High-throughput mapping of protein occupancy identifies functional elements without the restriction of a candidate factor approach.

There are a variety of in vivo and in vitro methods to determine the genome-wide specificity of a particular trans-acting factor. However there is an inherent limitation to these candidate approaches. Most biological studies focus on the regulation of particular genes, which are bound by numerous unknown trans-acting factors. Therefore, most biological inquiries would be better addressed by a method that maps all trans-acting factors that bind particular regions rather than identifying all regions bound by a particular trans-acting factor. Here, we present a high-throughput binding assay that returns thousands of unbiased measurements of complex formation on nucleic acid. We applied this method to identify transcriptional complexes that form on DNA regions upstream of genes involved in pluripotency in embryonic stem cells (ES cells) before and after differentiation. The raw binding scores, motif analysis and expression data are used to computationally reconstruct remodeling events returning the identity of the transcription factor(s) most likely to comprise the complex. The most significant remodeling event during ES cell differentiation occurred upstream of the REST gene, a transcriptional repressor that blocks neurogenesis. We also demonstrate how this method can be used to discover RNA elements and discuss applications of screening polymorphisms for allelic differences in binding.

Role of selected muscles of respiration as influenced by posture and tidal volume.

Studies of the activity of accessory respiratory muscles were conducted in 30 normal subjects (15 male and 15 female subjects, age 5 to 62 years). Electromyograms were recorded over the right serratus anterior muscle and the adjacent sixthe intercostal space, and the results were correlated with tidal volume. Phasic respiratory activity in the serratus anterior muscle was detected in every subject but was markedly affected by the prevailing posture and level of ventilation (appearing at mean tidal volumes equivalent to 60.5 percent of vital capacity when subjects were standing relaxed, and equivalent to 35.2 percent of vital capacity when subjects were seated, leaning forward with elbows supported). The activity was predominantly inspiratory in timing but in some subjects extended into early expiration. No significant differences were noted in subjects of different ages, sex, height, or weight. Similar results were recorded from the inspiratory intercostal muscle. On the basis of these findings, we conclude that, contrary to reports, the serratus anterior muscle should be classified as an accessory muscle of respiration, at least at increased levels of ventilation, and that its activity is most pronounced in postures that place the muscles' origin in an advantageous position for moving the ribs.

Influence of electrical stimulation on the morphological and metabolic properties of paralyzed muscle.

Selected morphological and metabolic properties of single fibers were studied in biopsy samples from the tibialis anterior of normal control and spinal cord-injured (SCI) subjects. In the SCI subjects, one muscle was electrically stimulated progressively over 24 wk, in 6-wk blocks for less than or equal to 8 h/day, while the contralateral muscle remained untreated. The percentage of fibers classified as type I [qualitative alkaline preincubation myofibrillar adenosinetriphosphatase (ATPase)] was significantly less in the unstimulated paralyzed muscles than in the muscles of normal control subjects. Electrical stimulation increased the proportion of type I fibers in the SCI subjects. For both type I and type II fibers, the cross-sectional area, activities of myofibrillar ATPase and succinate dehydrogenase, and the capillary-to-fiber ratio were also significantly less in the paralyzed muscles than in the normal control muscles. Electrical stimulation increased only the activity of succinate dehydrogenase in both fiber types of the SCI subjects. These data are discussed in relation to the electromechanical properties of the respective muscles described in an accompanying paper (J. Appl. Physiol. 72: 1393-1400, 1992). In general, the electrical stimulation protocol used in this study enhanced the oxidative capacity and endurance properties of the paralyzed muscles but had no effect on fiber size and strength.

Prevention of hip and knee injuries in ballet dancers.

Hip problems form about 10% (7.0 to 14.2%) of most published series of ballet injuries. The abnormally large range of external rotation needed for a perfect turnout is primarily due to soft tissue adaptation, more readily achieved in the young dancer. Insufficient range of motion at the hip throws considerable stress on the other lower limb segments. The snapping hip syndrome is common (43.8% of hip problems), with about one-third associated with pain. A tight iliotibial band may contribute to this, and balanced flexibility requires special attention to abductor stretching. The external clicking hip must be distinguished from the internal clicking hip, which is associated with the joint and psoas tendon. Stress fractures of the hip are easily overlooked and, if undetected, they may progress to a complete fracture. Knee problems account for 14.0 to 20% of complaints, and over 50% of these are peri- or retropatellar problems. This includes synovial plica, medial chondromalacia, lateral patella facet syndrome, subluxing patella and the fat pad syndrome. Specific diagnosis leads to specific treatment and the best chance of cure. Mild hyperextension of the knee may be aesthetically desirable, but excessive range leads to symptoms in the posterior capsule and poor control. Young dancers with a tendency to very lax joint structures should be identified early and protected from overstretching. In the author's series, meniscal lesions did not appear to be as big a problem as reported elsewhere in the literature. Ballerinas appear to have less leg strength than other groups of athletes, having only 77% of the weight-predicted norms. The introduction of strength training for male and female dancers may reduce injuries and improve balance, but it requires an intensive educational programme to dispense with the many myths. There are several references to the development of early arthritis but, while relatively common in the foot, symptomatic arthrosis in ballet dancers' hips and knees is not more prevalent than in the general population. The young age at which serious dance training begins, the long and rigorous hours of practice, the thin ballet slipper, dancing en pointe and unusual dietary regimens may all contribute to injury patterns in varying degrees.

Spine fractures in winter sports.

In a 7-year review of 1,447 spine fractures, 202 (14%) were due to sporting or recreational causes, of which 84 (42%) were associated with paralysis. This high incidence catastrophic injury is second only to motor vehicle accidents. Snowmobiling (10%), skiing (5%), tobogganing (5%) and ice hockey (3%) accounted for approximately one-quarter of these injuries. Snowmobile injuries rose steadily over this period, and the main contributing factors were alcohol, poor lighting, young age and inappropriate terrain. The skiing injuries occurred to novices and top class skiers alike, with one-third of those sustaining a fracture having associated paralysis. In view of the terrain and the speeds involved, the figure is unlikely to change. An alarming trend was the subtle increase in cervical fracture due to ice hockey, most of which were compression injuries with the neck in the neutral or slightly flexible position, and secondary to a collision with the boards. Being decked from behind contributed to the impact. The introduction of measures to reduce these injuries is mandatory, since cervical fractures secondary to ice hockey were associated with permanent paralysis in 67% of the cases. There are several points of initial management which require emphasis.

Ultrastructural events following acute muscle trauma.

The purpose of this study was to determine the ultrastructural events occurring in skeletal muscle following acute blunt trauma. Male rats weighing 250 g were subjected to a single impact trauma to the medial gastrocnemius muscle while under general anesthesia. Hemorrhage, inflammation, non-necrotic degeneration, and later regeneration were observed. In the short term following impact (6-24 h), the damaged segments showed gross tearing and degeneration. A large number of mononuclear cells were seen in the intercellular connective tissue and within the damaged muscle cells. By 24-48 h, there was an increase in the number of sarcolemmal nuclei, some of which were likely of satellite cell origin. By day 3, regenerating muscle cells displayed central nuclei and reorganizing sarcomeres. By day 6, further progression of regeneration was seen. Moreover, focal interstitial collagen formation suggested minimal to mild scar formation. On days 14, 21, and 30 after trauma, the muscle appeared to have healed and no abnormalities could be found at the site of injury. In parallel with the ultrastructural events noted, the injured muscles underwent a marked catabolic response and showed a reproducible fall (-27%, P less than 0.001) in total protein content within 48 h. Muscle protein accumulation commenced after day 3; however, complete repletion of the loss did not occur until day 21 post-injury.

Biofilms in drinking water systems: a possible reservoir for Helicobacter pylori.

A laboratory model system was utilised to investigate the persistence of Helicobacter pylori in mixed-species heterotrophic biofilms. A single-stage continuous culture vessel was linked to a modified-Robbins device (mRD) incorporating removable stainless steel coupons. The system was innoculated with H. pylori (NCTC 11637) and the fate of the organism monitored by polymerase chain reaction (PCR) analysis. Helicobacter pylori was detected in biofilm material for a period of up to 192 h. Theoretical washout would have occurred at around 48 h thus detection of H. pylori for a prolonged period after theoretical washout suggested that the organism possessed the ability to persist in the mixed-species heterotrophic biofilm. Preliminary studies using heat-inactivated H. pylori showed that the organism was not detected in biofilm material at any time post-challenge suggesting that the persistence of H. pylori in such material was a phenomenon requiring the organism to be in a viable state. Further investigations to assess the biological basis for the association of H. pylori with drinking water biofilms and the risk that this may pose to public health are being undertaken.

Multiple noncontiguous spine fractures.

The data from a prospective study of 508 spine injuries were reviewed to determine the incidence of multiple noncontiguous spine fractures. All patients were examined at admission and at 1 and 2 years postinjury. This series identified 77 (15.2%) multilevel fractures. Motor vehicle accidents were the primary cause of these fractures. The incidence of neurologic injury was not significantly different between multiple noncontiguous and single fractures. Failure to use seat belts and ejection from the vehicle were the main factors associated with multiple noncontiguous spine injuries. Seven major fracture patterns were identified, which accounted for 60% of these injuries. The prognosis for multilevel spine fractures was not significantly worse that that for single-level injuries.

Incomplete neural deficits in thoracolumbar and lumbar spine fractures. Reliability of Frankel and Sunnybrook scales.

Because neural status is used both as a treatment determiner and outcome measure, a universal, reliable scale is required. Experienced personnel, provided with concise definitions, demonstrated high inter-rater reliability of Frankel and Sunnybrook scales (Pearson correlation coefficients 0.71-0.91), with 94-100% intra-rater agreement. Both scales correspond to total sensory and motor function but are insensitive to walking and bladder function. Frankel's wide clinical use, reliability, and simplicity identify it to be the preferred measurement system until a better alternative is developed. Discussion of neural status must include description of bladder and walking function.

Factors predicting employment 1 year after traumatic spine fracture.

STUDY DESIGN: This prospective cohort study evaluates the employment status of 489 persons after traumatic spine fracture. OBJECTIVES: To determine the rate, type, and predictors of employment 1 year after traumatic spine fracture. SUMMARY OF BACKGROUND DATA: The limited existing literature regarding employment after spine fracture reports variable return-to-work rates, tends to be retrospective, and generally evaluates a limited number of predictor factors at a time. METHODS: Four hundred eighty-nine persons ranging in age from 15 to 64 years who had experienced a spine fracture were assessed by a single examiner at hospital discharge and 1 year postinjury. Employment status and type. discharge neural and functional status, pain level, demographics, injury level and severity, and early treatment details were evaluated. RESULTS: At 1 year postinjury, 54% of subjects were working. A higher percentage of the employed were working part time and for fewer weeks per year than preinjury. A higher percentage were working at unskilled clerical, sales, or service jobs than preinjury. The significant positive (+) and negative (-) predictors of employment were (from strongest to weakest); worked in year previous to injury (+); employed at time of injury (+); Worker's compensation Board coverage (-); spinal fracture surgery (+); high-level spine fracture (-); pain (-); Functional Independence Measure score (+); and days of stay in intensive care unit and spinal unit (-). CONCLUSIONS: For the first year after spinal fracture, unemployment is common. Those who do return to work are more likely to modify the amount and type of work they do and to have been employed preinjury.

Anterior compartment pressures in cross-country skiers. A comparison of classic and skating skis.

This paper compares the pressure changes in the anterior compartment of the leg when cross-country skiing using the skating method on either skating skis or classic skis. Intracompartmental pressures of the right leg were recorded from the tibialis anterior muscle of 10 subjects at rest and 15 seconds after 10 to 12 minutes of cross-country skiing on a designated course. All subjects completed two trials on different days. In one trial, subjects used skating skis and for the other trial, classic skis were used for the skating technique. Although the average pressure increase was higher for the classic ski trials than for the skating ski trials, the difference was not significant. This finding indicates that cross-country skiers who skate on a classic ski as opposed to a shorter skating ski do not experience a significantly greater increase in their anterior compartment pressure. Thus, it appears that the type of ski used is not the most significant factor contributing to chronic compartment syndrome.

Shoulder pain in wheelchair athletes. The role of muscle imbalance.

Shoulder rotator cuff impingement syndrome is a common and disabling problem for the wheelchair athlete. In this study we investigated the role of shoulder strength imbalance as a factor for the development of this syndrome. Nineteen paraplegic male athletes underwent clinical and isokinetic examination of both shoulders with peak torque values measured in abduction, adduction, and internal and external rotation. Twenty athletic, able-bodied men without shoulder problems were tested as controls. Ten (26%) of the paraplegic athletes had rotator cuff impingement syndrome. The results of the isokinetic testing demonstrated that 1) the paraplegics' shoulders were stronger than the controls in all directions (P < 0.05); 2) the strength ratio of abduction: adduction was higher for paraplegic athletes (P < 0.05); 3) paraplegics' shoulders with rotator cuff impingement syndrome were weaker in adduction and external and internal rotation than the paraplegic athletes without impingement syndrome (P < 0.05); and 4) paraplegics' shoulders with rotator cuff impingement syndrome had higher abduction:adduction and abduction:internal rotation strength ratios than the shoulders of paraplegics without impingement syndrome (P < 0.05). We concluded that shoulder muscle imbalance, with comparative weakness of the humeral head depressors (rotators and adductors), may be a factor in the development and perpetuation of rotator cuff impingement syndrome in wheelchair athletes.

Lower extremity flexibility patterns in classical ballet dancers and their correlation to lateral hip and knee injuries.

Knee and hip problems account for up to 40% of injuries in classical ballet. Despite apparent flexibility, many dancers appeared to have tight iliotibial bands that contributed to lower limb problems. Thirty senior female ballet dancers were contrasted with thirty age-matched active volunteers for hip and knee range of motion, and the information derived was correlated with their orthopaedic medical histories. Dancers spent a reasonable period of time warming up, but it was usually with an unbalanced routine that emphasized hip abduction and external rotation to the exclusion of adduction work. This was reflected in the significantly lower range of passive hip adduction and internal rotation compared to the controls. Furthermore, the older and more experienced the dancer, the more this trend was exaggerated. This unbalanced flexibility may play a role in the production of lateral knee pain (30% of the dancers) and anterior hip pain (33% of the dancers). It is suggested that more attention should be given to a balanced stretching regimen as part of the dancers' warmup in an effort to reduce the frequency of some of the chronic hip and knee complaints.

Helicobacter sp. recovered from drinking water biofilm sampled from a water distribution system.

Workers examining the transmission route(s) and reservoir(s) of infection for Helicobacter pylori have postulated several environmental reservoirs for the organism, including water. Such work has, to date, concentrated on the bulk liquid in drinking water systems rather than on biofilms. Previous investigations by the authors have suggested biofilms in water distribution systems are a possible reservoir of infection. This current study comprised of an analysis of a section of cast iron mains distribution pipe removed from an urban environment in the north-east of Scotland during routine maintenance work. Immediately upon removal of the pipe section, the interior lumen was swabbed to remove the biofilm layer. Subsequent analysis for the presence of Helicobacter DNA using a nested PCR approach produced a positive result. This data provides the first evidence for the existence of Helicobacter in biofilms found in water distribution systems anywhere in the world.

Movement is life.

Starting in utero, where movement is essential for the development of normal joints, a pattern is set up which is repeated throughout life. The evolution of the species is mirrored in the development of the individual, and movement, exercise and neuromuscular development form a central theme. The major skeletal changed are related to the changes in age. The emergence of disease patterns, the progress of the ageing process and the factor influencing morbidity and mortality are discussed. The role of the therapist as an expert in exercise, both prophylactic and therapeutic, is emphasized and particular attention is paid to the widening opportunities outside the sphere of the traditional clinical setting.

Isokinetic muscle strength parameters for shoulder movements.

A study was carried out on shoulder muscle strength using an isokinetic dynamometer device, and normal parameters were established on 20 men and 20 women for a total of 80 shoulders. This population consisted of fit, athletic individuals with a mean age of 26·65 years and 25·35 years for the women and men; respectively. Peak torque, angle of peak torque, and arc of maximum strength (= peak±2 N m) were measured. Emphasis was placed on the arc of maximum strength in that it may reflect a more functional measurement than the single angle value for peak torque. For all movements women were approximately 50% as strong as men. There were no significant differences between the means for dominant versus non-dominant arms. The strongest muscle group was the adductors, with a mean peak torque of 28·8 N m for women and 48·-0 N m for men. With 48 N m internal and external rotation, women had a significantly greater range of motion than men but the peak torques remained around the neutral position.

Manipulation in the treatment of tennis elbow.

With the increasing popularity of tennis there has been an increasing interest in the etiology and treatrnent of lateral epicondylitis. The current pathophysiology is assumed to be related to repeated wrist extension and rotation leading to microtrauma at the common wrist extensor origin with an ultimate change in the histology of the area. Treatment involves exercise, the use of many modalities to treat the area locally, and more specifically when tennis is the etiology a whole variety of functional adaptations as well as a modification of equipment. Specifically, manipulation of the elbow has played a large role in the treatment of resistant tennis elbow and the large number of different named maneuvers has led to a certain amount of confusion. The second half of the paper attempts to review these manipulations including that described by Mills, Cyriax, Kaltenborn, Mennell, and Stoddard. These manipulations seem to fall into two basic varieties: those that seek full extension and those that will produce a varus thrust. The manipulations done with the elbow in extension and the forearm in pronation have the greatest chance of affecting the contractile elements whereas those performed with a varus thrust at the elbow seem to act primarily on the capsular structures causing gapping and restoring joint play. While manipulation may be effective it always must be used in conjunction with a total treatment regime including exercise, modalities, and modification of the activities involved in the etiology. J Orthop Sports Phys Ther 1986;7(5):264-272.

Medial tarsal tunnel syndrome: a review.

The medial tarsal tunnel syndrome is a compression neuropathy involving the tibial nerve or its branches as they pass through the tarsal tunnel under the flexor retinaculum. Medial tarsal tunnel syndrome is not recognized as readily as its counterpart in the wrist. This syndrome can lead to a painful burning sensation in the medial border of the foot and into the great toe. In its fullest extent medial tarsal tunnel syndrome can involve sensory changes in the heel and the lateral part of the sole of the foot as well as the remaining toes. In addition, it may lead to weakness of the intrinsic muscles of the foot. This syndrome often goes unrecognized or misdiagnosed particularly in the athlete. While medial tarsal tunnel syndrome may respond initially to nonoperative techniques of ultrasound and modification of footwear, as it progresses surgical release of the nerve in the tunnel will be required for optimal results. This paper reviews the anatomy, etiology, pathology, clinical presentation, and treatment of the medial tarsal tunnel syndrome. In order to bring more attention to this condition, our clinical experience is presented.J Orthop Sports Phys Ther 1984;6(1):39-45.

The influence of velocity-specific resistance training on the in vivo torque-velocity relationship and the cross-sectional area of quadriceps femoris.

This work was supported by Sport Canada end Hydra-Fitness Industries. In order to investigate the effects of velocity-specific resistance training, 30 healthy, male varsity athletes were assigned to either high (HVR) or low (LVR) velocity training or control (CG) groups. Subjects completed two 20-sec sets of maximal exercise at each of six hydraulic resistance stations for the lower limb. Resistances were adjusted as necessary to maintain consistent average angular velocities of approximately 1.05 and 3.14 rad/sec for the LVR and HVR groups, respectively. Subjects trained on alternate days for 6 weeks, completing either two (weeks 1 and 2) or three (weeks 3-6) circuits of the six stations each session. Peak knee extension torques were improved (p < 0.05) for the LVR group at all of seven angular velocities tested between 1.05 and 4.19 rad/sec. Improvements (p < 0.05) were also observed for the HVR group, but only at angular velocities of 2.62, 3.14, 3.66, and 4.19 rad/sec. Cross-sectional area of the quadriceps femoris muscle group obtained from serial computer tomography (CT) scans was increased (p < 0.05) for both training groups. No significant changes in either strength or cross-sectional area were observed for control subjects. These results indicate that while both of the training programs resulted in increased cross-sectional area of the knee extensors, the observed changes in strength performance are likely due to other factors which may be mediated by the different training velocities. J Orthop Sports Phys Ther 1989;10(11):456-462.

Effect of high velocity resistance training on peak torque, cross sectional area and myofibrillar ATPase activity.

The purpose of this investigation was to determine the effect of high velocity resistance (HVR) training on peak torque (PT), cross sectional area (CSA) and myofibrillar ATPase activity of the knee extensors. HVR training was performed in a circuit on hydraulic exercise equipment, 4 times a week for 5 weeks at an angular velocity of approximately 3.14 rad.s-1. Knee extension PT was determined on a Cybex II isokinetic dynamometer and CSA of the quadriceps femoris muscle was assessed using computer tomography (CT) scanning. Muscle biopsies were obtained from the lateral quadriceps muscle and were analyzed for myofibrillar ATPase activity. Knee extension peak torque was significantly increased at 1.57, 2.09, 3.14, 3.66 and 4.19 rad.s-1. Myofibrillar ATPase activity and CSA was also significantly increased after HVR training. These findings showed that short-term high velocity resistance training enhances the in vivo torque/velocity curve especially at fast angular velocities and these changes are partly attributed to an increase in muscle CSA and activity of myofibrillar ATPase.