Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial.

OBJECTIVE: To compare the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: MTX-naive patients with active RA (Disease Activity Score in 28 joints >or= 4) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to randomization. Patients were randomly assigned to receive 15 mg/week of MTX either orally (2 7.5-mg tablets plus a dummy prefilled syringe; n=187 patients) or SC (prefilled syringe containing 10 mg/ml plus 2 dummy tablets; n=188 patients) for 24 weeks. At week 16, patients who did not meet the American College of Rheumatology criteria for 20% improvement (ACR20) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks, still in a blinded manner. The primary outcome was an ACR20 response at 24 weeks. RESULTS: At week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 (78% versus 70%) and ACR70 (41% versus 33%) responses. Patients with a disease duration >or= 12 months had even higher ACR20 response rates (89% for SC administration and 63% for oral). In 52 of the ACR20 nonresponders (14%), treatment was switched at week 16. Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX resulted in 30% and 23% ACR20 response rates, respectively, in these patients. MTX was well tolerated. The rate of adverse events was similar in all groups. CONCLUSION: This 6-month prospective, randomized, controlled trial is the first to examine oral versus SC administration of MTX. We found that SC administration was significantly more effective than oral administration of the same MTX dosage. There was no difference in tolerability.

Morphological Characterization of the Molecular Superstructure of Polyphenylene Ethynylene Derivatives.

Two different polyphenylene ethynylene derivatives, one partly hydrophobic and one hydrophilic, were investigated with a combination of X-ray and light scattering techniques and hydrodynamic techniques, as well as scanning force microscopy and transmission electron microscopy to elucidate their molecular structure and aggregation behavior in tetrahydrofuran and water, respectively. It turns out that both polymers possess a rod-like molecular architecture which, however, is the basis of a cascade of aggregation steps. Both, electron microscopy and X-ray analysis support the concept of a primary back-to-back aggregation of polymer chains into cylindrically shaped aggregates with high anisometry. The thickness of these aggregates was between 4.0 and 4.5 nm. The aggregates of the hydrophobic polymer further associate into fibrils and these fibrils form clusters of globular shape, though with high internal anisometry. Copyright 1999 Academic Press.

Cisapride increases gallbladder volume in gallstone patients before and after extracorporeal shock wave lithotripsy.

We have previously shown that oral cisapride causes a dose-related increase of fasting gallbladder volume in healthy subjects. The present study investigates the effect of cisapride on gallbladder motility in 16 patients with gallbladder stones; 8 patients had no biliary symptoms, but the other 8 patients with symptomatic gallstone disease were studied before and 6 weeks after extracorporeal shock wave lithotripsy (ESWL). For each study the patients received a single oral dose of 20 mg cisapride; fasting gallbladder volume was measured by ultrasound before, and for 120 minutes after, drug administration. In the 8 asymptomatic patients a mean maximal increase of the fasting volume to 152.7 +/- 7.6% of the initial value was observed at a mean 97.5 +/- 8.3 minutes after cisapride ingestion. Similarly, in the 8 patients with biliary pain mean fasting volume after cisapride ingestion increased to 141.3 +/- 5.7% before ESWL treatment and to 145.0 +/- 5.8% after ESWL and 6 weeks of oral litholytic therapy. There were no significant differences between the results in the symptomatic and asymptomatic patients. Our results indicate that cisapride increases the gallbladder volume in gallstone patients regardless of biliary symptoms. Similar volume changes were observed before therapy and after ESWL with bile acid therapy. The therapeutic efficacy of litholytic agents could be diminished by simultaneous cisapride administration.

Cardiac involvement during and after malaria.

In 22 patients without a previous history of cardiac disease, we prospectively evaluated cardiac involvement during acute malaria and 9 +/- 5 months after recovery using non-invasive methods including resting electrocardiogram (ECG) and two-dimensional (2D) echocardiography. During the acute phase ECG abnormalities were common (5/22); pericardial effusion was found in 2 patients and global left ventricular hypokinesia in 1 patient infected with Plasmodium falciparum. At a follow-up of 19 patients, the resting ECG and echocardiography were normal or had normalized in all patients. The results of our study suggest that persistent cardiac damage following malarial infection seems to be rare; however, further trials in a larger patient population are needed to confirm our findings.

Failure of radiotherapy to resolve fatal lung damage due to paraquat poisoning.

The most effective treatment of severe paraquat poisoning in man is uncertain. In order to prevent pulmonary fibrosis, we employed radiotherapy of both lungs in a 23-year-old patient with severe paraquat poisoning; however, it failed to prevent the fatal outcome.

[Acute pneumocystosis during polychemotherapy following the MACOP-B protocol]. / Akute Pneumozystosen unter Polychemotherapie nach dem MACOP-B-Protokoll.

Four out of eleven patients--none of them HIV positive--who received treatment for non-Hodgkin lymphoma by the MACOP-B protocol between June 1989 and February 1990 were taken ill during or shortly after the conclusion of the course with fulminant pneumonia necessitating artificial ventilation. In three cases Pneumocystis carinii was identified as the pathogen, and in one patient the diagnosis of pneumocystosis seemed probable. The mean cumulative doses given before the outbreak of pneumonia were as follows: cyclophosphamide 2753 +/- 1161 mg, methotrexate 1590 +/- 667 mg, bleomycin 36 +/- 16.8 mg and prednisone 4378 +/- 1734 mg. The mean haemoglobin concentration was 10.7 +/- 0.5 g/dl, leucocyte count 5250 +/- 2100/microliters, lymphocyte count 1300 +/- 300/microliters and lactate dehydrogenase 227 +/- 34 U/l. The cumulative doses and laboratory findings in the seven patients not affected by pneumocytosis were not significantly different. The patients with pneumonia were supported by mechanical ventilation for 6-26 days and treated with large doses of corticosteroids and co-trimoxazole. One patient died after 17 days' ventilation. Three patients were successfully weaned from the ventilator. Chemotherapy protocols such as MACOP-B predispose to acute Pneumocystis pneumonia. The risk of infection is independent of the cumulative doses of the drugs employed. For this reason, prophylaxis with co-trimoxazole is normally mandatory.