Double-blind, multi-centre trial to compare a once-daily combination of trimethoprim and sulfamethopyrazine with ampicillin 4-times daily in patients with urinary infections.

Sixty-eight patients with urinary infection were allocated at random to receive treatment with either 500 mg ampicillin 4-times daily or a trimethoprim (250 mg)/sulfamethopyrazine (200 mg) combination given once daily after a double, loading dose on the first day. All patients complained of urinary symptoms and showed significant bacteriuria, E. coli being the pathogen most frequently recovered. Clinical and microbiological assessments were carried out on entry and, as a rule, after 3 to 4 days and 1 to 2 weeks of treatment. In the 35 patients receiving trimethoprim/sulfamethopyrazine, 40 (95%) of the 42 original infecting organisms were eradicated. In the 33 patients on ampicillin, the eradication rate was 32 (89%) out of 36 organisms. The course of urinary symptoms was similarly favourable in the two groups. Overall response was considered as 'excellent' or 'good' in 89% of the patients receiving the combination preparation and in 82% of those given ampicillin. Clinical and biological tolerance was satisfactory under both regimens. A longer follow-up control should confirm the value of the new combination in the treatment of urinary infections.

Double-blind controlled clinical evaluation of effectiveness of zidometacin by oral and rectal route in osteoarthritis.

Twenty patients were treated with zidometacin by either the oral or the rectal route in a double-blind, short-term, balanced cross-over study, using the techniques of the double dummy. They suffered from osteoarthritis of the hip or knee or both. Zidometacin was administered at the daily doses of 400 mg p.o., and 600 mg by rectal route. The duration of each treatment was ten days. Zidometacin either as capsules or as suppositories showed a statistically significant influence on pain and functional indices even in this short-term evaluation. The side-effects reported by patients were three cases of dizziness and one case of nausea with capsules and one case of anal burning with suppositories, none of them requiring the interruption of the treatment.

[Generalized secondary amyloidosis in patients with chronic rheumatoid arthritis (author's transl)]. / Generalisierte sekundäre Amyloidose bei chronischer Polyarthritis

During a period of 6 years (1968 to 1973) 177 patients with rheumatoid arthritis were submitted on one or more occasions to biopsy of the rectal mucosa for the diagnosis of amyloidosis. The indications for biopsy were as follows: 1. proteinuria, even in an intermittent form, 2. progressive type of rheumatoid arthritis with high inflammatory activity, 3. rheumatoid arthritis of longer than 2 years duration with a marked tendency to joint destruction. The histological specimens were stained with Congo red and investigated in polarized light. The biopsy for amyloidosis was positive in 80 patients (45.2%) of whom 14 showed no proteinuria, even of an intermittent nature. Patients with rheumatoid arthritis survived maximally 5 years after amyloidosis had been diagnosed. No successful therapy of amyloidosis has been devised.

[Treatment of interstitial pulmonary fibrosis with D-penicillamine in progressive scleroderma: a long-term study (author's transl)]. / Zur Behandlung der interstitiellen Lungenfibrose mit D-Penicillamin bei progressiver Sklerodermie (Langzeitstudie)

5 patients suffering from progressive scleroderma with interstitial pulmonary fibrosis have been treated since 1971 with D-penicillamine (Artamin) as basic therapeutic agent. All patients showed a significant tendency towards normalization of the pathological findings in regard to functional capacity of the lungs and scintigraphic and radiological assessment. These results, in our opinion, justify the recommendation of a new indication for D-penicillamine therapy, namely in cases of progressive scleroderma with interstitial pulmonary fibrosis.

[Parenteral gold therapy (Tauredon) in chronic polyarthritis]. / Erfahrungen mit parenteraler Goldtherapie (Tauredon) bei chronischer Polyarthritis.

Between 1972 and 1983, 519 patients with rheumatoid arthritis according to ARA criteria underwent basic antirheumatic treatment with Tauredon (sodium aurothiamalate). Patient age was 19 to 78 years, and the disease had been active for 6 months to 8 years. Results of treatment were recorded for periods of 14 days to 8 years. After a test dose of 10 mg intramuscular, patients received weekly injections of 20 to 50 mg for 4 to 6 months and were subsequently placed on a maintenance dose of 50 mg at intervals of 2 to 4 weeks for years. Clinical examinations and laboratory tests were scheduled at weekly intervals in the first month of treatment, at 2-weekly intervals in the next two months and subsequently once every month. In the first years of this trial (up to 1975) response to treatment was evaluated by the criteria reported by Fähndrich [2] and Steinbrocker [10]. Later Ritchie's joint index [6], laboratory parameters (sedimentation rate, CRP and alpha 2 globulin) as well as the consumption of non-steroidal antirheumatics and corticosteroids were equally used. Results were found to be excellent to good in 316 patients (= 60.8%) and satisfactory in 104 (= 20.1%). 99 patients (= 19.1%) were rated as failures. The drug was well tolerated in 391 cases (= 75.37%), but had to be withdrawn in 128 (= 24.6%) because of side effects. Among these, cutaneous and mucosal symptoms, which occurred in 70 patients (= 13.47% of the total), were most prominent. Serious side effects were absent throughout.

Oral gold therapy with auranofin (SK&F 39162). A multicenter open study in patients with rheumatoid arthritis.

One hundred and fifty patients with rheumatoid arthritis received 6 mg of auranofin daily for 2-24 months. Thirty patients were withdrawn from the study, and 82 patients were observed for 12 months. Statistical evaluation was available for 74 patients at weeks 24, 38, and 48, respectively. The major side effects observed were diarrhea, rash, and alopecia. Significant improvement was noted in the articular index, ESR, pain, and morning stiffness.

[Effect of naproxen on DNA synthesis and DNA repair of human lymphocytes in in vivo experiments]. / Uber den Einfluss von Naproxen auf die DNS-Synthese und DNS-Reparatur menschlicher Lymphozyten im In-vivo-Versuch

This investigation was conducted in order to evaluate the possibility of late defects caused by drugs. After their base-line blood levels had been assessed, 3 patients with classical rheumatoid arthritis (according to ARA criteria; American Rheumatism Association) received 500 mg of d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) daily (in capsules). At the peak of naproxen blood levels following the first naproxen dose, and once monthly for 7 months, thereafter, blood samples were drawn. After separating the lymphocytes from the whole blood, they were damaged by means of 60-Co. Hydroxyurea was added for the suppression of their semiconservative DNA-synthesis. The incorporation of 3-H-THYMIDINE INTO THE DNA of the cells was measured after radiation at different incubation periods. The results showed normal behaviour of the DNA-synthesis following naproxen administration in all three patients. The DNA-repair capacity was normal in one female patient, but slightly lowered in the remaining two.

[Effect and tolerance of naproxen. Testing of a new Galenic preparation of an anti-rheumatic agent in an open clinical trial]. / Wirksamkeit und Verträglichkeit von Naproxen. Prüfung einer neuen galenischen Zubereitung des Antirheumatikums in einer offenen klinischen Studie.

The non-steroidal antirheumatic drug naproxen has been available in capsule form since 1974. A new formulation, a film-coated tablet, has recently been developed and has various advantages, namely rapid release and absorption of the active substance, a lower volume, and a score-line. The efficacy and safety of the new tablet in a dose of 1000 mg daily was investigated in 30 patients in an open study. The substance was well tolerated, and there was no need to discontinue treatment in any patient. In the majority of patients the efficacy of the preparation was very good to good. An unsatisfactory effect was only obtained in two cases.

[Controlled double blind comparison of acemetacin to indomethacin in patients with chronic polyarthritis]. / Kontrollierter Doppelblindvergleich von Acemetacin zu Indometacin bei Patienten mit chronischer Polyarthritis.

In a double blind study [1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-acetoxy] acetic acid (acemetacin, TV 1322, Rantudil¿) was compared with indometacin in 2 x 20 patients suffering from rheumatoid arthritis. The duration of the study was 3 weeks. The patients received 3 x 30 mg/d acemetacin or 3 x 50 mg indometacin in capsules. The therapy was controlled at accurately defined intervals. Statistical evaluation of the data regarding the influence on pain and motility did not reveal any significant differences between the two drugs. Neither the evaluation of the recorded side effects nor the laboratory tests showed any statistical difference between the two therapies. The gastrointestinal complaints occurred more frequently in the indometacin group (5 of 20, of these 3 withdrawals) than in the acemetacin group (3 of 20, of these 1 withdrawal). However, this difference was not statistically secured. Evaluation of the therapeutic effect did not reveal any significant differences between acemetacin and indometacin at the administered molar dose ratio of 1:2. However, the acemetacin therapy had a markedly improved gastrointestinal tolerability.

[Results of a long-term study with acemetacin in the therapy of patients suffering from rheumatoid arthritis (author's transl)]. / Ergebnisse einer Langzeitstudie mit Acemetacin bei der Behandlung von Patienten mit chronischer Polyarthritis.

Within the framework of a long-term study the efficacy and tolerability of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-acetoxy] acetic acid (acemetacin, TV 1322, Rantudil) were tested in 26 female patients suffering from rheumatoid arthritis. The patients were aged between 32 and 78 years. The duration of therapy was 24 weeks. After daily doses of 90-180 mg acemetacin the functional impairment improved by approx. 47%, pain by approx. 44% and articular swelling by approx. 5%. These results were achieved although of 22 assessable cases 14 female patients had received indometacin for at least 4 weeks before the study and 8 female patients had received other non-steroidal antirheumatic agents. The tolerability of acemetacin was very good. Only one female patient complained of a gastrointestinal disorder which led to withdrawal of the therapy. The side effect disappeared after withdrawal of the therapy. None of the laboratory values produced any evidence that a long-term acemetacin therapy would unfavourably influence the haemopoietic system or the parenchymatous organs. The therapeutic efficacy observed in this study and the low side effect rate indicate the great safety of an acemetacin therapy.

[Aliphatic diamines and histamine in the serum of patients with chronic polyarthritis]. / Die Untersuchung der aliphatischen Diamine und des Histamins im Serum von Patienten mit chronischer Polyarthritis.

The concentration of histamine, cadaverine, putrescine as well as spermidine and spermine was measured in blood serum of patients with rheumatoid arthritis (RA). In comparison to normals there is no statistically significant difference in the concentration of putrescine and spermidine in blood serum of RA patients. Spermine which could be detected in all samples too did not show distinct abnormalities from healthy subjects. Histamine and cadaverine present in measurable amounts were only in particular cases. A relation between increased histamine and basophile count was not demonstrable. There is apparently no correlation between histidinemia which is reported in the literature for RA patients in blood serum and plasma, and histamine production in the blood.