonal pathology. Sural nerve biopsy showed mild to moderate selective loss of small- and medium-sized myelinated and small unmyelinated axons, although sensory nerve action potentials were not significantly decreased. Based on the presence or absence of sensory changes, the disease phenotype was initially defined as distal spinal muscular atrophy type V (dSMA-V) in three families, Charcot-Marie-Tooth disease type 2D (CMT2D) in a single family, and as either dSMA-V or CMT2D in patients of another large family. Linkage to chromosome 7p15 and the presence of disease-associated heterozygous GARS mutations have been identified in patients from each of the five studied families. We conclude that patients with GARS mutations present a clinical continuum of predominantly motor distal neuronopathy/axonopathy with mild to moderate sensory involvement that varies between the families and between members of the same family. Awareness of these overlapping clinical phenotypes associated with mutations in GARS will facilitate identification of this disorder in additional families and direct future research toward better understanding of its pathogenesis.

[Influence of treatment of inhaled corticosteroids on the function of the larynx in asthmatic patients]. / Wplyw glikokortykosteroidów wziewnych na czynnosc fonacyjna krtani u chorych na astme.

UNLABELLED: The objective of the study was to examine influence of inhaled glycocorticosteroids on phoniatric function of the larynx in patients suffering from asthma. MATERIAL AND METHODS: Thirty minutes after the administration and long-term therapy effect of the inhaled glycocorticosteroids on local condition of the phoniatric organ was assessed in 15 patients with recently diagnosed bronchial asthma. The diagnostics of asthma included: subjective and objective examination, prick tests, spirometry, total IgE and histamine test for bronchial hyperactivity. Evaluation of voice function was implemented subjectively and objectively with use of videolaryngostroboscopy (VLSS). Acoustic assessment of voice was also performed. RESULTS: Administration of glycocorticosteroids as inhaled discs resulted in incidents of cough, mouth and throat dryness, sensation of polydipsia and skin inflammation around the mouth. Occasionally, hoarseness and discomfort in the larynx area were noted. On long-term administration, dysphonia, hoarseness and voice fatigue due to dysfunction of innermost larynx muscles, particularly vocal fold adductors. After 30 minutes of the glycocorticosteroid administration in patients with recently diagnosed asthma, irritation of the pharynx and larynx mucosa was recorded. CONCLUSION: The long-term treatment with inhaled glycocorticosteroids resulted in myopathy of proper muscles of the larynx.

The influence of somatosensory and muscular deficits on postural stabilization: Insights from an instrumented analysis of subjects affected by different types of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder. CMT1 is primarily demyelinating, CMT2 is primarily axonal, and CMTX1 is characterized by both axonal and demyelinating abnormalities. We investigated the role of somatosensory and muscular deficits on quiet standing and postural stabilization in patients affected by different forms of CMT, comparing their performances with those of healthy subjects. Seventy-six CMT subjects (CMT1A, CMT2 and CMTX1) and 41 healthy controls were evaluated during a sit-to-stand transition and the subsequent quiet upright posture by means of a dynamometric platform. All CMT patients showed altered balance and postural stabilization compared to controls. Multivariate analysis showed that in CMT patients worsening of postural stabilization was related to vibration sense deficit and to dorsi-flexor's weakness, while quiet standing instability was related to the reduction of pinprick sensibility and to plantar-flexor's weakness. Our results show that specific sensory and muscular deficits play different roles in balance impairment of CMT patients, both during postural stabilization and in static posture. An accurate evaluation of residual sensory and muscular functions is therefore necessary to plan for the appropriate balance rehabilitation treatment for each patient, besides the CMT type.

Long term clinical outcome of dental implants placed in a patient with Singleton-Merten syndrome.

PATIENTS: Singleton-Merten syndrome is an extremely rare autosomal dominant condition with less than 10 reported cases in the literature. It is characterized by abnormal aortic calcifications and dental abnormalities. The goal of this case report is to discuss the abnormal oral clinical features and the modified treatment protocol that was used in order to achieve osseointegration of dental implants in a patient having abnormal bone density and bone turnover associated with Singleton-Merten Syndrome. DISCUSSION: Following extraction of the remaining teeth, titanium implants (Friadent GmbH, Mannheim, Germany and Straumann(®), Basel, Switzerland) were placed in the upper and lower jaw of the patient. The upper jaw which was treated with dental implants, received a bar supported implant retained prosthesis and the lower jaw an implant retained telescopic prosthesis. The patient was regularly followed up for the past 13 years during which, clinical and radiological evaluation of osseointegration was undertaken. All the loaded implants showed clinical and radiographic evidence of osseointegration. With a follow up of 13 years after insertion of the first implant, the patient reported functioning well with no complications. CONCLUSION: The treatment with dental implants in the extremely rare Singleton-Merten syndrome patients is a reasonable treatment option to rehabilitate maxillofacial aesthetics and establish normal function of the jaws.

Effect of tonic muscle pain on short-latency jaw-stretch reflexes in humans.

The modulation of human jaw-stretch reflexes by experimental muscle pain was studied in three experiments. Short-latency reflex responses were evoked in the masseter and temporalis muscles by fast stretches (1 mm displacement, 10 ms ramp time) before, during and 15 min after a period with tonic pain. In Expt. I, a dose of 5.8% hypertonic or 0.9% isotonic (control) saline was infused in random order into the left masseter for up to 15 min (n=12). The level of excitation of the left masseter was kept constant at 15% of maximal effort by visual feedback and on-line calculation of the root-mean-square value of the surface electromyogram (sEMG). In Expt. II, a dose of 5.8% saline was infused into the left masseter but with feedback from the right masseter sEMG (n=12). In Expt. III, both sEMG and intramuscular (im) EMG was recorded from the left and right masseter muscles. The feedback was from either the sEMG or imEMG of the left masseter in which 5.8% saline was infused (n=12). In all experiments, subjects continuously rated their perceived pain intensity on a 10-cm visual analogue scale (VAS). Infusion of 5.8% saline caused moderate levels of pain (mean VAS 4.9-5.0 cm) whereas infusion of 0.9% saline was almost pain-free (mean VAS 0.3 cm). The pre-stimulus EMG activity in the masseter, which served as the feedback muscle during the recording, was constant across the different conditions. During painful infusion of 5.8% saline in Expts. I and III, the pre-stimulus sEMG activity in the non-painful masseter was significantly higher than baseline when the sEMG on the painful side was used as feedback signal, and in Expt. II significantly lower on the painful side when the non-painful side served as feedback signal (Student-Newman-Keuls: P<0.05). Isotonic saline did not affect the pre-stimulus sEMG activity or the jaw-stretch reflex parameters. The peak-to-peak amplitude of the stretch reflex in the painful masseter normalized to the pre-stimulus EMG activity was significantly higher during the pain conditions compared with the pre- and post-infusion conditions in all experiments. These results indicate that experimental jaw-muscle pain facilitates the short-latency (8-9 ms), probably monosynaptic, jaw-stretch reflex as revealed by both sEMG and imEMG. This effect could not be accounted for by variability in pre-stimulus EMG activity. An increased sensitivity of the fusimotor system at this level of static muscle excitation is suggested as a possible mechanism, which could contribute to an increased stiffness of the jaw-muscles during pain.

The effect of experimental muscle pain on the background electrical brain activity.

The purpose of this project was to investigate whether specific effects in the background activity of the brain associated with the experience of pain can be depicted by means of quantitative electroencephalography (EEG). Lasting pain was induced by intramuscular infusion of hypertonic saline. The infusion was titrated to maintain pain for a sufficient time to obtain enough data for meaningful analysis. In a first study on 12 subjects, using a single, blind, repeated measures design with randomization of the administration of isotonic (0.9%) and hypertonic (5%) saline, and with subjects unaware of the fact that one substance was isotonic saline, a statistically significant pain response could be attributed to the administration of hypertonic saline. In a second study on 19 subjects, again using a randomized repeated measures design, topographic EEG measures were examined with respect to experimentally induced pain and pain from memory. Prior to each of these experimental stages, baseline recordings were obtained to satisfy the requirement of the crossover design. In addition to the common frequency bands used in EEG, we also obtained data in the frequency range of 35-100 Hz. The short-term variability of the selected EEG measures and their suitability as a sample estimate were assessed by computing the coefficient of variation from all selected epochs of a given subject at baseline. When compared to baseline, spectral analyzed EEG measures during experimental pain demonstrated statistically significant increases in the beta and 35-100 Hz frequency ranges, most notably at the temporal recording sites. There was no statistically significant difference between the EEG measures for (1) experimental pain vs. pain from memory, and (2) the 2 baseline recordings. The great variability in the topographical aspect of the between-subject response was interpreted as being strongly suggestive of the contamination of EEG measures by phenomena attributed to the jaw, facial and scalp musculature. In fact, Pearson correlation coefficients, as high as 0.92, were found between measures in the frequency band of 35-100 Hz and the beta frequency range. The unexplained variance in the heightened beta cortical power density can be attributed to the vigilance scanning of pain processes. Due to the fact that the statistically significant effect of pain on the topographic EEG measures were not different from imagined pain, we concluded that these effects are non-specific for pain.

Sports medicine for the internist.

Because of increasing participation in leisure sports and exercise rehabilitation programs, many patients are developing nonsurgical, soft tissue overuse syndromes. Many of these musculoskeletal problems arise because of underlying biomechanical difficulties, training errors, or improper use of equipment. Epidemiologic observations reveal that these individuals frequently visit a general medical practitioner before seeking the advice of an orthopedic specialist. Prompt diagnosis simply requires an appreciation of anatomy and an analytic understanding of sports biomechanics. Although compulsive about their level of physical activity, many of those affected with overuse syndromes are highly motivated individuals who will predictably improve with the judicious use of NSAIDs, elimination of training errors, and the use of appropriate sports equipment and footwear. Simple orthotics may be needed for correction of biomechanical problems. For many of these localized musculoskeletal disorders, strict adherence to gradual physical rehabilitation activities is advisable.

Haemodynamic changes induced by submaximal isometric contraction in painful and non-painful human masseter using near-infra-red spectroscopy.

Although mechanisms underlying chronic muscle pain are poorly understood, one prevalent theory is that it is due, in part, to localized hypoxia. The purpose of this study was to evaluate this theory using non-invasive near-infra-red spectroscopy that monitors relative changes in intramuscular haemoglobin (Hb) concentration and oxygen saturation levels. Data were collected for the human masseter muscle during and following three isometric 30-s trials at 50% maximum voluntary contraction. Ten females, with a history of chronic muscle pain in the jaw, and eight matched healthy females without muscle pain (controls) participated. Results showed that, upon initiation of masseter muscle contraction, there was a rapid reduction in the intramuscular Hb concentration concomitant with a reduction in oxygen saturation levels. After cessation of the contraction, the Hb concentration increased rapidly and then fell toward the baseline. Significant differences in the recovery profile for oxygen saturation were found between the first trial and the following two trials for both the muscle pain- and control group. Looking at the first trial only, and adjusting for covariates of height, weight and bite-force in the analysis, revealed a marginally significant postcontraction difference between the two groups with a lower level of oxygen saturation during recovery in the group with chronic muscle pain. Significant group differences were found in Hb concentrations without any significant trial effect. It is likely that the well-known changes in intramuscular blood flow that occur during and after contraction in human muscles are reflected in these altered relative Hb concentrations. The group with chronic muscle pain showed a clearly reduced magnitude of the Hb concentration change in the postcontraction recovery period. The results support the concept that patients with chronic muscle pain have a slower intramuscular reperfusion during the recovery phase after sustained isometric contractions.