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Caveolin-1 binding motif of alpha-hemolysin: its role in stability and pore formation.

We have identified a nine amino sequence in alpha-hemolysin (alpha-HL) of Staphylococcus aureus, which binds Caveolin-1. Surface plasmon resonance studies clearly show a concentration dependent interaction of alpha-HL with the scaffolding domain of Caveolin-1. Mutants of alpha-HL, devoid of Caveolin-1 recognition motif, exhibit an alpha-HL like proteinase K digestion profile but the resultant 'half-like' domains are highly susceptible to further proteolysis. They also had the same intrinsic fluorescence emission maxima as the native alpha-HL indicating normal folding. However, these mutants bind 1-anilino-8-naphthalene sulfonic acid probably due to exposure of their hydrophobic core. Moreover, these mutants are non-lytic and do not undergo conformational changes on rabbit RBC membrane surface. Purified Caveolin-1 blocks the hemolysis of RBCs by alpha-HL. Our studies indicate that the Caveolin-1 binding motif of alpha-HL provides stability and shields the hydrophobic core of alpha-HL. The motif also acts as trigger point for initiation of conformational changes.

Amino Acid Motifs↗

The ASH/ASCO clinical guidelines on the use of erythropoietin.

The only combined effort between the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) in practice guideline development was in studying the use of erythropoietin in chemotherapy-related anemia and in myelodysplasia. This process began with an application to the Agency for Health Care Policy and Research (AHCPR, now called the Agency for Healthcare Research and Quality, or AHRQ) jointly from ASH and ASCO. As part of a competitive review process, the topic was selected by the Agency for funding. Subsequently, as part of the Agency's Evidence-based Practice program, funding to conduct the review was awarded to the Evidence-based Practice Center of the Blue Cross/Blue Shield Technology Evaluation Center, which performed an extensive literature review using principals of evidence-based medicine and with input from representatives of ASH and ASCO. That evidence-based review was then shared with an ASH and ASCO guidelines committee funded by both organizations and made up of members from both organizations. The guideline was developed over a period of 21/2 years, culminating in simultaneous publication in both Blood and The Journal of Clinical Oncology in October 2002. This field is in flux and much of the guideline discussed potential future directions for research. Projected research topics include whether a hemoglobin level of 11g/dl as a clinical trigger point has clinical benefit; whether increasing hemoglobin levels greater than 12g/dL has clinical benefit; what role iron supplementation plays in erythropoietin treated patients; weekly versus more frequent dosing; and cost benefit analyses. Quality of life considerations are important, but the practice guideline committee felt that there was not enough data in this area to view it with the same importance as avoidance of transfusion or rises in hemoglobin value as therapeutic goals for patients being treated with erythropoietin.

Anemia↗

Fibromyalgia and myofascial pain syndromes and the workers' compensation environment: an update.

Fibromyalgia and myofascial pain syndromes are terms used to describe a constellation of complaints ranging from generalized aches to specific tender trigger points often accompanied by fatigue, depression, and sleep disturbances. In the past 5 years, research has been directed primarily at determining the pathophysiology of fibromyalgia and myofascial pain syndromes and the treatment of patients' comorbidities to alleviate their symptomatology. Controversy exists as to whether fibromyalgia and myofascial pain syndromes represent a specific pathology or are merely terms to describe clinical conditions that provide patients with the reassurance that their symptoms are real and help clinicians with therapeutic direction. In the occupational health setting, this uncertainty can lead to significant difficulty in determining short- and long-term disability and assigning culpability to an individual's work environment.

Adult↗

Review of enigmatic MTrPs as a common cause of enigmatic musculoskeletal pain and dysfunction.

This article explores how myofascial trigger points (MTrPs) may relate to musculoskeletal dysfunction (MSD) in the workplace and what might be done about it. The cause of much MSD and pain is often enigmatic to modern medicine and very costly, just as the cause of MTrPs has been elusive for the past century, despite an extensive literature that is confusing because of restricted regional approaches and a seemingly endless variety of names. MTrPs are activated by acute or persistent muscle overload, which is characteristic of MSD in the workplace. MTrPs can involve any, and sometimes many, of the skeletal muscles in the body and are a major, complex cause of musculoskeletal pain. The clinical and etiological characteristics of MTrPs have been underexplored by investigators, leading to undertraining of health care professionals, underappreciation of their clinical importance. MTrPs have no gold standard diagnostic criterion, and no routinely available laboratory or imaging test. MTrPs require a specific non-routine examination and muscle-specific treatment for prompt relief when acute, and also resolution of perpetuating factors when chronic. After identifying a critical false assumption, electrodiagnostic studies are now making encouraging progress toward clarifying the etiology of MTrPs based on the 5- or 6-step positive-feedback model of the integrated hypothesis. Specific research needs are noted. MTrPs are treatable and they deserve increased attention and consideration by research investigators and clinicians.

Humans↗

Pathophysiology of upper extremity muscle disorders.

A review of the literature on the pathophysiology of upper extremity muscle disorders (UEMDs) was performed. An overview is given of clinical findings and hypotheses on the pathogenesis of UEMDs. The literature indicates that disorders of muscle cells and limitations of the local circulation underlie UEMDs. However, these disorders identified do not necessarily lead to symptoms. The following mechanisms have been proposed in the literature: (1) selective recruitment and overloading of type I (Cinderella) motor units; (2) intra-cellular Ca(2+) accumulation; (3) impaired blood flow; (3b) reperfusion injury; (3.3c) blood vessel-nociceptor interaction; (4a) myofascial force transmission; (4b) intramuscular shear forces; (5) trigger points; (6) impaired heat shock response. The results of the review indicate that there are multiple possible mechanisms, but none of the hypotheses forms a complete explanation and is sufficiently supported by empirical data. Overall, the literature indicates that: (1) sustained muscle activity, especially of type I motor units, may be a primary cause of UEMDs; (2) in UEMDs skeletal muscle may show changes in morphology, blood flow, and muscle activity; (3) accumulation of Ca(2+) in the sarcoplasm may be the cause of muscle cell damage; (4) it seems plausible that suboptimal blood flow plays a role in pathogenesis of UEMDs; (5) since the presence of fiber disorders is not a sufficient condition for the development of UEMSDs additional mechanisms, such as sensitization, are assumed to play a role.

Biomechanical Phenomena↗

Binding linkage in a telomere DNA-protein complex at the ends of Oxytricha nova chromosomes.

Alpha and beta protein subunits of the telomere end binding protein from Oxytricha nova (OnTEBP) combine with telomere single strand DNA to form a protective cap at the ends of chromosomes. We tested how protein-protein interactions seen in the co-crystal structure relate to DNA binding through use of fusion proteins engineered as different combinations of domains and subunits derived from OnTEBP. Joining alpha and beta resulted in a protein that bound single strand telomere DNA with high affinity (K(D-DNA)=1.4 nM). Another fusion protein, constructed without the C-terminal protein-protein interaction domain of alpha, bound DNA with 200-fold diminished affinity (K(D-DNA)=290 nM) even though the DNA-binding domains of alpha and beta were joined through a peptide linker. Adding back the alpha C-terminal domain as a separate protein restored high-affinity DNA binding. The binding behaviors of these fusion proteins and the native protein subunits are consistent with cooperative linkage between protein-association and DNA-binding equilibria. Linking DNA-protein stability to protein-protein contacts at a remote site may provide a trigger point for DNA-protein disassembly during telomere replication when the single strand telomere DNA must exchange between a very stable OnTEBP complex and telomerase.

Animals↗

Upper crossed syndrome and its relationship to cervicogenic headache.

OBJECTIVE: To discuss the management of upper crossed syndrome and cervicogenic headache with chiropractic care, myofascial release, and exercise. CLINICAL FEATURES: A 56-year-old male writer had been having constant 1-sided headaches radiating into the right eye twice weekly for the past 5 years. Tenderness to palpation was elicited from the occiput to T4 bilaterally. Trigger points were palpated in the pectoralis major, levator scapulae, upper trapezius, and supraspinatus muscles bilaterally. Range of motion in the cervical region was decreased in all ranges and was painful. Visual examination demonstrated severe forward translation of the head, rounded shoulders, and right cervical translation. INTERVENTION AND OUTCOME: The patient was adjusted using high-velocity, short-lever arm manipulation procedures (diversified technique) and was given interferential myofascial release and cryotherapy 3 times weekly for 2 weeks. He progressed to stretching and isometric exercise, McKenzie retraction exercises, and physioball for proprioception, among other therapies. The patient's initial headache lasted 4 days. He had a second headache for 1.5 days during his exercise training. During the next 7 months while returning to the clinic twice monthly for an elective chiropractic maintenance program, his headaches did not recur. He also had improvement on radiograph. CONCLUSION: The principles of upper crossed syndrome and the use of exercise, chiropractic care, and myofascial release in the treatment of cervicogenic headache are discussed. A review of the literature indicates that analyzing muscle imbalance as well as vertebral subluxation may increase the effectiveness of chiropractic treatment for cervicogenic headache.

Accidents, Traffic↗

Improvement after chiropractic care in cervicocephalic kinesthetic sensibility and subjective pain intensity in patients with nontraumatic chronic neck pain.

OBJECTIVE: The objective of this study was to examine alteration in head repositioning accuracy (HRA), range of motion, and pain intensity in patients with chronic cervical pain syndrome without a history of cervical trauma. METHODS: The study was a prospective, randomized, controlled trial. Forty-one patients with chronic cervical pain were randomly assigned to either a control group or a chiropractic treatment group. All patients were clinically examined, given general information on cervical pain, and provided with training instructions based on the clinical evaluation. The treatment included sessions with high-velocity and low-amplitude manipulation, proprioceptive neuromuscular facilitation, ischemic compression of myofascial trigger points, and spinal rehabilitation exercises aiming to normalize cervical range of motion (CROM) and HRA. Subjective pain intensity, cervical kinesthetic sensibility, and CROM were recorded before and after the study period. RESULTS: There was no difference between the treatment patients and the control subjects at the beginning with regard to age, sex, subjective pain intensity, range of motion, and HRA. At the 5-week follow-up, the treatment patients showed significant reductions in pain and improvement of all HRA aspects measured whereas the control subjects did not show any reduction in pain and improvement in only one HRA aspect. No significant difference was detected in CROM. CONCLUSIONS: The results of this study suggest that chiropractic care can be effective in influencing the complex process of proprioceptive sensibility and pain of cervical origin. Short, specific chiropractic treatment programs with proper patient information may alter the course of chronic cervical pain.

Adult↗

Sensory and biomechanical characterization of two painful syndromes in the heel.

UNLABELLED: This study evaluated sensory and biomechanical assets in 2 heel pain conditions with similar symptoms, entrapment syndrome of the nerve to abductor digiti quinti and myofascial syndrome of abductor hallucis. Thirty-three patients with unilateral heel pain and 20 asymptomatic subjects underwent pressure pain threshold measurement in the painful area in site A (medial process of calcaneal tuberosity, trigger point site of abductor hallucis) and site B (1 cm posteriorly to site A, where the nerve to abductor digiti quinti becomes most superficial) and contralaterally; electroneurography of posterior tibial nerve; evaluation of ground-foot reaction on a dynamic platform. Eighteen patients had electric shock-type pain (entrapment syndrome, Group 1), 15 had cramp-like pain (myofascial syndrome, Group 2). Pain thresholds on the affected side versus contralaterally were significantly lower in site B in Group 1 and in site A in Group 2 (P < .001). Nerve conduction velocity was slightly reduced in Group 1 (P = .05). Ground-foot reaction was significantly altered on the affected side in all patients versus asymptomatic subjects; a significant difference between the 2 sides was found for peak of force (F1) in Group 1 and for all parameters except temporal phase of peak of force (TF3) (P = .05) for Group 2 (P < .0001). The different sensory and biomechanical patterns of the 2 examined syndromes help the differential diagnosis and consequent therapeutic approach. PERSPECTIVE: This study shows different sensory and biomechanical patterns in 2 algogenic conditions of the heel with similar pain location. These distinct patterns reflect different pathophysiologic mechanisms in the 2 cases, which has a potential significant impact on treatment.

Adult↗

Spatial summation of pressure pain: effect of body region.

The characteristics of spatial summation of pressure pain are not clear. Pressure pain threshold (PPT) and perceived pressure pain intensity were measured in the hand, painfree back and myofascial trigger points (MTPs) in the back, using three different stimulus areas (0.5, 1 and 2 cm(2)). PPT decreased and perceived pain increased significantly with an increase in stimulation area in all the regions (e.g. PPT in the back, from 406+/-168 to 205+/-102kPa, P<0.0001). The magnitude of spatial summation of pressure pain was not significantly different between the regions. However, PPT in the back was significantly higher compared to the hand and MTPs (e.g. for 2 cm(2): mean of 205+/-102 vs 175+/-75 and 159+/-72kPa, P<0.01, respectively). Irrespective of body region, the quality of pain evoked with the large areas (1 and 2 cm(2)) was of pressure whereas in the small area (0.5 cm(2)) it was perceived as a prick. In conclusion, both PPT and perceived pressure pain intensity are subject to a considerable spatial summation in all the regions tested. The quality of pressure-evoked pain is probably determined by this spatial summation. Body region significantly affects the PPT level for a fixed stimulation area but not the magnitude of its spatial summation for areas up to 2 cm(2), which are probably within the receptive field of single spinal nociceptive neurons.

Adult↗

Referred pain pattern of the pronator quadratus muscle.

Pain patterns of the myofascial trigger points (TrP) for most muscles of the forearm have been documented. However, there are no published reports on the referred pain patterns for the pronator quadratus (PQ) muscle. The purpose of this study was to determine the referred pain pattern of the TrP in the PQ. Thirty-five arms of 35 healthy adult volunteers with no history of neck pain, arm pain or paresthesia were studied. Following skin sterilization, a Teflon-coated syringe needle was inserted into the PQ of the non-dominant forearm under electromyographic guidance, and 0.3mL of 6% hypertonic saline was injected. Subjects drew in their pain areas on a pain diagram, and this drawing was transferred into the Pain Chart System for analysis. Two main pain patterns were observed. The most common pattern involved pain spreading both distally and proximally from the injection site, along the medial aspect of the forearm (57%). In half of these cases, the pain area extended to the medial epicondyle proximally and the fifth digit distally. The second main pattern revealed pain spreading distally to the third and/or fourth finger (29%). The pain patterns originating from the PQ resemble the C8-T1 dermatomes, and ulnar and median nerve sensory distributions. Thus, myofascial pain of the PQ should be considered as a possible cause of pain in the medial forearm and hand, especially when no other neurological abnormalities are present.

Adult↗

Local anesthetic myotoxicity.

Skeletal muscle toxicity is a rare and uncommon side effect of local anesthetic drugs. Intramuscular injections of these agents regularly result in reversible myonecrosis. The extent of muscle damage is dose dependent and worsens with serial or continuous administration. All local anesthetic agents that have been examined are myotoxic, whereby procaine produces the least and bupivacaine the most severe muscle injury.The histologic pattern and the time course of skeletal muscle injury appear rather uniform: hypercontracted myofibrils become evident directly after injection, followed by lytic degeneration of striated muscle sarcoplasmic reticulum, and by myocyte edema and necrosis over the next 1 to 2 days. Myoblasts, basal laminae, and connective tissue elements remain intact in most cases, which permits muscular regeneration within 3 to 4 weeks. Subcellular pathomechanisms of local anesthetic myotoxicity are still not understood in detail. Increased intracellular Ca2+ levels appear to be the most important element in myocyte injury; since denervation, inhibition of sarcolemmal Na+ channels, and direct toxic effects on myofibrils have been excluded as sites of action. In this respect, the quantitative impact of further mitochondria-mediated pathways--at least in bupivacaine toxicity--is still to be established. Although experimental myotoxic effects are impressively intense and reproducible, only a few case reports of myotoxic complications in patients after local anesthetic administrations have been published. In particular, the occurrence of clinically relevant myopathy and myonecrosis has been described after continuous peripheral blocks, infiltration of wound margins, trigger point injections, and peri- and retrobulbar blocks.

Anesthetics, Local↗

Chronic regional pain syndrome, type 1: Part II.

Chronic regional pain syndrome, type 1 (CRPS1) is a complex neurologic disease characterized by chronic, severe, burning pain; hyperesthesia; soft tissue swelling; dystrophy; hyperhidrosis; vasomotor and sudomotor instability; joint stiffness; and patchy osteoporosis. Five to six million people in the United States alone suffer from CRPS1. To date, CRPS1 is poorly understood and often is not recognized clinically. This syndrome requires early detection, pain control, and treatment in tandem with physical therapy to the affected area. Part I (published in September) discussed background information on CRPS1 and sympathetic nerve blocks. Part II focuses on the remaining treatment modalities (e.g., sympathectomy, physical therapy, stimulators, trigger point injections, acupuncture, tourniquet effects, placebo effects, amputation).

Chronic Disease↗

Soft-tissue rheumatism: diagnosis and treatment.

Soft tissue rheumatism is one of the most common and most misunderstood categories of disorders facing the primary care physician. Among the more common types are subacromial bursitis, epicondylitis, trochanteric bursitis, anserine bursitis, and fibromyalgia. The keys to the diagnosis of soft-tissue rheumatism are the history and, more importantly, the physical examination. Extensive laboratory testing and radiographs are not as helpful in evaluating patients with these complaints. Treatment consists of nonsteroidal anti-inflammatory drugs (NSAIDs) and nonnarcotic analgesics. Especially in patients with localized disorders, intralesional injections of corticosteroids are particularly effective and safe and should be part of the armamentarium of the primary care practitioner. Fibromyalgia is a particularly challenging form of nonarticular rheumatism. The clinical presentation is rather characteristic, with the patient typically being a woman 30-60 years of age who presents with diffuse somatic pain. Patients often give a history of sleep disturbance, may be depressed, and show characteristic tender areas, or trigger points. Laboratory findings are normal. Management includes reassurance, correction of the underlying sleep disturbance with low doses of a tricyclic antidepressant, treatment with muscle relaxants and nonnarcotic analgesics or NSAIDs, and an exercise program with a strong aerobic component.

Bursitis↗

Shoulder impingement in tennis/racquetball players treated with subscapularis myofascial treatments.

Conservative care of the athlete with shoulder impingement includes activity modification, application of ice, nonsteroidal anti-inflammatory drugs, subacromial corticosteroid injections, and physiotherapy. This case report describes the clinical treatment and outcome of three patients with shoulder impingement syndrome who did not respond to traditional treatment. Two of the three were previously referred for arthroscopic surgery. All three were treated with subscapularis trigger point dry needling and therapeutic stretching. They responded to treatment and had returned to painless function at follow-up 2 years later.

Adult↗

The prevalence of thumb problems in Australian physiotherapists is high: an observational study.

QUESTION: What is the lifetime and current prevalence of thumb problems in Australian physiotherapists and what are the factors associated with thumb problems? DESIGN: Survey of a random cross-section of physiotherapists. PARTICIPANTS: 1562(approximately 10% of the total) registered Australian physiotherapists. OUTCOME MEASURES: General questions covered demographic information, area of practice, hours worked per week, and years worked as a physiotherapist. Specific questions about thumb problems covered thumb affected, symptoms, onset of symptoms, treatment sought, relevance of work-related factors, and joint hypermobility. RESULTS: 1102 (71%) questionnaires were returned and 961 (68%) completed. The lifetime prevalence of thumb problems was 65% and the current prevalence was 41%. Factors that were significantly associated with thumb problems included: working in orthopaedic outpatients (OR 3.2, 95% CI 1.8 to 5.8); using manual therapy (OR 2.3 to 3.4, 95% CI 1.7 to 5.1), trigger point therapy (OR 2.3, 95% CI 1.7 to 3.0) and massage (OR 2.1, 95% CI 1.6 to 2.8); having thumb joint hypermobility (OR 2.2 to 2.6, 95% CI 1.4 to 4.5); or an inability to stabilise the joints of the thumb whilst performing physiotherapy techniques (OR 4.2, 95% CI 2.9 to 5.9). Of those respondents who reported thumb problems, 19% had changed their area of practice and 4% had left the profession as a result of their thumb problems. CONCLUSION: The prevalence of thumb problems in Australian physiotherapists appears to be high and can be of sufficient severity to impact on careers.

Adult↗

Familial prostate cancer cases before and after radical prostatectomy do not show any aggressiveness compared with sporadic cases.

OBJECTIVES: To compare the clinical and biologic features at diagnosis between sporadic and familial clinically localized prostate cancer (CaP), and to compare the prognosis of familial with that of sporadic cases after radical prostatectomy in southwestern Europe. METHODS: Eighty-five sporadic (one case of CaP) and 37 familial (two or more CaP cases in the family) patients with clinically localized CaP undergoing radical prostatectomy were compared regarding preoperative (mean age, clinical status, mean prostate-specific antigen level, and mean Gleason score at diagnosis) and postoperative (pT, pN, and pathologic Gleason score) parameters using the Student t test, Fisher's exact test, and the chi-square test. The biochemical relapse-free survival for each group was compared using the Kaplan-Meier method and the log-rank test. RESULTS: The mean follow-up was about 51.8 months (range 1 to 156) in the sporadic group and 35 months (range 1 to 96) in the familial group. No specific preoperative and postoperative clinical or biologic feature was associated with familial CaP. Biochemical relapse occurred in 40.5% (15 of 37) of cases when the proband had a positive family history of CaP versus 32.9% (28 of 85) in the sporadic cases (P = 0.42). Biochemical relapse-free survival curves did not display any difference (P = 0.46) between familial and sporadic CaP. CONCLUSIONS: In this population, the outcome after radical prostatectomy is similar in those with and without a family history. Thus, the natural history of CaP seems to follow the same path whether the triggering point is inherited or acquired for this subset of patients during this period.

Follow-Up Studies↗

A control, double-blind comparison of mepivacaine injection versus saline injection for myofascial pain.

In a double-blind study 28 patients with acute, localised muscle pain received four local injections of mepivacaine 0.5%, and 25 patients with the same type of pain received local injections of an equivalent volume of physiological saline. The group receiving saline tended to have more relief of pain, especially after the first injection. The results thus show that pain relief is not due merely to the local anaesthetic. The study therefore raises questions about the mechanism by which local injections into muscle relieves pain, since there is the possibility that a similar effect might also be achieved by merely inserting a needle into the trigger point. Physiological saline is considered to be a more appropriate fluid for injection therapy than local anaesthetics since it is less likely to produce side-effects.

Clinical Trials as Topic↗