[Radiologic findings in gout]. / Radiologische Befunde bei der Gicht.

Radiological gout manifestations are detectable in the early stage, but also especially in the chronic stage of gout. Whereas in the early stage only soft tissue mutations (bursitis inflammation) and light calcium deposits are usually discernible, chronic gout leads to asymmetrical, diverse forms of osseous destruction, favouring smaller joints, but also affecting larger ones, which are caused by the intra-articular and extra-articular deposit of tophus material, corresponding to the progression and degree of severity of the illness. Radiologically-detectable changes in other organs, such as the kidneys, will be addressed. The high number of, and to some extent very characteristic, osseous mutations are compared with those mutations which are very similar to the diagnoses of other syndromes affecting the joints. Specifically, problems in differentiating diagnosis of rheumatoid arthritis, arthritis psoriatica, chondrocalcinosis, and other diseases of the joints will receive special mention. Reference is also made to the extreme diagnostic difficulties resulting from the rare but nevertheless conceivable influence of gout on the spine or sacroiliac joints. The method of magnetic resonance imaging for gout shows a characteristic signal behaviour of the tophus material. It has been determined that, through magnetic resonance tomography, interosseous tophi can be detected earlier and in a more widespread manner than with the aid of native X-ray images, such that an increase in the use of this method is to be expected.

Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee.

Glucosamine sulfate is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In clinical trials, glucosamine sulfate was more effective than placebo in controlling the symptoms of osteoarthritis (OA). In order to better characterize this therapeutic activity, we conducted a randomized, double-blind, parallel-group study of glucosamine sulfate 500 mg t.i.d. vs ibuprofen 400 mg t.i.d., orally for 4 weeks. The study included 200 hospitalized patients with active OA of the knee, symptoms for at least 3 months and a Lequesne's index of at least 7 points. Patients were evaluated weekly. Response was defined as a reduction in the Lequesne's index by at least 2 points if the enrollment value was higher than 12 points, or by at least 1 point if the enrollment value was 12 or less points, together with a positive overall assessment by the investigator. The improvement tended to be sooner under ibuprofen (48% responders vs 28% after the 1st treatment week; P = 0.06, Fisher's Exact test), but there was no difference from the 2nd week onward, with a success rate of 52% in the ibuprofen group and of 48% in the glucosamine group (P = 0.67) at the end of treatment. The average Lequesne's index at enrollment was around 16 points and decreased by over 6 points in both groups, again with the above described trend. On the other hand, 35% of patients on ibuprofen reported adverse events, mainly of gastrointestinal origin, vs 6% adverse events with glucosamine (P < 0.001, Fisher's Exact test). The number of adverse event related drop-outs was different between the two groups (7% vs 1%, respectively; P = 0.035). Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.

Variability in the stereoselective disposition of ibuprofen in patients with rheumatoid arthritis.

1. Patients suffering from rheumatoid arthritis received oral doses of 600 mg racemic ibuprofen (n = 25; RAC) or 400 mg (S)-ibuprofen (n = 25; S-IBU) in a double-blind, randomized parallel-group study. 2. The pharmacokinetic parameters of (S)-ibuprofen were not statistically different between treatments (P > 0.05). Comparing (S)- and (R)-ibuprofen within the group receiving the racemate significantly higher Cmax (20.3 +/- 5.3 vs 17.7 +/- 4.4 micrograms ml-1; P < 0.02; 95% confidence interval for differences (CI): 0.5-4.6), AUC (86.2 +/- 23.5 vs 67.6 +/- 26.6 micrograms ml-1 h; P < 0.001; CI: 9.5-27.6), mean residence time (4.5 +/- 1.1 vs 4.1 +/- 1.2 h; P < 0.01; CI: 0.1-0.6) and renal clearance (0.8 +/- 0.6 vs 0.0 +/- 0.0 ml min-1; P < 0.001; CI: 0.5-1.0) values were observed for the (S)-enantiomer. 3. No difference was found (P > 0.05) between treatments in the percentage of the dose recovered in the urine as (R)- or (S)-ibuprofen plus metabolites (S-IBU: 80.2 +/- 8.47 vs RAC: 74.1 +/- 14.0%). 4. Interindividual variation in the pharmacokinetics of (S)-ibuprofen following administration of the racemate was similar to that following the administration of the single isomer suggesting that chiral inversion is not a major factor contributing to variability in the disposition of this drug.

[Therapy of non-steroidal antirheumatic drug-induced gastrointestinal lesions with misoprostol]. / Die Therapie NSAR-induzierter gastrointestinaler Läsionen mit Misoprostol.

In a multicenter placebo-controlled double-blind study in patients with degenerative or inflammatory rheumatic diseases the prostaglandin analogue misoprostol, in a dose of 200 micrograms twice daily after meals, was administered for the treatment of NSAID-induced lesions and symptoms of the upper gastrointestinal tract. Treatment with an NSAID was continued. Misoprostol treatment was demonstrated to be clearly superior to placebo in respect of reduction of gastroduodenal lesions and gastrointestinal pain. In addition, the physician's global assessment of gastrointestinal complaints was also statistically significantly better. No difference between the groups was found with respect to antirheumatic action of the NSAIDs.

S-ibuprofen versus ibuprofen-racemate. A randomized double-blind study in patients with rheumatoid arthritis.

Ibuprofen (ibu) is a racemic 2-arylpropionic acid non-steroidal anti-inflammatory drug whose activity is due mainly to the S-enantiomer. So far only the racemic compound is in clinical use. A double-blind randomized trial was carried out for a 2-week period in 50 patients with classical rheumatoid arthritis (RA) (Steinbrocker II-III) to compare the effectiveness and tolerance of S-ibu (400 mg T.I.D.) with that of the racemic compound (600 mg T.I.D.). Ritchie-index, limitation of movement, joint pain on pressure and pain at night decreased significantly in both groups. Due to lack of effectiveness, the dose had to be increased in 3 patients from the S-ibu group as well as in 6 patients from the racemic group resulting in mean daily doses of 1220 mg S-ibuprofen and 1870 mg racemic ibu. No statistically significant difference could be found between both groups concerning efficacy and unwanted effects. Therefore, S-ibu given alone may be advantageous because the metabolic load to the human body is reduced and patients are more likely to comply with drug doses of 1.2 g/day as compared to 1.8 g/day.

Pharmacokinetics of S(+)- and R(-)-ibuprofen in volunteers and first clinical experience of S(+)-ibuprofen in rheumatoid arthritis.

S(+)-, R(-)- or racemic ibuprofen was administered orally to volunteers in doses of 150 mg, 300 mg and 500 mg pure S(+)-, 300 mg pure R(-)- and 600 mg racemic ibuprofen. The pharmacokinetic parameters in humans showed that S(+)-ibuprofen was not inverted to R(-)-ibuprofen, whereas R(-)-ibuprofen was inverted to S(+)-ibuprofen to a variable degree. S(+)-ibuprofen and R(-)-ibuprofen given alone more rapidly reached significantly higher maximal plasma concentrations than after the same doses of the racemic compound. The elimination half-lives and clearance values for all three forms of ibuprofen were comparable. The mean residence time of S(+)-ibuprofen after R(-)- and racemic ibuprofen was significantly longer than after administration of the pure S(+)-enantiomer. Judged by the AUC, the bioavailability of S(+)-ibuprofen was independent of the dose within the range tested. Administration of S(+)-ibuprofen to 6 rheumatic patients showed that the pharmacokinetic behaviour of S(+)-ibuprofen in patients was similar to that found in volunteers. S(+)-ibuprofen proved to be an effective analgesic antirheumatic drug in the dose range 1 to 1.5 g/day.

Pharmacological differences between R(-)- and S(+)-ibuprofen.

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug exhibiting optical isomerism. Only the racemate is in clinical use. In in vitro studies it has been demonstrated that only the S(+)-enantiomer inhibits the PG synthetase system. Nevertheless, it is widely believed that the sole use of the active isomer does not comprise any advantages since the inactive isomer is converted within the human body. In a triple cross-over study (300 mg S(+), 300 mg R(-), 600 mg racemic IBU; n = 8), we could show that the converted R(-)-IBU after racemate administration provides for only one third of the AUC of S(+)-IBU obtained after S(+)-application. Highest S(+)-peak plasma levels were reached after S(+)-IBU, lower ones after racemate. We, therefore, studied 4 patients with classical rheumatoid arthritis treated with 2-3 doses of 500 mg of S(+)-IBU/day over a two week period. Significant clinical recovery (Ritchie-index p less than 0.01; analogue scale pain p less than 0.05, motion p less than 0.01) was reached after one week. The results indicate that a reduction of dose and of metabolic load is possible if the S(+)-enantiomer is administrated.

[Ulcer healing with ranitidine and antacids despite continued therapy with non-steroidal anti-rheumatic drugs]. / Ulkusabheilung unter Ranitidin und Antazida trotz fortgesetzter Therapie mit nichtsteroidalen Antirheumatika.

The aim of this study was to investigate the course of gastric and duodenal ulcers under ranitidin and antacid treatment during continuous NSAID therapy, and to answer the question of whether ulcers are an absolute contraindication for NSAID treatment. A total of 21 patients (17 females; four males; average age 58 years) with rheumatoid arthritis (18 patients), ankylosing spondylitis (two patients), and cervical spine syndrome (one patient) with gastric and/or duodenal ulcers, demonstrated by endoscopy, entered the study. Because of the severe course of the rheumatic disease present in every patient, there was a need to continue NSAID therapy. Gastric or duodenal ulcers were treated with 300 mg ranitidin and an aluminium-magnesium-hydroxide-containing antacid with an acid binding capacity of 280 mval/day. The course of healing of the ulcers was checked endoscopically and in part by biopsies (gastric ulcers). Within the period of 31 +/- 11 days, all duodenal ulcers under observation had healed. Of the gastric ulcers, 50% had healed completely while the others showed definite improvement. NSAID-induced ulcers were located in or close to the pylorus, contrary to the location of peptic ulcers. These data show that NSAIDs--if administration is absolutely necessary because of the severe course of the rheumatic disease--can be continued even in the presence of gastric or duodenal ulcers when administered with ranitidin and antacids. Because of hemorrhage and perforation in NSAID-induced ulcers, close clinical and endoscopic checks are necessary. Failures, even with the use of H2-blockers, have also been described.

[Immunomodulating therapy in chronic polyarthritis with thymopentin. A multicenter placebo-controlled study of 119 patients]. / Immunmodulierende Therapie der chronischen Polyarthritis mit Thymopentin. Eine multizentrische placebokontrollierte Studie an 119 Patienten.

In a multicenter, placebo-controlled and randomized double-blind trial 119 patients with rheumatoid arthritis were treated with thymopentin, an immunoregulating drug. The data of 107 patients were complete enough to be evaluated: 51 were given intravenous injections over ten minutes of 50 mg thymopentin three times weekly, 56 were similarly treated with a placebo solution. Significant improvement of five among nine clinical criteria were obtained with thymopentin after the third week of treatment. The response rate (improvement of a clinical parameter by at least 40%) was significantly greater for all clinical parameters in the thymopentin group. Regression to a functionally more favourable class (Steinbrocker's classification) occurred in seven thymopentin-treated, but in none of the placebo-treated patients. The improvement gradually subsided over four weeks after the end of treatment. There were no changes during the trial with respect to immunological, biochemical or haematological findings. Except for one systemic allergic reaction there were no side effects.

[Short-term therapy of painful muscular disorders. Results of a multicenter double-blind test of 2 new suppository preparations with and without codeine]. / Kurzzeittherapie schmerzhafter muskulärer Beschwerden. Ergebnis einer multizentrischen Doppelblind-Prüfung von 2 neuen Zäpfchen-Präparaten mit und ohne Kodein.

A report is given about a multicentric double-blind test for proof of effectiveness of two new suppository preparations with and without codeine against comparable remedies. Dolo Visano Supp. sine codeino showed a slight superiority over the reference preparation. This was proved above all for the influence upon pain and muscular overstrain. The better tolerability was marked. Dolo Visano Supp. (with codeine) showed advantages against the reference preparation. It was used in cases of severe pain, and in 88% it had a very good effect, whereas for the reference preparation this applied only in 67,9%. The assessments of physician and patients were almost alike. The myotonolytic effect has been proved equally for both of the new suppository preparations.

[Treatment of painful muscular disorders of various degrees of severity. Comparison of 2 new suppository preparations]. / Behandlung schmerzhafter muskulärer Beschwerden unterschiedlicher Schwere. Zwei neue Suppositorien-Präparate im Vergleich.

In clinical rheumatology, the hazardousness of mixed preparations containing cortisone is being stressed even more, their use is only recommended in very special cases and only for short periods. Dolo Visano Supp. sine codeino and Dolo Visano Supp. are remedies which are indicated, like other mixed preparations not containing steroids, in cases of painful muscular overstrain and psychomuscular kinesalgia (symptom range of non-articular rheumatism). In our study, they were used in acute and severe pain conditions in intermediate or short-term therapy until complaints improved. Dolo Visano Supp. sine codeino and Dolo Visano Supp. (with codeine) can contribute in limiting the use of the risky preparations containing cortisone, which have hitherto been applied so frequently.

Activated osteoarthrosis (osteoarthritis) and its treatment with indomethacin and benoxaprofen: a double-blind crossover study.

Forty patients with osteoarthritis of the hips or knees entered a double-blind crossover study, in which 50 mg t.i.d. indomethacin was compared to a single daily dose of 600 mg benoxaprofen. Patients were randomly allocated to either indomethacin or benoxaprofen for four weeks and then transferred to the alternate drug without a washout period. Thirty-one patients completed the entire trial period. Both indomethacin and benoxaprofen led to a statistically significant improvement (alpha less than or equal to 0.05) of the subjective (measured by a pain score) and the objective joint status (range of motion evaluation) as compared to the pretreatment status. With regard to efficacy, there was no statistically significant difference between the two drugs. Benoxaprofen proved to be the better tolerated compound, causing four dropouts. Six patients were excluded from the indomethacin treatment due to severe gastrointestinal side effects. There also was a higher number of other side effects with indomethacin, but none severe enough to discontinue treatment. With the doses used, both compounds proved to be similar in efficacy in osteoarthritic conditions although benoxaprofen was the better tolerated drug.

[Flurbiprofen and indomethacin in chronic polyarthritis and gonarthrosis - a comparative multicentric double-blind cross-over study]. / Flurbiprofen und Indometacin bei chronischer Polyarthritis und Gonarthrose --eine vergleichende multizentrische Doppelblind-cross-over-Studie.

In two multicenter double-blind cross-over studies efficacy and safety of flurbiprofen and indomethacin were compared. Nineteen patients with rheumatoid arthritis and twenty with osteoarthrosis of the knee were treated. Both drugs were effective and almost equal. Also safety was good, however three patients on indomethacin and one on flurbiprofen had to be withdrawn from the trial because of side-effects.

[Nasal septum perforation in disseminated lupus erythematosus, case report and literature review]. / Perforation des Nasenseptums bei Lupus erythematodes disseminatus (LED), Fallbeschreibung und Literaturübersicht.

Perforation of Nasal Septum in Systemic Lupus Erythematosus: Report of a Case and Review of the Literature. Perforation of the nasal septum in systemic lupus erythematosus (SLE) is rare. Report of a case and review of the literature revealed the total of 13 patients with this lesion. There was only one male. The complication is most likely to occur during an exacerbation of SLE months or years after the diagnosis has been established. Epistaxis is a constant initial symptom. A frequent association with the Raynaud's phenomenon favours speculations, that the lesion may be due to local vasospasms following exposure to cold inspired air. The septum perforaton gradually increases in most cases virtually independent from drug treatment and favouring conservative management.

[Enelbin rheumatism ointment in rheumatic diseases. Results of a double-blind study for the determination of efficacy]. / Enelbin-Rheuma-Salbe bei Erkrankungen des rheumatischen Formenkreises. Ergebnisse einer Doppelblind-Studie zum Wirksamkeitsnachweis.

Enelbin-Rheuma-ointment and a reference ointment were compared with regard to effectiveness in a double-blind trial in 100 patients with gonarthrosis, osteoarthrosis of the spine and humeroscapular periarthropathy. Both ointments showed good results regarding spontaneous pain, pain on pressure and motion, reduction of mobility, swelling and muscular tension. The success of treatment was statistically significantly better in the Enelbin-Rheuma-ointment treated patients.