A randomised, placebo controlled, comparative trial of the gastrointestinal safety and efficacy of AZD3582 versus naproxen in osteoarthritis.

OBJECTIVE: To evaluate the gastrointestinal safety and efficacy of the COX inhibiting nitric oxide donator AZD3582 in patients with hip or knee osteoarthritis. METHODS: 970 patients were randomised (7:7:2) to AZD3582 750 mg twice daily, naproxen 500 mg twice daily, or placebo twice daily in a double blind study. The primary end point was the six week incidence of endoscopic gastroduodenal ulcers (diameter > or =3 mm). Overall damage measured on the Lanza scale was a secondary end point. Safety and tolerability assessments included endoscopic upper gastrointestinal erosions and the gastrointestinal symptom rating scale (GSRS). Efficacy was primarily assessed by WOMAC. RESULTS: The incidence of ulcers with AZD3582 was 9.7% and with naproxen 13.7% (p = 0.07, NS), v 0% on placebo. The incidence of Lanza scores >2 was higher with naproxen (43.7%) than with AZD3582 (32.2%) (p<0.001). Compared with baseline, significantly fewer ulcers and erosions developed in stomach and stomach/duodenum combined, and fewer erosions developed in stomach, duodenum, and both combined on AZD3582 than on naproxen. GSRS reflux and abdominal pain subscale scores were lower for AZD3582 than for naproxen but there was no difference for indigestion, constipation, and diarrhoea. AZD3582 was as effective as naproxen at improving WOMAC scores. Both agents were well tolerated, with no significant effects on blood pressure. CONCLUSIONS: At doses with similar efficacy in relieving osteoarthritis symptoms, the primary end point of six week endoscopic gastroduodenal ulcer incidence was not significantly different between AZD3582 and naproxen. Most secondary endoscopic gastrointestinal end points favoured AZD3582.

[Problems of differential diagnosis in synovial sarcoma]. / Differenciáldiagnosztikai problémát okozó synovialis sarcoma.

The authors present a woman's case (age 50), who was hospitalised several times as she often had pain in her left leg and knee for one year. The pain increased in the last 2 months. The final diagnosis, the primer synovial sarcoma of the left knee was justified only post mortem. Not only this alteration in the knee caused the pain in the left leg. The symptoms of sciatic pain caused by lumbal discus herniation also occurred which made the diagnosis more difficult. Referring to relevant data in literature the authors analyse the differential diagnostic aspects of the final diagnosis and the clinical spectrum of the illness.

[Caudal epidural injection in the management of lumbosacral nerve pain syndromes]. / Caudalis epiduralis injekció az akut lumbosacralis gyöki fájdalomszindrómák kezelésében.

The effect of epidural steroid injections was assessed in 39 patients with lumbar nerve root compression syndromes in a double-blind controlled trial, the patients were allocated at random to 3 groups. In group A (n = 13) the patients received a caudal epidural injection of 1 ml (7 mg) bethametason (Diprophos) in 10 ml normal saline and 20 ml local anesthetic (Lignocaine 1%). The second group B (n = 13) received a caudal epidural injection of 20 ml local anaesthetic (Lignocaine 1%) and 10 ml normal saline. The third group C (n = 13) received a superficial injection of 1 ml (7 mg) bethametason around of the sacral hiatus. All injections were performed by the same experienced anaesthesiologist. An independent physician, who was not aware which type of injection had been given, carried out the clinical measurements and the evaluation. Taking of analgesic drug Tramadol was permitted. The symptoms were assessed by visual analogue scale (VAS 100 mm), lumbar flexion (Schober and finger-floor distance), the angle of raised leg sign (RLS degrees), and by complete neurological examination, the investigation was made 5 times (1 hour, 24 hours, 48 hours, 1 week, and 4 weeks after epidural injections). The results between 0-1 week and 0-4 week were statistically analysed by Student-, Wilcoxon-, and Mann-Whitney test and analysis of variance (ANOVA). The mean VAS values decreased in time in all patient groups. There was no difference between the three treatment groups either after one or after 4 weeks by ANOVA. The mobility of the lumbar spine improved in all patient groups, but there was no significant difference between the three treatment groups. The raised led sign--values improved in all patient groups. There was a significant difference between the three treatment groups by ANOVA after one week, due to the difference between group A and C. After four weeks there was no significant difference. No major complications or side effects were seen in our trial. The raised leg sign due to epidural steroid injection showed better results in comparison to steroid injection around of the sacral hiatus were seen.

Non-steroidal anti-inflammatory drugs in everyday practice.

Problems of theoretical and practical importance of non-steroidal anti-inflammatory drug therapies have been reviewed on the basis of data of references. Recent observations, which may explain the differences in the clinical effectiveness and toxicity of the different products, have been emphasized. Attention has been called to the great individual variations in the patients' responses and the development of unwanted effects. The risks of the use of non-steroidal anti-inflammatory drugs in elderly have been pointed out. The author stresses the importance of a proper drug selection and calls attention to the fact that the continuous use of a non-steroidal anti-inflammatory agents is not necessary in a great number of cases.

[Acetylator phenotype in spondylarthritis ankylopoietica]. / Acetilátor fenotípus vizsgálata spondylarthritis ankylopoeticában.

The authors studied the distribution of acetylator phenotypes among 136 AS patients (100 male, 36 female). 67 per cent of all patients were slow acetylators, 72 per cent of the males. Both rates are higher than that of the healthy Hungarian population. The authors draw attention to the clinical importance of investigating the acetylator type before sulphasalazine treatment because it may help in prescribing the effective dose and avoiding side effects.

Occupation and osteoarthritis.

From the aspect of industry, OA is one of the most important diseases as it frequently affects the active age group of the population and is the source of considerable loss of working hours and of disability. In addition, it has a detrimental effect on the quality of life. Epidemiological investigations fail to provide sufficient proof as to whether mechanical overloading of occupational origin, or due to sports, will lead to a higher incidence of OA. Mechanical and occupational stress is more likely to play a role in the articular localization of the disease. It is difficult to prove the occupational origin of OA and, in consequence, there is a considerable difference in the adoption of preventative measures in various countries. The clarification of the relationship between occupation and OA requires further, carefully planned, prospective epidemiological studies, including the investigation of both radiological and clinical symptoms and signs. Compressive, torsional, pulling and angular movements common in certain occupations or sports may result in injuries of soft tissue, thus increasing the development of OA. Consequently, the main task is prevention at the place of work or in sporting activities.

PHA- and Con A-induced chemiluminescence of human blood mononuclear cells and granulocytes in luminol or lucigenin.

Phytohemagglutinin (PHA) and concanavalin A (Con A) can evoke a chemiluminescence (CL) response both in granulocytes and blood mononuclear cells. We have used two parallel systems to compare the quantity and quality of oxygen radicals produced during activation. While the luminol-enhanced CL response is linked to the myeloperoxidase-H2O2-chloride system, the lucigenin-dependent light production measures only the superoxide radical. PHA produced higher CL response in the presence of luminol than with lucigenin. Con A showed high CL response only in the lucigenin-enhanced system. The results suggest that while Con A induces mostly superoxide production, the membrane stimulus evoked by PHA produces light through the myeloperoxidase-H2O2-halide system. Granulocytes are less sensitive to PHA than the blood mononuclear cells. The sensitivity of the responses to several scavengers and enzymes support the differential production of oxygen radicals following activation via these two lectins.