Effects of a novel tyrosine kinase inhibitor in rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: Biologicals have revolutionised the treatment of rheumatoid arthritis (RA). However, progressive joint destruction can still be observed in many patients and the search for novel molecular therapies targeting specific signalling pathways is ongoing. In the present study, we investigated the effects of GW282974, a novel compound directed against tyrosine kinase activity with respect to the potential suppression of inflammation and destruction. METHODS: Synovial tissue specimens were obtained from RA patients undergoing surgical joint replacement. Rheumatoid arthritis synovial fibroblasts (RASFs) were stimulated with cytokines and GW282974 was added in different concentrations. Gene expression was checked by TaqMan PCR, using 18S as housekeeping gene. Protein analysis was quantified by ELISA. Cell growth and proliferation was measured using the "ViaLight" proliferation assay. RESULTS: EGF had no effect on the gene expression profile of RASFs when used as single stimulatory agent. In combination with pro-inflammatory mediators however, EGF showed a synergistic effect. The expression of matrix metalloproteinases, inflammatory cytokines and cyclooxygenase-2 on mRNA levels was strongly increased, whereas the addition of GW282974 abrogated these effects in a dose-dependent manner. These data could be confirmed on protein/lipid levels analysing the supernatants of RASFs by ELISA. Similarly, cell growth and proliferation of RASFs were inhibited by GW282974 in a dose- and time-dependent manner. By contrast, no cytotoxic effects were seen within the concentrations used. DISCUSSION: GW282974 appears to interfere with the inflammatory and the destructive pathways in RASFs and might therefore be used as novel therapeutic strategy for the treatment of RA.

Management of ankle sprains: a randomised controlled trial of the treatment of inversion injuries using an elastic support bandage or an Aircast ankle brace.

BACKGROUND: Lateral ligament ankle sprains are the single most common sports injury. OBJECTIVE: To determine the functional outcome of the ankle joint after a moderate or severe inversion injury, comparing standard treatment with an elastic support bandage against an Aircast ankle brace. DESIGN: Prospective, randomised controlled trial. SETTING: Two accident and emergency departments. METHOD: Fifty patients presenting consecutively were randomised into two equal groups: one group was treated with an elastic support bandage and the other with an Aircast ankle brace. All patients were given a standardised advice sheet referring to rest, ice, compression, and elevation. Patients were reviewed after 48-72 hours, 10 days, and one month. PRIMARY OUTCOME MEASURE: Ankle joint function assessed at 10 days and one month using the modified Karlsson scoring method (maximum score 90). SECONDARY OUTCOME MEASURE: The difference in ankle girth (swelling) and pain score at 10 days. RESULTS: Seventeen patients in the elastic support bandage group (six defaulted, two excluded) and 18 patients in the Aircast ankle brace group (six defaulted, one excluded) completed the study. There were no significant differences between the two groups at presentation in terms of age (mean 35.3 and 32.6 years respectively), sex, dominant leg, left or right ankle injured, previous injury, time to presentation (median three and four hours respectively), difference in ankle girth (mean 14.5 and 14.3 mm respectively), and pain scores (mean 6.2 and 5.8 respectively). The Karlsson score was significantly higher in the Aircast ankle cast group than in the elastic bandage group at 10 days (mean 50 v 35, p = 0.028, 95% confidence interval (CI) 1.7 to 27.7) and one month (mean 68 v 55, p = 0.029, 95% CI 1.4 to 24.8) (Student's t test). There was no difference between the groups in the secondary outcome measures (swelling, p = 0.09; pain, p = 0.07). When hierarchical multiple regression analysis was used to correct for possible baseline confounding factors, the Aircast ankle brace group was significantly associated with higher Karlsson scores at 10 days (p = 0.009) and one month (p = 0.024). CONCLUSION: The use of an Aircast ankle brace for the treatment of lateral ligament ankle sprains produces a significant improvement in ankle joint function at both 10 days and one month compared with standard management with an elastic support bandage.

An audit of sports injuries in children attending an Accident & Emergency department.

OBJECTIVE: To assess the incidence of attendance, type of injury, sport involved and management of sports injuries in children attending an Accident & Emergency (A&E) department. METHOD: Children, aged between 5-16 years, presenting with an injury related to sport, were studied over a period of three months. RESULTS: 1858 children attended the A&E department during the three month period. 238 (12.8%) were classified as sports injuries. Boys (71%) were injured more frequently than girls (29%). Injury rates in boys peaked at 14 years whereas in girls a peak occurred earlier at 12 years. Football was the most common sport implicated in injuries (39%). Rollerblading (14%), Rugby (8%), Basketball (7%) and Physical Education at school (7%) were the next most frequently involved sports. Soft tissue injuries dominated (61%). The upper limb was the most common anatomical area injured (46%). Other injuries involved the lower limb (36%), head and neck (15%) and the trunk (3%). Injuries to the wrist were the most frequent presentation accounting for 30 fractures and 30 soft tissue injuries (25%). The majority of children were discharged from the A&E department after treatment (71%). 26% were reviewed at out-patient clinics and 3% required hospital admission. No children were referred for physiotherapy. CONCLUSION: Children participate in sport and can be injured. The majority of sports injuries presenting to an A&E department appear to be of a minor nature and could be managed with simple first aid techniques by parents, teachers and coaches at the scene or by attending primary care in the first instance. Supervision of children, participation in organised sport and the use of protection devices may help to prevent serious injury.

Effect of innappropriate naltrexone use in a heroin misuser.

Naltrexone is a long acting opioid receptor antagonist used in controlled opioid withdrawal drug programmes. When taken by an opioid dependent patient an acute withdrawal reaction will be precipitated. The case is presented where a known opioid drug misuser inadvertently ingested naltrexone in conjunction with heroin resulting in severe agitation, requiring heavy sedation followed by general anaesthesia to enable investigation and management of his clinical condition.

Impact of a newly opened prison on an accident and emergency department.

OBJECTIVE: To determine the impact of a newly opened prison on an accident and emergency (A&E) department. METHOD: A new category B prison opened in April 1999, the first privately run prison in Scotland and the third largest in population. All prisoners referred to the A&E department for treatment were identified prospectively during the first year after the opening of the prison. RESULTS: 99 prisoners and four members of staff attended during the one year period. Ages ranged from 18-64 years with a mean age of 29.8 years. Presentations were as a result of deliberate self harm (22%), injury after violence (18%), sports injury (15%), surgical condition (15%), medical illness (13%), accidental injury (9%), ENT problem (2%), and miscellaneous (6%). Thirty seven prisoners (35.6%) were admitted to the hospital. Further review at outpatient clinics was arranged for 15 prisoners. One prisoner died, the result of suicide by hanging. The remaining prisoners were returned to the prison for further management by the prison medical and nursing team. Twelve prisoners re-attended a total of 37 times, ranging from twice to a maximum of eight visits. Some 42.3% of attendances were during "working hours" (09.00-17.00) and 57.7% attended "out of hours" (17.00-09.00). Twenty four referrals (23.1%) were deemed inappropriate by the prison medical team on retrospective review. Sixteen of these occurred "out of hours". Forty one prisoners (39.4%) were known to have a history of injecting drug misuse. Including re-attenders, 59 presentations (56.7%) to the A&E department had a history of injecting drug misuse. Of these 41 prisoners, 11 (26.8%) were hepatitis C positive, with eight of these having a positive polymerase chain reaction test. No prisoners had HIV and only one prisoner was hepatitis B positive. CONCLUSION: The opening of the prison resulted in only a slight increase in the workload of the A&E department. A significant proportion of prisoners were admitted to the hospital highlighting the practical and logistical problems of managing people restrained and in custody. Most cases can be safely referred back to the prison. Increased input is required from the prison medical team when dealing with deliberate self harm, frequent attenders, and "out of hours" referrals. All A&E staff must be aware of the increased risk of hepatitis C infection when dealing with a confined prison population.

Unintentional rapid opioid detoxification.

Naltrexone is a long acting opioid antagonist that is used in rehabilitation programmes to maintain heroin abstinence. It is a relatively new drug prescribed by specialists in substance misuse. Its actions and effects may not be familiar to many accident and emergency doctors or even to the people who take it. A case report is described where accidental ingestion of naltrexone results in a medical emergency by precipitating acute withdrawal in a heroin addict.

Rollerblading injuries in children attending an accident & emergency department: should the use of wrist splints be compulsory?

Our aim was to determine the incidence and nature of injuries in children from rollerblading attending a district general hospital Accident & Emergency (A&E) department in Scotland. Children, aged between 5-16 years, presenting with an injury from rollerblading, were studied prospectively over a three month period. A total of 34 children attended the department with a rollerblading injury. Boys (53%) and girls (47%) were injured almost equally. The wrist was the most frequently injured area of the body (62%) with 12 fractures and 9 soft tissue injuries. No children were wearing any form of protective equipment. Rollerblading is an increasingly popular, but expensive, activity amongst children in Scotland. Wrist injuries from falling were the most common presentation which may result in prolonged school absenteeism. Emphasis is normally placed on protective headgear, however, with wrist injuries more common, consideration must be given to the active promotion of injury prevention and the wearing of wrist splints.

Gamma hydroxybutyric acid (GHB): an increasing trend in drug abuse.

The use of recreational drugs in society is becoming a widespread problem increasing the workload of all the emergency services. Gamma hydroxybutyric acid (GHB) is one of these, a drug used primarily for its euphoric effect. Toxic effects of ingestion include bradycardia, slow respiration or apnoea, coma and death. We present seven cases, all of which had consumed GHB either alone or in conjunction with other drugs and alcohol. The presentation, clinical features and management of these cases are described. All health care personnel involved in the emergency setting need to know of its existence, toxic effects and initial management with particular reference to airway control and possible assisted ventilation.

Hydrochloric acid inhalation: who needs admission?

Nine pharmaceutical workers were exposed to hydrochloric acid (HCl) fumes. Four were discharged with no symptoms after a 4 h observation period in the accident and emergency (A&E) department. The remaining five were admitted to the medical unit because of severe symptoms, reduced peak expiratory flow rate (PEFR), or hypoxaemia. Treatment was symptomatic and discharge followed 24 h later. Only one patient, discharged from the medical unit, developed long term airway hyper-reactivity, superimposed on a background of chronic obstructive airways disease. Thus patients who are minimally symptomatic with normal PEFR and oxygen saturation values can be safely discharged from the A&E department after a short observation period of 4 h with advice to return if dyspnoea occurs. Caution should be employed in severely symptomatic patients, those with pre-existing lung pathology or reduced PEFR, and hypoxaemic patients, where observation for at least 24 h is recommended.