Comparison between semiquantitative and quantitative methods for the assessment of knee synovitis in osteoarthritis using non-enhanced and gadolinium-enhanced MRI.

OBJECTIVE: To compare different semiquantitative and quantitative methods using both non-enhanced and gadolinium-enhanced MRI techniques for the assessment of synovitis in knee osteoarthritis (OA). METHODS: Knees with end-stage clinical OA in patients undergoing total knee replacement surgery were included in this cross-sectional study. MRI was performed on all knees. Standard non-enhanced and gadolinium-enhanced sequences were acquired. Using non-enhanced MRI, we semiquantitatively assessed two features widely used as surrogates for synovitis: effusion-synovitis and Hoffa-synovitis. Using gadolinium-enhanced sequences, we semiquantitatively assessed synovial thickness. We quantitatively evaluated the total synovial volume on the gadolinium-enhanced sequences as well. We assessed the correlations of effusion-synovitis and Hoffa-synovitis with synovial thickness and volume, applying Spearman correlation analysis. The diagnostic performance of both synovitis features on non-enhanced MRI was assessed using synovial thickness on gadolinium-enhanced MRI as the reference. RESULTS: A total of 104 subjects (one knee per subject) were included. Correlations of effusion-synovitis with synovial thickness and volume were r = 0.41 and r = 0.43 (P < .001) r = 0.32 and r = 0.39 (P < .0001). CONCLUSION: Using synovial thickness assessed on gadolinium-enhanced sequences as the reference, effusion-synovitis showed superior correlations and sensitivity. Effusion-synovitis should be preferred over Hoffa-synovitis as a surrogate marker for synovial thickening, in studies of knee OA for which gadolinium-enhanced sequences are not available.

Reporting of data from out-of-hospital cardiac arrest has to involve emergency medical dispatching--taking the recommendations on reporting OHCA the Utstein style a step further.

OBJECTIVES: As a part of the chain of survival, the emergency medical communication centre (EMCC) and the emergency medical dispatcher (EMD) has an important role in early identification of out-of-hospital cardiac arrests (OHCA). The EMD may provide instructions to the caller and thereby initiate cardiopulmonary resuscitation in a substantial number of subjects and thus contribute to increased survival. The EMCC provides a response with first responders, ambulances, physician manned units and potentially other health care providers. EMCC in many cases initiates the communication with experts in the referral hospital and provide added value to the post resuscitation care by providing advanced transport, logistics and follow up. In research there is a growing focus on the EMCC/EMDs impact on survival in OHCA. The lack of standards in reporting results from medical dispatching is an obstacle for thorough evaluation of results in this area and comparison of data. The objective for this paper is to introduce a framework for uniform reporting of the dispatching process for quality improvement, collecting and reporting data and exchanging information regarding OHCA.

Nabilone produces marked impairments to cognitive function and changes in subjective state in healthy volunteers.

This was a double-blind, randomised, placebo-controlled, crossover study of the acute cognitive and subjective effects of nabilone 1-3 mg in healthy male volunteers. The Cognitive Drug Research computerised system (CDR system) was used to assess changes in attention, working and episodic memory. In addition, a number of self-ratings were conducted including those of mood, alertness and perceived drug effects. Impairments to attention, working and episodic memory and self-ratings of alertness were evident. Volunteers also experienced a number of subjective drug effects. These data demonstrate that acute doses of nabilone in the range 1-3 mg produce clear cognitive and subjective effects in healthy volunteers, and therefore they may be used as reference data in the future study of peripherally acting cannabinoids believed to be free from such effects.

Recommended guidelines for reporting on emergency medical dispatch when conducting research in emergency medicine: the Utstein style.

OBJECTIVES: To establish a uniform framework describing the system and organisation of emergency medical response centres and the process of emergency medical dispatching (EMD) when reporting results from studies in emergency medicine and prehospital care. DESIGN AND RESULTS: In September 2005 a task force of 22 experts from 12 countries met in Stavanger; Norway at the Utstein Abbey to review data and establish a common terminology for medical dispatch centres including core and optional data to be used for health monitoring, benchmarking and future research.

Improving assessment of postoperative pain in surgical wards by education and training.

PROBLEM: There is a need to improve postoperative pain organisation and management in hospitals. One of the most important factors in achieving this is to improve active assessment of pain in the postoperative phase. DESIGN: Repeated audits on an annual basis over a 3 year period. Ward nurses, appointed as "pain control representatives", performed the data collection. SETTING: Departments of general surgery and orthopaedics in a university hospital with 1200 beds. KEY MEASURE FOR IMPROVEMENT: Assessment of postoperative pain intensity using a numerical rating scale. STRATEGIES FOR CHANGE: On the basis of the first audit in 1999 the team decided to introduce a mandatory training programme in postoperative pain management for all involved staff, including surgeons and ward nurses. Guidelines for postoperative care were upgraded and made accessible through the intranet. Regular staff meetings in the surgical wards with representatives from the acute pain service team were introduced. EFFECTS OF CHANGE: The assessment of pain according to protocols increased from 71% to 91% in the surgical wards and from 60% to 88% in the orthopaedic wards between 1999 and 2001/2. LESSONS LEARNT: To increase the awareness of pain and improve pain assessment, the importance of mandatory training, regular staff meetings and regular audits must be emphasised. It is also imperative to give feedback on the regular audits to the ward and staff members involved.

Intrathecal adenosine increases spinal cord blood flow in the rat: measurements with the laser-Doppler flowmetry technique.

BACKGROUND: Adenosine and adenosine analogues induce antinociception both after systemic and intrathecal (i.t.) administration in animal models. Further, patients with neuropathic pain have been treated successfully with i.t. adenosine. Prior to introducing new analgesic drugs for regular spinal use in humans, experimental studies must be undertaken to evaluate the risks of neurotoxicity. It is important to evaluate the possibility of cytotoxic effects and that antinociception may be due to decreased spinal cord blood flow (SCBF) and neural ischaemia. The present study evaluates whether adenosine or isotonic mannitol induces changes in SCBF as assessed by laser-Doppler flowmetry (LDF). METHODS: After laminectomy and insertion of i.t. catheters, seven rats received adenosine 50 microg in isotonic mannitol 500 microg, six rats received isotonic mannitol 500 microg and eight rats received saline 0.9%. SCBF was registered by the LDF technique continuously for 3 h after injection. Arterial blood pressure was also assessed. RESULTS: In the adenosine in mannitol group, SCBF increased up to 230% of baseline levels for almost 40 min, P = 0.044 and then declined. In the mannitol group, SCBF increased up to 180% of baseline (P < 0.011) before declining. At 60 min, SCBF had returned to saline levels and remained stable during the rest of the experiment. CONCLUSION: Intrathecal administration of adenosine in mannitol and of mannitol both increased SCBF in rats, compared with saline. It is unlikely that the effects on SCBF induced by adenosine and mannitol could result in neurotoxicity of the spinal cord.

The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury.

BACKGROUND: Pain following spinal cord injury (SCI) is a therapeutic challenge. Only a few treatments have been assessed in randomized, controlled trials. The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury. We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments resulted in changes of sensibility. METHODS: Ten patients with spinal cord injury and neuropathic pain below the level of injury were included. The analgesic effect of ketamine 0.4 mg kg(-1) and lidocaine 2.5 mg kg(-1) was investigated. Saline was used as placebo. The drugs were infused over 40 min. A randomized, double-blind, three-period, three-treatment, cross-over design was used. Systemic plasma concentrations of ketamine and lidocaine were assessed. Pain rating was performed using a visual analogue scale (VAS). Sensory function was assessed with a combination of traditional sensory tests and quantitative measurement of temperature thresholds. RESULTS: Response to treatment, defined as 50% reduction in VAS-score during infusion, was recorded in 5/10 in the ketamine, 1/10 in the lidocaine and 0/10 in the placebo groups. Neither ketamine nor lidocaine changed temperature thresholds or assessments of mechanical; dynamic and static sensibility. Nor could these sensory assessments predict response to treatment in this setting. Lidocaine and particularly ketamine were associated with frequent side-effects. CONCLUSION: Ketamine but not lidocaine showed a significant analgesic effect in patients with neuropathic pain after spinal cord injury. The pain relief was not associated with altered temperature thresholds or other changes of sensory function.

The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain.

BACKGROUND: Neuropathic pain is often severe and resistant to pharmacological treatment. The aims of the present study were to assess the analgesic effect of ketamine and lidocaine and to investigate if measurement of different variables of sensibility could be used to identify responders. We also wanted to study if treatment resulted in changes of sensibility. METHODS: Twelve patients with long-lasting peripheral neuropathic pain of traumatic origin were included. The effects of ketamine hydrochloride (Ketalar, Parke Davis) 0.4 mg/kg and lidocaine hydrochloride (Xylocain, Astra) 2.5 mg/kg were investigated. Saline was used as placebo. The intensity of continuous pain was measured by a visual analogue scale (VAS). Warm and cold perception as well as heat and cold pain thresholds were assessed. Sensibility to touch was also tested. Systemic plasma concentrations of lidocaine and ketamine were assessed. RESULTS: The mean reduction in VAS-scores was 55%, 34% and 22% for ketamine, lidocaine and placebo, respectively. A significant difference was registered between ketamine and placebo (P = 0.009). Response to treatment (50% reduction in VAS-score during infusion) was recorded in 7/12 in the ketamine, 4/12 in the lidocaine and 2/12 in the placebo group. Quantitative sensory testing (QST) of thermal sensitivity and sensory tests for mechanical stimuli could not separate responders from non-responders and neither were the results from these assessments changed by the infusion of the drugs. Lidocaine and particularly ketamine were associated with frequent side-effects, the most common being somnolence and dizziness. CONCLUSION: Ketamine showed a significant analgesic effect. The clinical usefulness is, however, limited by disturbing side-effects.

Prehospital thrombolysis: lessons from Sweden and their application to the United Kingdom.

OBJECTIVE: To study the successful implementation of paramedic administered prehospital thrombolysis in Sweden, and to consider the implications of this for the UK. METHODS: A series of research visits were undertaken, including visits to Uppsala Hospital and dispatch centre, ambulance stations in several counties of Sweden and Dalarna County, which has one of the longest experiences of telemedicine supported prehospital thrombolysis in Europe. Data relating to prehospital thrombolysis, stages in successful implementation, and potential barriers to change were identified. RESULTS: Two thirds of the hospitals in Sweden now have some form of prehospital thrombolysis. A nationally agreed and standardised training programme and the fact that many ambulance paramedics are also qualified nurses has facilitated successful introduction, but Sweden's low population density is also an important factor. Data from Dalarna County indicate that the median "pain to needle" time has been reduced by 45 minutes with a concurrent reduction in complications from 50% to 25% (p=0.018). Inhospital mortality has also reduced from 12% to 6%, but with the small numbers involved this improvement does not achieve statistical significance (p=0.36). CONCLUSION: If the outcome of acute myocardial infarction in the United Kingdom is to be improved, and National Service Framework targets met, then prehospital thrombolysis is an important development. Several technical solutions already exist, and a single bolus thrombolytic agent is now available, but the main barriers to full implementation are related to the establishment of an effective training programme and the organisational changes that will facilitate this new practice. High quality research is urgently needed to guide the implementation of prehospital thrombolysis in a clinically and cost effective way.

The incidence of chronic post-sternotomy pain after cardiac surgery--a prospective study.

BACKGROUND: Post-sternotomy pain is sometimes a sequela of cardiac surgery. The incidence, characteristics and clinical course of post-sternotomy pain are not well known. The aim of our study was to determine the incidence of chronic post-sternotomy pain in patients undergoing sternotomy for cardiac surgery in general and according to the specific surgical procedure. METHOD: In a prospective manner, a group of 349 consecutive patients were evaluated for chronic post-sternotomy pain one year after surgery. The patients were asked in a postal questionnaire to describe and score any persistent pain following the surgical procedure. The patients were classified into 3 sub-groups according to surgical procedure. The first group consisted of patients operated for coronary artery by-pass grafting (CABG) including internal thoracic artery grafting (ITAG). The second group included patients operated with CABG without ITAG and the third group of patients with valve replacement without CABG. RESULT: A total of 318 patients (91%) answered the questionnaire of whom 90 (28%) reported chest discomfort different from what they experienced before surgery. The scoring on the visual analogue scale (VAS, 0-100 mm) showed that 41 patients (13%) reported maximum pain intensity > or =30 mm (moderate pain), and 14 of these patients (4%) scored > or =54 mm (severe pain). There was no statistically significant difference in pain incidence and pain intensity when comparing the patients subjected to different surgical procedures. CONCLUSIONS: This prospective study shows that the overall incidence of non-cardiac pain after sternotomy for cardiac surgery is high (28%). Most patients experience a modest pain intensity but some (1%) report severe pain, never being lower than 54 mm on VAS. The study also indicates that the incidence of pain after sternotomy is not only associated with harvest of the ITA and additional aetiological factors must be sought.

Systemic adenosine infusion reduces the area of tactile allodynia in neuropathic pain following peripheral nerve injury: a multi-centre, placebo-controlled study.

Systemic adenosine has been shown in earlier case reports and a small placebo-controlled study to reduce pathological sensory dysfunction such as tactile allodynia in neuropathic pain. To evaluate this further, the effects of systemic adenosine infusion (50 microg/kg/min for 60 min) on tactile sensory dysfunction and pain was evaluated in 26 patients suffering peripheral neuropathic pain characterized by dynamic tactile allodynia. A randomized, cross-over, double-blind, placebo-controlled technique was used in this multi-centre study. Psychophysical methods were used to evaluate sensory dysfunction and spontaneous pain. The area of dynamic tactile allodynia was significantly reduced by adenosine compared with placebo (p=0.043), but spontaneous pain and tactile pain threshold were not significantly improved compared with the effects of placebo treatment. As a secondary outcome, a higher incidence of positive subjective effects on the clinical pain condition, in a few cases with long duration (several months), following adenosine treatment was found when the global effect of respective treatment was assessed (p=0.028). The results demonstrate involvement of adenosine receptor-sensitive pain mechanisms in some aspects of the sensory dysfunction often found in neuropathic pain.

Telemedicine and decision support in emergency ambulances in Uppsala.

In Sweden, as in many other countries, paramedics or nurses constitute the majority of prehospital personnel. If tasks usually performed by doctors are to be performed by these personnel, there is a need for guidelines and triage in the handling of medical emergencies. We describe an information management system used in ambulances for data communication, documentation, triaging and presentation of checklists. In most cases, data are input while the patient is being cared for. The information is collected and stored together with data automatically received from the dispatch centre. The latter date are transferred by a mobile radio network to the ambulance. Medical date (e.g. electrocardiograms) are transferred from the ambulance over the data network to the receiving medical facility. All transferred data are finally collected in a database for statistical analysis and follow-up.

Spinal cord morphology after chronic intrathecal administration of adenosine in the rat.

BACKGROUND: The endogenous compound adenosine is known to have various modulatory effects both in the peripheral and central nervous system. Adenosine and its analogues induce antinociception in animal models when administrated systemically and intrathecally (IT), both in acute and chronic models of pain. Before a new drug is introduced for spinal pain treatment in humans, experimental studies of neurotoxicity must be undertaken. METHODS: This study was performed in rats in order to reveal morphological or morphometric signs of spinal cord damage after chronic (two weeks) administration of adenosine. After insertion of IT catheters, the animals were injected twice a day during two weeks with adenosine (100 microg) or saline (controls). Potential spinal neurotoxicity was evaluated morphologically by light and electron microscopy supplemented by a morphometric analysis. RESULTS: There were no signs of histologic changes indicating neurotoxic effects by any of the methods of analysis. The morphological findings in the adenosine treated rats did not differ in any case from those of the saline treated animals. CONCLUSION: The results suggest that chronic IT administration of a high dose of adenosine is not associated with neurotoxicity in the rat spinal cord.

Sameridine--intrathecal injection in the rat. Morphometric and morphologic analysis after chronic administration and effects on spinal cord blood flow.

BACKGROUND: Sameridine is a type of compound with both local anaesthetic and analgesic effects with the clinical intention to be used intrathecally (i.t.) in order to provide both surgical anaesthesia and prolonged postoperative analgesia. Before new drugs are introduced for clinical use, they must be tested for potential toxic effects. METHODS: In the present study sameridine (5 or 10 mg/ml), bupivacaine (5 mg/ml) or saline (9 mg/ml) was injected intrathecally in rats twice, daily (at 07:00 and 19:00), 5 days a week for 2 weeks. Thereafter, the rats were anaesthetised, perfused and the spinal cords were prepared for microscopic investigation. A morphologic method, using light and electron microscopic examination of the cross-section of the spinal cord, was combined with a quantitative morphometric analysis of the number and size of neuronal cells in the dorsal horn as a sensitive indicator of neurotoxicity. Using the laser-Doppler flowmetry technique, the effects of saline and sameridine (1, 5 and 10 mg/ml) on spinal cord blood flow (SCBF) was studied. RESULTS: No signs of neurotoxicity could be seen in any of the animals and no significant differences were seen when comparing the cell number or cell sizes in the groups injected with sameridine, bupivacaine or saline. After i.t. administration of 10 mg/ml sameridine a significant, short-lasting, decrease in SCBF (72% of pre-drug value) was seen. CONCLUSION: In conclusion, our studies do not show any signs of neurotoxic effects of i.t. administration of sameridine in the rat. A transient decrease in SCBF was noted after i.t. injection of sameridine 10 mg/ml.

Spinal cord blood flow after intrathecal injection of ropivacaine and bupivacaine with or without epinephrine in rats.

BACKGROUND: Ropivacaine is a new local anaesthetic available for spinal and epidural anaesthesia. When new drugs are being introduced for spinal application, their effect on spinal cord blood flow (SCBF) should be studied for safety and toxicological aspects. In the present study, SCBF was studied after intrathecal (i.t.) application of ropivacaine and bupivacaine with and without epinephrine. METHOD: SCBF was measured continuously in spontaneously breathing, enflurane/N2O anaesthetized rats, using laser-Doppler flowmetry technique. The spinal cord was exposed by laminectomy at the L1-L2 level, and a laser-Doppler probe was placed over the dorsal horn, allowing on-line registration of SCBF in a tissue hemisphere of 1-2 mm. Relative changes in SCBF were then measured on-line after i.t. administration of increasing doses of ropivacaine, bupivacaine or bupivacaine with epinephrine. RESULTS: Ropivacaine and bupivacaine decreased SCBF in a dose-dependent manner. In contrast, the reduction in SCBF produced by bupivacaine + epinephrine (Bupi + Epi) was equal for all doses of bupivacaine. The order of magnitude of SCBF decreases was Bupi + Epi > ropivacaine > bupivacaine. The maximal decrease in SCBF at the highest concentration given (10 mg/ml) was 37 +/- 6% for ropivacaine, 27 +/- 7% for bupivacaine and 40 +/- 6% for bupivacaine + epinephrine. CONCLUSION: Ropivacaine and bupivacaine produce a dose-related, transient decrease in SCBF following i.t. administration in anaesthetized rats. However, the decrease in SCBF produced by both ropivacaine, when epinephrine was added in a concentration of 5 micrograms/ml. These results suggest that ropivacaine, like bupivacaine, may be used for spinal anaesthesia without important effects on SCBF.

How do drugs relieve neurogenic pain?

Neurogenic pain is experienced by about 1% of the population. The efficacy of drug treatment for this condition has been poorly evaluated, and only recently have certain treatments been shown to have significant analgesic effects. Monotherapy with topical agents such as capsaicin is not usually sufficient. Oral agents that have proven effective in treating neurogenic pain states include tricyclic antidepressants, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and anticonvulsants. Local anaesthetics, administered intravenously, have been reported to relieve pain in selected patients, but data from controlled trials are sparse. Multiple mechanisms contribute to the generation of neurogenic pain. In the future, drug treatment for neurogenic pain is likely to target these mechanisms. Recent studies have shown that N-methyl-D-aspartate (NMDA) receptor antagonists, adenosine receptor agonists and nitric oxide synthase inhibitors may become useful in the treatment of neurogenic pain.

Spinal cord blood flow after intrathecal injection of ropivacaine: a screening for neurotoxic effects.

The study of spinal cord blood flow (SCBF) after spinal drug application is an important aspect of preclinical neurotoxicological screening. This investigation was designed to study how a new local anesthetic, ropivacaine, affects SCBF after intrathecal (IT) administration in the rat. SCBF was measured continuously in spontaneously breathing, enflurane/N2O-anesthetized rats, using the laser-Doppler flowmetry technique. The spinal cord was exposed by laminectomy, and a laser-Doppler probe was placed over the dorsal horn, allowing on-line registration of spinal blood flow in a tissue hemisphere of 1-2 mm. Relative changes in spinal blood flow over time were then measured after IT administration of either 0.9% saline, 5 mg/mL ropivacaine, i.e., a concentration within the pharmacological range, or a high, provocative concentration of 20 mg/mL ropivacaine. A minor and transient decrease in SCBF was seen after administration of 5 mg/mL ropivacaine (50 micrograms given IT), but this decrease was not significantly different from that in the saline group. SCBF decreased significantly to approximately 45% of the predrug value after the high concentration of 20 mg/mL ropivacaine (200 micrograms given IT), and this reduction was reversible within a period of 20 - 40 min after the injection. Whereas a high concentration of ropivacaine caused a definite reduction in spinal cord blood flow when administered IT to anesthetized rats, clinically relevant concentrations induced only minor changes. These results suggest that ropivacaine may be used to induce spinal anesthesia without causing clinically relevant effects on SCBF.

Blood flow regulation in the transplanted fetal endocrine pancreas. Acquisition of a nitric oxide-dependent glucose-induced increase in blood flow.

Islet-like cell clusters (ICCs) were prepared from the fetal porcine pancreas by a culture technique. The ICCs (approximately 500) were implanted under the left renal capsule of nude (nu/nu) C57BL/6J mice. Six weeks, months, 12 months, or 16-24 months later, the animals were anesthetized and the blood flows to the xenogeneic islet graft and the adjacent kidney parenchyma were measured with laser-Doppler flowmetry. After the blood flow measurements, the graft-bearing kidneys were prepared for enzyme and immunohistochemistry. The blood perfusion of the graft was higher than that of the kidney at all times investigated. Intraperitoneal administration of glucose caused only slight and parallel changes in renal and graft blood flows 6 weeks, 6 months, or 12 months after transplantation. However, in all but 1 animal (n=16) transplanted >16 months before the blood flow measurements, glucose caused a marked increase in graft blood flow but did not affect renal blood flow. Injection of 2-deoxy-glucose also increased graft blood perfusion in animals transplanted > 16 months earlier (n=5). Treatment with NG-monomethyl-L-arginine (n=6), an inhibitor of nitric oxide synthase, prevented this glucose-induced flow increase. Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry revealed nitric oxide synthase only in the endothelium and media of graft arterioles in animals in the oldest age group. Thus, with the passage of time after implantation, the grafted xenogeneic ICCs seem to achieve an autonomous blood flow regulation, different from that of the implantation organ. The reactivity to an increment in blood glucose concentration in the graft is similar to that seen in native islets in the pancreas but is not present until >16 months after implantation. The mechanisms for the glucose-induced blood flow increase are obscure but probably depend on local release of nitric oxide within graft arterioles.