Complex regional pain syndrome.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a chronic pain condition that can occur after a minor trauma or surgery. It is a multifactorial condition with a complex cause and even more complex pathophysiology. There are disturbances and changes in the sympathetic, somatosensory and motor nervous system, resulting in severe pain and disability. Patients with CRPS can have their quality of life and functional ability greatly affected and they need appropriate and interdisciplinary interventions. PURPOSE: This article contributes towards an up-to-date knowledge and an overall view of CRPS, which can contribute to a structured and systematic rehabilitation process for patients. IMPLICATIONS: This Masterclass describes a functional restoration algorithm to assist therapists in the development of a treatment plan based on the available evidence and international guidelines. Early diagnosis and treatment is of great importance as patients (adults and children), can be severely affected in their functional capacity and quality of life.

The role of neuroplasticity in experimental neck pain: a study of potential mechanisms impeding clinical outcomes of training.

Training is a mainstay in the clinical management of neck pain, yet, effects of various training protocols are only small to moderate and improvements are required. Previous investigations of the nervous system indicate a correlation between neuroplastic adaptation to training and functional recovery. The interaction between neck pain and training thus needs further exploration. This was a randomized experimental study of the effects of experimental neck pain and training on corticomotor excitability. Healthy volunteers were randomized to training and experimental neck pain, training and no pain, and pain and no training. Primary endpoints were corticomotor excitability assessed by transcranial magnetic stimulation and electromyography measured as changes in amplitudes and latencies of motor evoked potentials (MEPs), recorded at baseline and after 30 min, 1 h, and 1 week. Additionally, correlations between changes in MEPs and motor learning, effects of pain and concomitant neck training on pain, muscle strength, and fatigue were investigated. Data were analyzed by repeated measurement ANOVA, paired t tests, Grubbs' outlier test and correlation coefficients. Results indicated that neck pain and training significantly enhanced the inhibition of the amplitudes of the MEPs for 1 week. The results indicate that moderate neck pain and training induce long-lasting inhibition of the corticomotor pathways. This inhibition may limit the outcome of neck training in painful conditions in contrast to pain-free training conditions.

Specific neck training induces sustained corticomotor hyperexcitability as assessed by motor evoked potentials.

STUDY DESIGN: Experimental investigation of short-term and long-term corticomotor effects of specific neck training, coordination training, and no training. OBJECTIVE: To determine the effects of different training programs on the motor neurons controlling the neck muscles as well as the effects of training on muscle strength and muscle fatigue, and the correlations between corticomotor control and motor learning. SUMMARY OF BACKGROUND DATA: Training is usually recommended for unspecific neck pain and consists of neck and upper body coordination, strengthening, and endurance exercises. However, it is unclear which type of training is the most effective. No studies have previously investigated the neural effect of neck training and the possible differential effect of specific versus coordination training on corticomotor control. METHODS: Transcranial magnetic stimulation and electromyography were used to elicit and monitor motor evoked potentials (MEPs) from the trapezius and thumb muscles before and 30 minutes, 1 hour, and 7 days after training. Parameters measured were MEP amplitude, MEP latency, strength, learning effects, and muscle fatigue. RESULTS: Only specific neck training yielded a 67% increase in MEP amplitudes for up to 7 days after training compared with baseline (P < 0.001). No significant changes were seen after coordination training, no training, and in the within-subject control muscle. The mean muscle strength increased immediately after specific neck training from 56.6 to 61 kg (P < 0.001). No subjective or objective measures of fatigue were observed. CONCLUSION: Specific neck training induced a sustained hyperexcitability of motor neurons controlling the neck muscles compared with coordination training and controls. These findings may prove valuable in the process of developing more effective clinical training programs for unspecific neck pain.

A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: a double-blinded, randomised controlled trial.

INTRODUCTION: Critically ill patients are predisposed to venous thromboembolism. We hypothesized that higher doses of enoxaparin would improve thromboprophylaxis without increasing the risk of bleeding. Peak anti-factor Xa (anti-Xa) levels of 0.1 to 0.4 IU/ml reflect adequate thromboprophylaxis for general ward patients. Studies conducted in orthopaedic patients demonstrated a statistically significant relationship between anti-Xa levels and wound haematoma and thrombosis. Corresponding levels for critically ill patients may well be higher, but have never been validated in large studies. METHODS: Eighty critically ill patients weighing 50 to 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40 mg BID, or 1 mg/kg QD, each administered for three days. Anti-Xa activity was measured at baseline, and daily at 4, 12, 16 and 24 hours post administration. Antithrombin, fibrinogen, and platelets were measured at baseline and twice daily thereafter. RESULTS: Two patients were transferred prior to participation. On day 1, doses of 40 mg QD (n = 20) and 40 mg BID (n = 19) yielded mean peak anti-Xa of 0.20 IU/ml and 0.17 IU/ml respectively. A dose of 30 mg BID (n = 20) resulted in much lower levels (0.08 IU/ml). Patients receiving 1 mg/kg QD (n = 19) achieved near steady-state mean peak anti-Xa levels from day 1 (0.34 IU/ml). At steady state (day 3), mean peak anti-Xa levels of 0.13 IU/ml and 0.15 IU/ml were achieved with doses of 40 mg QD and 30 mg BID respectively. This increased significantly to 0.33 IU/ml and 0.40 IU/ml for doses of 40 mg BID and 1 mg/kg QD respectively. Thus anti-Xa response profiles differed significantly over the three days between enoxaparin treatment groups (P <0.0001). Doses of 40 mg BID and 1 mg/kg QD enoxaparin yielded target anti-Xa levels for over 80% of the study period. There were no adverse effects. CONCLUSIONS: Doses of 40 mg QD enoxaparin (Europe) or 30 mg BID (North America) yield levels of anti-Xa which may be inadequate for critically ill patients. A weight-based dose yielded the best anti-Xa levels without bioaccumulation, and allowed the establishment of near steady-state levels from the first day of enoxaparin administration. TRIAL REGISTRATION: Current Controlled Trials ISRCTN91570009.

Thermodynamic and biological evaluation of a thrombin binding aptamer modified with several unlocked nucleic acid (UNA) monomers and a 2'-C-piperazino-UNA monomer.

Thrombin binding aptamer is a DNA 15-mer which forms a G-quadruplex structure and possess promising anticoagulant properties due to specific interactions with thrombin. Herein we present the influence of a single 2'-C-piperazino-UNA residue and UNA residues incorporated in several positions on thermodynamics, kinetics and biological properties of the aptamer. 2'-C-Piperazino-UNA is characterized by more efficient stabilization of quadruplex structure in comparison to regular UNA and increases thermodynamic stability of TBA by 0.28-0.44 kcal/mol in a position depending manner with retained quadruplex topology and molecularity. The presence of UNA-U in positions U3, U7, and U12 results in the highest stabilization of G-quadruplex structure (ΔΔG(37)(°)=-1.03kcal/mol). On the contrary, the largest destabilization mounting to 1.79 kcal/mol was observed when UNA residues were placed in positions U7, G8, and U9. Kinetic studies indicate no strict correlation between thermodynamic stability of modified variants and their binding affinity to thrombin. Most of the studied variants bind thrombin, albeit with decreased affinity in reference to unmodified TBA. Thrombin time assay studies indicate three variants as being as potent as TBA in fibrin clotting inhibition.

[Treatment of whiplash-associated disorders]. / Behandling af gener efter whiplash.

Treatment of whiplash-associated disorders starts with a thorough clinical examination, which may be repeated after 1-3 weeks. For optimal results it is essential that the patient receives clear information about the condition and that any pain is treated effectively with analgesics. Risk factors for persistent symptoms can often be identified early and should be addressed adequately. If symptoms persist and conservative treatments are chosen, these should be active and they should focus on sustaining or regaining usual activities.

Enoxaparin, effective dosage for intensive care patients: double-blinded, randomised clinical trial.

INTRODUCTION: Intensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low-molecular-weight heparins, such as enoxaparin, are increasingly used because of predictable pharmacokinetics. This study aims to determine the subcutaneous (SC) dose of enoxaparin that would give the best anti-factor Xa levels in ICU patients. METHODS: The 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into four groups to receive 40, 50, 60, or 70 mg SC enoxaparin for a period of 24 hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours after administration. An AFXa level between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity. RESULTS: Median peak (4 hours after administration), aFXa levels increased significantly with an increase in enoxaparin dose, from 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg, and 0.29 IU/ml at 70 mg (P = 0.002). At 12 hours after administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P = 0.02). CONCLUSIONS: Our study confirmed that a standard dose of 40 mg enoxaparin yielded subtherapeutic levels of aFXa in critically ill patients. Higher doses resulted in better peak aFXa levels, with a ceiling effect observed at 60 mg. The present study seems to suggest inadequate dosage as one of the possible mechanisms for the higher failure rate of enoxaparin in ICU patients. TRIAL REGISTRATION: ISRCTN03037804.

Direct crystallographic observation of an acyl-enzyme intermediate in the elastase-catalyzed hydrolysis of a peptidyl ester substrate: Exploiting the "glass transition" in protein dynamics.

The crystal structure of the acyl complex of porcine pancreatic elastase with its peptidyl ester substrate N-acetyl-ala-ala-ala-methyl ester (Ac(Ala)3OMe) has been determined at 2.5 A resolution. The complex was stabilized by exploiting the "glass transition" in protein dynamics that occurs at around -53 degrees C (220 K). Substrate was flowed into the crystal in a cryoprotective solvent above this temperature, and then the crystal was rapidly cooled to a temperature below the transition to trap the species that formed. The use of a flow cell makes the experiment a kinetic one and means that the species prior to the rate determining transition state has a chance to accumulate. The resulting crystal structure shows an acyl-enzyme intermediate in which the leaving group is absent and the carbonyl carbon of the C-terminal alanine residue is covalently bound to the gamma oxygen of the active site serine. The ester carbonyl shows no significant distortion from planarity, with the carbonyl oxygen forming one hydrogen bond with the oxyanion hole. The tripeptide is bound in an extended antiparallel beta-sheet with main chain residues of the enzyme. The geometry and interactions of this acyl-enzyme suggest that it represents a productive intermediate. To test this hypothesis, the same crystal was then warmed above the glass transition temperature and a second data set was collected. The resulting electron density map shows no sign of the substrate, indicating hydrolysis of the intermediate followed by product release. This experiment provides direct evidence for the importance of dynamic properties in catalysis and also provides a blueprint for the stabilization of other short-lived species for direct crystallographic observation.

[Sexual knowledge, attitudes and behavior among young Danes. A questionnaire study]. / Seksuel viden, holdning og adfaerd blandt unge danskere. En spørgeskemaundersøgelse.

INTRODUCTION: The aim of this study was to present selected key figures concerning the sexual knowledge, attitudes, and behaviour among Danish teenagers. MATERIAL AND METHODS: 7355 Danish adolescents (aged 13-25) participated in a comprehensive questionnaire survey concerning sexual knowledge, attitudes, and behaviour. RESULTS: The median age at coital debut was 16.8 and in all age groups > 13, girls were more experienced and active than boys. The coital frequency was increased by age, as was girls' experience with orgasm in the years following their debut. The prevalence of same-gender sex appeared to be modest, and anal sex was reported by less than 10 per cent. A significant and increasing amount of youngsters did not discuss sexual matters at home, whereas the vast majority had received sexual education in school. One fourth of the girls regarded doctors as desired sexual interlocutors. Almost one fourth of the youngsters did not use contraception at their sexual debut, and 7 per cent of the sexually experienced girls had had an induced abortion. 9 per cent of the girls and 5 per cent of the boys had been infected with chlamydia, and 17 per cent of those sexually active had taken at least one HIV test. DISCUSSION: The age at coital debut seems to be stable, whereas the prevalences of unsafe sex and STDs are still high. New didactic methods are incessantly needed, just as supplementary empirical studies are encouraged.